Stem Cells & Wnt

ROCK Inhibitors as an Alternative Therapy for Corneal Grafting: A Systematic Review

329 | Feb 15 2024

The review on ROCK inhibitors for corneal wound healing showcases their diverse therapeutic potential across various ocular conditions, offering promise as an effective alternative to human donor tissue for addressing the significant unmet medical need in corneal blindness. [Read the Full Post]

Frailty and risk of serious infections in patients with rheumatoid arthritis treated with biologic or targeted-synthetic DMARDs

110 | Feb 04 2024

Frailty significantly amplifies the risk of serious infections and hospitalizations in rheumatoid arthritis patients starting biologic or targeted synthetic disease-modifying drugs, emphasizing the crucial need for tailored interventions in higher-risk populations. [Read the Full Post]

Isolinderalactone Induces Apoptosis, Autophagy, Cell Cycle Arrest and MAPK Activation through ROS-Mediated Signaling in Colorectal Cancer Cell Lines

164 | Jan 23 2024

Isolinderalactone demonstrates significant potential as a therapeutic agent for colorectal cancer by inducing G2/M phase arrest, apoptosis, autophagy, and MAPK pathway activation via ROS-mediated signaling in human CRC cells. [Read the Full Post]

Chaetocin-mediated SUV39H1 inhibition targets stemness and oncogenic networks of diffuse midline gliomas and synergizes with ONC201

190 | Jan 22 2024

Targeting the SUV39H1-H3K9me3 pathway in DIPG cells with chaetocin, and combining it with a DRD2 antagonist like ONC201, presents a promising strategy for effective treatment by exploiting vulnerabilities and overcoming resistance mechanisms. [Read the Full Post]

Contribution of Telomere Length to Systemic Sclerosis Onset: A Mendelian Randomization Study

105 | Jan 21 2024

The study utilizing Mendelian randomization suggests a causal link between longer leukocyte telomere length and a reduced risk of systemic sclerosis, implicating the influence of specific genetic variants in TERC and TERT genes. [Read the Full Post]

Astragalus polysaccharide ameliorates insulin resistance in HepG2 cells through activating the STAT5/IGF-1 pathway

152 | Jan 21 2024

Astragalus polysaccharide alleviates insulin resistance in HepG2 cells by activating the STAT5/IGF-1 pathway, as evidenced by its restoration of impaired glucose uptake and modulation of IGF-1, IGF-1 receptor, AKT, and STAT5 signaling, findings reinforced by the counteraction of its effects by the STAT5 inhibitor AG490. [Read the Full Post]

JAK2 Inhibitor, Fedratinib, Inhibits P-gp Activity and Co-Treatment Induces Cytotoxicity in Antimitotic Drug-Treated P-gp Overexpressing Resistant KBV20C Cancer Cells

102 | Jan 17 2024

Fedratinib's combination with vincristine demonstrates promising cytotoxicity specifically in P-glycoprotein-overexpressing drug-resistant cancer cells, suggesting its potential as an effective co-treatment strategy for multidrug-resistant cancers. [Read the Full Post]

Novel Janus-kinase (JAK) Inhibitors in Myelofibrosis

103 | Jan 11 2024

This comprehensive review highlights the evolving landscape of JAK inhibitors in myelofibrosis treatment, emphasizing their varying efficacy in addressing symptoms and the need for further studies to ascertain their precise impact and facilitate more personalized therapeutic approaches. [Read the Full Post]

Outcomes and Safety of Suprapubic vs Urethral Catheterization Following Pelvic Fascia Sparing Robotic Prostatectomy

62 | Jan 10 2024

Suprapubic catheters post Pelvic Fascia Sparing Robotic-Assisted Radical Prostatectomy (PFS-RARP) exhibit a notable advantage over urethral catheters by enabling earlier continence recovery and higher continence rates at catheter removal, potentially enhancing overall patient satisfaction without compromising quality of life. [Read the Full Post]

Wnt signaling pathway inhibitor promotes mesenchymal stem cells differentiation into cardiac progenitor cells in vitro and improves cardiomyopathy in vivo

72 | Jan 04 2024

"IWP-4 treatment of mesenchymal stem cells from human umbilical cord tissue enhances cardiac differentiation, leading to improved myocardial regeneration and functional recovery in a myocardial infarction rat model." [Read the Full Post]

Evolution of Ritlecitinib Population Pharmacokinetic Models During Clinical Drug Development

110 | Dec 31 2023

The iterative development of a population pharmacokinetic model for ritlecitinib, integrating data from diverse clinical trials, culminated in a refined two-compartment model with direct-response non-stationary clearance, informing critical clinical decisions and shaping the drug's label across varied conditions. [Read the Full Post]

CCT251545 enhances drug delivery and potentiates chemotherapy in multidrug-resistant cancers by Rac1-mediated macropinocytosis

101 | Dec 30 2023

The study's findings suggest that CCT251545 in combination with chemotherapy demonstrates a potent synergistic effect by enhancing drug uptake through Rac1-dependent macropinocytosis and elevating NAD levels, providing a promising avenue for managing multidrug-resistant cancers. [Read the Full Post]

Effects of combined exposure to ethanol and delta-9-tetrahydrocannabinol during adolescence on synaptic plasticity in the prefrontal cortex of Long Evans rats

92 | Dec 29 2023

Exposure to ethanol, THC, or their combination during adolescence in rats resulted in reduced body weight gain, altered substance intake, and disrupted long-term depression in the medial prefrontal cortex, potentially implicating lasting changes in GABA and GSK3β signaling pathways. [Read the Full Post]

Nanoparticles overcome adaptive immune resistance and enhance immunotherapy via targeting tumor microenvironment in lung cancer

68 | Dec 25 2023

"Through nanoparticle-based modulation of the tumor microenvironment, this review underscores a promising avenue to overcome immune resistance to PD-1/PD-L1 blockade in lung cancer, potentially revolutionizing the landscape of immunotherapy for these patients." [Read the Full Post]

Correlating Basal Gene Expression across Chemical Sensitivity Data to Screen for Novel Synergistic Interactors of HDAC Inhibitors in Pancreatic Carcinoma

120 | Dec 22 2023

This study employs a bioinformatics screening protocol integrating drug-sensitivity data and basal gene expression to predict synergistic combinations of histone deacetylase inhibitors (HDACi), identifying the sphingolipid signaling pathway as a promising target; further experimental validation reveals novel synergisms between HDACi and a Rho-associated protein kinase (ROCK) inhibitor RKI-1447, as well as between HDACi and a sphingosine 1-phosphate (S1P) receptor agonist fingolimod in the treatment of pancreatic ductal adenocarcinoma (PDAC). [Read the Full Post]

In vitro antineoplastic effects of MK0752 in HPV-positive head and neck squamous cell carcinoma

113 | Dec 19 2023

The study demonstrates the potential therapeutic efficacy of the gamma-secretase inhibitor MK0752 in head and neck squamous cell carcinoma, particularly inducing apoptosis in human-papillomavirus-positive tumors, suggesting its viability as a targeted treatment option pending further validation and mechanistic exploration. [Read the Full Post]

Synthesis and biological evaluation of 4-(pyridin-4-oxy)-3-(3,3-difluorocyclobutyl)-pyrazole derivatives as novel potent transforming growth factor-β type 1 receptor inhibitors

85 | Dec 19 2023

Compound 15r, a novel 4-(pyridin-4-oxy)-3-(3,3-difluorocyclobutyl)-pyrazole derivative, demonstrated potent inhibition of the TGF-β type 1 receptor (ALK5), with favorable pharmacokinetic properties, superior bioavailability to LY-3200882, and significant efficacy in inhibiting tumor growth in a CT26 xenograft mouse model. [Read the Full Post]

Pseudolycorine chloride ameliorates Th17 cell-mediated central nervous system autoimmunity by restraining myeloid-derived suppressor cell expansion

101 | Dec 18 2023

Pseudolycorine chloride (PLY), a constituent of Narcissus tazetta L. var. Chinensis Roem, demonstrates immunomodulatory effects by inhibiting myeloid-derived suppressor cells (MDSCs) and Th17 cell-mediated inflammation, making it a promising candidate for the treatment of multiple sclerosis and other autoimmune diseases. [Read the Full Post]

Claudin-3 facilitates the progression and mediates the tumorigenic effects of TGF-β in glioblastoma multiforme

83 | Dec 17 2023

The study demonstrates that upregulated Claudin-3 in glioblastoma multiforme stimulates tumor cell growth, promotes epithelial-mesenchymal transition, and enhances the tumorigenic effects of transforming growth factor-β, suggesting that specific inhibitors targeting Claudin-3 could represent a promising approach for treating this aggressive brain tumor. [Read the Full Post]

5-HT6 receptor antagonists. Design, synthesis, and structure-activity relationship of substituted 2-(1-methyl-4-piperazinyl)pyridines

124 | Dec 16 2023

The study presents a novel series of 6-piperazinyl-7-azaindoles demonstrating potent 5-HT6 receptor antagonism, with a focus on optimizing the lead structure and exploring structure-activity relationships, highlighting Compound 29 as a promising candidate for further drug development. [Read the Full Post]

Cardiac RGS7 and RGS11 drive TGFβ1-dependent liver damage following chemotherapy exposure

59 | Dec 14 2023

The research findings reveal that RGS7 controls the release of TGFβ1 from the heart, influencing the multiorgan damage caused by chemotherapy and emphasizing the importance of cardiokine signaling in this process. [Read the Full Post]

Regulatory mechanism of NOV/CCN3 in the inflammation and apoptosis of lung epithelial alveolar cells upon lipopolysaccharide stimulation

58 | Dec 12 2023

In the LPS-induced acute lung injury model, CCN3 knockdown significantly attenuated inflammatory cytokine expression, reduced apoptosis in alveolar epithelial cells, and inhibited NF-κB activation, indicating its pivotal role in regulating lung inflammation and apoptosis via the TGF-β/p-Smad or NF-κB pathway. [Read the Full Post]

Inhibition of DNA methylation attenuates lung ischemia-reperfusion injury after lung transplantation

80 | Dec 11 2023

"Inhibition of DNA methylation, particularly through azathioprine treatment, attenuates lung ischemia-reperfusion injury by suppressing inflammation, oxidative stress, and endothelial dysfunction, highlighting its therapeutic potential for improving outcomes in lung transplantation." [Read the Full Post]

Retinoic acid delays murine palatal shelf elevation by inhibiting Wnt5a-mediated noncanonical Wnt signaling and downstream Cdc-42/F-actin remodeling in mesenchymal cells

111 | Dec 10 2023

This study elucidates the mechanism by which retinoic acid disrupts palate development, causing cleft palate in mice, revealing the crucial role of Wnt5a-mediated noncanonical Wnt signaling downstream of Rho GTPase Cdc42 in regulating cytoskeletal remodeling and cell migration during the process. [Read the Full Post]

Dnmt3a is downregulated by Stat5a and mediates G0/G1 arrest by suppressing the miR-17-5p/Cdkn1a axis in Jak2V617F cells

106 | Dec 06 2023

**In Jak2V617F positive classical myeloproliferative neoplasms, aberrant activation of Stat5a downregulates Dnmt3a through binding to its promoter, leading to dysregulation of the miR-17-5p/Cdkn1a axis and G0/G1 cell cycle arrest, providing a potential therapeutic target.** [Read the Full Post]

Regional regulatory harmonisation initiatives: Their potential contribution to the newly established African medicines agency

276 | Nov 30 2023

The study highlights the foundational role of regional medicines regulatory harmonization programs, such as the African Medicines Regulatory Harmonisation (AMRH) and East African Community Medicines Regulatory Harmonisation (EAC-MRH) initiatives, in supporting the operationalization of the African Medicine Agency (AMA), emphasizing the importance of strong national regulatory authorities and increased ratification of the AMA Treaty for ensuring access to essential medical products and technologies for the African people. [Read the Full Post]

Lauric Acid, a Dietary Saturated Medium-Chain Fatty Acid, Elicits Calcium-Dependent Eryptosis

108 | Nov 29 2023

The study demonstrates that lauric acid induces eryptosis, a programmed cell death in red blood cells, and disrupts leukocyte distribution, providing key insights into its role in cardiovascular diseases and informing dietary interventions for prevention and management. [Read the Full Post]

Overfit deep neural network for predicting drug-target interactions

267 | Nov 27 2023

The OverfitDTI framework utilizes intentionally overfitted deep neural networks to accurately capture the intricate relationships between drugs and targets, enabling precise drug-target interaction predictions, as demonstrated by the successful identification and experimental validation of TEK inhibitors. [Read the Full Post]

Direct Differentiation of Bone Marrow Mononucleated Cells Into Insulin-Producing Cells Using 4 Specific Soluble Factors

114 | Nov 23 2023

The study developed a differentiation method using a unique combination of four differentiation-inducing factors to transform bone marrow-derived stem cells into mature insulin-producing cells, offering a potential novel approach for cell-based therapy in diabetes mellitus. [Read the Full Post]

Identifying promising GSK3β inhibitors for cancer management: a computational pipeline combining virtual screening and molecular dynamics simulations

126 | Nov 21 2023

The computational screening study identified BMS-754807 and GSK429286A as promising GSK3β inhibitors with high binding affinities, suggesting their potential as novel anticancer drugs pending experimental validation. [Read the Full Post]

Hydrogen Sulfide Improves Outcomes in a Murine Model of Necrotizing Enterocolitis via the Cys440 Residue on Endothelial Nitric Oxide Synthase

171 | Nov 17 2023

GYY4137 administration improves clinical outcomes, attenuates intestinal and lung injury, and enhances perfusion in a murine model of necrotizing enterocolitis, with these protective effects being contingent upon the presence of the Cys440 residue in endothelial nitric oxide synthase (eNOS). [Read the Full Post]

Scutellarin suppresses the metastasis of triple-negative breast cancer via targeting TNFα/TNFR2-RUNX1-triggered G-CSF expression in endothelial cells

257 | Nov 13 2023

Scutellarin (SC) inhibits metastasis in triple-negative breast cancer (TNBC) by disrupting the TNFα/TNFR2-initiated RUNX1 activation and subsequent G-CSF production in TNBC-associated endothelial cells (ECs). [Read the Full Post]

Tumor-associated astrocytes promote tumor progression of Sonic Hedgehog medulloblastoma by secreting lipocalin-2

203 | Nov 12 2023

The research reveals that tumor-associated astrocytes (TAAs) secrete lipocalin-2 (LCN2) through the STAT3 signaling pathway, promoting the progression of Sonic Hedgehog (SHH) subgroup medulloblastoma (MB) and indicating LCN2's potential as a prognostic marker and therapeutic target. [Read the Full Post]

The Anti-Breast Cancer Stem Cell Potency of Copper(I)-Non-Steroidal Anti-Inflammatory Drug Complexes

74 | Nov 10 2023

A series of copper(I) complexes combining non-steroidal anti-inflammatory drugs (NSAIDs) and triphenylphosphine ligands demonstrated potent anti-breast cancer stem cell activity, reducing cell viability and increasing intracellular reactive oxygen species (ROS) levels, potentially opening new avenues for breast cancer treatment. [Read the Full Post]

Targeting GSTP1 as Therapeutic Strategy against Lung Adenocarcinoma Stemness and Resistance to Tyrosine Kinase Inhibitors

157 | Nov 07 2023

The study reveals that upregulation of Glutathione S-transferase pi (GSTP1) in lung adenocarcinoma (LUAD) supports cancer stem cells, tumor self-renewal, metastasis, and resistance to targeted therapies, making it a promising therapeutic target for long-term control of LUAD. [Read the Full Post]

Comprehensive Analysis of the Expression, Prognostic Value, and Immune Infiltration Activities of GABRD in Colon Adenocarcinoma

87 | Nov 03 2023

GABRD expression in colon adenocarcinoma is significantly elevated and correlated with advanced clinical stage, poor prognosis, immune cell infiltration patterns, and potential drug resistance. [Read the Full Post]

Dynamic expression of IGFBP3 modulate dual actions of mineralization micro-environment during tooth development via Wnt/beta-catenin signaling pathway

96 | Oct 31 2023

This study demonstrates that IGFBP3 regulates the mineralization microenvironment during tooth development through its modulation of the DKK1-Wnt/beta-catenin axis, highlighting its potential importance in tooth regeneration and dental care. [Read the Full Post]

Tumor lysates-constructed hydrogel to potentiate tumor immunotherapy

82 | Oct 29 2023

An injectable tumor lysates-constructed hydrogel has been developed to address the challenges of T cell-based immunotherapy, providing a robust antigen reservoir, preventing T cell exhaustion, and suppressing immune evasion, thereby enhancing the effectiveness of tumor treatment. [Read the Full Post]

Identification of Tau-Tubulin Kinase 1 Inhibitors by Microfluidics-based Mobility Shift Assay from a Kinase Inhibitor Library

156 | Oct 29 2023

This study identified a peptide substrate for human TTBK1 and developed a microfluidics-based assay, enabling the screening of kinase inhibitors and the potential development of novel hTTBK1 inhibitors for Alzheimer's disease prevention. [Read the Full Post]

Inhibiting STAT5 significantly attenuated Ang II-induced cardiac dysfunction and inflammation

104 | Oct 28 2023

Inhibition of STAT5 using STAT5-IN-1 effectively reduces cardiac hypertrophy in Ang II-induced mice by decreasing inflammation, suggesting a potential therapeutic strategy for mitigating hypertrophy. [Read the Full Post]

A novel denoising method for low-dose CT images based on transformer and CNN

112 | Oct 28 2023

The paper proposes a novel LDCT image denoising method based on a transformer combined with a convolutional neural network (CNN), which effectively removes noise and improves image quality, outperforming state-of-the-art models in evaluation metrics such as PSNR, SSIM, and RMSE. [Read the Full Post]

Bioengineered stem cell membrane functionalized nanoparticles combine anti-inflammatory and antimicrobial properties for sepsis treatment

109 | Oct 27 2023

The novel nanometer drug loading system, FZ/MER-AgMOF@Bm, effectively combats sepsis by delivering anti-inflammatory and antibacterial agents to infectious microenvironments, reducing inflammation, eliminating bacteria, and improving survival outcomes in a mouse model of sepsis. [Read the Full Post]

Traf2 and NCK Interacting Kinase Is a Critical Regulator of Procollagen I Trafficking and Hepatic Fibrogenesis in Mice

187 | Oct 27 2023

The study identified TNIK as a key kinase involved in procollagen I trafficking and demonstrated its potential as a therapeutic target for hepatic fibrosis. [Read the Full Post]

YAP and β-catenin cooperate to drive H. pylori-induced gastric tumorigenesis

117 | Oct 26 2023

This study provides evidence that the interaction between Yes-associated protein 1 (YAP) and β-catenin synergistically promotes H. pylori-induced gastric carcinogenesis and identifies shared downstream genes, CDX2, LGR5, and RUVBL1, potentially contributing to the pathogenesis of H. pylori-associated gastric cancer. [Read the Full Post]

RBM15 silencing promotes ferroptosis by regulating the TGF-β/Smad2 pathway in lung cancer

123 | Oct 22 2023

Silencing of RNA binding motif protein 15 (RBM15) promotes ferroptosis and inhibits lung cancer cell growth through the TGF-β/Smad2 pathway, offering potential therapeutic implications for lung cancer treatment. [Read the Full Post]

Double crosslinked biomimetic composite hydrogels containing topographical cues and WAY-316606 induce neural tissue regeneration and functional recovery after spinal cord injury

90 | Oct 21 2023

The study presents a multifunctional biomaterial system composed of acellularized spinal cord matrix, gelatin-acrylated-β-cyclodextrin-polyethene glycol diacrylate hydrogel, and aligned polycaprolactone microfibers, loaded with WAY-316606, which effectively promotes neural tissue regeneration and significantly improves motor function in rats with spinal cord injury. [Read the Full Post]

[Efficacy of Tyrosine Kinase Inhibitor Combined with Decitabine, Homoharringtonine, Interferon in the Maintenance Therapy of Blast Phase Chronic Myeloid Leukemia]

105 | Oct 21 2023

The combination of tyrosine kinase inhibitor (TKI) with decitabine, homoharringtonine, and interferon as maintenance therapy significantly prolongs event-free survival, duration of remission, and overall survival in blast phase chronic myeloid leukemia (CML-BP) patients who have achieved a major hematological response compared to TKI combined with conventional chemotherapy. [Read the Full Post]

Bioactive components and molecular mechanisms of Salvia miltiorrhiza Bunge in promoting blood circulation to remove blood stasis

177 | Oct 16 2023

Salvia miltiorrhiza Bunge (SM) contains phenolic acids and tanshinones that synergistically target multiple signaling pathways to enhance blood circulation and alleviate blood stasis, making it an effective herbal medicine for the treatment of blood stasis syndrome. [Read the Full Post]

BMP9-ID1 Signaling Activates HIF-1α and VEGFA Expression to Promote Tumor Angiogenesis in Hepatocellular Carcinoma

101 | Oct 15 2023

The study indicates that targeting BMP9-ID1 signaling may serve as a promising therapeutic strategy for advanced hepatocellular carcinoma (HCC) by inhibiting angiogenesis. [Read the Full Post]

Apatinib Inhibits Stem Properties and Malignant Biological Behaviors of Breast Cancer Stem Cells by Blocking Wnt/β-catenin Signal Pathway through Downregulating LncRNA ROR

50 | Oct 12 2023

Apatinib effectively inhibits the stem-like properties and malignant behaviors of breast cancer stem cells (BCSCs) by suppressing the Wnt/β-catenin pathway through downregulation of lncRNA ROR. [Read the Full Post]

CRIP1 supports the growth and migration of AML-M5 subtype cells by activating Wnt/β-catenin pathway

103 | Oct 10 2023

CRIP1, an oncogene overexpressed in AML cells, promotes cell survival and migration through the activation of the Wnt/β-catenin pathway, making it a potential therapeutic target for AML-M5 treatment. [Read the Full Post]

Anti-hepatocellular carcinoma activity of the cyclin-dependent kinase inhibitor AT7519

140 | Oct 07 2023

The research findings suggest that AT7519, a CDK inhibitor, shows potential as a monotherapy or in combination with drugs like gefitinib or cabozantinib, to improve the effectiveness of treatments for hepatocellular carcinoma. [Read the Full Post]

Inhibition of tumor propellant glutathione peroxidase 4 induces ferroptosis in cancer cells and enhances anticancer effect of cisplatin

95 | Oct 06 2023

The study confirms that GPX4 acts as an oncogene, inhibits ferroptosis in cancer cells, and its inhibition enhances the anticancer effect of cisplatin. [Read the Full Post]

Ultrasound-triggered in situ gelation with ROS-controlled drug release for cartilage repair

66 | Oct 05 2023

A novel ROS-responsive in situ nanocomposite hydrogel loaded with kartogenin (KGN) and bone marrow-derived stem cells (BMSCs) effectively promotes chondrogenic differentiation and improves cartilage regeneration, offering potential for efficient cartilage repair. [Read the Full Post]

The Novel Small-Molecule SR18662 Efficiently Inhibits the Growth of Colorectal Cancer In Vitro and In Vivo

67 | Oct 03 2023

The study demonstrated that the small-molecule compound SR18662, which inhibits Krüppel-like factor 5 (KLF5), significantly reduced the growth and proliferation of colorectal cancer cells, induced cell cycle arrest and apoptosis, modulated key signaling pathways, and inhibited xenograft growth in mice, indicating its potential as a therapeutic candidate for colorectal cancer. [Read the Full Post]

Effectiveness of netarsudil 0.02% in lowering intraocular pressure in patients with secondary glaucoma

133 | Oct 01 2023

Netarsudil, 0.02%, was found to be effective in lowering intraocular pressure (IOP) in patients with secondary forms of glaucoma, especially uveitic glaucoma. [Read the Full Post]

Bone impact after two years of low-dose oral contraceptive use during adolescence

184 | Sep 29 2023

The present study indicates that the use of combined hormonal contraceptives in healthy adolescents is associated with compromised bone mass acquisition, with a more pronounced negative impact observed in those using contraceptives containing 30 μg of Ethinylestradiol. [Read the Full Post]

TXNIP Suppresses the Osteochondrogenic Switch of Vascular Smooth Muscle Cells in Atherosclerosis

90 | Sep 28 2023

TXNIP is identified as a novel regulator of atherosclerotic calcification by suppressing bone morphogenetic protein signaling and inhibiting the phenotypic transition of vascular smooth muscle cells towards an osteochondrogenic phenotype. [Read the Full Post]

ERK inhibitor ASN007 effectively overcomes acquired resistance to EGFR inhibitor in non-small cell lung cancer

76 | Sep 27 2023

The study demonstrates that targeting the ERK signaling pathway with the selective inhibitor ASN007 in combination with EGFR TKIs holds promise for overcoming acquired resistance and inhibiting tumor growth in EGFR-mutated non-small cell lung cancer (NSCLC) patients. [Read the Full Post]

RNF112-mediated FOXM1 ubiquitination suppresses the proliferation and invasion of gastric cancer

203 | Sep 27 2023

RNF112 suppresses gastric cancer progression by directly ubiquitinating FOXM1, making the RNF112/FOXM1 axis a potential prognostic biomarker and therapeutic target in gastric cancer. [Read the Full Post]

Effectiveness of netarsudil 0.02% in lowering intraocular pressure in patients with secondary glaucoma

181 | Sep 27 2023

Netarsudil, 0.02%, was found to effectively lower intraocular pressure in patients with secondary forms of glaucoma, particularly uveitic glaucoma, based on a retrospective study. [Read the Full Post]

Development and Therapeutic Implications of Tyrosine Kinase 2 Inhibitors

114 | Sep 19 2023

Selective TYK2 inhibitors, such as deucravacitinib and ropsacitinib, offer a promising approach for treating inflammatory and autoimmune diseases with improved efficacy and safety profiles compared to broad JAK inhibitors. [Read the Full Post]

Novel Therapies in Plaque Psoriasis: A Review of Tyrosine Kinase 2 Inhibitors

127 | Sep 18 2023

Deucravacitinib, an allosteric tyrosine kinase 2 inhibitor, has been approved as a first-in-class treatment for moderate-to-severe plaque psoriasis and shows improved safety compared to orthosteric Janus kinase inhibitors. [Read the Full Post]

Deuterium in drug discovery: progress, opportunities and challenges

173 | Sep 05 2023

Deuteration, the substitution of a hydrogen atom with its heavy isotope deuterium, has emerged as a promising strategy in drug discovery and development, offering the potential to enhance drug efficacy and safety through improved pharmacokinetic and toxicity profiles. [Read the Full Post]

Clinical Utility of Deucravacitinib for the Management of Moderate to Severe Plaque Psoriasis

150 | Sep 05 2023

Deucravacitinib, a first-in-class TYK2 small molecule inhibitor, shows significant clinical efficacy and a favorable safety profile in the treatment of moderate-to-severe psoriasis based on a systematic review and meta-analysis of randomized controlled trials. [Read the Full Post]

Evaluation of KRASG12C inhibitor responses in novel murine KRASG12C lung cancer cell line models

172 | Aug 30 2023

The generation of three novel murine KRASG12C-driven lung cancer cell lines provides valuable models for studying and improving therapeutic combination strategies with KRASG12C inhibitors. [Read the Full Post]

Efficacy and Safety of Tyrosine Kinase 2/Janus Kinase 1 Inhibitor Brepocitinib for Active Psoriatic Arthritis: A Phase IIb Randomized Controlled Trial

94 | Aug 28 2023

The phase IIb study showed that brepocitinib at doses of 30 mg and 60 mg once daily (QD) was more effective than placebo in reducing symptoms of psoriatic arthritis (PsA) and demonstrated a favorable safety profile throughout the 52-week study. [Read the Full Post]

Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases

124 | Aug 25 2023

This comprehensive review highlights the structure, biological functions, and therapeutic potential of CLKs and their inhibitors, shedding light on their significance in various human diseases and paving the way for future clinical treatments. [Read the Full Post]

Comparison of multiple synthetic chondroinductive factors in pellet culture against a TGF-β positive control

132 | Aug 25 2023

The current study found that, despite the promising potential of CM10, CK2.1, kartogenin, and SM04690 as chondroinductive agents, they did not exhibit higher gene expression of chondrogenic markers compared to the positive control TGF-β3, suggesting the need for further research and identification of new chondroinductive factors. [Read the Full Post]

Comparing how well abrocitinib and dupilumab treat atopic dermatitis signs and symptoms: a plain language summary

80 | Aug 25 2023

The summary discusses a clinical study that found abrocitinib to be more effective than dupilumab in quickly improving the signs and symptoms of moderate to severe atopic dermatitis (AD) in individuals who did not respond to prescribed topical medications. [Read the Full Post]

Efficacy and safety of abrocitinib for moderate-to-severe atopic dermatitis in adolescents and adults: Meta-analysis

152 | Aug 25 2023

This meta-analysis suggests that abrocitinib is both safe and effective in treating moderate-to-severe atopic dermatitis in adolescents and adults, with the 200 mg dose showing a greater efficacy compared to the 100 mg dose. [Read the Full Post]

Pulsatilla Saponins Inhibit Experimental Lung Metastasis of Melanoma via Targeting STAT6-Mediated M2 Macrophages Polarization

93 | Aug 21 2023

Pulsatilla saponins derived from Pulsatilla chinensis effectively suppress tumor progression by inhibiting the polarization of M2 macrophages through the STAT6 signaling pathway, revealing a novel mechanism for their anti-tumor activity. [Read the Full Post]

Results of an open-label phase 1b study of the ERK inhibitor MK-8353 plus the MEK inhibitor selumetinib in patients with advanced or metastatic solid tumors

75 | Aug 21 2023

The combination of MK-8353 and selumetinib at 50/25 mg and 100/50 mg doses demonstrated acceptable safety and tolerability in patients with advanced solid tumors, while the 150/75 mg dose level was found to be intolerable with no observed objective responses. [Read the Full Post]

Pro-inflammatory role of Wnt/β-catenin signaling in endothelial dysfunction

144 | Aug 21 2023

The inhibition of the Wnt/β-catenin signaling pathway with iCRT-14 improved endothelial function by reducing inflammation and monocyte adhesion but also exhibited pro-coagulatory effects and hindered wound healing, which may impact its suitability as a therapy for atherosclerosis and vein graft failure. [Read the Full Post]

Caveolae-associated protein 3 promotes adipogenic differentiation of porcine preadipocytes by promoting extracellular signal-regulated kinase phosphorylation

72 | Aug 10 2023

The study demonstrated that CAVIN3 promotes adipogenic differentiation of porcine preadipocytes by enhancing ERK phosphorylation, providing insights into the molecular mechanism of porcine fat deposition. [Read the Full Post]

Progress in on-line, at-line, and in-line coupling of sample treatment with capillary and microchip electrophoresis over the past 10 years: A review

105 | Aug 05 2023

The review evaluates the progress of on-line, at-line, and in-line sample treatment coupled with capillary and microchip electrophoresis over the past decade, focusing on the development of flow-gating interfaces, the coupling of extraction techniques, and the design of sequential analyzers, with applications in studying living organisms and monitoring substances in diverse samples. [Read the Full Post]

Mitochondrial impairment and downregulation of Drp1 phosphorylation underlie the antiproliferative and proapoptotic effects of alantolactone on oral squamous cell carcinoma cells

82 | Jul 28 2023

The study found that alantolactone (ALT) inhibited the proliferation and promoted apoptosis of oral squamous cell carcinoma (OSCC) cells by disrupting mitochondrial homeostasis and regulating dynamin-related protein 1 (Drp1), suggesting its potential as a therapeutic candidate for OSCC. [Read the Full Post]

Diminishing the Pathogenesis of the Food-Borne Pathogen Serratia marcescens by Low Doses of Sodium Citrate

57 | Jul 24 2023

Sodium citrate, when used at low concentrations, exhibits significant anti-virulence and anti-biofilm activity against Serratia marcescens, making it a safe and effective food additive for preventing contamination and spoilage. [Read the Full Post]

Inflammatory Response and Exosome Biogenesis of Choroid Plexus Organoids Derived from Human Pluripotent Stem Cells

82 | Jul 22 2023

This study investigates the impact of Wnt signaling on inflammatory response and extracellular vesicle biogenesis in choroid plexus organoids derived from human-induced pluripotent stem cells, providing a model for drug screening and designing drug delivery systems for neurological disorders such as Alzheimer's disease and ischemic stroke. [Read the Full Post]

Krüppel-like factor 5 accelerates the pathogenesis of Alzheimer's disease via BACE1-mediated APP processing

111 | Jul 22 2023

The study reveals that Krüppel-like factor 5 (KLF5) positively regulates β-secretase (BACE1) and promotes amyloidogenic cleavage of amyloid precursor protein (APP), suggesting that targeting KLF5 or its downstream effects could be a potential strategy for preventing Alzheimer's disease progression. [Read the Full Post]

A case of nocardiosis in a patient with ulcerative colitis on chronic corticosteroids, infliximab, and upadacitinib

134 | Jul 21 2023

Immunosuppressed patients, particularly those with ulcerative colitis, are at an increased risk of unmasking obscure infections, necessitating early detection and treatment to mitigate the associated morbidity and mortality. [Read the Full Post]

The differential effects of upadacitinib treatment on skin rashes of four anatomical sites in patients with atopic dermatitis

75 | Jul 21 2023

Upadacitinib demonstrated higher therapeutic efficacy in reducing skin rashes in the lower limbs compared to the trunk and head and neck in patients with moderate-to-severe atopic dermatitis. [Read the Full Post]

The tumor stroma influences immune cell distribution and recruitment in a PDAC-on-a-chip model

199 | Jul 20 2023

This study utilized a 3D PDAC model to investigate the interaction between tumor stroma and immune cells, revealing that stromal cells create a physical and biochemical barrier that hinders immune cell infiltration, and targeting the stroma can increase immune cell infiltration, offering potential therapeutic strategies for PDAC. [Read the Full Post]

Pharmacotherapeutic advances for splenomegaly in myelofibrosis

0 | Jul 15 2023

Myelofibrosis, a hematologic malignancy characterized by splenomegaly, is primarily treated with JAK inhibitors, although spleen size reduction is not consistent, and new pharmacotherapies and combination treatments are being explored to improve outcomes. [Read the Full Post]

Comprehensive profiling of clinical JAK inhibitors in myeloproliferative neoplasms

147 | Jul 15 2023

The comprehensive profiling of four JAK2 inhibitors revealed their distinct clinical profiles, including differential effects on JAK-STAT signaling, inflammatory response, erythroid colony formation, leukemic engraftment, and iron regulation, providing valuable insights for personalized therapy in myeloproliferative neoplasm patients. [Read the Full Post]

Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors

98 | Jul 12 2023

The phase 3 clinical trial showed that nirogacestat, an oral γ-secretase inhibitor, significantly improved progression-free survival, objective response rates, and patient-reported outcomes while presenting common but mostly low-grade adverse events in adults with progressing desmoid tumors. [Read the Full Post]

Timed Notch Inhibition Drives Photoreceptor Fate Specification in Human Retinal Organoids

160 | Jul 12 2023

In this study, the researchers demonstrated that timing the inhibition of the Notch signaling pathway in human retinal organoids can enhance and synchronize the differentiation of photoreceptor cells, potentially leading to an enriched population of early cone or rod photoreceptors for transplantation therapies in vision loss disorders. [Read the Full Post]

A Phase I Study to Investigate the Safety, Tolerability and Pharmacokinetics of Napabucasin Combined with Sorafenib in Japanese Patients with Unresectable Hepatocellular Carcinoma

100 | Jul 10 2023

This phase I study in Japanese patients with unresectable hepatocellular carcinoma (HCC) demonstrated that the combination of napabucasin and sorafenib showed promising preliminary antitumor activity with manageable side effects. [Read the Full Post]

Topical Ripasudil for the Treatment of Segmental Corneal Edema: A Case Series

198 | Jul 10 2023

Topical ripasudil has shown promising results in improving vision and resolving corneal edema in patients with focal corneal edema following anterior segment surgeries, serving as an effective treatment option that may reduce the need for endothelial transplantation. [Read the Full Post]

Ripasudil-Brimonidine Fixed-Dose Combination vs Ripasudil or Brimonidine: Two Phase 3 Randomized Clinical Trials

140 | Jul 10 2023

The results of the study demonstrated that the ripasudil-brimonidine fixed-dose combination (RBFC) had a greater ability to lower intraocular pressure (IOP) compared to ripasudil or brimonidine alone. [Read the Full Post]

Apoptotic cell death in disease-Current understanding of the NCCD 2023

249 | Jul 09 2023

The Nomenclature Committee on Cell Death (NCCD) critically summarizes the extensive pre-clinical literature linking the core apoptotic apparatus to organismal homeostasis in various disease contexts, highlighting its role in both disease etiology and potential therapeutic interventions. [Read the Full Post]

Comparative transcriptome profile of mouse macrophages treated with the RhoA/Rock pathway inhibitors Y27632, Fingolimod (Gilenya), and Rezurock (Belumosudil, SLx-2119)

113 | Jul 07 2023

The transcriptome profiling study comparing macrophages treated with Y27632, Fingolimod, and Rezurock revealed distinct downregulation of GTPase and actin pathways in cell migration for Y27632 and Fingolimod, while Rezurock specifically downregulated fibrosis-related genes, providing insights into the differences in their anti-chronic rejection properties and aiding in the development of targeted therapies. [Read the Full Post]

Discovery of indoline-based derivatives as effective ROCK2 inhibitors for the potential new treatment of idiopathic pulmonary fibrosis

163 | Jul 07 2023

A new series of selective ROCK2 inhibitors based on indoline, particularly compound 9b, showed promising results in inhibiting collagen gel contraction, suppressing fibrotic markers, and exhibiting anti-pulmonary fibrosis effects in a bleomycin-induced IPF rat model, suggesting its potential as a lead compound for IPF treatment. [Read the Full Post]

Isoxazole 9 (ISX9), a small molecule targeting Axin, activates Wnt/β-catenin signalling and promotes hair regrowth

121 | Jul 05 2023

The study identified ISX9 as a novel activator of the Wnt/β-catenin pathway, promoting hair regrowth and suggesting its potential as a therapeutic agent for alopecia treatment. [Read the Full Post]

ISX-9 potentiates CaMKIIδ-mediated BMAL1 activation to enhance circadian amplitude

82 | Jul 05 2023

ISX-9, a neurogenic small molecule, has shown promising effects in improving circadian amplitude, metabolic rhythms, sleep homeostasis, and locomotive activity, making it a potential candidate for treating circadian-related disorders. [Read the Full Post]

Long non‑coding RNA LINC01960‑201 hinders decidualization of endometrial stromal cell in endometriosis: Relevance to endometrial receptivity

167 | Jul 03 2023

The study suggests that LINC01960-201 may play a regulatory role in the decidualization of endometrial stromal cells in women with endometriosis during the window of implantation, potentially affecting endometrial receptivity and recurrent abortions. [Read the Full Post]

Itacitinib Population Pharmacokinetics and Exposure-Response in Patients With Acute Graft-Versus-Host Disease

84 | Jul 01 2023

This article presents a population pharmacokinetic analysis and exposure-response assessment of itacitinib for the treatment of acute graft-versus-host disease, revealing significant predictors of treatment response and recommending dose reductions when co-administered with strong CYP3A inhibitors. [Read the Full Post]

Anna Karenina principle in personalized treatment of bladder cancer according to oncogram: which drug for which patient?

66 | Jun 28 2023

The ex vivo application of chemotherapy, immunotherapy, and targeted agents using the oncogram method showed higher good response rates compared to the control group in bladder cancer patients, with variations observed on a per-patient basis. [Read the Full Post]

Prognostic implication and immunotherapy response prediction of a ubiquitination-related gene signature in breast cancer

94 | Jun 23 2023

[Read the Full Post]

Small molecule drugs promote repopulation of transplanted hepatocytes by stimulating cell dedifferentiation

0 | Jun 23 2023

In summary, our findings suggest that the utilization of small molecule compounds that promote hepatocyte dedifferentiation may enhance the proliferation and efficacy of transplanted hepatocytes, offering potential advancements in hepatocyte therapy for end-stage liver disease. [Read the Full Post]

FOXK1 regulates epithelial-mesenchymal transition and radiation sensitivity in nasopharyngeal carcinoma via the JAK/STAT3 signaling pathway

141 | Jun 20 2023

Interference with FOXK1 in nasopharyngeal carcinoma cells through the JAK/STAT3 pathway regulates EMT, enhances radiosensitivity, and inhibits tumor progression [Read the Full Post]

JAK inhibitors for rheumatoid arthritis

0 | Jun 20 2023

JAK inhibitors have shown promise in treating rheumatoid arthritis by selectively modulating immune and inflammatory pathways, although their in vivo selectivity and long-term safety profile still require further investigation. [Read the Full Post]

Constitutive JAK/STAT signaling is the primary mechanism of resistance to JAKi in TYK2-rearranged acute lymphoblastic leukemia

180 | Jun 19 2023

The study demonstrates that sustained treatment with the JAK/TYK2 inhibitor cerdulatinib leads to JAK1 overexpression and enhanced JAK/STAT signaling in TYK2-rearranged ALL cells, but withdrawal of the drug reverses these effects, while histone deacetylase inhibitor (HDACi) therapies show efficacy against cerdulatinib-resistant cells, offering a potential alternative treatment approach for TYK2-rearranged B-ALL patients who have developed resistance to JAKi. [Read the Full Post]

Health Status, Quality of Life, Psychosocial Well-being, and Wearables Data of Patients With Active Ulcerative Colitis Receiving Filgotinib Therapy (FilgoColitis Study): Protocol for a Real-world Observational Study

124 | Jun 18 2023

The FilgoColitis study is a prospective observational study evaluating the long-term effectiveness of filgotinib in patients with active ulcerative colitis, focusing on patient-reported outcomes and incorporating the use of innovative wearables to collect physical activity data. [Read the Full Post]

Efficacy and safety of selective JAK 1 inhibitor filgotinib in active rheumatoid arthritis patients with inadequate response to methotrexate: comparative study with filgotinib and tocilizumab examined by clinical index as well as musculoskeletal ultrasound assessment (TRANSFORM study): study protocol for a randomized, open-label, parallel-group, multicenter, and non-inferiority clinical trial

80 | Jun 18 2023

This interventional clinical trial aims to compare the effectiveness of filgotinib monotherapy to tocilizumab monotherapy in rheumatoid arthritis patients with an inadequate response to methotrexate, utilizing clinical disease activity indices, musculoskeletal ultrasound, and serum biomarkers as evaluation parameters. [Read the Full Post]

A Non-Canonical Role for the Glycosyltransferase Enzyme UGT2B17 as a Novel Constituent of the B Cell Receptor Signalosome

125 | Jun 18 2023

Elevated expression of glycosyltransferase UGT2B17 in chronic lymphocytic leukemia (CLL) is associated with poor survival, enhanced BCR pathway signaling, and increased phosphorylation of Bruton tyrosine kinase (BTK), highlighting its potential as an oncogenic factor and therapeutic target. [Read the Full Post]

Erk1/2-Dependent HNSCC Cell Susceptibility to Erastin-Induced Ferroptosis

80 | Jun 15 2023

The study demonstrated that erastin-induced ferroptosis in HNSCC cells is dependent on the expression of Erk1/2, suggesting that Erk1/2 activation can serve as a predictor for the response of HNSCC cells to erastin treatment, thereby highlighting its potential as a therapeutic strategy for HNSCC. [Read the Full Post]

Effect of Extracellular Signal-Regulated Protein Kinase 5 Inhibition in Clear Cell Renal Cell Carcinoma

88 | Jun 13 2023

The study demonstrates that the inhibition of ERK5, regulated by miR-143, holds promise as a potential therapeutic target for the treatment of clear cell renal cell carcinoma (ccRCC). [Read the Full Post]

Astragaloside IV Alleviates Brain Injury Induced by Hypoxia via the Calpain-1 Signaling Pathway

129 | Jun 07 2023

AS-IV can inhibit hypoxia-induced oxidative stress and apoptosis in hippocampal neurons by downregulating the calpain-1/HIF-1α/caspase-3 pathway. [Read the Full Post]

Blockade of STAT3/IL-4 overcomes EGFR T790M-cis-L792F-induced resistance to osimertinib via suppressing M2 macrophages polarization

62 | Jun 04 2023

The study suggests that targeting the EGFR T790M-cis-L792F/STAT3 Tyr705/IL-4 pathway could be a potential strategy to suppress osimertinib resistance in NSCLC. [Read the Full Post]

Rapid direct conversion of bovine non-adipogenic fibroblasts into adipocyte-like cells by a small-molecule cocktail

57 | May 30 2023

The study established a rapid chemically induced platform for transdifferentiation of bovine ear fibroblasts into adipocyte-like cells using a small-molecule cocktail and provided valuable evidence to deepen our understanding of the molecular mechanism of small molecule cocktails in regulating adipogenesis. [Read the Full Post]

Inhibition of GSK-3β Enhances Osteoblast Differentiation of Human Mesenchymal Stem Cells through Wnt Signalling Overexpressing Runx2

72 | May 29 2023

The study demonstrates that 1-Azakenpaullone, a highly selective inhibitor of GSK-3β, effectively induces osteoblastic differentiation and mineralization of human MSCs mediated by the activation of Wnt signaling and upregulation of Runx2, making it a promising osteo-promotor factor for bone tissue engineering. [Read the Full Post]

ID3 mediates BMP2-induced downregulation of ICAM1 expression in human endometiral stromal cells and decidual cells

76 | May 24 2023

This study highlights a potential molecular mechanism by which BMP2 regulates ICAM1 in the human endometrium, which could have therapeutic implications for unexplained recurrent pregnancy loss (uRPL). [Read the Full Post]

Commiphora myrrha stimulates insulin secretion from β-cells through activation of atypical protein kinase C and mitogen-activated protein kinase

152 | May 22 2023

The study investigated the molecular mechanism of action of Commiphora myrrha (CM)-induced insulin secretion and found that CM directly stimulates insulin secretion through activating known downstream effectors of insulin-stimulus secretion coupling, which is completely dependent on protein kinase activation, particularly the phosphorylation and activation of PKCζ and ERK1/2. [Read the Full Post]

Coronarin A modulated hepatic glycogen synthesis and gluconeogenesis via inhibiting mTORC1/S6K1 signaling and ameliorated glucose homeostasis of diabetic mice

45 | May 21 2023

Coronarin A, a natural compound isolated from Hedychium gardnerianum, has potential therapeutic effects in the treatment of type 2 diabetes mellitus by stimulating glycogen synthesis and suppressing gluconeogenesis via activation of the PI3K/Akt/GSK3β and ERK/Wnt/β-catenin pathways and inhibition of mTORC1/S6K1 signaling. [Read the Full Post]

Solubilization, purification, and ligand binding characterization of G protein-coupled receptor SMO in native membrane bilayer using styrene maleic acid copolymer

97 | May 21 2023

The study demonstrates the use of SMA-nanodiscs to solubilize and purify the SMO transmembrane domain in a native-like lipid environment for investigating the structure, function, and drug development of SMO proteins. [Read the Full Post]

Small molecule drugs promote repopulation of transplanted hepatocytes by stimulating cell dedifferentiation

117 | May 20 2023

Small molecule compounds promoting hepatocyte dedifferentiation may facilitate the growth of transplanted hepatocytes in vivo and improve the efficacy of hepatocyte therapy for end-stage liver disease. [Read the Full Post]

Smoking-related epigenetic modifications are associated with the prognosis and chemotherapeutics of patients with bladder cancer

74 | May 19 2023

The study identified smoking-related epigenetic modifications in bladder cancer and constructed a corresponding prognostic model, which was linked to different sensitivities to chemotherapeutics. [Read the Full Post]

PYCR1 promotes the malignant progression of lung cancer through the JAK-STAT3 signaling pathway via PRODH-dependent glutamine synthesize

125 | May 18 2023

PYCR1 has clinical significance in the diagnosis and prognosis of lung cancer, and its pro-tumorigenic role in lung cancer may be attributed to its regulation of the JAK-STAT3 signaling pathway and the metabolism link between proline and glutamine. [Read the Full Post]

ETC-159, an Upstream Wnt inhibitor, Induces Tumour Necrosis via Modulation of Angiogenesis in Osteosarcoma

113 | May 09 2023

ETC-159, a PORCN inhibitor, has shown potential as a treatment for osteosarcomas by inhibiting the Wnt pathway and leading to increased tumour necrosis and reduced vascularity, providing a new window of vulnerability for therapy development. [Read the Full Post]

JAK inhibitors for rheumatoid arthritis

187 | Apr 29 2023

JAK inhibitors represent a promising class of drugs for the treatment of rheumatoid arthritis, with varying degrees of selectivity for different JAK isoforms, and precision medicine approaches may enhance their effectiveness in the future. [Read the Full Post]

Adequacy of energy and macronutrients intake in differently active slovenian adolescents

280 | Apr 21 2023

The study found that a significant proportion of Slovenian adolescents are not meeting national recommendations for energy and macronutrient intake, and there were differences in energy/macronutrient intake between boys of different physical activity levels, highlighting the need for interventions to encourage healthy eating and physical activity behaviors. [Read the Full Post]

Perinatal Stressors as a Factor in Impairments to Nervous System Development and Functions: Review of In Vivo Models

212 | Apr 21 2023

This review evaluates different models of perinatal pathology and their relationship with psychoemotional stressors in understanding the impact of stress on the developing brain and behavior. [Read the Full Post]

Disruption of NOTCH signaling by a small molecule inhibitor of the transcription factor RBPJ

148 | Apr 17 2023

RBPJ Inhibitor-1 (RIN1) is a new class of small molecule inhibitor that disrupts the interaction between NOTCH and RBPJ, which can be exploited for chemical biology and therapeutic applications, and may lead to more specific and targeted therapies for diseases involving NOTCH signaling. [Read the Full Post]

Targeted inhibition of RBPJ transcription complex alleviates the exhaustion of CD8+ T cells in hepatocellular carcinoma

81 | Apr 17 2023

This study suggests that targeting the RBPJ transcription complex with a small molecule compound may be a promising strategy for immunotherapy of hepatocellular carcinoma by inhibiting the malignant behaviors of HCC cells and alleviating T cell exhaustion. [Read the Full Post]

Muscle-Specific Ablation of Glucose Transporter 1 (GLUT1) Does Not Impair Basal or Overload-Stimulated Skeletal Muscle Glucose Uptake

197 | Apr 15 2023

The study found that GLUT1 is not necessary for basal muscle glucose uptake and suggests a novel glucose transport mechanism mediates overload-stimulated glucose uptake. [Read the Full Post]

Effects of Modulation of the Hedgehog and Notch Signaling Pathways on Osteoblast Differentiation Induced by Titanium with Nanotopography

93 | Apr 15 2023

This study demonstrates that Hedgehog and Notch signalling pathways modulate osteoblast differentiation and regulate receptor expression on nanostructured titanium surfaces, with synergistic effects observed with the combination of Hedgehog activation and Notch inhibition. [Read the Full Post]

Pirfenidone suppresses tumor necrosis factor-alpha, enhances interleukin-10 and protects mice from endotoxic shock

156 | Apr 12 2023

The study found that pirfenidone provided prophylactic and therapeutic benefits for murine endotoxic shock by inhibiting pro-inflammatory cytokines, enhancing interleukin-10, and suppressing apoptotic cells and TGF-beta1 in the liver. [Read the Full Post]

Inhaled pirfenidone solution (AP01) for IPF: a randomised, open-label, dose-response trial

124 | Apr 11 2023

The phase 1b trial evaluated the safety, tolerability, and efficacy of inhaled pirfenidone in patients with IPF and showed that the treatment was well-tolerated and may be a safe and effective alternative to oral pirfenidone or nintedanib. [Read the Full Post]

Omicron-induced interferon signalling prevents influenza A H1N1 and H5N1 virus infection

152 | Apr 09 2023

Recent research shows that Omicron but not Delta induces a strong interferon response in primary human cells, protects cells from super-infection with influenza A viruses, and the response is mediated via MDA5 recognition of double-stranded RNA and involves the production of biologically active type I (α/β) and III (λ) interferons. [Read the Full Post]

Excellent Repigmentation of Generalized Vitiligo with Oral Baricitinib Combined with NB-UVB Phototherapy

121 | Apr 09 2023

Oral baricitinib combined with NB-UVB phototherapy has shown to be a successful treatment option for refractory vitiligo by blocking the JAK-STAT pathway and stimulating melanocyte production. [Read the Full Post]

Design, synthesis and bioevaluation of 1,2,4-thiadiazolidine-3,5-dione derivatives as potential GSK-3β inhibitors for the treatment of Alzheimer's disease

169 | Apr 07 2023

The development of compound 10a as a potential GSK-3β inhibitor for Alzheimer's disease shows promising results in vitro and in vivo. [Read the Full Post]

The Current Role of Disease-modifying Osteoarthritis Drugs

147 | Apr 07 2023

The review explores the potential of disease-modifying osteoarthritis drugs (DMOADs) to induce repair and regeneration of articular tissues, but their clinical effectiveness has not yet been demonstrated for managing OA. [Read the Full Post]

The role of transforming growth factor-β2 in cigarette smoke-induced lung inflammation and injury

250 | Apr 06 2023

The study found that TGF-β2 attenuated CSE-induced IL-8 production in PBECs and alleviated lung inflammation/injury in CS-exposed mice through the Smad3 signaling pathway. [Read the Full Post]

Patient-reported outcomes in capmatinib-treated patients with METex14-mutated advanced NSCLC: Results from the GEOMETRY mono-1 study

92 | Apr 05 2023

Capmatinib showed meaningful improvements in cough and preserved quality of life in patients with METex14-mutated advanced non-small cell lung cancer, as reported by patient-reported outcomes in the GEOMETRY mono-1 study. [Read the Full Post]

Real-world outcomes in non-small-cell lung cancer patients with MET Exon 14 skipping mutation and brain metastases treated with capmatinib

136 | Apr 05 2023

This retrospective medical record review study demonstrated that capmatinib is effective in treating non-small-cell lung cancer patients with MET exon 14 skipping mutation and brain metastases in a real-world setting, with high response rates and progression-free survival. [Read the Full Post]

An evaluation of fedratinib for adult patients with newly diagnosed and previously treated myelofibrosis

186 | Apr 01 2023

Fedratinib is a selective JAK2 inhibitor that has been approved by the FDA for the treatment of intermediate-2 or high-risk primary or secondary MF, providing a second-line treatment option for patients who failed or discontinued ruxolitinib, but new combinations with other targeted therapies are needed to improve management of the disease. [Read the Full Post]

Pharmacotherapeutic advances for splenomegaly in myelofibrosis

197 | Apr 01 2023

Myelofibrosis is a hematologic malignancy characterized by splenomegaly in most patients, with JAK inhibitors being the primary pharmacologic treatment option, but alternative therapies and non-pharmacologic approaches may also be considered, and novel combination therapies are being explored. [Read the Full Post]

CDH6 as a prognostic indicator and marker for chemotherapy in gliomas

89 | Apr 01 2023

The study suggests that CDH6 may act as a promising target for glioma therapy, based on its positive correlation with tumor grade, negative correlation with patient prognosis, and associations with cell-cell interactions, immune processes, and potential drug targets. [Read the Full Post]

Hedgehog Signals Mediate Anti-Cancer Drug Resistance in Three-Dimensional Primary Colorectal Cancer Organoid Culture

174 | Mar 30 2023

The study suggests that targeting the Hedgehog signaling pathway and cancer stem cells using inhibitors like AY9944 and GANT61 can improve the sensitivity of anti-cancer drug treatment in colorectal tumor patient-derived ALI organoids and may be a useful combinational therapeutic strategy against metastatic colorectal cancer. [Read the Full Post]

Towards personalized treatment with clozapine

196 | Mar 30 2023

This study found that clozapine was more effective when used as a first- or second-line treatment, and identified factors associated with response to clozapine treatment and side effects, which could aid in the development of personalized treatment approaches for individuals with treatment-resistant schizophrenia. [Read the Full Post]

Derivation of Limbal Stem Cells from Human Adult Mesenchymal Stem Cells for the Treatment of Limbal Stem Cell Deficiency

112 | Mar 16 2023

This study presents a protocol for deriving human limbal stem cells from adipose-derived mesenchymal stem cells, which can aid in restoring vision for patients with LSC deficiency. [Read the Full Post]

LY450139 Inhibited Ti-Particle-Induced Bone Dissolution via Suppressing Notch and NF-κB Signaling Pathways

126 | Feb 27 2023

The study found that LY450139 has the potential to prevent the failure of joint implants by inhibiting the formation of osteoclasts, which break down bone, through the inhibition of the NF-κB and Notch signaling pathways. [Read the Full Post]

Endothelial-specific targeting of RhoA signaling via CD31 antibody-conjugated nanoparticles

314 | Feb 26 2023

The study aimed to develop a CD31-targeting liposome with Fasudil, a clinically-relevant Rho kinase inhibitor, to target the RhoA signaling in endothelial cells for potential anti-angiogenic therapy by minimizing toxicity. [Read the Full Post]

Predictive factors for improvement of symptomatic cerebral vasospasm following subarachnoid hemorrhage by selective intra-arterial administration of fasudil hydrochloride

336 | Feb 26 2023

Selective intra-arterial administration of fasudil improves neurological findings in 72.2% of patients with cerebral vasospasm following subarachnoid hemorrhage and is most effective when the spasm is limited to peripheral vessels and the patient is younger and does not have a large cerebral infarction in the spasm artery perfusion area. [Read the Full Post]

Pregabalin Mediates Retinal Ganglion Cell Survival From Retinal Ischemia/Reperfusion Injury Via the Akt/GSK3β/β-Catenin Signaling Pathway

103 | Feb 26 2023

Pregabalin protects retinal ganglion cells from ischemia/reperfusion injury-induced apoptosis by upregulating the Akt/GSK3β/β-catenin pathway. [Read the Full Post]

Aberrant MEK5 signalling promotes clear cell renal cell carcinoma development via mTOR activation

135 | Feb 24 2023

This study found that MEK5 is aberrantly expressed in clear cell renal cell carcinoma, activating the mTOR signaling pathway, and inhibiting MEK5 using BIX02189 shows promise as a new therapeutic strategy for ccRCC. [Read the Full Post]

Fludarabine or cyclophosphamide in combination with total body irradiation as myeloablative conditioning prior to allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia: an analysis by the Acute Leukemia Working Party of the EBMT

129 | Feb 22 2023

In this study, results showed that TBI/Cy conditioning was associated with reduced risk of relapse and increased risk of grade 2-4 acute GVHD, while a matched-pair analysis revealed a reduced rate of relapse and no significant effect on other transplantation outcomes when compared to TBI/Flu, leading to the conclusion that TBI/Cy should be considered a preferable regimen for allo-HCT in adult patients with ALL in complete remission. [Read the Full Post]

Staurosporine analogues from microbial and synthetic sources and their biological activities

249 | Feb 20 2023

Staurosporine and its analogues have strong inhibitory effects against a variety of kinases and have various biological properties such as antifungal, antibacterial, and immunosuppressive activities, but have limited clinical effectiveness due to cross-reactivity and poor selectivity. [Read the Full Post]

Current therapeutic modalities and chemopreventive role of natural products in liver cancer: Progress and promise

453 | Feb 19 2023

Liver cancer treatment options depend on the progression stage of the disease and may include surgery, ablation and radiotherapy, first-line drugs and immunotherapy, and second-line chemotherapeutic drugs, while natural compounds like resveratrol, curcumin and diallyl sulfide are emerging as promising anticancer agents to manage liver cancer. [Read the Full Post]

Transferrin receptor 2 deficiency promotes macrophage polarization and inflammatory arthritis

187 | Feb 18 2023

Tfr2 deletion results in increased joint swelling and bone erosion in a K/BxN serum-transfer arthritis model, which may be due to Tfr2's role in suppressing pro-inflammatory M1-like polarization in macrophages. [Read the Full Post]

Lithium affects the circadian clock in the choroid plexus - A new role for an old mechanism

71 | Feb 14 2023

Lithium affects the circadian clock in the choroid plexus of the ventricle barrier complex, influencing brain function and potentially improving it in psychiatric patients by aligning the clock with the sleep-wake cycle, with potential for personalized timing of treatment. [Read the Full Post]

STAT3 promotes differentiation of monocytes to MDSCs via CD39/CD73-adenosine signal pathway in oral squamous cell carcinoma

87 | Feb 01 2023

The study found that STAT3 blockade reduced the expression of CD39/CD73 and the synthesis of adenosine, inhibiting monocytes to MDSCs differentiation, leading to prominent anti-tumor efficacy in OSCC mouse model and suggesting STAT3 blockade as a promising therapeutic strategy for oral squamous cell carcinoma. [Read the Full Post]

Interactive webtool for analyzing drug sensitivity and resistance associated with genetic signatures of cancer cell lines

293 | Jan 19 2023

Myriam Boeschen et al. found support for the described sensitivity of H1047 mutants to GSK690693 targeting the AKT pathway. [Read the Full Post]

CRC Therapy Identifies Indian Hedgehog Signaling in Mouse Endometrial Epithelial Cells and Inhibition of Ihh-KLF9 as a Novel Strategy for Treating IUA

68 | Jan 12 2023

Xinhao Zhou et al. suggested a promising application of hedgehog inhibitors as a targeted drug in the IUA clinic. [Read the Full Post]

GSK3 inhibitor suppresses cell growth and metabolic process in FLT3-ITD leukemia cells

73 | Jan 11 2023

Jing Xia et al. suggested that BIO might be a promising therapeutic candidate for AML. [Read the Full Post]

A mitophagy-related gene signature associated with prognosis and immune microenvironment in colorectal cancer

238 | Dec 24 2022

Cong Zhang et al. developed a novel mitophagy-related gene signature that could be utilized not only as an independent predictive biomarker but also as a tool for tailoring personalizing treatment for CRC patients. [Read the Full Post]

Upfront autologous haematopoietic stem-cell transplantation versus carfilzomib-cyclophosphamide-dexamethasone consolidation with carfilzomib maintenance in patients with newly diagnosed multiple myeloma in England and Wales (CARDAMON): a randomised, phase 2, non-inferiority trial

206 | Dec 23 2022

Kwee Yong et al. thought that KCd did not meet the criteria for non-inferiority compared with autologous HSCT, but the marginal difference in progression-free survival suggested that further studies were warranted to explore deferred autologous HSCT in some subgroups. [Read the Full Post]

Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial

196 | Dec 23 2022

Keiko Imamura et al. found that the treatment-responsive patients could be distinguished by lower levels of plasma NFL. [Read the Full Post]

Recent updates on Wnt signaling modulators: a patent review (2014-2020)

49 | Dec 14 2022

Vishalgiri G Goswami et al. thought that targeting Wnt pathway could be a potential approach to design and develop novel therapeutic classes. [Read the Full Post]

Fifty Shades of Scandium: Comparative Study of PET Capabilities Using Sc-43 and Sc-44 with Respect to Conventional Clinical Radionuclides

86 | Dec 11 2022

Thiago V M Lima et al. thought that accurate quantitative scandium-43/44 PET/CT was achievable in commercial devices. [Read the Full Post]

Notch signaling-induced cyclin d1 in diabetes ameliorating effects of the isolated polysaccharide from Rosa canina: In vitro and in vivo studies

147 | Nov 30 2022

Soraya Sajadimajd et al. thought that upregulation of Notch signaling-induced cyclin d1 could be proposed as the underlying diabetes-reducing effects of the isolated polysaccharide derivative. [Read the Full Post]

Predictors of anemia response to momelotinib therapy in myelofibrosis and impact on survival

170 | Nov 27 2022

Naseema Gangat et al. suggested a short-term survival benefit associated with anemia response in momelotinib-treated patients with MF. [Read the Full Post]

MPN-379 Matching-Adjusted Indirect Comparison (MAIC) of Pelabresib (CPI-0610) in Combination With Ruxolitinib vs. JAK Inhibitor Monotherapy in Patients With Intermediate or High-Risk Myelofibrosis

178 | Nov 27 2022

Vikas Gupta et al. suggested that MAIC-adjusted improvements observed in SVR35 and TSS50 at Week 24 with pelabresib and ruxolitinib vs. ruxolitinib, fedratinib, or momelotinib monotherapy were consistent with unadjusted comparisons. [Read the Full Post]

LAMC2 marks a tumor-initiating cell population with an aggressive signature in pancreatic cancer

104 | Nov 23 2022

Donatella Delle Cave et al. identified a highly metastatic subpopulation of TICs marked by LAMC2. [Read the Full Post]

Role of the Glycogen Synthase Kinase 3-Cyclic AMP/Protein Kinase A in the Immobilization of Human Sperm by Tideglusib

83 | Nov 21 2022

Weiwei Wang et al. found the GSK3-cAMP/PKA regulatory loop in human sperm, which might mediate the immobilization effect of tideglusib at low of concentrations (e.g., 1.25 μM) on sperm motility. [Read the Full Post]

Novel Approaches in Non-Melanoma Skin Cancers-A Focus on Hedgehog Pathway in Basal Cell Carcinoma (BCC)

91 | Nov 16 2022

Paulina Chmiel et al. thought that a central role in the development of BCC was played by the Hedgehog (Hh) signalling pathway. [Read the Full Post]

Current approaches and strategies to identify Hedgehog signaling pathway inhibitors for cancer therapy

113 | Nov 15 2022

Zifan Feng et al. gave a systematic overview of the current status and characteristics of various approaches to developing the Hedgehog pathway inhibitors. [Read the Full Post]

Hedgehog Signaling as a Therapeutic Target for Airway Remodeling and Inflammation in Allergic Asthma

90 | Nov 10 2022

Anthony Tam et al. found that TGFβ1-induced airway remodeling was partially mediated through the hedgehog signaling pathway via the PTCH1-SMO-GLI axis. [Read the Full Post]

Therapeutic function of a novel rat induced pluripotent stem cell line in a 6‑OHDA‑induced rat model of Parkinson's disease

79 | Nov 02 2022

Jiajia Xu et al. found that RiPSCs‑6F/CR induced by small molecules could be used as potential donor material for neural grafting to remodel basal ganglia circuitry in neurodegenerative diseases. [Read the Full Post]

Hsa_circ_0044301 Regulates Gastric Cancer Cell's Proliferation, Migration, and Invasion by Modulating the Hsa-miR-188-5p/DAXX Axis and MAPK Pathway

66 | Oct 31 2022

Fei Jiang et al. thought that circRNA-0044301/miRNA-188-5p/DAXX (ERK1/2) might be a key axis in GC progression, and circRNA-0044301 had immense potential to be a therapeutic target for GC. [Read the Full Post]

TGF-β1 Promotes Zika Virus Infection in Immortalized Human First-Trimester Trophoblasts via the Smad Pathway

61 | Oct 22 2022

Quang Duy Trinh et al. found that TGF-β1 promotes the virus infection via the Smad pathway. [Read the Full Post]

Chai-Hu-San-Shen Capsule Ameliorates Ventricular Arrhythmia Through Inhibition of the CaMKII/FKBP12.6/RyR2/Ca2+ Signaling Pathway in Rats with Myocardial Ischemia

119 | Oct 20 2022

Longqing Chen et al. found that CHSSC might reduce the incidence of ventricular arrhythmias following myocardial ischemia through inhibition of the CaMKII/RyR2/FKBP12.6/Ca2+ signaling pathway. [Read the Full Post]

UC-MSCs promote frozen-thawed ovaries angiogenesis via activation of the Wnt/β-catenin pathway in vitro ovarian culture system

137 | Oct 16 2022

Wenjuan Xu et al. showed the beneficial effects of UC-MSCs on thawed ovaries and explored a potential mechanism inducing angiogenesis. [Read the Full Post]

Luteinizing Hormone Receptor Promotes Angiogenesis In Ovarian Endothelial Cells of Macaca fascicularis and Homo sapiens

91 | Oct 15 2022

Merete Lund et al. found that the LH surge may directly activate ovarian endothelial cells to stimulate angiogenesis of the ovulatory follicle. [Read the Full Post]

ATRA works synergistically with the γ-secretase inhibitor crenigacestat to augment BCMA on multiple myeloma and the efficacy of BCMA-CAR T-cells

81 | Oct 10 2022

Estefanía García-Guerrero et al. found that ATRA treatment lead to enhanced BCMA expression on MM cells and consecutively, enhanced reactivity of BCMA-CAR T-cells. [Read the Full Post]

Hepatocellular carcinoma-derived exosomal miRNA-761 regulates the tumor microenvironment by targeting the SOCS2/JAK2/STAT3 pathway

84 | Sep 30 2022

Xiao-Hu Zhou et al. found that exosomal miR-761 modulated the tumor microenvironment via SOCS2/JAK2/STAT3 pathway-dependent activation of CAFs. [Read the Full Post]

Reducing tumor invasiveness by ramucirumab and TGF-β receptor kinase inhibitor in a diffuse-type gastric cancer patient-derived cell model

62 | Sep 25 2022

Song-Yi Lee et al. confirmed that combination of TEW-7197 and ramucirumab reduced tumor spheroid and GC PDC-induced blood vessel formation concomitantly in the spheroid-on-a-chip model. [Read the Full Post]

Randomized, Double-Blind, Placebo-Controlled Phase III Study of Paclitaxel ± Napabucasin in Pretreated Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

54 | Sep 14 2022

Manish A Shah et al. showed that adding napabucasin to paclitaxel did not improve survival in patients with pretreated advanced gastric or GEJ adenocarcinoma. [Read the Full Post]

Identification of solamargine as a cisplatin sensitizer through phenotypical screening in cisplatin-resistant NSCLC organoids

103 | Sep 02 2022

Yi Han et al. found that a new direction for further treatment of advanced DDP-resistant lung cancer patients. [Read the Full Post]

Cebpb Regulates Skeletal Stem Cell Osteogenic Differentiation and Fracture Healing via the WNT/ β-Catenin Pathway

63 | Aug 30 2022

Jiansong Wang et al. proved that Cebpb knockdown promoted SSC osteogenic differentiation and fracture healing via the WNT/β-catenin signaling pathway. [Read the Full Post]

The first-in-class ERK inhibitor ulixertinib shows promising activity in MAPK-driven pediatric low-grade glioma models

45 | Aug 30 2022

Romain Sigaud et al. indicated a high clinical potential of ulixertinib for the treatment of pLGG and strongly supported its first clinical evaluation in pLGG as single agent and in combination therapy in a currently planned international phase I/II umbrella trial. [Read the Full Post]

Drug Repurposing Based on Protozoan Proteome: In Vitro Evaluation of In Silico Screened Compounds against Toxoplasma gondii

117 | Aug 27 2022

Débora Chaves Cajazeiro et al. found that interactions with the Na+/K+ ATPase transporter for Homo sapiens and Mus musculus, indicating a possible mechanism of action of this compound. [Read the Full Post]

MiR-630 suppresses non-small cell lung cancer by targeting vimentin

59 | Aug 26 2022

Bin Wang et al. thought that MiR-630 constrained the progression of NSCLC by inhibiting JAK2/STAT3 pathway and downregulating VIM expression. [Read the Full Post]

Down-regulated NEDD4L facilitates tumor progression through activating Notch signaling in lung adenocarcinoma

122 | Aug 25 2022

Liping Lin et al. demonstrated that down-regulated NEDD4L facilitated LUAD progression by activating Notch signaling, and NEDD4L might be a promising target to treat LUAD. [Read the Full Post]

Epiprofin Transcriptional Activation Promotes Ameloblast Induction From Mouse Induced Pluripotent Stem Cells via the BMP-Smad Signaling Axis

51 | Aug 14 2022

Xinchao Miaosuggested that Epfn was a promising target for inducing the differentiation of ameloblasts, which could be used in enamel and tooth regeneration. [Read the Full Post]

The CBP/β-Catenin Antagonist, ICG-001, Inhibits Tumor Metastasis via Blocking of the miR-134/ITGB1 Axis-Mediated Cell Adhesion in Nasopharyngeal Carcinoma

86 | Aug 11 2022

Luo Chen et al. showed that ICG-001 transient overexpression of miR-134 or stable overexpression of miR-134 could significantly reduce the lung metastasis of NPC cells. [Read the Full Post]

Effect of ALA-PDT on inhibition of oral precancerous cell growth and its related mechanisms

89 | Aug 09 2022

Jian-Qiu Jin et al. indicated that ALA-PDT could be a promising alternative treatment against oral precancerous lesions. [Read the Full Post]

Repeated exposure to sevoflurane in neonatal rats impairs cognition in adulthood via the PKA-CREB-BDNF signaling pathway

101 | Aug 08 2022

Jili Zhao et al. found that PKA-CREB-BDNF signaling served an important role in the cognitive decline caused by neonatal exposure to Sev. [Read the Full Post]

Inhibition of CBP/β-catenin signaling ameliorated fibrosis in cholestatic liver disease

75 | Aug 07 2022

Masamichi Kimura et al. highlighted the therapeutic effect of CBP/β-catenin inhibition in cholestatic liver diseases. [Read the Full Post]

Berberine encapsulated in exosomes derived from platelet-rich plasma promotes chondrogenic differentiation of the Bone Marrow Mesenchymal Stem Cells via the Wnt/β-catenin pathway

120 | Aug 05 2022

Bingjiang Dong et al. found that exos-Ber facilitated the differentiation of chondrogenic BMSCs by modulating the Wnt/β-catenin axis. [Read the Full Post]

Casein Kinase 2 Signaling in White Matter Stroke

195 | Aug 04 2022

Hung Nguyen et al. thought that miRNA regulation might be one of the protective actions of CX-4945 against WM ischemic injury. [Read the Full Post]

Anti-adipogenic and Pro-lipolytic Effects on 3T3-L1 Preadipocytes by CX-4945, an Inhibitor of Casein Kinase 2

172 | Aug 04 2022

Anil Kumar Yadav et al. found that CX-4945 had strong anti-adipogenic and pro-lipolytic effects on differentiating and differentiated 3T3-L1 cells, mediated by control of the expression and phosphorylation levels of CK2, C/EBP-α, PPAR-γ, FAS, ACC, perilipin A, AMPK, LKB-1, ERK-1/2, and HSL. [Read the Full Post]

Inhibition of AHNAK nucleoprotein 2 alleviates pulmonary fibrosis by downregulating the TGF-β1/Smad3 signaling pathway

64 | Jul 28 2022

Dongyi Zhu et al. thought that AHNAK2 was a potential therapeutic target for IPF. [Read the Full Post]

AMPK-ChREBP axis mediates de novo milk fatty acid synthesis promoted by glucose in the mammary gland of lactating goats

150 | Jul 21 2022

Hengbo Shi et al. thought that glucose supplementation promoted de novo fatty acid synthesis via the AMPK-ChREBP axis, hence increasing milk fat yield in the goat mammary gland. [Read the Full Post]

Antifungal activity of dehydrocurvularin for Candida spp. through the inhibition of adhesion to human adenocarcinoma cells

143 | Jul 21 2022

Hitoshi Kamauchi et al. reported that dehydrocurvularin (1), isolated from the marine-derived fungus Curvularia aeria, exhibited anti-fungal activities for Candida albicans and Candida auris. [Read the Full Post]

Comparative Efficacy and Safety of Janus Kinase Inhibitors and Secukinumab in Patients with Active Ankylosing Spondylitis: A Systematic Review and Meta-Analysis

261 | Jul 13 2022

Young Ho Lee suggested that tofacitinib 5 mg had the highest likelihood of being the best treatment for achieving the ASAS40 response rate, followed by upadacitinib 15 mg, secukinumab 150 mg, filgotinib 200 mg, and placebo. [Read the Full Post]

MicroRNA-26b regulates BMSC osteogenic differentiation of TMJ subchondral bone through β-catenin in osteoarthritis

99 | Jul 10 2022

Jinlu Yang et al. thought that miR-26b might modulate subchondral bone loss induced by abnormal occlusion and influence the osteogenic differentiation of subchondral BMSCs through β-catenin in the context of TMJ-OA progression. [Read the Full Post]

Giant Basal Cell Carcinoma of the Axilla: 8-year Follow-up of a Case Treated with Excision, Vismodegib, and Radiotherapy

128 | Jul 05 2022

Shih-Chiang Kuo et al. illustrated a rare disease with an 8-year follow-up, involving different therapeutic strategies against multiple recurrences. [Read the Full Post]

Construction and evaluation of detachable bone-targeting MOF carriers for the delivery of proteasome inhibitors

342 | Jun 17 2022

Hongbing Yang et al. provided a potential cascade targeting strategy for improving the delivery effects of bone targeted nanoparticles for the delivery of proteasome inhibitors. [Read the Full Post]

Systematic Evaluation for the Influences of the SOX17/Notch Receptor Family Members on Reversing Enzalutamide Resistance in Castration-Resistant Prostate Cancer Cells

253 | Jun 12 2022

Zhongbo Du et al. thought that the Notch1 and Notch4 inhibitors GSI-IX and RO4929097 were promising therapeutic agents for the treatment of CRPC. [Read the Full Post]

Synthesis, structural characterization, DFT calculations, molecular docking, and molecular dynamics simulations of a novel ferrocene derivative to unravel its potential antitumor activity

505 | Jun 12 2022

Mohamed M Hammoud et al. revealed the antitumor potential of ferrocene derivative (10) through targeting and inhibiting mitogen-activated protein (MAP) kinases interacting kinase (Mnk) 1.Communicated by Ramaswamy H. Sarma. [Read the Full Post]

Antithrombotic Therapy in Elderly Patients with Acute Coronary Syndromes

290 | Jun 11 2022

Clara Bonanad et al. it is imperative to deepen our knowledge regarding the management of these challenging patients through real-world data and specifically designed geriatric studies to help resolve the questions remaining in their disease management. [Read the Full Post]

ARHGAP9 inhibits colorectal cancer cell proliferation, invasion and EMT via targeting PI3K/AKT/mTOR signaling pathway

474 | Jun 10 2022

Jufeng Sun et al. thought that ARHGAP9 inhibited the malignant phenotypes of CRC cells via interdicting PI3K/AKT/mTOR signaling pathway. [Read the Full Post]

In vitro modeling of liver fibrosis in 3D microtissues using scalable micropatterning system

142 | Jun 08 2022

Ensieh Zahmatkesh et al. found that aHSCs could lead to EMT in hepatocytes during liver fibrogenesis. [Read the Full Post]

Insights into Immune Escape During Tumor Evolution and Response to Immunotherapy Using a Rat Model of Breast Cancer

137 | Jun 08 2022

Carlos R Gil Del Alcazar et al. demonstrated the usefulness of this preclinical model for immunotherapy and suggested examination to expand immunotherapy to a subset of patients with ER+ disease. [Read the Full Post]

RNF43 R117fs mutant positively regulates Wnt/β-catenin signaling by failing to internalize FZD expressed on the cell surface

156 | Jun 07 2022

A-Ri Cho et al. demonstrated that RNF43 frameshift mutations retained normal functionality; thus, targeted anti-cancer therapy could be developed according to the mutation type of RNF43. [Read the Full Post]

Human primary liver cancer-derived organoid cultures for disease modeling and drug screening

0 | Jun 01 2022

Laura Broutier et al. demonstrated the wide-ranging biomedical utilities of PLC-derived organoid models in furthering the understanding of liver cancer biology and in developing personalized-medicine approaches for the disease. [Read the Full Post]

Origin of M2 Mϕ and its macrophage polarization by TGF-β in a mice intervertebral injury model

212 | May 23 2022

Ayumu Kawakubo et al. suggested that M2 Mϕ following IVD injury might originate from resident Mϕ. [Read the Full Post]

Abrocitinib: A New FDA-Approved Drug for Moderate-to-Severe Atopic Dermatitis

410 | May 20 2022

Patrick O Perche et al. thought that abrocitinib was an efficacious oral JAK 1 inhibitor recently FDA-approved for patients ≥ 18 years old with moderate-to-severe AD who had not responded to systemic medications or when contraindicated otherwise. [Read the Full Post]

Premise and peril of Wnt signaling activation through GSK-3β inhibition

257 | May 19 2022

Samuel M Law et al. thought that caution was required when micromolar levels of CHIR-99021 were used for the purpose of activating the canonical Wnt signaling pathway. [Read the Full Post]

ARHGAP29 Regulates Keratinocyte Migration through the RhoA/ROCK Pathway

278 | May 15 2022

Lindsey Rhea et al. demonstrated that ARHGAP29 regulated keratinocyte morphology and promoted migration speed and directionality through the RhoA/ROCK pathway, providing potential insight into its importance in craniofacial development. [Read the Full Post]

Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR-mutated advanced non-small cell lung cancer: A single-group, open-label phase 2 trial (WJOG10818L)

406 | May 02 2022

Hidetoshi Hayashi et al. found that Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR- mutated advanced NSCLC did not meet its primary end point, despite the encouraging efficacy and safety profile of this treatment strategy. [Read the Full Post]

Treatment patterns, effectiveness, and patient-reported outcomes of palbociclib therapy in Chinese patients with advanced breast cancer: A multicenter ambispective real-world study

182 | Apr 28 2022

Lesang Shen et al. thought that Palbociclib was effective for front-line use and for treating endocrine-sensitive patients in real-world China and was generally well tolerated. [Read the Full Post]

SLFN11 biomarker status predicts response to lurbinectedin as a single agent and in combination with ATR inhibition in small cell lung cancer

450 | Apr 27 2022

Kiran Kundu et al. provided a rationale for lurbinectedin in combination with ATR inhibitors to overcome resistance in SCLC with low SLFN11 expression. [Read the Full Post]

Nuclear translocation of p85β promotes tumorigenesis of PIK3CA helical domain mutant cancer

637 | Apr 19 2022

Yujun Hao et al. found that the drug combination could be an effective therapeutic approach for PIK3CA helical domain mutant tumors. [Read the Full Post]

Response to netarsudil in goniotomy-treated eyes and goniotomy-naïve eyes: a pilot study

658 | Mar 29 2022

Haochen Xu et al.showed that netarsudil had a greater IOP-lowering effect in eyes treated with prior goniotomy and might serve as a promising adjunctive ocular hypotensive agent to further reduce IOP in eyes with prior goniotomy. [Read the Full Post]

Bone morphogenetic protein receptor inhibitors suppress the growth of glioblastoma cells

306 | Mar 28 2022

Joel Kaye et al. suggested the need for development of BMP inhibitors and evaluation as potential therapeutic for GBMs. [Read the Full Post]

What's new in myeloproliferative neoplasia

640 | Mar 19 2022

Stefan Schmidt et al. revealed components of the alarmin complex (S100A8 und S100A9) drove this local sterile inflammation process, which also represented a potential therapeutic target, as the S100A8 and A9 inhibitor Tasquinimod reduced fibrosis in a pre-clinical animal model. [Read the Full Post]

The role of the atypical chemokine receptor CCRL2 in myelodysplastic syndrome and secondary acute myeloid leukemia

557 | Mar 18 2022

Theodoros Karantanos et al. implicated CCRL2 as an MDS/sAML cell growth mediator, partially through JAK2/STAT signaling. [Read the Full Post]

Construction of an Immune-Autophagy Prognostic Model Based on ssGSEA Immune Scoring Algorithm Analysis and Prognostic Value Exploration of the Immune-Autophagy Gene in Endometrial Carcinoma (EC) Based on Bioinformatics

364 | Mar 13 2022

Xiaomin Xu et al. constructed the immuno-autophagy prognosis model of endometrial cancer and identified three high-risk immunoautophagy genes, including VEGFA, CCL2, and Ifng. [Read the Full Post]

GSK-3β manipulates ferroptosis sensitivity by dominating iron homeostasis

263 | Mar 03 2022

Lingjuan Wang et al. showed that the multifaceted Ser/Thr protein kinase GSK-3β acted as a positive modulator of the ferroptosis program. [Read the Full Post]

Baricitinib for relapsing giant cell arteritis: a prospective open-label 52-week pilot study

547 | Feb 23 2022

Matthew J Koster et al. showed that in this proof-of-concept study, baricitinib at 4 mg/day was well tolerated and discontinuation of GC was allowed in most patients with relapsing GCA. [Read the Full Post]

Drug survival of biologics and novel immunomodulators for rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, and psoriasis - A nationwide cohort study from the DANBIO and DERMBIO registries

409 | Feb 22 2022

Alexander Egeberg et al. emphasized that although these diseases had many overlaps in their pathogenesis, there was a need for an individualized treatment approach that considered the underlying disease, patient profile, and treatment history. [Read the Full Post]

Bidirectional Responses of Eight Neuroinflammation-Related Transcriptional Factors to 64 Flavonoids in Astrocytes with Transposable Insulated Signaling Pathway Reporters

325 | Feb 12 2022

Valeri V Mossine et al. conclude that transposable insulated reporters of transcriptional activation represent a convenient neurochemistry tool in screening for activators/inhibitors of signaling pathways. [Read the Full Post]

Paracrine production of IL-6 promotes a hypercoagulable state in pancreatic cancer

449 | Feb 09 2022

Silu Wang et al. found the key role of the Jagged/Notch/IL-6/STAT3 feedback loop in the development of a hypercoagulable state in pancreatic cance. [Read the Full Post]

γ-Secretase inhibitors for breast cancer and hepatocellular carcinoma: From mechanism to treatment

450 | Feb 09 2022

Hui Jia et al. thought that the γ-secretase complex was very important for activation of the Notch receptor and regulation of target-gene transcription. [Read the Full Post]

Transcriptome Analysis of Cells Exposed to Actinomycin D and Nutlin-3a Reveals New Candidate p53-Target Genes and Indicates That CHIR-98014 Is an Important Inhibitor of p53 Activity

226 | Feb 01 2022

Barbara Łasut-Szyszka et al. thought that an unidentified kinase inhibited by CHIR-98014, participated in modification of p53 and enabled it to activate a subset of its target genes. [Read the Full Post]

Role of epidermal growth factor receptor inhibitor-induced interferon pathway signaling in the head and neck squamous cell carcinoma therapeutic response

405 | Jan 31 2022

Sean P Korpela et al. found that heterogeneous, tumor cell-intrinsic, EGFR/ERBB inhibitor-induced IFN pathway activation in HNSCC and suggest that individual tumor responses to oncogene-targeted agents are a sum of direct growth inhibitory effects and variably-induced participation of host immune cells. [Read the Full Post]

The Effect of STAT3 Signal Pathway Activation on Retinopathy of Prematurity

268 | Jan 29 2022

Jianbing Ren et al. provided potential novel therapeutic approach to the prevention and treatment of ROP. [Read the Full Post]

Inhibitor GSK690693 extends Drosophila lifespan via reduce AKT signaling pathway

1045 | Jan 27 2022

Xingyi Cheng et al. indicated that GSK690693 might become an effective compound for anti-aging intervention. [Read the Full Post]

The Role of Prostaglandin E1 as a Pain Mediator through Facilitation of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 via the EP2 Receptor in Trigeminal Ganglion Neurons of Mice

256 | Jan 26 2022

Jean Kwon et al. discovered that PGE1 played a role in mechanical allodynia through HCN2 channel facilitation via the EP2 receptor in nociceptive neurons. [Read the Full Post]

Targeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics

390 | Jan 19 2022

Matthew Z Guo et al.discussed limitations of capmatinib, and highlighted ongoing trials of capmatinib in combinatorial approaches. [Read the Full Post]

Novel function of THEMIS2 in the enhancement of cancer stemness and chemoresistance by releasing PTP1B from MET

388 | Jan 18 2022

Wei-Chieh Huang et al. found that non-cytotoxic dosages of cryptotanshinone (CPT) could potently inhibit cancer stemness, chemoresistance and tumorigenicity by suppressing expression of THEMIS2. [Read the Full Post]

DR-5 and DLL-4 mAb Functionalized SLNs of Gamma-Secretase Inhibitors- An Approach for TNBC Treatment

529 | Jan 06 2022

Mamta Kumari et al. found that DLL4 mAb and GSIs were expected to act synergistically to block the Notch signal mediated BCSCs proliferation, differentiation, and metastasis. [Read the Full Post]

CYT387 Inhibits the Hyperproliferative Potential of Fibroblast-like Synoviocytes via Modulation of IL-6/JAK1/STAT3 Signaling in Rheumatoid Arthritis

482 | Jan 04 2022

Susmita Srivastava et al. found that CYT387 inhibits proliferation, migration, and pathogenic diseased potential of FLS isolated from adjuvant-induced arthritic (AA) rats via targeting IL-6/JAK1/STAT3 signaling cascade. [Read the Full Post]

A phase 1b study of erlotinib and momelotinib for the treatment of EGFR-mutated, tyrosine kinase inhibitor-naive metastatic non-small cell lung cancer

511 | Jan 03 2022

Sukhmani K Padda et al. showed that the JAK1/2 and TBK1 inhibitor momelotinib in combination with erlotinib did not appear to enhance benefit over the historical data of erlotinib monotherapy in patients with EGFR-mutated NSCLC. [Read the Full Post]

Penetration Cascade of Size Switchable Nanosystem in Desmoplastic Stroma for Improved Pancreatic Cancer Therapy

267 | Dec 31 2021

Xiaozheng Zhao et al. found that the inhibition of ECM hyperplasia by VAC allowed TAX more ready access to the cancer cells in addition to its small size. [Read the Full Post]

Differential time course of glycogen synthase kinase-3 inhibition in experimental autoimmune encephalomyelitis

391 | Dec 29 2021

A S Al-Zaidi et al. found that downregulation of Th1 and Th17 hallmark cytokines by Tideglusib in EAE might be associated with IL-10 production. [Read the Full Post]

Probing the multimodal fungiform papilla: complex peripheral nerve endings of chorda tympani taste and mechanosensitive fibers before and after Hedgehog pathway inhibition

228 | Dec 24 2021

Christopher R Donnelly et al. found that the complex, extragemmal nerve endings within and disbursed under the apical FP were the mechanosensitive nerve endings of the CT that remained after HH pathway inhibition. [Read the Full Post]

Evaluation of Hedgehog Pathway Inhibition on Nevoid Basal Cell Carcinoma Syndrome Fibroblasts and Basal Cell Carcinoma-Associated Fibroblasts: Are Vismodegib and Sonidegib Useful to Target Cancer-Prone Fibroblasts

241 | Dec 23 2021

Laura Eibenschutz et al. demonstrated that vismodegib and sonidegib impacting on fibroblast tumour supportive functions might be considered in therapy for BCC independently to the mutation status of Hh components in neoplastic cells. [Read the Full Post]

GLI1-targeting drugs induce replication stress and homologous recombination deficiency and synergize with PARP-targeted therapies in triple negative breast cancer cells

512 | Dec 17 2021

Chinnadurai Mani et al. found that Aberrantly activated GLI1 regulated HR-mediated DNA repair by transcriptionally regulating FANCD2 to overcome chemotherapy-induced replication stress and DNA damage. [Read the Full Post]

Peptide-coating 2D and small chemical molecules prolong the passage of porcine spermatogonia stem cells

335 | Dec 09 2021

Ying Zhang et al. found that feeder-free culture system optimized cell culture and might facilitate advanced research on SSC biology and genetic manipulation of germ cells. [Read the Full Post]

IL4/IL4R signaling promotes the osteolysis in metastatic bone of CRC through regulating the proliferation of osteoclast precursors

350 | Dec 07 2021

Qian Jin et al. thought that ravoxertinib could be a new therapeutical target for bone metastasis of CRC. [Read the Full Post]

TGFβ1 Secreted by Cancer-Associated Fibroblasts as an Inductor of Resistance to Photodynamic Therapy in Squamous Cell Carcinoma Cells

278 | Nov 28 2021

María Gallego-Rentero et al. found that the comparatively higher intrinsic resistance to PDT of SCC13 cells was mediated by the elevated levels of TGFβ1 secreted by this cell line. [Read the Full Post]

Cadherin-12 Regulates Neurite Outgrowth Through the PKA/Rac1/Cdc42 Pathway in Cortical Neurons

611 | Nov 26 2021

Beibei Guo et al. reported the effect of CDH12 on axonal extension in vitro and in vivo. [Read the Full Post]

The expression of Annexin A1 and A5 mRNA by gonadotropin-releasing hormone in LβT2 gonadotrope cells

424 | Nov 21 2021

Takuya Murata et al. found that ANXA1 mRNA expression was stimulated by GnRH through PKC like ANXA5, and the response of ANXA1 was much larger than that of ANXA5. [Read the Full Post]

Mutual regulation between chicken telomerase reverse transcriptase and the Wnt/β-catenin signalling pathway inhibits apoptosis and promotes the replication of ALV-J in LMH cells

652 | Nov 21 2021

Yong Xiang et al. found that chTERT not only shortened the cell cycle to promote proliferation but also inhibited apoptosis by downregulating the expression of Caspase 3, Caspase 9 and BAX. [Read the Full Post]

A phase 1b study of the Notch inhibitor crenigacestat (LY3039478) in combination with other anticancer target agents (taladegib, LY3023414, or abemaciclib) in patients with advanced or metastatic solid tumors

445 | Nov 16 2021

Analia Azaro et al. demonstrated that crenigacestat combined with different anticancer agents was poorly tolerated, leading to lowered dosing and disappointing clinical activity in patients with advanced or metastatic solid tumors. [Read the Full Post]

The Circadian Rhythms of STAT3 in the Rat Pineal Gland and Its Involvement in Arylalkylamine-N-Acetyltransferase Regulation

556 | Nov 09 2021

Simona Moravcová et al. suggested that the higher nocturnal endogenous level of STAT3 in the pineal gland decelerated or hampered the process of NA-induced AANAT activation or affected the AANAT enzyme stability. [Read the Full Post]

Reducing tumor invasiveness by ramucirumab and TGF-β receptor kinase inhibitor in a diffuse-type gastric cancer patient-derived cell model

291 | Nov 03 2021

Song-Yi Lee et al. confirmed that combination of TEW-7197 and ramucirumab reduced tumor spheroid and GC PDC-induced blood vessel formation concomitantly in the spheroid-on-a-chip model. [Read the Full Post]

A Novel Small Molecule, LCG-N25, Inhibits Oral Streptococcal Biofilm

386 | Oct 23 2021

Xiaoying Lyu et al. suggested that LCG-N25 may represent a promising antimicrobial agent that can be used as an adjuvant to the management of dental caries. [Read the Full Post]

Chemical Reprogramming of Somatic Cells in Neural Direction: Myth or Reality?

0 | Oct 22 2021

E M Samoilova et al. thought that reprogramming with small molecules without additional factors modifying gene expression did not allow reproducible production of human neural stem cell-like progenitors that could be used as the source of neural tissue for the regenerative therapy. [Read the Full Post]

"Petal-like" size-tunable gold wrapped immunoliposome to enhance tumor deep penetration for multimodal guided two-step strategy

383 | Oct 11 2021

Yanan Li et al. provided a synergistic treatment strategy that could broaden the conventional treatment alone. [Read the Full Post]

Genetic Prioritization, Therapeutic Repositioning and Cross-Disease Comparisons Reveal Inflammatory Targets Tractable for Kidney Stone Disease

374 | Oct 09 2021

Hai Fang et al. provided the rich information of how to target innate immune pathways, with the potential of advancing immunotherapeutic strategies for nephrolithiasis. [Read the Full Post]

FSH stimulated bovine granulosa cell steroidogenesis involves both canonical and noncanonical WNT signaling

363 | Oct 08 2021

M Ashry et al. found that both canonical and noncanonical WNT pathways activation was linked to FSH stimulation of E2 production by bovine granulosa cells. [Read the Full Post]

Dual Inhibition of Histone Deacetylases and the Mechanistic Target of Rapamycin Promotes Apoptosis in Cell Line Models of Uveal Melanoma

337 | Oct 08 2021

Ruchi P Patel et al. found that romidepsin in combination with mTOR inhibition could be an effective treatment strategy against uveal melanoma due in part to changes in apoptotic proteins. [Read the Full Post]

Successful treatment of hepatosplenic T-cell lymphoma with fludarabine, high-dose cytarabine and subsequent unrelated umbilical cord blood transplantation

721 | Oct 04 2021

Takaya Honda et al. found a heterozygous nonsense c.2961C>G (p.Tyr987Ter) variant of the KMT2C gene. [Read the Full Post]

The imbalance of Th17/Treg via STAT3 activation modulates cognitive impairment in P. gingivalis LPS-induced periodontitis mice

425 | Oct 03 2021

Xu Zhang et al. thought that the STAT3 signaling pathway might have immunoregulatory effects on the mouth-to-brain axis. [Read the Full Post]

γ-secretase inhibitors, DAPT and RO4929097, promote the migration of Human Glioma Cells via Smad5-downregulated E-cadherin Expression

1447 | Oct 01 2021

Shun-Fu Chang et al. showed that γ-secretase activity inhibition by DAPT and RO4929097 could promote LN18 and LN229 glioma cell migration via downregulating E-cadherin mRNA and protein expressions, but not via affecting E-cadherin protein processing. [Read the Full Post]

Graphene oxide-functionalized nanocomposites promote osteogenesis of human mesenchymal stem cells via enhancement of BMP-SMAD1/5 signaling pathway

463 | Sep 19 2021

Zhong Li et al. demonstrated the biological activity and mechanism of action of GO-based nanosheets in augmenting the osteogenic capability of hMSCs. [Read the Full Post]

Cannabinoid receptor 2 plays a central role in renal tubular mitochondrial dysfunction and kidney ageing

649 | Sep 16 2021

Shan Zhou et al. showed CB2 played a central role in renal tubular mitochondrial dysfunction and kidney ageing. [Read the Full Post]

High WHSC1L1 Expression Reduces Survival Rates in Operated Breast Cancer Patients with Decreased CD8+ T Cells: Machine Learning Approach

601 | Sep 15 2021

Hyung-Suk Kim et al. found that VX-11e, CZC24832, LY2109761, oxaliplatin and erlotinib were effective in inhibiting breast cancer cell lines with high WHSC1L1 expression. [Read the Full Post]

Dynamic Remodeling of Membranes and Their Lipids during Acute Hormone-Induced Steroidogenesis in MA-10 Mouse Leydig Tumor Cells

655 | Sep 13 2021

Sathvika Venugopal et al. suggested that PM-ER-mitochondria tethering might be involved in lipid trafficking between organelles. [Read the Full Post]

Tumor-promoting function of PIMREG in glioma by activating the β-catenin pathway

588 | Sep 12 2021

Dekang Wang et al. provided new insights into the molecular mechanism for glioma pathogenesis and treatment. [Read the Full Post]

Effect of High Cholesterol Regulation of LRP1 and RAGE on Aβ Transport Across the Blood-brain Barrier in Alzheimer's Disease

753 | Sep 11 2021

Rui Zhou et al. found that high cholesterol decreased LRP1 expression and increased RAGE expression in cerebral microvascular endothelial cells, which led to Aβ transport disorder in the blood-brain barrier. [Read the Full Post]

Small Molecule "Silmitasertib" Repurposed as Inhibitor of Transforming Growth Factor Beta 1 for the Development of Therapeutics for Oral Submucous Fibrosis

982 | Sep 10 2021

Nezar Boreak et al. suggested that the molecule could be validated and implemented for the treatment of OSMF. [Read the Full Post]

An Iron Shield to Protect Epigallocatehin-3-Gallate from Degradation: Multifunctional Self-Assembled Iron Oxide Nanocarrier Enhances Protein Kinase CK2 Intracellular Targeting and Inhibition

785 | Sep 10 2021

Luca Fasolato et al. found that the nanohybrid was able to successfully deliver EGCG into cancer cells, displaying impressive protein kinase CK2 inhibition comparable to that obtained with the most specific CK2 inhibitor, CX-4945 (5.5 vs. 3 µM). [Read the Full Post]

PM 2.5 and water-soluble components induce airway fibrosis through TGF-β1/Smad3 signaling pathway in asthmatic rats

444 | Sep 03 2021

Hongyan Wu et al. thought that TGF-β1/Smad3 signaling pathway might be responsible for the pathological process of airway fibrosis in asthmatic rats following PM2.5 and water-soluble components exposure. [Read the Full Post]

Notch inhibitors induce diarrhea, hypercrinia and secretory cell metaplasia in the human colon

812 | Aug 30 2021

Michael Collins et al. confirmed the role of Notch signaling in intestinal homeostasis in humans. [Read the Full Post]

Limb Remote Ischemic Conditioning Ameliorates Cognitive Impairment in Rats with Chronic Cerebral Hypoperfusion by Regulating Glucose Transport

809 | Aug 27 2021

Changhong Ren et al. suggested that supplemental activation of glucose transport after CCH might provide a clinically applicable intervention for improving cognitive impairment. [Read the Full Post]

Tofacitinib Ameliorates Lupus Through Suppression of T Cell Activation Mediated by TGF-Beta Type I Receptor

1039 | Aug 20 2021

Qing Yan et al. thought that tofacitinib could suppress T cell activation by upregulating TGFβRI expression, which provided a possible molecular mechanism underlying clinical efficacy of tofacitinib in treating SLE patients. [Read the Full Post]

Wnt-C59 inhibits proinflammatory cytokine expression by reducing the interaction between β-catenin and NF-κB in LPS-stimulated epithelial and macrophage cells

846 | Aug 17 2021

Jaewoong Jang et al. suggested that the anti-inflammatory effect of Wnt-C59 was mediated by the reduction of the cellular level of β-catenin and the interaction between β-catenin and NF-κB. [Read the Full Post]

Wnt-Signaling Inhibitor Wnt-C59 Suppresses the Cytokine Upregulation in Multiple Organs of Lipopolysaccharide-Induced Endotoxemic Mice via Reducing the Interaction between β-Catenin and NF-κB

433 | Aug 16 2021

Jaewoong Jang et al. thought that Wnt-C59 might be useful for the suppression of the multiple-organ dysfunction during sepsis. [Read the Full Post]

Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial

467 | Aug 12 2021

Alexander J Stratigos et al. found that cemiplimab exhibited clinically meaningful antitumour activity and an acceptable safety profile in patients with locally advanced basal cell carcinoma after HHI therapy. [Read the Full Post]

MLN4924 inhibits hedgehog signaling pathway and activates autophagy to alleviate mouse laser-induced choroidal neovascularization lesion

491 | Aug 09 2021

Laiqing Xie et al. found that MLN4924 relieved the formation of mouse laser-induced CNV lesion might via up-regulating hedgehog pathway-regulated autophagy. [Read the Full Post]

Outcome of COVID-19 infection in 50 multiple myeloma patients treated with novel drugs: single-center experience

1258 | Jul 27 2021

Marta Krejci et al. found that the course of COVID-19 disease in MM pts was mostly moderate or serious with 56% of hospitalizations and 18% of deaths. [Read the Full Post]

Incidence, predictors, and outcomes of DAPT non-compliance in planned vs. ad hoc PCI in chronic coronary syndrome

968 | Jul 21 2021

Jahanzeb Malik et al. provided an insight on additional predictors of non-compliance to DAPT, helping us to identify and address specific patient-related factors for disruption. [Read the Full Post]

Angiokinase inhibition of VEGFR-2, PDGFR and FGFR and cell growth inhibition in lung cancer: Design, synthesis, biological evaluation and molecular docking of novel azaheterocyclic coumarin derivatives

1329 | Jul 21 2021

Eman Y Ahmed et al. found that 4a was capable of arresting the cell cycle at pre-G1 phase and S phase and inducing apoptosis. [Read the Full Post]

Peptide 11R‑VIVIT promotes fracture healing in osteoporotic rats

2716 | Jul 20 2021

Changju Hou et al. demonstrated that 11R‑VIVIT promoted fracture healing in osteoporotic rats and enhanced the osteogenic differentiation of osteoporotic BMSCs by dysregulating the AKT/NFATc1 signaling pathway. [Read the Full Post]

TGF-β Alters the Proportion of Infiltrating Immune Cells in a Pancreatic Ductal Adenocarcinoma

450 | Jul 18 2021

Kasia Trebska-McGowan et al. found that TGF-β had an overall immunosuppressive effect mediated by TAM PD-L1 expression and decreased presence of DCs. [Read the Full Post]

Synthesis and Evaluation of Chiral Rhodanine Derivatives Bearing Quinoxalinyl Imidazole Moiety as ALK5 Inhibitors

412 | Jul 18 2021

Li-Min Zhao et al. suggested that the synthesized rhodanine compounds had good ALK5 inhibitory activity and could be used for further research and development as potential antifungal drugs. [Read the Full Post]

Targeting ERK combined with apatinib may be a promising therapeutic strategy for treating oral squamous cell carcinoma

490 | Jul 14 2021

Tong-Chao Zhao et al. suggested that the combination of apatinib and SCH772984 was a potent OSCC therapy. [Read the Full Post]

Dual Targeting of Sorafenib-Resistant HCC-Derived Cancer Stem Cells

397 | Jul 04 2021

Ritu Shrestha et al. found that the combined targeting of EMT and immune checkpoint molecules with Sorafenib could effectively target the CSC tumour subpopulation. [Read the Full Post]

Using JAK inhibitor to treat cytokine release syndrome developed after chimeric antigen receptor T cell therapy for patients with refractory acute lymphoblastic leukemia: A case report

823 | Jun 30 2021

Fu Ming Zi et al. found that Ruxolitinib could be used as an alternative therapeutic approach for severe and refractory CRS without impairing CAR-T amplification and anti-tumor effect. [Read the Full Post]

GSK3ß inhibitor CHIR 99021 modulates cerebral organoid development through dose-dependent regulation of apoptosis, proliferation, differentiation and migration

711 | Jun 29 2021

Chloe Delepine et al. revealed new mechanisms of the pleiotropic effects of GSK3β during organoid development, providing essential information for the improvement of organoid production and ultimately shedding light on the mechanisms of embryonic brain development. [Read the Full Post]

A Rho Kinase (ROCK) Inhibitor, Y-27632, Inhibits the Dissociation-Induced Cell Death of Salivary Gland Stem Cells

919 | Jun 23 2021

Kichul Kim et al. demonstrated the protective effects of Y-27632 against dissociation-induced apoptosis of SGSCs during their culture in vitro. [Read the Full Post]

Efficacy of tyrosine kinase inhibitors against lung cancer with EGFR exon 18 deletion: Case report and pooled analysis

995 | Jun 08 2021

Rafael Rubiera-Pebe et al. showed that afatinib was associated with a greater tumor response rate and a longer PFS than the first generation TKIs. [Read the Full Post]

β-Sitosterol-D-Glucopyranoside Mimics Estrogenic Properties and Stimulates Glucose Utilization in Skeletal Muscle Cells

411 | Jun 03 2021

Jyotsana Pandey et al. found the estrogenic activity of BSD to stimulate glucose utilization in skeletal muscle cells via PI-3K/AKT-dependent mechanism. [Read the Full Post]

Phase 1 study of the ATR inhibitor berzosertib (formerly M6620, VX-970) combined with gemcitabine ± cisplatin in patients with advanced solid tumours

965 | Jun 02 2021

Mark R Middleton et al. found that Berzosertib + gemcitabine was well tolerated in patients with advanced solid tumours and showed preliminary efficacy signs. [Read the Full Post]

Inhibition of the Histone Methyltransferase EZH2 Enhances Protumor Monocyte Recruitment in Human Mesothelioma Spheroids

893 | May 17 2021

Silvia Mola et al. found that TAMs were a driving force for MPM growth, progression, and resistance to tazemetostat. [Read the Full Post]

Netarsudil: A new ophthalmic drug in the treatment of chronic primary open angle glaucoma and ocular hypertension

785 | Apr 18 2021

Mansi Batra et al. showed that the discovery of netarsudil was a breakthrough in the therapy of glaucoma with proven efficacy in a wide range of eye pressures and was well tolerated in cases with ocular hypertension and chronic glaucoma. [Read the Full Post]

ALK3-SMAD1/5 Signaling Mediates the BMP2-Induced Decrease in PGE2 Production in Human Endometrial Stromal Cells and Decidual Stromal Cells

455 | Apr 16 2021

Yu Zhang et al. found that BMP2 decreased PGE2 production by downregulating COX-1 expression. [Read the Full Post]

In vivo Pharmacokinetic Drug-Drug Interaction Studies Between Fedratinib and Antifungal Agents Based on a Newly Developed and Validated UPLC/MS-MS Method

928 | Apr 04 2021

Congrong Tang et al. thought that the toxicity of fedratinib should be avoided when the concurrent use of fedratinib with CYP3A4 inhibitors might occur. [Read the Full Post]

Current Clinical Investigations in Myelofibrosis

1023 | Apr 04 2021

Sangeetha Venugopal et al. provided insight into the novel therapies under clinical evaluation. [Read the Full Post]

Pharmacological inhibition of IKKβ dampens NLRP3 inflammasome activation after priming in the human myeloid cell line THP-1

825 | Mar 25 2021

Adeline Unterreiner et al. suggested that IκKβ might fulfill a dual role in coupling priming and activation of the NLRP3 inflammasome. [Read the Full Post]

Wnt Activation After Inhibition Restores Trabecular Meshwork Cells Toward a Normal Phenotype

447 | Mar 15 2021

Kamesh Dhamodaran et al. found that, in normal hTM cells, activation of the Wnt pathway reversed the pathological phenotype caused by Wnt inhibition and might thus be a viable therapeutic for lowering IOP. [Read the Full Post]

Immediate Effect of Baricitinib on Arthritis and Biological Disease-Modifying Antirheumatic Drug-Induced Psoriasis-Like Skin Lesions in Two Patients with Rheumatoid Arthritis

846 | Mar 05 2021

Yoshifumi Tada et al. found that baricitinib was initiated because of RA flare and resulted in immediate beneficial effects on arthritis as well as skin lesions. [Read the Full Post]

In-vitro evaluation of the immunomodulatory effects of baricitinib: implication for COVID-19 therapy

882 | Mar 04 2021

Linda Petrone et al. found that exogenous addition of baricitinib decreased the in-vitro SARS-CoV-2-specific response in COVID-19 patients using a whole-blood platform. [Read the Full Post]

EGR1 knockdown alleviates the cerebral injury in rats with intracerebral hemorrhage (ICH) via STAT3/NF-κB pathway by reducing RXRα acetylation level

563 | Feb 23 2021

Lijuan Xie et al. found that EGR1 increased RXRα acetylation level by regulating p300, thereby aggravating brain damage in ICH rat model and dysfunction in BMECs, which might through the STAT3/NF-κB pathway. [Read the Full Post]

More Insights on the Use of γ-Secretase Inhibitors in Cancer Treatment

736 | Feb 21 2021

Pilar López-Nieva et al. suggested that selective targeting γ-secretase might offer an improved efficacy and toxicity profile over the effects caused by broad-spectrum GSIs. [Read the Full Post]

Active notch protects MAPK activated melanoma cell lines from MEK inhibitor cobimetinib

712 | Feb 19 2021

Letizia Porcelli et al. unveiled a coordinate action of MAPK and Notch signaling in promoting proliferation of BRAFV600E MM and GNAQQ209L UM cells. [Read the Full Post]

Immune checkpoint inhibition in syngeneic mouse cancer models by a silicasome nanocarrier delivering a GSK3 inhibitor

522 | Feb 17 2021

Sean D Allen et al. provided proof-of-principal demonstration of the feasibility of using encapsulated delivery of a GSK3 inhibitor to provide cancer immunotherapy, with the possibility to be used as a monotherapy or in combination with chemotherapy or other immunomodulatory agents. [Read the Full Post]

Stomatin-like Protein 2 Promotes Tumor Cell Survival by Activating the JAK2-STAT3-PIM1 Pathway, Suggesting a Novel Therapy in CRC

663 | Feb 07 2021

Qiang Liu et al. suggested that SLP-2 controlled the JAK2-STAT3-PIM1 oncogenic pathway, offering a rationale for a novel therapeutic strategy with combined SGI-1776 and TG-101348 in CRC. [Read the Full Post]

The apoptotic effect of GSK-3 inhibitors: BIO and CHIR 98014 on H1975 lung cancer cells through ROS generation and mitochondrial dysfunction

393 | Feb 07 2021

Theodore Lemuel Mathuram et al. found that the use of GSK-3 inhibitors showed promising apoptotic abilities in clinical cancer treatments, particularly for lung cancer cells. [Read the Full Post]

STAT3 Is an Upstream Regulator of Granzyme G in the Maternal-To-Zygotic Transition of Mouse Embryos

453 | Feb 05 2021

Huan Ou-Yang et al. suggested that STAT3, a maternal protein, was a critical transcription factor and regulated Gzmg transcription activity in preimplantation mouse embryos. [Read the Full Post]

G ATA2 mediates the negative regulation of the prepro-thyrotropin-releasing hormone gene by liganded T3 receptor β2 in the rat hypothalamic paraventricular nucleus

443 | Feb 02 2021

Go Kuroda et al. suggested that GATA2 transactivated the rat prepro-TRH gene and that liganded TRβ2 interfered with this activation via a tethering mechanism as in the case of the TSHβ gene. [Read the Full Post]

Augmenter of Liver Regeneration (ALR) regulates bile acid synthesis and attenuates bile acid-induced apoptosis via glycogen synthase kinase-3β (GSK-3β) inhibition

1435 | Feb 02 2021

Sara Ibrahim et al. thought that rALR might contribute to protecting hepatocytes from toxic concentrations of bile acids by down-regulating their denovo synthesis, attenuating apoptosis by activation of PI3K/Akt - GSK3β pathway and inhibition of JNK signaling. [Read the Full Post]

Differential functional roles of fibroblasts and pericytes in the formation of tissue-engineered microvascular networks in vitro

679 | Jan 27 2021

Natalia Kosyakova et al. described the differential effects that two widely used stromal cell populations, fibroblasts (FBs) and pericytes (PCs), had on μVN formation. [Read the Full Post]

Suppression of MET signaling mediated by pitavastatin and capmatinib inhibits oral and esophageal cancer cell growth

738 | Jan 26 2021

Bo Xu et al. suggested that the combination of pitavastatin with capmatinib was a useful therapeutic strategy in OSCC and ESCC. [Read the Full Post]

Nanog maintains stemness of Lkb1-deficient lung adenocarcinoma and prevents gastric differentiation

834 | Jan 15 2021

Xinyuan Tong et al. uncovered a previously unappreciated plasticity of LKB1-deficient tumors and identified the Nanog-Notch axis in regulating gastric differentiation, which hold important therapeutic implication for the treatment of mucinous lung cancer. [Read the Full Post]

MOMENTUM: momelotinib vs danazol in patients with myelofibrosis previously treated with JAKi who are symptomatic and anemic

700 | Jan 13 2021

Srdan Verstovsek et al.showed that the MOMENTUM Phase III study was designed to confirm and extend observations of safety and clinical activity of MMB. [Read the Full Post]

CYT387, a Novel JAK2 Inhibitor, Suppresses IL-13-Induced Epidermal Barrier Dysfunction Via miR-143 Targeting IL-13Rα1 and STAT3

800 | Jan 13 2021

Yan Zu et al. revealed that the protective effects and the underlying mechanisms of CYT387 in AD, which provided evidence that miR-143 might be a novel therapeutic target for AD. [Read the Full Post]

Inhibition of TGF-β signalling in combination with nal-IRI plus 5-Fluorouracil/Leucovorin suppresses invasion and prolongs survival in pancreatic tumour mouse models

334 | Jan 09 2021

Eunji Hong et al. suggested that combination therapy of nal-IRI/5-FU/LV with vactosertib could provide clinical benefits to pancreatic cancer patients. [Read the Full Post]

Ebselen, Disulfiram, Carmofur, PX-12, Tideglusib, and Shikonin Are Nonspecific Promiscuous SARS-CoV-2 Main Protease Inhibitors

599 | Jan 07 2021

Chunlong Ma et al. suggested that these six compounds were nonspecific SARS-CoV-2 Mpro inhibitors and urged the scientific community to be stringent with hit validation. [Read the Full Post]

The Role of Actin in Muscle Spasms in a Case Series of Patients with Advanced Basal Cell Carcinoma Treated with a Hedgehog Pathway Inhibitor

418 | Jan 03 2021

Natalie Teh et al. presented a case series of patients with muscle spasms during treatment with sonidegib and proposed an alternate etiology related to increased actin expression. [Read the Full Post]

A Vismodegib Experience in Elderly Patients with Basal Cell Carcinoma: Case Reports and Review of the Literature

498 | Jan 02 2021

Anna Passarelli et al. reported two case reports of BCC elderly patients in order to demonstrate both efficacy and safety of the Hedgehog inhibitors. [Read the Full Post]

Gli affects the stemness and prognosis of epithelial ovarian cancer via homeobox protein NANOG

619 | Dec 28 2020

Huan Zhao et al. found that Gli and NANOG might be effective indicators of platinum resistance and prognosis in EOC. [Read the Full Post]

Small molecular compounds efficiently convert human fibroblasts directly into neurons

483 | Dec 21 2020

Jijuan Yang et al. provided a novel combination of existing small molecular compounds that efficiently reprogramed human fibroblasts into neurons. [Read the Full Post]

A Phase Ib Study to Evaluate the MEK Inhibitor Cobimetinib in Combination with the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors

406 | Dec 19 2020

Colin Weekes et al. thought that overlapping AEs and cumulative toxicity could not be adequately managed on either dosing schedule, restricting the ability to further develop this combination. [Read the Full Post]

GPR91 antagonist and TGF-β inhibitor suppressed collagen production of high glucose and succinate induced HSC activation

516 | Dec 10 2020

Mutsuko Sakai et al. determined that even though HSCs had already been activated by high glucose or succinate conditions which persisted after activation, the GPR91 antagonist and the TGF-β1 receptor inhibitor were able to reduce the production of type I collagen from activated HSCs. [Read the Full Post]

Scabronine G Methyl Ester Improves Memory-Related Behavior and Enhances Hippocampal Cell Proliferation and Long-Term Potentiation via the BDNF-CREB Pathway in Olfactory Bulbectomized Mice

694 | Dec 08 2020

Osamu Nakagawasai et al. revealed the potential of SG-ME in improving memory impairments by enhancing cell proliferation and LTP via activation of the BDNF/CREB signaling pathway in neurons. [Read the Full Post]

LGR5 induces β activation and augments tumor progression by activating STAT3 in human intrahepatic cholangiocarcinoma

1062 | Dec 04 2020

Keishi Kawasaki et al. thought that LGR5 was an excellent prognostic predictor and a promising therapeutic target for ICC. [Read the Full Post]

Component of nicotine-induced intracellular calcium elevation mediated through α3- and α5-containing nicotinic acetylcholine receptors are regulated by cyclic AMP in SH-SY 5Y cells

525 | Dec 03 2020

Tamayo Takahashi et al. suggested that α3 * and α5 * nAChR-mediated Ca2+ influx was possibly regulated by cAMP at the transcriptional level. [Read the Full Post]

Phase 1 study to evaluate Crenigacestat (LY3039478) in combination with dexamethasone in patients with T-cell acute lymphoblastic leukemia and lymphoma

625 | Nov 28 2020

Gautam Borthakur et al. found that crenigacestat demonstrated limited clinical activity at the recommended dose in adult patients with relapsed/refractory T-ALL/T-LBL. [Read the Full Post]

Cucurbitacin E and I target the JAK/STAT pathway and induce apoptosis in Sézary cells

1507 | Nov 18 2020

Isabella J Brouwer et al. suggested that STAT3 played a preferential role in the mechanism of action of these cucurbitacins. [Read the Full Post]

To inhibit TrxR1 is to inactivate STAT3-Inhibition of TrxR1 enzymatic function by STAT3 small molecule inhibitors

506 | Oct 29 2020

Sander Busker et al. suggested that targeting of TrxR1 might be a common feature for many small molecules that inhibited cellular STAT3 function. [Read the Full Post]

Chemical Reprogramming of Somatic Cells in Neural Direction: Myth or Reality?

838 | Oct 27 2020

E M Samoilova et al. found that reprogramming with small molecules without additional factors modifying gene expression did not allow reproducible production of human neural stem cell-like progenitors that could be used as the source of neural tissue for the regenerative therapy. [Read the Full Post]

Neuroprotective Effects of the Sonic Hedgehog Signaling Pathway in Ischemic Injury through Promotion of Synaptic and Neuronal Health

420 | Oct 13 2020

Sen Yin et al.demonstrated that activation of the Shh signaling pathway played a neuroprotective role in response to ischemic exposure via promotion of synaptic and neuronal health. [Read the Full Post]

NRAS Status Determines Sensitivity to SHP2 Inhibitor Combination Therapies Targeting the RAS-MAPK Pathway in Neuroblastoma

427 | Oct 04 2020

Ivette Valencia-Sama et al. suggested that conventional therapy-resistant, relapsed neuroblastoma might be effectively treated via combined inhibition of SHP2 and MEK or ERK of the RAS-MAPK pathway. [Read the Full Post]

Inhibition of the ERK/RSK kinase cascade limits Chlamydia trachomatis infection

465 | Oct 04 2020

Yaohua Xue et al. demonstrated not only that the ERK/RSK pathway played a critical role in Chlamydia infection, but also that these kinases had potential as targets for host-directed therapy against Chlamydia trachomatis. [Read the Full Post]

A Slug-dependent mechanism is responsible for tumor suppression of p53-stabilizing compound CP-31398 in p53-mutated endometrial carcinoma

375 | Oct 03 2020

Ling Liu et al. showed that CP-31398-regulated Slug downregulation repressed the p53-mutated EC via the p53/Wnt/Puma pathway. [Read the Full Post]

A study of human leukocyte antigen-haploidentical hematopoietic stem cells transplantation combined with allogenic mesenchymal stem cell infusion for treatment of severe aplastic anemia in pediatric and adolescent patients

676 | Sep 29 2020

Li Ding et al. suggested that cotransplantation of HLA-haploidentical HSC and allogenic mesenchymal stem cell might provide an effective and safe treatment for children and adolescents with SAA who lacked matched donors. [Read the Full Post]

Xanthatin alleviates airway inflammation in asthmatic mice by regulating the STAT3/NF-κB signaling pathway

462 | Sep 28 2020

Jingxia Chang et al. concluded that Xanthatin attenuated airway inflammation in asthmatic mice through blocking the STAT3/NFκB signaling pathway, indicating the potential of Xanthatin as a useful therapeutic agent for asthma. [Read the Full Post]

Targeting the Notch and TGF-β signaling pathways to prevent retinal fibrosis in vitro and in vivo

860 | Sep 27 2020

Jiawen Fan et al. foung that inhibiting Notch signaling might be an effective way to prevent retinal fibrosis. [Read the Full Post]

Structural Basis of Activin Receptor-Like Kinase 2 (R206H) Inhibition by Bis-heteroaryl Pyrazole-Based Inhibitors for the Treatment of Fibrodysplasia Ossificans Progressiva Identified by the Integration of Ligand-Based and Structure-Based Drug Design Approaches

470 | Sep 13 2020

Tomohiro Sato et al. indicated the existence of the additional hydrogen bond via water molecules restricting the attachment point in the pyrazole scaffold [Read the Full Post]

Effective Reconstruction of Functional Urethra Promoted With ICG-001 Delivery Using Core-Shell Collagen/Poly(Llactide-co-caprolactone) [P(LLA-CL)] Nanoyarn-Based Scaffold: A Study in Dog Model

431 | Sep 08 2020

Kaile Zhang et al. applied a novel drug-delivering nanoyarn scaffold in urethroplasty in dog model, which continuously delivered ICG-001 during tissue reconstruction, and could effectively promote urethral recovery and resume fully functional urethra within 12 weeks. [Read the Full Post]

Mast cells (MCs) induce ductular reaction mimicking liver injury in mice via MC-derived TGF-β1 signaling

568 | Sep 02 2020

Konstantina Kyritsi et al. demonstrated that reintroduction of MCs mimics cholestatic liver injury and MC-derived TGF-β1 might be a target in chronic cholestatic liver disease. [Read the Full Post]

Bucladesine Attenuates Spatial Learning and Hippocampal Mitochondrial Impairments Induced by 3, 4-Methylenedioxymethamphetamine (MDMA)

536 | Aug 31 2020

Ghorban Taghizadeh et al. highlighted the role of cAMP/PKA signaling in MDMA-induced memory and mitochondrial defects. [Read the Full Post]

Combined treatment with CBP and BET inhibitors reverses inadvertent activation of detrimental super enhancer programs in DIPG cells

479 | Aug 30 2020

Maria Wiese et al. found that combinatorial treatment with CBP and BET inhibitors was highly efficient in H3K27M-mutant DIPG due to reversal of inadvertent activation of detrimental SE programs in comparison with monotherapy. [Read the Full Post]

Quercetin promotes human epidermal stem cell proliferation through the estrogen receptor/β-catenin/c-Myc/cyclin A2 signaling pathway

529 | Aug 28 2020

Zhaodong Wang et al.showed that EpSCs were used not only in clinic to treat skin wounds but also as seed cells in skin tissue engineering.Quercetin was a useful reagent to expand EpSCs for basic research, skin wound treatment, and skin tissue engineering. [Read the Full Post]

Protein Kinase CK2 in Cancer Energetics

959 | Aug 27 2020

Eduardo Silva-Pavez et al. proposed that the specific inhibition of CK2 might lead to a catastrophic death of cancer cells, which could become a feasible therapeutic strategy to beat this devastating disease. [Read the Full Post]

Casein kinase 2 inhibitor CX-4945 elicits an anti-Warburg effects through the downregulation of TAp73 and inhibits gastric tumorigenesis

856 | Aug 27 2020

Shengli Tang et al. suggested that CX-4945 elicited an anti-Warburg effects in gastric cancer overexpressing Tap73 and inhibited gastric tumorigenesis. [Read the Full Post]

CircPlekha7 plays an anti-fibrotic role in intrauterine adhesions by modulating endometrial stromal cell proliferation and apoptosis

364 | Aug 18 2020

Wei Xie et al. indicated that circPlekha7 played an anti-fibrotic role in IUA and might serve as a promising prognostic biomarker for patients with IUA. [Read the Full Post]

Tumour-associated neutrophils orchestrate intratumoural IL-8-driven immune evasion through Jagged2 activation in ovarian cancer

797 | Aug 12 2020

Moran Yang et al. found that JAG2+TANs were closely linked to IL-8-driven immune evasion microenvironment and might serve as a promising therapeutic target for the reinvigoration of anti-tumour immunity. [Read the Full Post]

Irisin ameliorates high glucose-induced cardiomyocytes injury via AMPK/mTOR signal pathway

731 | Aug 10 2020

Jingyu Deng et al. showed that Irisin played a significant role in anti-apoptosis, anti-inflammation, anti-oxidative stress in HG-induced CMs via AMPK/mTOR signaling pathway. [Read the Full Post]

Proteasome Inhibitor PS-341 Effectively Blocks Infection by the Severe Fever with Thrombocytopenia Syndrome Virus

1001 | Aug 07 2020

Sihua Liu et al. indicated that targeting of cellular interferon pathways and apoptosis during acute infection might serve as the bases of future therapeutics for the treatment of SFTSV infections. [Read the Full Post]

Pentraxin-3 Mediates Prosurvival Actions of Interferon Tau in Bovine Luteinized Granulosa Cells

740 | Aug 06 2020

Raghavendra Basavaraja et al. suggested a novel role for PTX3 during early pregnancy, as mediator of IFNT prosurvival actions supporting CL maintenance during this reproductive stage. [Read the Full Post]

Effectiveness and Costs Among Rheumatoid Arthritis Patients Treated with Targeted Immunomodulators Using Real-World U.S. Data

830 | Jul 28 2020

Mahdi Gharaibeh et al. showed that the range of patients who were effectively treated with first-line therapy was higher for certain tumor necrosis factor inhibitors and tocilizumab. [Read the Full Post]

Exosomal release of microRNA-454 by breast cancer cells sustains biological properties of cancer stem cells via the PRRT2/Wnt axis in ovarian cancer

363 | Jul 23 2020

Ling Wang et al. discovered that C59 reversed the repressive role of exosomes in stemness of CSCs. When being evaluated in a mouse model, exosomal miR-454 led to an efficacious effect in suppressing the tumor weight and volume in vivo. [Read the Full Post]

Differentiation of Human Cardiac Atrial Appendage Stem Cells into Adult Cardiomyocytes: A Role for the Wnt Pathway?

409 | Jul 23 2020

Leen Willems et al. indicated that Wnt signaling had limited effects on CASC clonogenicity, proliferation, and differentiation. [Read the Full Post]

Cohort analysis of safety and efficacy of vismodegib in Italian patients from the Phase II, multicenter STEVIE study

438 | Jul 19 2020

Paolo Bossi et al. showed a safety profile consistent with the whole population; older age did not affect safety or efficacy. [Read the Full Post]

Phosphoproteomics of short-term hedgehog signaling in human medulloblastoma cells

460 | Jul 14 2020

Tamara Scheidt et al. provided evidence that phosphorylation triggered in response to SMO modulation dictated the localization of hedgehog pathway components within the primary cilium and affected the regulation of the SMO-SUFU-GLI axis. [Read the Full Post]

Sequential Bortezomib and Temozolomide Treatment Promotes Immunological Responses in Glioblastoma Patients With Positive Clinical Outcomes: A Phase 1B Study

1000 | Jun 25 2020

Mohummad A Rahman et al. found that Sequential BTZ + TMZ treatment was safe and promotes Th1-driven immunological responsed in selected patients with improved clinical outcomes (Clinicaltrial.gov (NCT03643549)). [Read the Full Post]

Notch Signaling Pathway Is a Potential Therapeutic Target for Extracranial Vascular Malformations

0 | Jun 22 2020

Reema B Davis et al. provided further rationale to support testing of Notch inhibitors in patients with extracranial vascular malformations. [Read the Full Post]

Overexpression of Fibroblast Growth factor-21 (FGF-21) Protects Mesenchymal Stem Cells Against Caspase-Dependent Apoptosis Induced by Oxidative Stress and Inflammation

1358 | Jun 22 2020

Gabriel R Linares et al. provided compelling evidence that FGF-21 played a crucial role in protecting MSCs from apoptosis induced by oxidative stress and inflammation, and merited further investigation as a strategy for enhancing the therapeutic efficacy of stem cell-based therapies. [Read the Full Post]

Effects of the PI3K/Akt Signaling Pathway on the Apoptosis of Early Host Cells Infected With Eimeria Tenella

1305 | Jun 21 2020

Xuesong Zhang et al. investigated the role of PI3K/Akt signaling pathway on host cell apoptosis in the early infection of Eimeria tenella,the early development of E. tenella could inhibit host cell apoptosis by downregulating the Caspase-3 activity. [Read the Full Post]

A Systematic Review of the Studies That Evaluate the Performance of the DAPT Score

875 | Jun 21 2020

Chun Shing Kwok et al. showd that the DAPT score had modest predictive value for ischemic and bleeding outcomes.A prospective randomized controlled trial was needed to evaluate the clinical benefits of utilising the DAPT score in guiding continued DAPT therapy beyond 1 year. [Read the Full Post]

DAPT Score and the Impact of Ticagrelor Monotherapy During the Second Year After PCI

909 | Jun 18 2020

Ply Chichareon et al. found that the DAPT score can stratify ischemic but not bleeding risk in a contemporary PCI population during the second year. [Read the Full Post]

Staurosporine and NEM Mainly Impair WNK-SPAK/OSR1 Mediated Phosphorylation of KCC2 and NKCC1

1312 | Jun 18 2020

Jinwei Zhang et al. identified phospho-sites that are responsive to staurosporine or NEM application. [Read the Full Post]

Xiaochaihu Decorction Relieves Liver Fibrosis Caused by Schistosoma Japonicum Infection via the HSP47/TGF-β Pathway

435 | Jun 16 2020

Yuzheng Huang et al. demonstrated that the hepatic protective effects of Xiaochaihu decoction were mediated by HSP47/TGF-β axis. [Read the Full Post]

LGR5 Controls Extracellular Matrix Production by Stem Cells in the Developing Intestine

447 | Jun 14 2020

Valeria Fernandez Vallone et al. provided that Lgr5 antagonizes the Rspondin 2-Wnt-mediated response in ISCs in organoids, revealing a sophisticated regulatory process for Wnt signaling in ISCs. [Read the Full Post]

Promotion of Liver Regeneration and Anti‑fibrotic Effects of the TGF‑β Receptor Kinase Inhibitor Galunisertib in CCl4‑treated Mice

928 | Jun 14 2020

Atsutaka Masuda et al. suggested that galunisertib might be an effective treatment for liver cirrhosis. [Read the Full Post]

Loss of HAT1 Expression Confers BRAFV600E Inhibitor Resistance to Melanoma Cells by Activating MAPK Signaling via IGF1R

460 | Jun 07 2020

Suresh Bugide et al. showed that the loss of HAT1 expression confered acquired BRAFi resistance by activating the MAPK signaling pathway via IGF1R. [Read the Full Post]

Generation of Liver Bipotential Organoids With a Small-Molecule Cocktail

852 | Jun 05 2020

Xin Wang et al. demonstrated that Wnt/β-catenin, NMII-Rac, and PKA-ERK are core signaling pathways essential and sufficient for mouse liver progenitor expansion. [Read the Full Post]

Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2 Emergency and Similar Future Global Health Threats

875 | Jun 05 2020

Marco Malavolta et al. explored the idea that an exacerbated inflammatory response, in particular that mediated by IL-6, migtht drive the deleterious consequences of the infection. [Read the Full Post]

Hypoxia Upregulates Cxcl12 in Hepatocytes by a Complex Mechanism Involving Hypoxia-Inducible Factors and Transforming Growth Factor-β

908 | May 27 2020

Jenna Strickland et al. demonstrated that hypoxia upregulated Cxcl12 in primary mouse hepatocytes by a mechanism that involved HIFs and TGF-β. [Read the Full Post]

Essential Thrombocythemia Treatment Algorithm 2018

780 | May 24 2020

Ayalew Tefferi et al. provided a point-of-care treatment algorithm that was risk-adapted and based on evidence and decades of experience. [Read the Full Post]

CHIR-99021 Regulates Mitochondrial Remodelling via β-Catenin Signalling and miRNA Expression During Endodermal Differentiation

0 | May 22 2020

Yuejiao Ma et al. demonstrated that CHIR-99021 played a role in mitochondrial structure and function remodelling via activation of the β-catenin signalling pathway and inhibited the expression of miRNAs during definitive endodermal differentiation. [Read the Full Post]

Discovery of suppressors of CRMP2 phosphorylation reveals compounds that mimic the behavioral effects of lithium on amphetamine-induced hyperlocomotion

523 | May 18 2020

Zhao WN et al. not only provided insights into the neural substrates regulated by lithium, but also provided novel human neuronal assays for supporting the development of mechanism-based therapeutics for BD and related neuropsychiatric disorders. [Read the Full Post]

Glucagon-like peptide 1 reverses myocardial hypertrophy through cAMP/PKA/RhoA/ROCK2 signaling.

1002 | May 14 2020

Fan S et al. suggested that GLP-1 might reverse myocardial hypertrophy through the PKA/RhoA/ROCK2 signaling pathway. [Read the Full Post]

The Rho-associated kinase inhibitor fasudil can replace Y-27632 for use in human pluripotent stem cell research

1361 | May 12 2020

So S et al. suggested that fasudil can replace Y-27632 for use in stem research. [Read the Full Post]

FAM83A Promotes Lung Cancer Progression by Regulating the Wnt and Hippo Signaling Pathways and Indicates Poor Prognosis

512 | May 07 2020

Zheng YW et al. found that FAM83A promotes the proliferation and invasion of lung cancer cells by regulating the Wnt and Hippo signaling pathways and EMT process. [Read the Full Post]

GSK-3 Inhibitors: A Double-Edged Sword? - An Update on Tideglusib

549 | May 05 2020

Mathuram TL et al. concluded the emergence of GSK-3 inhibitors as a 'double-edged sword' in the treatment against human diseases cautioning researchers about the potential ramifications of off-target pharmacological effects. [Read the Full Post]

NVP-LDE-225 (Erismodegib) Inhibits Epithelial-Mesenchymal Transition and Human Prostate Cancer Stem Cell Growth in NOD/SCID IL2Rγ Null Mice by Regulating Bmi-1 and microRNA-128

717 | Apr 30 2020

R Nanta et al. suggested that inhibition of the Shh signaling pathway could therefore be a novel therapeutic option in treating prostate cancer. [Read the Full Post]

NVP-LDE225, a Potent and Selective SMOOTHENED Antagonist Reduces Melanoma Growth in Vitro and in Vivo

500 | Apr 30 2020

Ahmad Jalili et al. concluded that inhibition of SHH-GLI signaling pathway in human melanoma by the specific smoothened inhibitor NVP-LDE225 could have potential therapeutic application in human melanoma even in the absence of BRAF(V600E) mutation and warrants further investigations. [Read the Full Post]

GANT61 Alleviates Arthritic Symptoms by Targeting Fibroblast-Like Synoviocytes in CIA Rats

490 | Apr 20 2020

Suping Qin et al. indicated the GANT61 inhibit the proliferation of FLS and alleviated the arthritic symptoms in CIA rats, this implied the GANT61 may be recommended as a possible candidate for the therapy of RA. [Read the Full Post]

Notch signaling pathway is a potential therapeutic target for extracranial vascular malformations

0 | Apr 11 2020

Davis RB et al. provided further rationale to support testing of Notch inhibitors in patients with extracranial vascular malformations. [Read the Full Post]

Impact of high on-treatment platelet reactivity after angioplasty in patients with peripheral arterial disease

692 | Apr 10 2020

Busch L et al. suggested that MALE might be associated with dual HTPR. [Read the Full Post]

Crenigacestat, a selective NOTCH1 inhibitor, reduces intrahepatic cholangiocarcinoma progression by blocking VEGFA/DLL4/MMP13 axis

0 | Apr 06 2020

Mancarella S et al. provided new knowledge on Notch signaling in iCCA, and support the inhibition of the Notch cascade as a promising strategy for the treatment of this disease. [Read the Full Post]

Small molecule inhibitor RepSox prevented ovariectomy-induced osteoporosis by suppressing osteoclast differentiation and bone resorption

418 | Mar 22 2020

Mei L et al. suggested that RepSox regulates osteoclast differentiation, bone resorption, and OVX-induced OP via the suppression of the Smad3 and JNK/AP-1 pathways. [Read the Full Post]

A First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors

478 | Mar 17 2020

Varga A et al. indicated that GDC-0994 had an acceptable safety profile and pharmacodynamic effects were observed by FDG-PET and in serial tumor biopsies. Single-agent activity was observed in 2 patients with BRAF-mutant colorectal cancer. [Read the Full Post]

Precision-cut lung slices from bleomycin treated animals as a model for testing potential therapies for idiopathic pulmonary fibrosis

453 | Mar 04 2020

Cedilak M et al. suggested that PCLS may be a suitable in vitro model for compound testing during drug development process. [Read the Full Post]

T-cell death-associated gene 8 accelerates atherosclerosis by promoting vascular smooth muscle cell proliferation and migration

687 | Mar 02 2020

Chen LD et al. demonstrated that Tdag8 mediated phenotype transformation, proliferation and migration of VSMCs via the cAMP/PKA signaling pathway, thus partially contributing to atherosclerosis. [Read the Full Post]

Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial

590 | Feb 25 2020

Basset-Séguin N et al. showed the primary analysis of STEVIE demonstrates that vismodegib is tolerable in typical patients in clinical practice; safety profile is consistent with that in previous reports. Long-term exposure was not associated with worsening severity/frequency of TEAEs. Investigator-assessed response rates showed high rate of tumour control. [Read the Full Post]

Crenigacestat, a Selective NOTCH1 Inhibitor, Reduces Intrahepatic Cholangiocarcinoma Progression by Blocking VEGFA/DLL4/MMP13 Axis

1253 | Feb 23 2020

Serena Mancarella et al. developed and validated a new iCCA PDX model to test in vivo the activity of LY3039478, demonstrating its inhibitory role in Notch-dependent angiogenesis. Thus, the present data provide new knowledge on Notch signaling in iCCA, and support the inhibition of the Notch cascade as a promising strategy for the treatment of this disease. [Read the Full Post]

The JAK2 inhibitor AZD1480 inhibits hepatitis A virus replication in Huh7 cells

750 | Feb 12 2020

Jiang X et al. proposed that AZD1480 can inhibit HAV IRES activity and HAV replication through the inhibition of the La protein. [Read the Full Post]

Rho-kinase ROCK inhibitors reduce oligomeric tau protein

1099 | Feb 10 2020

Hamano T et al. suggested that ROCK inhibitors represent a viable therapeutic route to reduce the pathogenic forms of tau protein in tauopathies, including Alzheimer's disease. [Read the Full Post]

Non-Photoinduced Biological Properties of Verteporfin

0 | Jan 23 2020

Gibault F et al. indicated that VP is a multi-target drug interacting with several proteins implicated in major cellular processes. Although this does not impact its clinical use, VP does not seem to be the ideal drug for pharmacological inhibitions of YAP/TEAD. [Read the Full Post]

Automobile exhaust-derived PM2.5 induces blood-testis barrier damage through ROS-MAPK-Nrf2 pathway in sertoli cells of rats

0 | Jan 19 2020

Liu B et al. indicated that PM2.5 derived from automobile exhaust causes oxidative stress, which in turn causes cellular apoptosis of SCs and damage of the blood-testis barrier, resulting male spermatogenesis dysfunction, in which ROS-MAPK-Nrf-2 pathways may play a key role. [Read the Full Post]

Cirrhotic Human Liver Extracellular Matrix 3D Scaffolds Promote Smad-Dependent TGF-β1 Epithelial Mesenchymal Transition

478 | Jan 18 2020

Mazza G found that the inherent features of cirrhotic human liver ECM micro-environment were dissected and characterized for the first time as key pro-carcinogenic components in HCC development. [Read the Full Post]

Profiling of lincRNAs in human pluripotent stem cell derived forebrain neural progenitor cells

0 | Jan 10 2020

Grassi DA et al. were able to identify many previously uncharacterized long intergenic non-coding RNAs that display dynamic expression during human forebrain neurogenesis. [Read the Full Post]

Napabucasin: An Update on the First-in-Class Cancer Stemness Inhibitor

0 | Jan 05 2020

Hubbard JM and Grothey A indicated that napabucasin may prove useful in targeting cancer stem cells, with the potential to suppress metastasis and prevent relapse in patients with varying cancer types. [Read the Full Post]

Generation of Urine Cell-Derived Non-integrative Human iPSCs and iNSCs: A Step-by-Step Optimized Protocol

0 | Jan 03 2020

Cheng L et al. showed the optimized protocol is an easy and fast procedure to yield both iPSC and iNSC lines from a convenient source of human urine in a single experiment. [Read the Full Post]

Identification of RNPC3 as a novel JAK2 fusion partner gene in B-acute lymphoblastic leukemia refractory to combination therapy including ruxolitinib

743 | Dec 31 2019

Chen X et al. suggested the potential need for a diagnostic FISH analysis as well as RNA-Seq in the appropriate clinical setting. [Read the Full Post]

Pharmacological inhibition of Hippo pathway, with the novel kinase inhibitor XMU-MP-1, protects the heart against adverse effects during pressure overload

388 | Dec 25 2019

Triastuti E et al. indicated the Hippo pathway inhibitor, XMU-MP-1, reduced cellular hypertrophy and improved survival in cultured cardiomyocytes and, in vivo, preserved cardiac function following pressure overload. [Read the Full Post]

One Hundred Faces of Cyclopamine

523 | Dec 15 2019

Iovine V et al. indicated that the aim of the present work is to review the main synthetic strategies to cyclopamine and its derivatives, with particular emphasis on the challenging chemical modifications aimed at improving the biological activity of the molecule. [Read the Full Post]

LKB1 deficiency renders non-small-cell lung cancer cells sensitive to ERK inhibitors.: ERK inhibitors in LKB1 mutated NSCLC

462 | Dec 11 2019

Caiola E et al. showed that ERK inhibitors are effective in LKB1 and LKB1/KRAS mutated tumors, thus offering a therapeutic strategy for this prognostically unfavorable subgroup of patients. Since ERK inhibitors are already in clinical development, our findings could be easily translatable to the clinic. Importantly, the lack of effect in cells expressing wild-type LKB1, predicts that treatment of LKB1 mutated tumors with ERK inhibitors should have a favorable toxicity profile. [Read the Full Post]

In Silico Screening Reveals Histone Deacetylase 7 and ERK1/2 as Potential Targets for Artemisinin Dimer and Artemisinin Dimer Hemisuccinate

457 | Dec 11 2019

Ishola AA et al. suggested that artemisinin dimer and artemisinin dimer hemisuccinate could be promising anticancer drug agents, with better therapeutic efficacy than ulixertinib and apicidin in the treatment of cancer via inhibition of HDAC7, ERK1 and ERK2. [Read the Full Post]

Raloxifene inhibits adipose tissue inflammation and adipogenesis through Wnt regulation in ovariectomized rats and 3 T3-L1 cells

512 | Dec 10 2019

Shen HH et al. showed that distinct activation of canonical β-catenin on inhibition of adipogenesis and non-canonical SFRP5 on suppression of WAT inflammation may contribute to the beneficial effects of RAL. Therefore, this study provides a rationale for the therapeutic potential of RAL for postmenopausal obesity. [Read the Full Post]

Fludarabine-PET in a murine model of multiple myeloma

974 | Dec 08 2019

Hovhannisyan N et al. suggested that [18F]fludarabine-PET might represent an alternative and perhaps more specific modality for MM imaging when compared to [18F]FDG. Nevertheless, more investigations are required to extend this conclusion to humans. [Read the Full Post]

Pre-metastatic niche triggers SDF-1/CXCR4 axis and promotes organ colonisation by hepatocellular circulating tumour cells via downregulation of Prrx1

552 | Dec 04 2019

Tang Y et al. demonstrated that decreased expression of Prrx1 stimulates SDF-1/CXCR4 signalling and contributes to organ colonisation with blood CTCs in HCC. STAT3 inhibition and specific blockade of CXCR4 have clinical potential as therapeutics for eliminating organ metastasis in advanced HCC. [Read the Full Post]

Anti-myeloma effect of pharmacological inhibition of Notch/gamma-secretase with RO4929097 is mediated by modulation of tumor microenvironment

737 | Dec 02 2019

Pisklakova A et al. indicated that targeting Notch may be considered as a new strategy to be tested for MM therapy. [Read the Full Post]

Generation of pig induced pluripotent stem cells using an extended pluripotent stem cell culture system

586 | Nov 27 2019

Xu J et al. demonstrated that stable iPS cells could be generated in LCDM medium, which could give rise to both embryonic and extraembryonic cells in vivo. However, the efficiency and level of chimeric contribution of pig LCDM-iPS cells were found low. [Read the Full Post]

Isolation of induced pluripotent stem cell-derived endothelial progenitor cells from sac-like structures

635 | Nov 27 2019

Aoki H et al. improved regenerative medicine and facilitate basic studies on the endothelial lineage. [Read the Full Post]

Differential cellular responses induced by dorsomorphin and LDN-193189 in chemotherapy-sensitive and chemotherapy-resistant human epithelial ovarian cancer cells

480 | Nov 18 2019

Ali JL et al. showed that DM and LDN possess drug characteristics suitable for adjuvant agents used to treat chemotherapy-sensitive and -resistant EOC. [Read the Full Post]

ICG-001 suppresses growth of gastric cancer cells and reduces chemoresistance of cancer stem cell-like population

0 | Nov 17 2019

Liu Y et al. suggested that ICG-001 suppresses GC cell line growth, metastasis and reduces its stem cell-like properties and chemoresistance, indicating that ICG-001 is a potentially useful small molecule therapeutic for GC. [Read the Full Post]

LY2109761 enhances cisplatin antitumor activity in ovarian cancer cells

616 | Nov 14 2019

Gao Y et al. showed that chemotherapeutic approaches using LY2109761 might enhance the treatment benefit of the cisplatin in the treatment of ovarian cancer patients. [Read the Full Post]

Treatment with XAV-939 prevents in vitro calcification of human valvular interstitial cells

524 | Nov 10 2019

Dittfeld C et al. indicated that XAV-939 was therefore able to prevent calcification of human VIC cultures, and XAV-939 treatment was accompanied by upregulation of active non-phospho-β-catenin. Although XAV-939 does not downregulate active β-catenin, treatment with XAV-939 results in Sox9 upregulation that may prevent the calcification process. [Read the Full Post]

The novel inhibitor PRI-724 for Wnt/β-catenin/CBP signaling ameliorates bleomycin-induced pulmonary fibrosis in mice

1412 | Nov 10 2019

Okazaki H et al. suggested that the β-catenin/CBP inhibitor PRI-724 is a potent antifibrotic agent that acts by modulating the activity of macrophages in the lungs. [Read the Full Post]

CX-4945: the protein kinase CK2 inhibitor and anti-cancer drug shows anti-fungal activity

992 | Nov 07 2019

Masłyk M et al. indicated their data unveil the dual-activity of CX-4945; when used in anti-cancer therapy, it may simultaneously prevent cancer-associated candidiasis. [Read the Full Post]

CHIR-99021 regulates mitochondrial remodelling via β-catenin signalling and miRNA expression during endodermal differentiation

1148 | Nov 05 2019

Ma Y et al. demonstrated that CHIR-99021 plays a role in mitochondrial structure and function remodelling via activation of the β-catenin signalling pathway and inhibits the expression of miRNAs during definitive endodermal differentiation. [Read the Full Post]

TAZ promotes the proliferation and osteogenic differentiation of human periodontal ligament stem cells via the p-SMAD3

522 | Oct 28 2019

Gu K et al. indicated that Hippo/TAZ plays a positive role inside the proliferation, stemness maintenance, and osteogenic specialization of h-PDLSCs, and the specific downstream factor of osteogenic differentiation is SMAD3. [Read the Full Post]

Nuclear localization of β-catenin and expression of target genes are associated with increased Wnt secretion in oral dysplasia

1345 | Oct 27 2019

Reyes M et al. indicated that secretion of Wnt ligands is critical for β-catenin nuclear localization and expression of target genes in oral dysplasia. [Read the Full Post]

Exogenous mesenchymal stem cells affect the function of endogenous lung stem cells (club cells) in phosgene-induced lung injury

0 | Oct 21 2019

Ye K et al. showed that MSCs reduced the secretion of club cells. And MSCs enhanced the proliferation of club cells partly via activating the Notch signaling pathway, which promoted lung injury repair. [Read the Full Post]

Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis

862 | Oct 09 2019

Sandborn WJ et al. showed that in patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo. [Read the Full Post]

Influence of Wilms' tumor suppressor gene WT1 on bovine Sertoli cells polarity and tight junctions via non-canonical WNT signaling pathway

507 | Oct 01 2019

Wang X et al. indicated that WT1 mediates the regulation of several proteins involved in bovine SCs polarity maintenance and intercellular tight junctions (TJ) by non-canonical WNT signaling pathway. [Read the Full Post]

Pharmacokinetics and Biodistribution of GDC-0449 Loaded Micelles in Normal and Liver Fibrotic Mice

610 | Sep 26 2019

Dutta R et al. showed that M6P-conjugated GDC-0449 loaded mixed micelles may be used as a potential drug delivery vehicle for treating liver fibrosis. [Read the Full Post]

Cellular Cholesterol Directly Activates Smoothened in Hedgehog Signaling

532 | Sep 23 2019

Huang P et al. proposed that the endogenous Smoothened activator is cholesterol, not oxysterols, and that vertebrate Hedgehog signaling controls Smoothened by regulating its access to cholesterol. [Read the Full Post]

NK2 receptor mediated detrusor muscle contraction involves Gq/11-dependent activation of voltage-dependent calcium channels and the RhoA-Rho kinase pathway

1117 | Aug 30 2019

Dér B et al. identified potential therapeutic targets of bladder dysfunctions related to upregulation of TKs. [Read the Full Post]

Notch signaling pathway is a potential therapeutic target for extracranial vascular malformations

1751 | Aug 18 2019

Davis RB et al. showed that two gamma secretase inhibitors (GSIs), DAPT (GSI-IX) and RO4929097, cause dose-dependent inhibition of Notch target gene expression (Hey1) and rate of migration of monolayer cultures of lymphatic endothelial cells (hLECs) and blood endothelial cells (HUVEC). GSIs also inhibit HUVEC network formation. hLECs are more sensitive to GSIs compared to HUVEC. GSIs have been found to be safe in clinical trials in patients with Alzheimer's disease or cancer. Our results provide further rationale to support testing of Notch inhibitors in patients with extracranial vascular malformations. [Read the Full Post]

Clinical relevance of ticagrelor monotherapy following 1-month dual antiplatelet therapy after bifurcation percutaneous coronary intervention: Insight from GLOBAL LEADERS trial

715 | Aug 16 2019

Kogame N et al. found that after PCI for bifurcation lesions using 1-month of DAPT followed by ticagrelor monotherapy for 23 months did not demonstrate explicit benefit regarding all-cause death or new Q-wave MI as in the overall trial. [Read the Full Post]

Use of Antiplatelet Therapy/DAPT for Post-PCI Patients Undergoing Noncardiac Surgery

771 | Aug 14 2019

Banerjee S et al. present3 commonly encountered clinical scenarios that lead into an evidence-based discussion of practical strategies for managing perioperative antiplatelet therapy in patients following percutaneous coronary intervention. [Read the Full Post]

First-in-human dose study of the novel transforming growth factor-β receptor I kinase inhibitor LY2157299 monohydrate in patients with advanced cancer and glioma

1217 | Aug 12 2019

Rodon J et al. showed that on the basis of the safety, pharmacokinetics, and antitumor activity in patients with glioma, the intermittent administration of LY2157299 at 300 mg/day is safe for future clinical investigation. [Read the Full Post]

The Wnt inhibitor LGK-974 enhances radiosensitivity of HepG2 cells by modulating Nrf2 signaling

553 | Aug 11 2019

Tian D et al. found that HepG2 cells became more sensitive to radiation with increasing LGK-974 concentrations. Upon 2 Gy or 4 Gy irradiation, the cells treated with LGK-974 more frequently underwent apoptosis and grew less rapidly. PCR and western blot results showed that inhibiting the secretion of Wnt3A blocked the Wnt signaling pathway and prevented Nrf2 signaling. Notably, the Wnt inhibitor may serve as a radiosensitizing drug. [Read the Full Post]

Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway

538 | Aug 11 2019

Herbertz S et al. summarized the past and current experiences with different pharmacological treatments that enabled galunisertib to be investigated in patients. [Read the Full Post]

Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis

1010 | Aug 07 2019

Verstovsek S et al. indicated that INCB018424 was associated with marked and durable clinical benefits in patients with myelofibrosis for whom no approved therapies existed. [Read the Full Post]

Human primary liver cancer-derived organoid cultures for disease modeling and drug screening

622 | Aug 04 2019

Broutier L et al. demonstrated the wide-ranging biomedical utilities of PLC-derived organoid models in furthering the understanding of liver cancer biology and in developing personalized-medicine approaches for the disease. [Read the Full Post]

Conversion of Terminally Committed Hepatocytes to Culturable Bipotent Progenitor Cells with Regenerative Capacity

621 | Aug 03 2019

Katsuda T et al. reported that a cocktail of small molecules, Y-27632, A-83-01, and CHIR99021, can convert rat and mouse MHs in vitro into proliferative bipotent cells, which we term chemically induced liver progenitors (CLiPs). CLiPs can differentiate into both MHs and biliary epithelial cells that can form functional ductal structures. CLiPs in long-term culture did not lose their proliferative capacity or their hepatic differentiation ability, and rat CLiPs were shown to extensively repopulate chronically injured liver tissue. Thus, our study advances the goals of liver regenerative medicine. [Read the Full Post]

Radiosensitization of Non-Small Cell Lung Cancer Cells by Inhibition of TGF-β1 Signaling With SB431542 Is Dependent on p53 Status

1435 | Jul 22 2019

Zhao Y et al. concluded that the radiosensitizing effect of inhibition of TGF-β1 signaling in NSCLC cells by SB431542 was p53 dependent, suggesting that using TGF-β1 inhibitor in radiotherapy may be more complicated than previously thought and may need further investigation. [Read the Full Post]

Cytotoxicity and activation of the Wnt/beta-catenin pathway in mouse embryonic stem cells treated with four GSK3 inhibitors

0 | Jul 18 2019

Naujok O et al. indicated that out of the four tested GSK3 inhibitors, only CHIR-99021 and CHIR-98014 proved to be potent pharmacological activators of the Wnt/beta-catenin signaling pathway. But only in the case of CHIR-99021 high potency was combined with very low toxicity. [Read the Full Post]

Antiproliferative and Antimigratory Effects of a Novel YAP-TEAD Interaction Inhibitor Identified Using in Silico Molecular Docking

530 | Jul 13 2019

Smith SA et al. reported the identification of a novel compound (CPD3.1) with the ability to disrupt YAP-TEAD protein-protein interaction and inhibit TEAD activity, cell proliferation, and cell migration. The YAP-TEAD complex is a viable drug target, and CPD3.1 is a lead compound for the development of more potent TEAD inhibitors for treating cancer and other hyperproliferative pathologies. [Read the Full Post]

Airway Progenitor Clone Formation Is Enhanced by Y-27632-Dependent Changes in the Transcriptome

1273 | Jul 10 2019

Reynolds SD et al. concluded that Y-27632 fundamentally alters cell-cell and cell-ECM interactions, which preserves basal progenitor cells and allows greater cell amplification. [Read the Full Post]

JAK1/2 Inhibitors AZD1480 and CYT387 Inhibit Canine B-Cell Lymphoma Growth by Increasing Apoptosis and Disrupting Cell Proliferation

918 | Jul 08 2019

Lu Z et al. justified further phase I/II clinical investigations of the safety and efficacy of JAK1/2 inhibitors in canine DLBCL and suggest new opportunities for novel anticancer therapies. [Read the Full Post]

Exogenous mesenchymal stem cells affect the function of endogenous lung stem cells (club cells) in phosgene-induced lung injury

787 | Jul 05 2019

Ye K et al. showed that MSCs reduced the secretion of club cells. And MSCs enhanced the proliferation of club cells partly via activating the Notch signaling pathway, which promoted lung injury repair. [Read the Full Post]

Safety, Tolerability, and Preliminary Efficacy of the Anti-Fibrotic Small Molecule PRI-724, a CBP/β-Catenin Inhibitor, in Patients with Hepatitis C Virus-related Cirrhosis: A Single-Center, Open-Label, Dose Escalation Phase 1 Trial

702 | Jun 19 2019

Kimura K et al. showed that administration of 10 or 40mg/m2/day intravenous PRI-724 over 12weeks was well-tolerated by patients with HCV cirrhosis; however, liver injury as a possible related serious adverse event was observed in the 160mg/m2/day cohort. [Read the Full Post]

Effect of bucladesine, pentoxifylline, and H-89 as cyclic adenosine monophosphate analog, phosphodiesterase, and protein kinase A inhibitor on acute pain

525 | Jun 09 2019

Salehi F et al. indicated PTX, H-89, and Db-cAMP affect the thermal-induced pain by probably interacting with intracellular cAMP and cGMP signaling pathways and cyclic nucleotide-dependent protein kinases. [Read the Full Post]

CX-4945, a Selective Inhibitor of Casein Kinase 2, Synergizes with B Cell Receptor Signaling Inhibitors in Inducing Diffuse Large B Cell Lymphoma Cell Death

957 | Jun 08 2019

Mandato E et al. suggested a role for CK2 downstream of the BCR in controlling survival pathways crucial for cell growth of different DLBCL subtypes. Also, the use of CX-4945 in combination with BCR signaling blockers could represent a novel rational therapeutic approach in the DLBCL. [Read the Full Post]

Small molecules dorsomorphin and LDN-193189 inhibit myostatin/GDF8 signaling and promote functional myoblast differentiation

563 | Jun 05 2019

Horbelt D et al. suggested these inhibitors as suitable tools to promote functional myogenesis. [Read the Full Post]

Regulation of Skeletal Muscle DRP-1 and FIS-1 Protein Expression by IL-6 Signaling

764 | Jun 03 2019

Fix DK et al. elevated IL-6 can directly induce DRP-1 and FIS-1 expression through gp130 signaling in cultured myotubes and skeletal muscle. Furthermore, ERK 1/2 signaling is necessary for the IL-6 induction of DRP-1 and FIS-1 expression in myotubes. [Read the Full Post]

KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells

1025 | May 31 2019

Diep DTV et al. indicated that KD025suppresses adipocyte differentiation by modulation of key factors activated at the intermediate stage of differentiation, and not by inhibition of ROCK2. [Read the Full Post]

Strategies to Enhance Metabolic Stabilities

517 | May 29 2019

Khatri B et al. noted that any chemical modification that helps in providing either local or global conformational rigidity to these macrocyclic peptides aids in improving their metabolic stability typically by slowing the cleavage kinetics by the proteases. [Read the Full Post]

Targeting ERK1/2 protein-serine/threonine kinases in human cancers

0 | May 29 2019

Roskoski R Jr indicated that Ulixertinib, MK-8353, and GDC-0994 are orally effective, potent, and specific inhibitors of ERK1/2 that are in early clinical trials for the treatment of various advanced/metastatic solid tumors. These agents are effective against cell lines that are resistant to B-Raf and MEK1/2 inhibitor therapy. Although MK-8353 does not directly inhibit MEK1/2, it decreases the phosphorylation of ERK1/2 as well as the phosphorylation of RSK, an ERK1/2 substrate. The decrease in RSK phosphorylation appears to be a result of ERK inhibition and the decrease in ERK1/2 phosphorylation is related to the inability of MEK to catalyze the phosphorylation of the ERK-MK-8353 complex; these decreases characterize the ERK dual mechanism inhibition paradigm. Additional work will be required to determine whether ERK inhibitors will be successful in the clinic and are able to forestall the development of drug resistance of the MAP kinase pathway. [Read the Full Post]

Targeting ERK1/2 protein-serine/threonine kinases in human cancers

0 | May 23 2019

Roskoski R Jr showed that Ulixertinib, MK-8353, and GDC-0994 are orally effective, potent, and specific inhibitors of ERK1/2 that are in early clinical trials for the treatment of various advanced/metastatic solid tumors. These agents are effective against cell lines that are resistant to B-Raf and MEK1/2 inhibitor therapy. Although MK-8353 does not directly inhibit MEK1/2, it decreases the phosphorylation of ERK1/2 as well as the phosphorylation of RSK, an ERK1/2 substrate. The decrease in RSK phosphorylation appears to be a result of ERK inhibition and the decrease in ERK1/2 phosphorylation is related to the inability of MEK to catalyze the phosphorylation of the ERK-MK-8353 complex; these decreases characterize the ERK dual mechanism inhibition paradigm. Additional work will be required to determine whether ERK inhibitors will be successful in the clinic and are able to forestall the development of drug resistance of the MAP kinase pathway. [Read the Full Post]

Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial

1101 | May 21 2019

Rummel M et al. indicated that in combination with rituximab, bendamustine was more effective than fludarabine, suggesting that bendamustine plus rituximab may be the preferred treatment option for patients with relapsed indolent and mantle-cell lymphomas. [Read the Full Post]

Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway.

603 | May 17 2019

Herbertz S et al. summarized the past and current experiences with different pharmacological treatments that enabled galunisertib to be investigated in patients. [Read the Full Post]

First-in-human dose study of the novel transforming growth factor-β receptor I kinase inhibitor LY2157299 monohydrate in patients with advanced cancer and glioma

567 | May 16 2019

On the basis of the safety, pharmacokinetics, and antitumor activity in patients with glioma, the intermittent administration of LY2157299 at 300 mg/day is safe for future clinical investigation. [Read the Full Post]

Embryonic stem cells differentiated into neuron-like cells using SB431542 small molecule on nanofibrous PLA/CS/Wax scaffold

604 | May 03 2019

Hoveizi E et al. revealed that electrospun PLA/CS/Wax scaffolds associated with the induction medium can assemble proper conditions for stem cell differentiation into NLCs. [Read the Full Post]

Targeting ERK1/2 protein-serine/threonine kinases in human cancers

556 | Apr 28 2019

Roskoski R Jr indicated that Ulixertinib, MK-8353, and GDC-0994 are orally effective, potent, and specific inhibitors of ERK1/2 that are in early clinical trials for the treatment of various advanced/metastatic solid tumors. These agents are effective against cell lines that are resistant to B-Raf and MEK1/2 inhibitor therapy. Although MK-8353 does not directly inhibit MEK1/2, it decreases the phosphorylation of ERK1/2 as well as the phosphorylation of RSK, an ERK1/2 substrate. The decrease in RSK phosphorylation appears to be a result of ERK inhibition and the decrease in ERK1/2 phosphorylation is related to the inability of MEK to catalyze the phosphorylation of the ERK-MK-8353 complex; these decreases characterize the ERK dual mechanism inhibition paradigm. Additional work will be required to determine whether ERK inhibitors will be successful in the clinic and are able to forestall the development of drug resistance of the MAP kinase pathway. [Read the Full Post]

Thromboembolic events in polycythemia vera

1096 | Apr 27 2019

Griesshammer M et al. discussed factors associated with thrombosis and recent data on current treatments, including anticoagulation, highlighting the need for more controlled studies to determine the most effective cytoreductive therapies for reducing the risk of thrombosis in patients with PV. [Read the Full Post]

Mechanisms of Action of Ruxolitinib in Murine Models of Hemophagocytic Lymphohistiocytosis

1213 | Apr 26 2019

Ruxolitinib operates through IFNγ-dependent and independent mechanisms to dampen HLH by targeting the deleterious effects of T cells and neutrophils, the latter representing an unappreciated and understudied cell type that contributes to HLH pathogenesis. [Read the Full Post]

CK2 inhibition with silmitasertib promotes methuosis-like cell death associated to catastrophic massive vacuolization of colorectal cancer cells

946 | Apr 13 2019

Silva-Pavez E et al. suggested that an aberrantly elevated expression/activity of CK2 may play a key role in CRC, promoting cell viability and proliferation in untreated cells, however, its inhibition with silmitasertib promotes methuosis-like cell death associated to massive catastrophic vacuolization, accounting for decreased tumorigenicity at later times. These characteristics of silmitasertib support a potential therapeutic use in CRC patients and probably other CK2-dependent cancers. [Read the Full Post]

Combining Smoothened Agonist and NEL-Like Protein-1 Enhances Bone Healing

795 | Apr 12 2019

Lee S et al. suggested that combining the hedgehog signaling agonist SAG and NELL-1 has potential as a novel therapeutic strategy for the healing of critical-size bone defects. Future directions will include optimization of dosage and delivery strategy for an SAG and NELL-1 combination product. [Read the Full Post]

Napabucasin: An Update on the First-in-Class Cancer Stemness Inhibitor

875 | Apr 11 2019

Hubbard JM et al. showed that napabucasin may prove useful in targeting cancer stem cells, with the potential to suppress metastasis and prevent relapse in patients with varying cancer types. [Read the Full Post]

ICG-001 suppresses growth of gastric cancer cells and reduces chemoresistance of cancer stem cell-like population

696 | Apr 10 2019

Liu Y et al. suggested that ICG-001 suppresses GC cell line growth, metastasis and reduces its stem cell-like properties and chemoresistance, indicating that ICG-001 is a potentially useful small molecule therapeutic for GC. [Read the Full Post]

Exploration of MST1-Mediated Secondary Brain Injury Induced by Intracerebral Hemorrhage in Rats via Hippo Signaling Pathway

499 | Apr 09 2019

Zhang P et al. revealed that MST1 played an important role in the SBI following ICH, and inhibition of MST1 could alleviate ICH-induced SBI. Therefore, MST1 may be considered as a potential therapeutic target for SBI following ICH. [Read the Full Post]

White light emitting diode induces autophagy in hippocampal neuron cells through GSK-3-mediated GR and RORα pathways

697 | Apr 03 2019

Yang Y et al. demonstrated that GSK-3-mediated GR/RORα signaling pathway is involved in white LED light-induced autophagy in hippocampal neuron cells. [Read the Full Post]

Grem2 mediates podocyte apoptosis in high glucose milieu

698 | Apr 02 2019

Wen H et al. indicated high glucose increases Grem2 expression in kidney cells. Grem2 mediates podocyte apoptosis through Smads. [Read the Full Post]

Mechanisms of U46619-induced contraction in mice intrarenal arteries

1297 | Mar 27 2019

Yan H et al. suggested that the U46619-induced contraction of mouse intrarenal arteries is mediated by Cav1.2 and SOC channel, through the activation of thromboxane-prostanoid receptors and its downstream signaling pathway. [Read the Full Post]

Generation of Urine Cell-Derived Non-integrative Human iPSCs and iNSCs: A Step-by-Step Optimized Protocol

1298 | Mar 24 2019

Cheng L et al. showed the optimized protocol is an easy and fast procedure to yield both iPSC and iNSC lines from a convenient source of human urine in a single experiment. [Read the Full Post]

IWR-1 Inhibits Collagen-Induced Platelet Activation and Protects against Thrombogenesis

743 | Mar 12 2019

Wang W et al. demonstrated that IWR-1 could effectively block collagen-induced platelet activity in vitro and in vivo, and suggest its candidacy as a new antiplatelet agent. [Read the Full Post]

UBE2S mediates tumor progression via SOX6/β-Catenin signaling in endometrial cancer

1683 | Mar 03 2019

Lin M et al. suggested UBE2S may serve as a promising prognostic factor and function as an oncogene in EMC. The newly identified UBE2S/SOX6/β-Catenin axis represents a new potential therapeutic target for EMC intervention. [Read the Full Post]

Cyclopamine: from cyclops lambs to cancer treatment

635 | Mar 01 2019

Lee ST et al. showed inhibitors of the Hh signaling pathway, including cyclopamine derivatives, have been targeted as potential treatments for certain cancers and other diseases associated with the Hh signaling pathway. [Read the Full Post]

LY2109761 inhibits metastasis and enhances chemosensitivity in osteosarcoma MG-63 cells

735 | Feb 27 2019

Ren XF et al. indicated that LY2109761 suppresses OS metastasis and enhanced chemosensitivity by targeting S100A4. LY2109761 may have important implications for the development of strategies for inhibiting metastasis and overcoming OS cell resistance to chemotherapy. [Read the Full Post]

Potent in vivo lung cancer Wnt signaling inhibition via cyclodextrin-LGK974 inclusion complexes

694 | Feb 21 2019

Guimaraes PPG et al. indicated the development of these complexes enables safer and repeated oral or parenteral administration of Wnt signaling inhibitors, which hold promise for the treatment of multiple types of malignancies. [Read the Full Post]

Ionizing Radiation Blocks Hair Cell Regeneration in Zebrafish Lateral Line Neuromasts by Preventing Wnt Signaling

787 | Feb 15 2019

Li R et al. suggested that radiation suppressed hair cell regeneration in zebrafish lateral line neuromasts through inhibition of Wnt signaling in supporting cells possibly by secreting anti-proliferation factors like dkk2. Maintaining a healthy supporting cell pool is vital for regeneration of hair cells. [Read the Full Post]

Mechanisms of Pinometostat (EPZ-5676) Treatment-Emergent Resistance in MLL-Rearranged Leukemia

531 | Feb 11 2019

Campbell CT et al. demonstrated TER models of the DOT1L inhibitor pinometostat and provided useful tools for investigating clinical resistance. [Read the Full Post]

Inhibition of the NOTCH pathway using γ-secretase inhibitor RO4929097 has limited antitumor activity in established glial tumors

2777 | Feb 05 2019

Dantas-Barbosa C et al. indicated that RO4929097-mediated effects were independent of NOTCH1 mutation status or expression levels, but associated with low IL-6 levels. In established glial tumor models, NOTCH inhibition had limited effects as a single agent, but enhanced efficacy when combined with DNA-interfering agents. These preclinical data need to be considered for further clinical development of NOTCH inhibitors in glial tumors. [Read the Full Post]

Molecular regulation of apoptotic machinery and lipid metabolism by mTORC1/mTORC2 dual inhibitors in preclinical models of HER2+/PIK3CAmut breast cancer

679 | Jan 30 2019

Qian J et al. found that the basal levels of carnitine palmitoyltransferase 1A and lipid catabolism were elevated in HER2+/PIK3CAmut breast cells and were inhibited upon mTOR-KI treatment. [Read the Full Post]

Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment

0 | Jan 27 2019

Du J et al. suggested SBE as a novel drug candidate for NSCLC which specifically and sensitively targets SHH signaling pathway. [Read the Full Post]

The thrombopoietin/MPL axis is activated in the Gata1low mouse model of myelofibrosis and is associated with a defective RPS14 signature

1306 | Dec 30 2018

Zingariello M et al. showed that Gata1low mice are a bona fide model of MF, which recapitulates the hyperactivation of the TPO/MPL/JAK2 axis observed in megakaryocytes from myelofibrotic patients. [Read the Full Post]

Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice

0 | Dec 30 2018

Satoh M et al. indicated that interactions between NKT cells and CD1d-expressing adipocytes producing endogenous NKT cell ligands play a critical role in the induction of inflammation and functional modulation of adipose tissue that leads to obesity. [Read the Full Post]

WNT5A: a motility-promoting factor in Hodgkin lymphoma

863 | Dec 22 2018

Linke F et al. proposed a model where WNT signaling has an important role in regulating tumor-promoting processes. [Read the Full Post]

PI3K Catalytic Isoform Alteration Promotes the LIMK1-related Metastasis Through the PAK1 or ROCK1/2 Activation in Cigarette Smoke-exposed Ovarian Cancer Cells

0 | Dec 18 2018

Park GB et al. showed that characterization of the p110 isotypes of PI3K is critical for regulating cancer metastasis; LIMK1 could be a common therapeutic target of ovarian cancer metastasis. [Read the Full Post]

FAM83A is amplified and promotes cancer stem cell-like traits and chemoresistance in pancreatic cancer

1228 | Dec 15 2018

Chen S et al. indicated that FAM83A has a vital oncogenic role to promote pancreatic cancer progression and may represent a potential clinical target. [Read the Full Post]

Testosterone improves the differentiation efficiency of insulin-producing cells from human induced pluripotent stem cells

746 | Dec 12 2018

Liu H et al. found that T improves the differentiation efficiency of insulin-producing cells from hiPSCs. The addition of T into routine differentiation formula for pancreatic β cells increases the differentiation efficiency from 12% to 35%. The administration of T promotes the expression of key genes associated with β cells differentiation including NGN3, NEUROD1 and INS. This finding benefits the ongoing process to optimize the differentiation protocol of pancreatic β cells from hiPSCs, and provides some degree of understanding the clinical management of T for type 2 diabetes. [Read the Full Post]

TGF-β sensu stricto signaling regulates skeletal morphogenesis in the sea urchin embryo

1983 | Dec 11 2018

Sun Z et al. revealed that this model morphogenetic process involves an even more diverse suite of cell signaling pathways than previously appreciated and show that PMCs integrate a complex set of both generalized and spatially localized cues in assembling the endoskeleton. [Read the Full Post]

Integrated High Throughput Analysis Identifies GSK3 as a Crucial Determinant of p53-Mediated Apoptosis in Lung Cancer Cells

794 | Dec 03 2018

Zhang Y et al. provided us with new insights regarding the mechanism by which p53 mediates A549 apoptosis and may cast light on the development of more efficient p53-based strategies for treating lung cancer. [Read the Full Post]

Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment

786 | Nov 30 2018

Du J et al. suggested SBE as a novel drug candidate for NSCLC which specifically and sensitively targets SHH signaling pathway. [Read the Full Post]

SOCS3 overexpression enhances ADM resistance in bladder cancer T24 cells

1357 | Nov 28 2018

Li MZ et al. indicated that SOCS3 reduction was associated with bladder cancer sensitivity to ADM. SOCS3 overexpression decreased JAK-STAT3 signaling pathway activity, declined Bcl-2 expression, inhibited cell proliferation, elevated cell apoptosis, and enhanced ADM sensitivity in T24 cells. [Read the Full Post]

Cancer stem cell marker phenotypes are reversible and functionally homogeneous in a preclinical model of pancreatic cancer

0 | Nov 27 2018

Dosch JS et al. showed that the hierarchical organization of CSCs in human disease is not recapitulated in a commonly used mouse model of pancreatic cancer and therefore provide a new view of the phenotypic and functional heterogeneity of tumor cells. [Read the Full Post]

DCLK1 is correlated with MET and ERK5 expression, and associated with prognosis in malignant pleural mesothelioma

633 | Nov 22 2018

Wang H et al. suggested that DCLK1 is regulated by MET/ERK5 signaling in human mesothelioma, and the MET/ERK5/DCLK1 signaling cascade could be further developed into a promising therapeutic target against mesothelioma. [Read the Full Post]

Host Serine/Threonine Kinases mTOR and Protein Kinase C-α Promote InlB-Mediated Entry of Listeria monocytogenes

6040 | Nov 21 2018

Bhalla M et al. identified mTOR and PKC-α to be host factors exploited by Listeria to promote infection. PKC-α controls Listeria entry, at least in part, by regulating the actin cytoskeleton downstream of the Met receptor. [Read the Full Post]

JAK2 inhibitor CEP-33779 prevents mouse oocyte maturation in vitro

1229 | Nov 15 2018

Wu C et al. suggested that JAK2 regulated the microfilaments aggregation during the mouse oocyte maturation. [Read the Full Post]

Treatment to sustain a Th17-type phenotype to prevent skewing toward Treg and to limit premalignant lesion progression to cancer

774 | Nov 05 2018

Young MR et al. showed that the treatment approach not only sustained the Th17 phenotype, but also increased distal spleen cell and regional lymph node cell production of other stimulatory/inflammatory mediators and slowed premalignant lesion progression to cancer. [Read the Full Post]

Stress-induced dynamic regulation of mitochondrial STAT3 and its association with cyclophilin D reduce mitochondrial ROS production

926 | Nov 03 2018

Meier JA et al. outlined a role for mitochondrially localized STAT3 in sensing and responding to external stimuli. [Read the Full Post]

Vitamin D prevents articular cartilage erosion by regulating collagen II turnover through TGF-β1 in ovariectomized rats

796 | Nov 02 2018

Li S et al. showed protective effects in OVX-induced OA partly through the TGF-β1 pathway. [Read the Full Post]

Construction of a novel cell-based assay for the evaluation of anti-EGFR drug efficacy against EGFR mutation

0 | Oct 25 2018

Hoshi H et al. successfully developed a novel cell-based assay for evaluating the efficacy of anti-EGFR drugs against EGFR mutation. [Read the Full Post]

Construction of a novel cell-based assay for the evaluation of anti-EGFR drug efficacy against EGFR mutation

1674 | Oct 20 2018

Hoshi H et al. successfully developed a novel cell-based assay for evaluating the efficacy of anti-EGFR drugs against EGFR mutation. [Read the Full Post]

Retinoic acid and TGF-β signalling cooperate to overcome MYCN-induced retinoid resistance

2097 | Oct 15 2018

Duffy DJ et al. provided a powerful precision oncology tool for identifying the driving signalling networks for malignancies not primarily driven by somatic mutations, such as paediatric cancers. By applying global omics approaches to the signalling networks regulating neuroblastoma differentiation and stemness, we have determined the pathways involved in the MYCN-mediated retinoid resistance, with TGF-β signalling being a key regulator. These findings revealed a number of combination treatments likely to improve clinical response to retinoid therapy, including co-treatment with retinoids and KGN, which may prove valuable in the treatment of high-risk MYCN-amplified neuroblastoma. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 | Oct 14 2018

Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

Activation of Wnt/β-catenin signalling is required for TGF-β/Smad2/3 signalling during myofibroblast proliferation

874 | Oct 12 2018

Xu L et al. found that a major outcome of this study is improved insight into the mechanisms by which epithelial and mesenchymal cells activated by TGFβ1-smad2/3 signalling through Wnt/β-catenin contribute to lung fibrosis. [Read the Full Post]

Novel role of STRAP in progression and metastasis of colorectal cancer through Wnt/β-catenin signaling

0 | Oct 06 2018

Yuan G et al. suggest that STRAP increases invasion and metastasis of CRC partly through inhibiting ubiquitin-dependent degradation of β-catenin and promoting Wnt/β-catenin signaling. [Read the Full Post]

TGF-β and NF-κB signaling pathway crosstalk potentiates corneal epithelial senescence through an RNA stress response

914 | Sep 29 2018

Li ZY et al. indicated that TGF-β-driven NF-κB activation contributes to corneal epithelial senescence via RNA metabolism and the inflammation blockade can attenuate TGF-β-induced senescence. [Read the Full Post]

Dual inhibition of Bcl-2 and Bcl-xL strikingly enhances PI3K inhibition-induced apoptosis in human myeloid leukemia cells through a GSK3- and Bim-dependent mechanism

931 | Sep 23 2018

Rahmani M et al. argued that combining PI3K/AKT/mTOR inhibitors with BH3 mimetics warrants attention in AML, particularly in the setting of basal AKT activation and/or addiction. [Read the Full Post]

Identification of ACTG2 functions as a promoter gene in hepatocellular carcinoma cells migration and tumor metastasis

1321 | Sep 11 2018

Wu Y et al. revealed a critical role of ACTG2 in HCC tumor metastasis, and renders it a novel target for the treatment of HCC. [Read the Full Post]

Fascin Is Critical for the Maintenance of Breast Cancer Stem Cell Pool Predominantly via the Activation of the Notch Self-Renewal Pathway

1314 | Sep 11 2018

Barnawi R et al. demonstrated fascin as a critical regulator of breast CSC pool at least partially via activation of the Notch self-renewal signaling pathway and modification of the expression embryonic transcriptional factors. Targeting fascin may halt CSCs and thus presents a novel therapeutic approach for effective treatment of breast cancer. [Read the Full Post]

JAK/STAT signaling pathway-mediated immune response in silkworm (Bombyx mori) challenged by Beauveria bassiana

1009 | Sep 09 2018

Geng T et al. suggested that BmCTL5 might be one pattern recognition receptors for JAK/STAT signaling pathway in silkworm. These findings yield insights for better understand the molecular mechanisms of JAK/STAT signaling pathway in antifungal immune response in silkworm. [Read the Full Post]

microRNA-200a silencing protects neural stem cells against cerebral ischemia/reperfusion injury

1016 | Sep 09 2018

Ma J et al. indicated miR-200a silencing protects NSCs from OGD/R-induced injury, possibly via regulating the STATs/c-Myc and MAPK/c-Myc signalings. [Read the Full Post]

Differences in gene expression and alterations in cell cycle of acute myeloid leukemia cell lines after treatment with JAK inhibitors

1383 | Sep 07 2018

Gunerka P et al. suggested that observed effect of JAK2 inhibitors on transcription and cell cycle level in different cell lines are associated not with activity within JAK family, but presumably with other off-target activities. [Read the Full Post]

Niclosamide inhibition of STAT3 synergizes with erlotinib in human colon cancer

0 | Sep 05 2018

Shi L et al. suggested that erlotinib and niclosamide combination provides an effective therapeutic approach to improving the prognosis of colon cancer. [Read the Full Post]

MicroRNA-17 regulates autophagy to promote hepatic ischemia/reperfusion injury via suppression of signal transductions and activation of transcription-3 expression

908 | Sep 02 2018

Li S et al. showed that high levels of miR-17 expression can function to up-regulate autophagy to aggravate hepatic IRI by suppressing Stat3 expression. Liver Transplantation 22 1697-1709 2016 AASLD. [Read the Full Post]

Upregulation of programmed cell death ligand 1 promotes resistance response in non-small-cell lung cancer patients treated with neo-adjuvant chemotherapy

2566 | Aug 26 2018

Zhang P et al. suggested that the upregulation of PD-L1 promotes a resistance response in lung cancer cells that might be through activation of the phosphatidylinositol 3-kinase/protein kinase B pathway and suppression of tumor-infiltrating lymphocytes. The high expression of PD-L1 after NAC could be an indication of therapeutic resistance and poor prognosis in patients with non-small-cell lung cancer. [Read the Full Post]

Downregulation of the Syk Signaling Pathway in Intestinal Dendritic Cells Is Sufficient To Induce Dendritic Cells That Inhibit Colitis

1585 | Aug 22 2018

Hang L et al. indicated that downmodulation of Syk expression and phosphorylation in intestinal DCs could be important mechanisms through which helminths induce regulatory DCs that limit colitis. [Read the Full Post]

BMS-708163 and Nilotinib restore synaptic dysfunction in human embryonic stem cell-derived Alzheimer's disease models

1581 | Aug 07 2018

Nishioka H et al. suggested that the AD models we developed are promising materials for the discovery of AD drugs that target the expression of pre-synaptic proteins and synaptic function. [Read the Full Post]

Cellular Prion Protein Mediates Pancreatic Cancer Cell Survival and Invasion through Association with and Enhanced Signaling of Notch1

1413 | Jul 29 2018

Wang Y et al. unraveled a novel molecular pathway driven by interactions between PrP and Notch1 in the progression of PDAC, supporting a critical tumor-promoting role of Notch1 in PrP-expressing PDAC tumors. [Read the Full Post]

Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ formation

1476 | Jul 27 2018

Figueiredo M et al. offered novel evidence on the role of Notch signalling in T/PT common primordium development, in an Hh-dependent manner. [Read the Full Post]

Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis

1420 | Jul 27 2018

Hasebe T et al. provided evidence for evolutionarily conserved role of Notch signaling in intestinal cell fate determination but more importantly reveal, for the first time, an important role of Notch pathway in the formation of adult intestinal stem cells during vertebrate development. Stem Cells 2017;35:1028-1039. [Read the Full Post]

Aberrant Notch Signaling in the Bone Marrow Microenvironment of Acute Lymphoid Leukemia Suppresses Osteoblast-Mediated Support of Hematopoietic Niche Function

1527 | Jul 25 2018

Wang W et al. suggested that therapeutically targeting the leukemia-infiltrated hematopoietic niche may restore HSPC homeostasis and improve the outcome of ALL patients. [Read the Full Post]

Cross-talk between Notch and Hedgehog regulates hepatic stellate cell fate in mice

1173 | Jul 14 2018

Xie G, et al. found that the Notch and Hedgehog pathways interact to control the fate of key cell types involved in adult liver repair by modulating epithelial-to-mesenchymal-like/mesenchymal-to-epithelial-like transitions. [Read the Full Post]

B7-H4 facilitates proliferation of esophageal squamous cell carcinoma cells through promoting interleukin-6/signal transducer and activator of transcription 3 pathway activation

1639 | Jul 13 2018

Chen X et al. provided the first evidence that B7-H4 facilitated ESCC cell proliferation through promoting IL-6/STAT3 positive loopback pathway activation. [Read the Full Post]

Inhibiting PLK1 induces autophagy of acute myeloid leukemia cells via mammalian target of rapamycin pathway dephosphorylation

2145 | Jul 10 2018

Tao YF et al. provided new insights into the molecular mechanism of PLK1 in regulating autophagy. [Read the Full Post]

Fibroblastic foci, covered with alveolar epithelia exhibiting epithelial-mesenchymal transition, destroy alveolar septa by disrupting blood flow in idiopathic pulmonary fibrosis

975 | Jul 10 2018

Yamaguchi M et al. showed that inhibition of transforming growth factor-β signaling, which can suppress EMT of the alveolar epithelial cells in vitro, is a potential strategy for treating IPF. [Read the Full Post]

Adenovirus-mediated TIPE2 overexpression inhibits gastric cancer metastasis via reversal of epithelial-mesenchymal transition

1212 | Jun 25 2018

Yin H et al. provided the first evidence that TIPE2 inhibits gastric cancer cell migration, invasion and metastasis very probably via reversal of EMT, revealing that TIPE2 may be a novel therapeutic target for human gastric cancer EMT and metastasis. [Read the Full Post]

AT13148, a first-in-class multi-AGC kinase inhibitor, potently inhibits gastric cancer cells both in vitro and in vivo

3526 | Jun 20 2018

Xi Y et al. supported the progression of this molecule into future evaluation as a valuable anti-gastric cancer candidate. [Read the Full Post]

Niclosamide inhibition of STAT3 synergizes with erlotinib in human colon cancer

1540 | May 28 2018

Shi L et al. suggested that erlotinib and niclosamide combination provides an effective therapeutic approach to improving the prognosis of colon cancer. [Read the Full Post]

Unique roles of Akt1 and Akt2 in IGF-IR mediated lung tumorigenesis

1880 | May 21 2018

Franks SE et al. suggested that compounds selectively targeting AKT1 may prove more effective than compounds that inhibit all three AKT isoforms at least in the treatment of lung adenocarcinoma. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 | May 21 2018

Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

PI3Kα isoform-dependent activation of RhoA regulates Wnt5a-induced osteosarcoma cell migration

6204 | May 20 2018

Zhang A et al. demonstrated that RhoA acts as the downstream of PI3K/Akt signaling (specific PI3Kα, Akt1 and Akt2 isoforms) and mediated Wnt5a-induced the migration of osteosarcoma cells. [Read the Full Post]

Gli1-Mediated Regulation of Sox2 Facilitates Self-Renewal of Stem-Like Cells and Confers Resistance to EGFR Inhibitors in Non-Small Cell Lung Cancer

1110 | May 18 2018

Bora-Singhal N et al. demonstrated a cooperative functioning of the EGFR signaling and Hedgehog pathways in governing the stem-like functions of NSCLC cancer stem cells and presents a novel therapeutic strategy to combat NSCLC harboring EGFR mutations. [Read the Full Post]

Long non-coding RNA NKILA inhibits migration and invasion of non-small cell lung cancer via NF-κB/Snail pathway

3262 | May 17 2018

Lu Z et al. found that the expression of NKILA was downregulated in tumor tissues of NSCLC, which improved the metastasis of NSCLC patients. In vitro studies further clarified that the expression of NKILA was regulated through classical TGF-β signal pathway, which subsequently inhibited migration and invasion of NSCLC cells through interfering NF-κB/Snail signal pathway in NSCLC cells. [Read the Full Post]

FAM83D associates with high tumor recurrence after liver transplantation involving expansion of CD44+ carcinoma stem cells

0 | May 17 2018

Lin B et al. indicated that FAM83D promotes HCC recurrence by promoting CD44 expression and CD44+ CSCs malignancy. FAM83D provides a novel therapeutic approach against HCC recurrence after LT. [Read the Full Post]

Jumonji AT-rich interactive domain 1B overexpression is associated with the development and progression of glioma

1071 | May 05 2018

Fang L et al. suggested that JARID1B is involved in the pathogenesis of glioma, and that the downregulation of JARID1B in glioma cells may be a therapeutic target for the treatment of patients with glioma. [Read the Full Post]

FGF19 promotes epithelial-mesenchymal transition in hepatocellular carcinoma cells by modulating the GSK3β/β- catenin signaling cascade via FGFR4 activation

3164 | May 03 2018

Zhao H et al. indicated that FGFR4/GSK3β/β-catenin axis may play a pivotal role in FGF19-induced EMT in HCC cells. As FGF19 and its specific receptor FGFR4 are frequently amplified in HCC cells, selective targeting this signaling node may lend insights into a potential effective therapeutic approach for blocking metastasis of HCC. [Read the Full Post]

GSK3ß-dependent dysregulation of neurodevelopment in SPG11-patient iPSC model

3325 | May 02 2018

Mishra HK et al. provided the first evidence for an early neurodevelopmental phenotype in SPG11, with GSK3ß as a potential novel target to reverse the disease phenotype. This article is protected by copyright. All rights reserved. [Read the Full Post]

Pharmacologic Inhibition of JAK1/JAK2 Signaling Reduces Experimental Murine Acute GVHD While Preserving GVT Effects

1838 | Apr 24 2018

Carniti C et al. provided further evidence that JAK inhibition represents a new and potentially clinically relevant approach to GVHD prevention. [Read the Full Post]

Novel Akt activator SC-79 is a potential treatment for alcohol-induced osteonecrosis of the femoral head

1834 | Apr 09 2018

Chen YX et al. showed that alcohol-induced ONFH is associated with suppression of p-Akt-Ser473 in the Akt/GSK3β/β-catenin signaling pathway in bone mesenchymal stem cells. We propose that SC-79 treatment to rescue Akt activation could be tested in the clinic as a potential therapeutic approach to preventing the development of alcohol-induced ONFH. [Read the Full Post]

Cancer-associated fibroblasts attenuate Cisplatin-induced apoptosis in ovarian cancer cells by promoting STAT3 signaling

1147 | Apr 06 2018

Yan H et al. suggested that CAFs could activate the anti-apoptotic STAT3 signaling, thereby decrease the Cisplatin-induced apoptosis and promote chemoresistance in ovarian cancer. [Read the Full Post]

Anti-leukaemic activity of the TYK2 selective inhibitor NDI-031301 in T-cell acute lymphoblastic leukaemia

2122 | Mar 23 2018

Akahane K et al. supported selective inhibition of TYK2 as a promising potential therapeutic strategy for T-ALL. [Read the Full Post]

MST2 phosphorylation at serine 385 in mitosis inhibits its tumor suppressing activity

1158 | Mar 20 2018

Chen X et al. revealed a novel layer of regulation for MST2 in mitosis and its role in tumorigenesis. [Read the Full Post]

CCND1 mutations increase protein stability and promote ibrutinib resistance in mantle cell lymphoma

1132 | Mar 20 2018

Mohanty A et al. uncover a new mechanism that is critical for the regulation of CCND1 protein levels, and is directly relevant to primary ibrutinib resistance in MCL. [Read the Full Post]

NF-YA promotes invasion and angiogenesis by upregulating EZH2-STAT3 signaling in human melanoma cells

1784 | Mar 15 2018

Xu Z et al. indicated that overexpression of NF-YA contributes to tumor angiogenesis through EZH2-STAT3 signaling in human melanoma cells, highlighting NF-YA as a potential therapeutic target in human melanoma. [Read the Full Post]

Endothelial STAT3 Activation Increases Vascular Leakage Through Downregulating Tight Junction Proteins: Implications for Diabetic Retinopathy

1642 | Mar 15 2018

Yun JH et al. suggested the potential importance of IL-6/STAT3 signaling in regulating endothelial permeability and provide a therapeutic target to prevent the pathology of diabetic retinopathy. [Read the Full Post]

Aberrant activation of hedgehog signaling promotes cell proliferation via the transcriptional activation of forkhead Box M1 in colorectal cancer cells

1281 | Mar 13 2018

Wang D et al. indicated the dysregulation of the Hh-Gli1-FoxM1 axis is essential for the proliferation and growth of human CRC cells and offers a potent target for therapeutic intervention in CRC. [Read the Full Post]

A Novel Antifibrotic Mechanism of Nintedanib and Pirfenidone. Inhibition of Collagen Fibril Assembly

1429 | Mar 12 2018

Knüppel L et al. indicated both drugs act on important regulatory levels in collagen synthesis and processing. Nintedanib was more effective in down-regulating profibrotic gene expression and collagen secretion. Importantly, both drugs inhibited collagen I fibril formation and caused a reduction in and an altered appearance of collagen fibril bundles, representing a completely novel mechanism of action for both drugs. [Read the Full Post]

Nek2A/SuFu feedback loop regulates Gli-mediated Hedgehog signaling pathway

1220 | Mar 12 2018

Zhou F et al. uncovered one of the mechanisms by which Nek2A acts as a modulator of the Hh signaling pathway in the context of a novel negative-feedback loop, which may offer new insights into Gli-mediated Hh signaling regulation in development and human diseases. [Read the Full Post]

PI-3K Inhibitors Preferentially Target CD15+ Cancer Stem Cell Population in SHH Driven Medulloblastoma

1164 | Feb 28 2018

Singh AR, et al. suggested a sequential combination of PI-3K inhibitors and chemotherapy will have augmented efficacy in the treatment of this disease. [Read the Full Post]

Tsc1 expression by dendritic cells is required to preserve T-cell homeostasis and response

1805 | Feb 27 2018

Luo Y et al. identified Tsc1 as a crucial signaling checkpoint in DCs essential for preserving T-cell homeostasis and response. [Read the Full Post]

Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency

1201 | Feb 24 2018

Yang Y et al. found a first step toward capturing pluripotent stem cells with extraembryonic developmental potentials in culture and open new avenues for basic and translational research. VIDEO ABSTRACT. [Read the Full Post]

Principles of early human development and germ cell program from conserved model systems

1264 | Feb 22 2018

Kobayashi T et al. used human, porcine and monkey in vivo and in vitro models provides synthetic insights into early human development. [Read the Full Post]

Inhibition of TGF-β signaling promotes expansion of human epidermal keratinocytes in feeder cell co-culture

1196 | Feb 10 2018

Suzuki D et al. found important implications for the use of TGF-β signaling inhibition as a viable therapeutic strategy for improving Green's methodology and for more efficient production of customized skin autografts with human feeder cells. [Read the Full Post]

Cocktail of chemical compounds robustly promoting cell reprogramming protects liver against acute injury

1184 | Feb 05 2018

Tang Y et al. offered proof-of-concept evidence that cocktail of clinical compounds improving cell reprogramming favors tissue recovery after acute damages, which is an attractive strategy for regenerative purpose. [Read the Full Post]

ERK5 activation is essential for osteoclast differentiation

840 | Jan 29 2018

Amano S et al. showed that activation of the MEK5/ERK5 pathway with M-CSF is required for osteoclast differentiation, which may induce differentiation through the induction of c-Fos. [Read the Full Post]

Differentiation of induced pluripotent stem cell-derived neutrophil granulocytes from common marmoset monkey (Callithrix jacchus).

1968 | Jan 27 2018

Schrimpf C et al. indicated cj-iPSC-derived neutrophils bare high hopes in hematologic cell replacement therapy. They exhibit high morphologic similarity to native neutrophils and present neutrophil-specific surface antigens, antimicrobial proteins, and gene products yielding an auspicious approach for continuative experiments including tests in living animals. [Read the Full Post]

The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer

0 | Jan 24 2018

Beadnell TC et al. demonstrated that up-front combined inhibition with dasatinib and MEK1/2 or ERK1/2 inhibitors drives synergistic inhibition of growth and induction of apoptosis, indicating that combined inhibition may overcome mechanisms of survival in response to single-agent inhibition. [Read the Full Post]

Extracellular heat shock protein 90α mediates HDM-induced bronchial epithelial barrier dysfunction by activating RhoA/MLC signaling

1726 | Jan 04 2018

Dong HM et al. suggested that eHsp90α is a potential therapeutic target for treatment of asthma. [Read the Full Post]

Tyrosine receptor kinase B is a drug target in astrocytomas

3265 | Dec 31 2017

Ni J et al. proposed NTRK2 as a potential therapeutic target in the subset of astrocytoma patients defined by QKI-NTRK2 fusion. [Read the Full Post]

PD-L1 Is Upregulated by Simultaneous Amplification of the PD-L1 and JAK2 Genes in Non-Small Cell Lung Cancer

2015 | Dec 25 2017

Ikeda S et al. suggested that expression of PD-L1 protein is upregulated by the simultaneous amplification of the PD-L1 and JAK2 genes through JAK-STAT signaling in NCSLC. [Read the Full Post]

THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors

1441 | Dec 14 2017

Cayrol F et al. showed that the combination of THZ1 and the BH3 mimetic obatoclax improves lymphoma growth control in a primary PTCL ex vivo culture and in two STAT3-mutant PTCL xenografts, delineating a potential targeted agent-based therapeutic option for these patients. [Read the Full Post]

Interleukin-6 suppression reduces tumour self-seeding by circulating tumour cells in a human osteosarcoma nude mouse model

1397 | Dec 12 2017

Zhang Y et al. provided a novel strategy for future therapeutic interventions to prevent osteosarcoma progression and recurrence. [Read the Full Post]

CK2α' Drives Lung Cancer Metastasis by Targeting BRMS1 Nuclear Export and Degradation

0 | Dec 02 2017

Liu Y et al. identified a therapeutically exploitable posttranslational mechanism by which CK2α-mediated degradation of BRMS1 promotes metastases in lung cancer. [Read the Full Post]

Integrative Network Analysis Combined with Quantitative Phosphoproteomics Reveals Transforming Growth Factor-beta Receptor type-2 (TGFBR2) as a Novel Regulator of Glioblastoma Stem Cell Properties

1242 | Nov 28 2017

Narushima Y et al. indicated that transforming growth factor-β receptor type-2 could play an important role as a novel cell fate determinant in glioblastoma stem cell regulation. [Read the Full Post]

Activation of anaphase-promoting complex by p53 induces a state of dormancy in cancer cells against chemotherapeutic stress

1506 | Nov 28 2017

Dai Y et al. provided a mechanism to unravel cancer cell dormancy and reactivation of the cancer cell population. [Read the Full Post]

MicroRNA-520e suppresses non-small-cell lung cancer cell growth by targeting Zbtb7a-mediated Wnt signaling pathway

1471 | Nov 26 2017

Zhijun Z et al. indicated that overexpressing miR-520e is involved in regulating the NSCLC cell growth, invasion and migration by targeting Zbtb7a partly depending on Wnt signaling. [Read the Full Post]

Hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells

1452 | Nov 25 2017

Sun M et al. suggested that NC may be a potential anticancer agent for breast cancer. [Read the Full Post]

Photodynamic therapy activated STAT3 associated pathways: Targeting intrinsic apoptotic pathways to increase PDT efficacy in human squamous carcinoma cells

2043 | Nov 23 2017

Qiao L et al. confirmed that 5-ALA-PDT might be an effective treatment for human squamous carcinoma by inhibiting the tumor cell A431growth and for the first time demonstrated that the expression of STAT3 was significantly reduced at 24h after 5-ALA-PDT treatment. [Read the Full Post]

AZGP1 suppresses epithelial-to-mesenchymal transition and hepatic carcinogenesis by blocking TGFβ1-ERK2 pathways

3898 | Nov 19 2017

Xu MY et al. showed that loss of AZGP1 could trigger EMT induced by TGFβ1-ERK2 signaling, confuse in energy metabolism, reduce cell proliferation and apoptosis, activate survival signals and promote invasion. Up-regulation of AZGP1 should be proposed to reverse EMT and might be a new promising therapy for HCC. [Read the Full Post]

JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma

2271 | Nov 05 2017

Nairismägi ML et al. showed that inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available. [Read the Full Post]

Inhibition of β-Catenin to Overcome Endocrine Resistance in Tamoxifen-Resistant Breast Cancer Cell Line

0 | Oct 31 2017

Won HS et al. suggested that beta-catenin plays a role in tamoxifen-resistant breast cancer, and the inhibition of beta-catenin may be a potential target in tamoxifen-resistant breast cancer. [Read the Full Post]

Coordinate involvement of Nodal-dependent inhibition and Wnt-dependent activation in the maintenance of organizer-specific bmp2b in zebrafish

1489 | Oct 30 2017

Xue Y et al. suggested that maintenance of organizer-specific bmp2b expression involves opposite and concerted regulation by Nodal and Wnt signaling. [Read the Full Post]

Enhancement of macrophage inflammatory responses by CCL2 is correlated with increased miR-9 expression and downregulation of the ERK1/2 phosphatase Dusp6

1000 | Oct 29 2017

Carson WF 4th et al. indicated that CCL2 supports the classical activation of macrophages, with miR-9 mediated down-regulation of Dusp6 and enhanced ERK-mediated signal transduction possibly mediating this enhanced pro-inflammatory gene expression. [Read the Full Post]

Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment

2357 | Oct 24 2017

Katsushima K et al. showed that highlight the importance of the Notch-lncRNA axis in regulating self-renewal of glioma cells and provide a strong rationale for targeting TUG1 as a specific and potent therapeutic approach to eliminate the GSC population. [Read the Full Post]

Transforming growth factor-β1 suppresses bone morphogenetic protein-2-induced mesenchymal-epithelial transition in HSC-4 human oral squamous cell carcinoma cells via Smad1/5/9 pathway suppression

1590 | Oct 21 2017

Chiba T et al. suggested that TGF-β positively regulates hOSCC invasion in the primary tumor, whereas BMP-2 facilitates cancer cell colonization at secondary metastatic sites. Thus, the invasive and metastatic characteristics of hOSCC appear to be reciprocally regulated by BMP and TGF-β. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

4294 | Oct 09 2017

Grygielewicz P et al. provide experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

STAT1 as a downstream mediator of ERK signaling contributes to bone cancer pain by regulating MHC II expression in spinal microglia

1917 | Oct 04 2017

Song Z et al. suggested that STAT1 contributes to bone cancer pain as a downstream mediator of ERK signaling by regulating MHC II expression in spinal microglia. [Read the Full Post]

Malignant gliomas induce and exploit astrocytic mesenchymal-like transition by activating canonical Wnt/β-catenin signaling

1694 | Sep 29 2017

Lu P et al. established that glioma cells remarkably activated astrocytes via upregulating Wnt/β-catenin signaling, with obviously mesenchymal-like transition and increased migration and invasion ability, indicating that glioma cells may stimulate adjacent astrocytes to degrade extracellular matrix and thereby promoting tumor invasiveness. [Read the Full Post]

Serpine2, a potential novel target for combating melanoma metastasis

0 | Sep 15 2017

Wu QW et al. suggested a novel mechanism underlying the metastasis of melanoma cells which might serve as a new intervention target for the treatment of melanoma. [Read the Full Post]

Anterior-Posterior Patterning of Definitive Endoderm Generated from Human Embryonic Stem Cells Depends on the Differential Signaling of Retinoic Acid, Wnt-, and BMP-Signaling

1698 | Sep 10 2017

Davenport C et al. provided new insights into the mechanisms behind cell specification of human DE derived from pluripotent stem cells. VHL deficiency is dependent on HIF activation. Moreover, HIF1α or HIF2α overexpression in CC-RCCVHL cells is sufficient to sensitize them to ROCK inhibition. Finally, Y-27632 treatment inhibited growth of subcutaneous 786-OT1 CC-RCC tumors in mice. Thus, ROCK inhibitors represent potential therapeutics for VHL-deficient CC-RCC. [Read the Full Post]

Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma

2339 | Sep 09 2017

Thompson JM et al. suggested that synthetic lethality between ROCK inhibition and VHL deficiency is dependent on HIF activation. Moreover, HIF1α or HIF2α overexpression in CC-RCCVHL cells is sufficient to sensitize them to ROCK inhibition. Finally, Y-27632 treatment inhibited growth of subcutaneous 786-OT1 CC-RCC tumors in mice. Thus, ROCK inhibitors represent potential therapeutics for VHL-deficient CC-RCC. [Read the Full Post]

Regulation of TRPM7 Function by IL-6 through the JAK2-STAT3 Signaling Pathway

1436 | Sep 05 2017

Liu A et al. indicated IL-6 inhibits the inward TRPM7 current via the JAK2-STAT3 signaling pathway. [Read the Full Post]

Interleukin 6 induces cell proliferation of clear cell renal cell carcinoma by suppressing hepaCAM via the STAT3-dependent up-regulation of DNMT1 or DNMT3b

1754 | Aug 17 2017

Quan Z et al. provided a novel signal pathway regulating cell proliferation, potentially representing a therapeutic target for RCC. [Read the Full Post]

Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma

1968 | Aug 17 2017

Dai M et al. demonstrated for the first time the crucial role of the insulin/STAT3/DHCR24/PGR axis in the progression of EC by modulating the metastasis and progesterone response, which could serve as potential therapeutic targets for the treatment of EC with progesterone receptor loss. [Read the Full Post]

Lipopolysaccharide increases IL-6 secretion via activation of the ERK1/2 signaling pathway to up-regulate RANKL gene expression in MLO-Y4 cells

1671 | Aug 16 2017

Yu K et al. indicated that LPS up-regulates osteocyte expression of RANKL and IL-6, and the increased RANKL is associated with the up-regulation of IL-6, which involves the ERK1/2 pathway. [Read the Full Post]

BRG1 targeting STAT3/VEGFC signaling regulates lymphangiogenesis in colorectal cancer

1593 | Aug 09 2017

Zhu X et al. demonstration of the important roles of the BRG1/STAT3/VEGFC in tumor-associated lymphangiogenesis might lead to the discovery of novel therapeutic targets in the treatment of cancers with BRG1 loss of function. [Read the Full Post]

Essential role of Notch4/STAT3 signaling in epithelial-mesenchymal transition of tamoxifen-resistant human breast cancer

2339 | Jul 25 2017

Bui QT et al. concluded Notch4 could be a potential target to prevent metastasis in TAM-resistant breast cancer. [Read the Full Post]

Endosulfan inhibits proliferation through the Notch signaling pathway in human umbilical vein endothelial cells

2342 | Jul 25 2017

Wei J et al. demonstrated that endosulfan inhibited proliferation through the Notch signaling pathway as a result of oxidative stress. In addition, endosulfan can damage the cytoskeleton and block mitosis, which may add another layer of toxic effects on endothelial cells. [Read the Full Post]

Synergistic effects of CD44 and TGF-β1 through AKT/GSK-3β/β-catenin signaling during epithelial-mesenchymal transition in liver cancer cells

1472 | Jul 21 2017

Park NR et al. demonstrated the synergistic interactions between CD44 and TGF-β1 in EMT induction and CSC properties through the AKT/GSK-3β/β-catenin pathway in HCC cells. [Read the Full Post]

Effect of alpha lipoic acid on retinal ganglion cell survival in an optic nerve crush model

2609 | Jul 17 2017

Liu R et al. conclude that the endogenous EPO/EPOR signaling pathway may contribute to the protective effects of ALA in the retina after ONC injury. [Read the Full Post]

The positional identity of iPSC-derived neural progenitor cells along the anterior-posterior axis is controlled in a dosage-dependent manner by bFGF and EGF

0 | Jul 14 2017

Zhou S et al. indicated that different concentrations of bFGF and EGF supplemented during propagation of neural rosettes are involved in altering the identity of the resultant neural cells. [Read the Full Post]

WNT/β-catenin signaling promotes VSMCs to osteogenic transdifferentiation and calcification through directly modulating Runx2 gene expression.

0 | Jul 08 2017

Cai T et al. suggested that high-phosphate may activate WNT/β-catenin signaling through different pathways, and the activated WNT/β-catenin signaling, through direct downstream target Runx2, could play an important role in promoting VOT and AMC. [Read the Full Post]

Suppression of Virulent Porcine Epidemic Diarrhea Virus Proliferation by the PI3K/Akt/GSK-3α/β Pathway

4063 | Jul 04 2017

Kong N et al. suggested that PI3K/Akt/GSK-3α/β signaling pathway is activated by PEDV and functions in inhibiting PEDV replication. [Read the Full Post]

Generation of Cardiomyocytes from Pluripotent Stem Cells

1705 | Jul 03 2017

Nakahama H et al. described two different methods for acquiring CMs from human pluripotent lines. One method involves the generation of embryoid bodies, which emulates the natural developmental process, while the other method chemically activates the canonical Wnt signaling pathway to induce a monolayer of cardiac differentiation. [Read the Full Post]

Role of Wnt/β-catenin, Wnt/c-Jun N-terminal kinase and Wnt/Ca2+ pathways in cisplatin-induced chemoresistance in ovarian cancer

3969 | Jul 03 2017

Huang L et al. indicated that β-catenin, JNK and CaMKII are potential therapeutic targets in chemoresistant ovarian cancers. [Read the Full Post]

Structural basis of Smoothened regulation by its extracellular domains

1835 | Jun 22 2017

Byrne EF et al. clarified the structural mechanism by which the activity of a GPCR is controlled by ligand-regulated interactions between its extracellular and transmembrane domains. [Read the Full Post]

Cdk5 is required for the neuroprotective effect of transforming growth factor-β1 against cerebral ischemia-reperfusion

3523 | Jun 21 2017

Zhao W et al. concluded that Cdk5 contributes to the neuroprotective function of TGF- β1 via ERK1/2 signaling. [Read the Full Post]

Acquired Resistance to the Hsp90 Inhibitor, Ganetespib, in KRAS-Mutant NSCLC Is Mediated via Reactivation of the ERK-p90RSK-mTOR Signaling Network

2100 | Jun 20 2017

Chatterjee S et al. offered a way forward for Hsp90 inhibitors through the rational design of Hsp90 inhibitor combinations that may prevent and/or overcome resistance to Hsp90 inhibitors, providing an effective therapeutic strategy for KRAS-mutant NSCLC. [Read the Full Post]

Platelet-derived growth factor (PDGF)-induced activation of Erk5 MAP-kinase is dependent on Mekk2, Mek1/2, PKC and PI3-kinase, and affects BMP signaling

5939 | Jun 14 2017

Tsioumpekou M et al. found that PDGF-BB-induced Erk5 activation involves parallel stimulatory and inhibitory pathways and promotes Smad1/5/8 signaling. [Read the Full Post]

Analysis of Endogenous Protein Interactions of Polycomb Group of Proteins in Mouse Embryonic Stem Cells.

2753 | Jun 14 2017

Morey L et al. described several methods to study Polycomb architecture, and identification of novel interactors in both pluripotent and differentiating mouse embryonic stem cells. [Read the Full Post]

Transmembrane protein 88 attenuates liver fibrosis by promoting apoptosis and reversion of activated hepatic stellate cells

2032 | Jun 13 2017

Cai SP et al. found that Tmem88 played an important role in HSCs activation, proliferation and apoptosis, and Tmem88 expression might be modulated by Dnmt3a. [Read the Full Post]

DDX17 nucleocytoplasmic shuttling promotes acquired gefitinib resistance in non-small cell lung cancer cells via activation of β-catenin

4322 | Jun 12 2017

Li K et al. revealed a novel and important mechanism by which DDX17 contributes to acquired gefitinib resistance through exportin/importin-dependent cytoplasmic shuttling and followed by activation of β-catenin, and DDX17 inhibition may be a promising strategy to overcome acquired resistance of gefitinib in NSCLC patients. [Read the Full Post]

Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice

3620 | Jun 11 2017

Satoh M et al. indicated that interactions between NKT cells and CD1d-expressing adipocytes producing endogenous NKT cell ligands play a critical role in the induction of inflammation and functional modulation of adipose tissue that leads to obesity. [Read the Full Post]

Combretastatin A-1 phosphate, a microtubule inhibitor, acts on both hepatocellular carcinoma cells and tumor-associated macrophages by inhibiting the Wnt/β-catenin pathway

1574 | Jun 09 2017

Mao J et al. indicated that CA1P has great potential to impact both cancer cells and the microenvironment. [Read the Full Post]

Inhibition of green tea polyphenol EGCG((-)-epigallocatechin-3-gallate) on the proliferation of gastric cancer cells by suppressing canonical wnt/β-catenin signalling pathway

1950 | Jun 08 2017

Yang C et al. established that EGCG suppressed gastric cancer cell proliferation and demonstrate that this inhibitory effect is related to canonical Wnt/β-catenin signalling. [Read the Full Post]

Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model

3295 | Jun 06 2017

Guo SC et al. provided evidence of the probable molecular mechanisms underlying the PRP effect on healing of chronic ulcers and describe a promising resource of growth factors from exosomes without species restriction. [Read the Full Post]

The Expression and Regulation of Interleukin-33 in Human Epidermal Keratinocytes: A New Mediator of Atopic Dermatitis and Its Possible Signaling Pathway

2961 | May 26 2017

Du HY et al. found that IL-33 plays an important role in the pathogenesis of immune inflammatory responses in AD, which might be a possible therapeutic target in the treatment of AD. [Read the Full Post]

Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells

0 | May 22 2017

Massa MG et al. provided an avenue for studies with a greater cell- and human-specific focus, specifically in the context of genetic contributions to neurodegeneration and drug discovery. [Read the Full Post]

Identification of Novel Inhibitors of the Type I Interferon Induction Pathway Using Cell-Based High-Throughput Screening

2811 | May 17 2017

Gage ZO et al. demonstrate that one of these compounds acts at or upstream of IRF3 phosphorylation. [Read the Full Post]

Myocardial commitment from human pluripotent stem cells: Rapid production of human heart grafts

0 | May 16 2017

Garreta E et al. provided a suitable platform for cardiac engineering and disease modeling in the human setting. [Read the Full Post]

Fast and Efficient Transfection of Mouse Embryonic Stem Cells Using Non-Viral Reagents.

0 | May 11 2017

Tamm C et al. demonstrated that simplified and highly efficient transfection method will be valuable for both basic research and high-throughput applications. [Read the Full Post]

Transforming growth factor-β-dependent Wnt secretion controls myofibroblast formation and myocardial fibrosis progression in experimental autoimmune myocarditis

0 | May 08 2017

Blyszczuk P et al. identified TAK1-mediated rapid Wnt protein secretion as a novel downstream key mechanism of TGF-β-mediated myofibroblast differentiation and myocardial fibrosis progression in human and mouse myocarditis. [Read the Full Post]

GLI inhibitor GANT61 kills melanoma cells and acts in synergy with obatoclax

0 | May 05 2017

Vlčková K et al. found that GANT61 treatment might become a hopeful and effective anti-melanoma targeted therapy, especially when combined with the BCL2 family inhibitor obatoclax. [Read the Full Post]

Induction and differentiation of human induced pluripotent stem cells into functional cardiomyocytes on a compartmented monolayer of gelatin nanofibers

1633 | May 05 2017

Tang Y et al. showed that representative field potential waveforms of matured cardiac tissues with appropriate drug responses. [Read the Full Post]

Fast and Efficient Transfection of Mouse Embryonic Stem Cells Using Non-Viral Reagents

1897 | Apr 30 2017

Tamm C et al. found that simplified and highly efficient transfection method will be valuable for both basic research and high-throughput applications. [Read the Full Post]

Cell alignment induced by anisotropic electrospun fibrous scaffolds alone has limited effect on cardiomyocyte maturation

0 | Apr 28 2017

Han J et al suggested that electrospun anisotropic fibrous scaffolds, as a single method, have limited effect on improving the maturation of hPSC-CMs. [Read the Full Post]

Induction and differentiation of human induced pluripotent stem cells into functional cardiomyocytes on a compartmented monolayer of gelatin nanofibers

1420 | Apr 28 2017

Tang Y et al. found that representative field potential waveforms of matured cardiac tissues with appropriate drug responses. [Read the Full Post]

GLI inhibitor GANT61 kills melanoma cells and acts in synergy with obatoclax

1795 | Apr 27 2017

Vlčková K et al. found that GANT61 treatment might become a hopeful and effective anti-melanoma targeted therapy, especially when combined with the BCL2 family inhibitor obatoclax. [Read the Full Post]

High glucose-induced Matrilin-2 expression in mouse mesangial cells was mediated by transforming growth factor beta 1 (TGF-β1).

1565 | Apr 24 2017

Zhang S et al showed that high-glucose-induced Matrilin-2 expression that was mediated by the TGF-β1/Smad3 signaling pathway might play a role in Diabetic nephropathy (DN) pathogenesis and our finding provided a potential diagnostic and/or therapeutic target for DN. [Read the Full Post]

MAP3K19-Is-a-Novel-Regulator-of-TGF-B-Signaling-That-Impacts-Bleomycin-Induced-Lung-Injury-and-Pulmonary-Fibrosis

8803 | Apr 23 2017

Boehme SA et al suggested that inhibition of MAP3K19 may have a beneficial therapeutic effect in the treatment of IPF and represents a novel strategy to target this disease. [Read the Full Post]

Electrochemical biosensor for protein kinase A activity assay based on gold nanoparticles-carbon nanospheres, phos-tag-biotin and β-galactosidase

3084 | Apr 21 2017

Zhou Y et al. found the fabricated biosensor can be applied to detect PKA in human normal gastricepithelial cell line and human gastric carcinoma cell line with satisfactory results. [Read the Full Post]

Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1

2818 | Apr 19 2017

Baris S et al. found thatJAK kinase inhibitors may potentially be useful in some patients as adjunct therapy pending definitive treatment with bone marrow transplantation. [Read the Full Post]

Developmental expression of STATs, nuclear factor-κB and inflammatory genes in the jejunum of piglets during weaning

2807 | Apr 18 2017

Yi H et al found weaning caused severe inflammation associated with activation of the NF-κB and STAT-3 pathways and suppression of STAT-1 and STAT-6 in the jejunum of piglets. [Read the Full Post]

"RNA polymerase III component Rpc9 regulates hematopoietic stem and progenitor cell maintenance in zebrafish. "

0 | Apr 17 2017

Wei Y et al illustrated that Rpc9, a component of Pol III, plays an important tissue-specific role in HSPC maintenance during zebrafish embryogenesis and might be conserved across vertebrates, including mammals. [Read the Full Post]

A chemical with proven clinical safety rescues Down-syndrome-related phenotypes in through DYRK1A inhibition

2479 | Apr 06 2017

Kim H et al. demonstrated that CX-4945 is a potent DYRK1A inhibitor and also suggested that it has therapeutic potential for DYRK1A-associated diseases. [Read the Full Post]

Distinct MicroRNA Expression Signatures of Porcine Induced Pluripotent Stem Cells under Mouse and Human ESC Culture Conditions

1571 | Apr 04 2017

Zhang W et al. found that significant differences in the miRNA signatures of hpiPSCs and mpiPSCs under different pluripotent states that were derived from different culture conditions. [Read the Full Post]

SMO Gene Amplification and Activation of the Hedgehog Pathway as Novel Mechanisms of Resistance to Anti-Epidermal Growth Factor Receptor Drugs in Human Lung Cancer

1883 | Feb 21 2017

Della Corte CM, et al.'s result supports the role of the Hh pathway in mediating resistance to anti-EGFR-TKIs through the induction of EMT and suggests new opportunities to design new treatment strategies in lung cancer. [Read the Full Post]

Targeting hedgehog signaling reduces self-renewal in embryonal rhabdomyosarcoma

0 | Feb 20 2017

Satheesha S, et al.‘s ’ work identifies novel functional aspects of hedgehog signaling in ERMS, redefines the rationale for its targeting as means to control ERMS self-renewal and underscores the importance of studying functional tumor heterogeneity in pediatric cancers. [Read the Full Post]

Targeting Wnt pathway in mantle cell lymphoma-initiating cells

0 | Feb 20 2017

Mathur R, et al.‘s’ results suggest that Wnt signaling is critical for the maintenance and survival of MCL-ICs, and effective MCL therapy should aim to eliminate MCL-ICs through Wnt signaling inhibitors. [Read the Full Post]

Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma

0 | Feb 19 2017

Brun SN, et al.'s studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease. [Read the Full Post]

Opposing roles of TGF-β and EGF in the regulation of TRAIL-induced apoptosis in human breast epithelial cells

1906 | Feb 15 2017

Li W et al. revealed a fine regulation by EGF and TGF-β of sensitivity of human breast epithelial cells to TRAIL which may be relevant during morphogenesis. [Read the Full Post]

AKT and 14-3-3 Regulate Notch4 Nuclear Localization

3281 | Feb 06 2017

Ramakrishnan G, et al.'s findings provide a novel mechanism for Notch4-ICD regulation, suggesting a negative regulatory role for the PI3K-AKT pathway in Notch4 nuclear signaling. [Read the Full Post]

Wnt/b-Catenin-Signaling and the Formation of M€uller Glia-Derived Progenitors in the Chick Retina

1900 | Feb 04 2017

Gallina D, et al 's findings indicate that Wnt-signaling is part of a network initiated by FGF2/MAPK or retinal damage, and activation of canonical Wnt-signaling is required for the formation of proliferating MGPCs. [Read the Full Post]

Delayed Administration of WP1066, an STAT3 Inhibitor, Ameliorates Radiation-Induced Lung Injury in Mice

3360 | Jan 28 2017

The activation of STAT3 pathway might play an important part in the pathogenesis of radiation-induced lung injury. The protective effects of delayed treatment of WP1066 suggested STAT3 signaling could be a therapeutic target for radiation pneumonitis. [Read the Full Post]

GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats

1760 | Jan 27 2017

Wang W et al. suggested that TWS119 reduces rtPA-induced HT and attenuates blood-brain barrier disruption, possibly through activation of the Wnt/β-catenin signaling pathway. This study provides a potential therapeutic strategy to prevent tPA-induced HT after acute ischemic stroke. [Read the Full Post]

Wnt/β-catenin-signaling and the formation of Müller glia-derived progenitors in the chick retina

0 | Jan 26 2017

Gallina D et al. indicated that Wnt-signaling is part of a network initiated by FGF2/MAPK or retinal damage, and activation of canonical Wnt-signaling is required for the formation of proliferating MGPCs. [Read the Full Post]

SMO Gene Amplification and Activation of the Hedgehog Pathway as Novel Mechanisms of Resistance to Anti-Epidermal Growth Factor Receptor Drugs in Human Lung Cancer

1426 | Jan 11 2017

Della Corte CM et al. found that the role of the Hh pathway in mediating resistance to anti-EGFR-TKIs through the induction of EMT and suggests new opportunities to design new treatment strategies in lung cancer. [Read the Full Post]

Targeting Wnt pathway in mantle cell lymphoma-initiating cells

4488 | Jan 10 2017

Mathur R, et al.'s results suggest that Wnt signaling is critical for the maintenance and survival of MCL-ICs, and effective MCL therapy should aim to eliminate MCL-ICs through Wnt signaling inhibitors. [Read the Full Post]

Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma

1780 | Jan 09 2017

Brun SN, et al.'s studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease. [Read the Full Post]

Targeting hedgehog signaling reduces self-renewal in embryonal rhabdomyosarcoma

1865 | Jan 09 2017

Satheesha S, et al.'s work identifies novel functional aspects of hedgehog signaling in ERMS, redefines the rationale for its targeting as means to control ERMS self-renewal and underscores the importance of studying functional tumor heterogeneity in pediatric cancers. [Read the Full Post]

Wnt/β-catenin-signaling and the formation of Müller glia-derived progenitors in the chick retina

1961 | Jan 01 2017

Gallina D et al. indicated that Wnt-signaling is part of a network initiated by FGF2/MAPK or retinal damage, and activation of canonical Wnt-signaling is required for the formation of proliferating MGPCs. [Read the Full Post]

AKT and 14-3-3 Regulate Notch4 Nuclear Localization

3727 | Dec 29 2016

Ramakrishnan G, et al.'s findings provide a novel mechanism for Notch4-ICD regulation, suggesting a negative regulatory role for the PI3K-AKT pathway in Notch4 nuclear signaling. [Read the Full Post]

WNT/β-catenin signaling promotes VSMCs to osteogenic transdifferentiation and calcification through directly modulating Runx2 gene expression.

2225 | Dec 21 2016

Cai T et al.'s study suggested that high-phosphate may activate WNT/β-catenin signaling through different pathways, and the activated WNT/β-catenin signaling, through direct downstream target Runx2, could play an important role in promoting VOT and AMC. [Read the Full Post]

The positional identity of iPSC-derived neural progenitor cells along the anterior-posterior axis is controlled in a dosage-dependent manner by bFGF and EGF

2729 | Dec 17 2016

The results of Zhou S et al. indicated that different concentrations of bFGF and EGF supplemented during propagation of neural rosettes are involved in altering the identity of the resultant neural cells. [Read the Full Post]

Synergistic effects of CD44 and TGF-β1 through AKT/GSK-3β/β-catenin signaling during epithelial-mesenchymal transition in liver cancer cells

2123 | Dec 16 2016

Park NR, et al. demonstrated the synergistic interactions between CD44 and TGF-β1 in EMT induction and CSC properties through the AKT/GSK-3β/β-catenin pathway in HCC cells. [Read the Full Post]

Synergistic effects of CD44 and TGF-β1 through AKT/GSK-3β/β-catenin signaling during epithelial-mesenchymal transition in liver cancer cells

2240 | Dec 15 2016

Park NR et al.'s study demonstrated the synergistic interactions between CD44 and TGF-β1 in EMT induction and CSC properties through the AKT/GSK-3β/β-catenin pathway in HCC cells [Read the Full Post]

Hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells

1745 | Dec 09 2016

The study of Sun M et al. suggested that NC may be a potential anticancer agent for breast cancer. [Read the Full Post]

Serpine2, a potential novel target for combating melanoma metastasis

2295 | Nov 30 2016

Wu QW et al. suggested a novel mechanism underlying the metastasis of melanoma cells which might serve as a new intervention target for the treatment of melanoma. [Read the Full Post]

Inhibition of β-Catenin to Overcome Endocrine Resistance in Tamoxifen-Resistant Breast Cancer Cell Line

2511 | Nov 11 2016

Won HS et al. suggested that β-catenin plays a role in tamoxifen-resistant breast cancer, and the inhibition of β-catenin may be a potential target in tamoxifen-resistant breast cancer. [Read the Full Post]

Opposing roles of TGF-β and EGF in the regulation of TRAIL-induced apoptosis in human breast epithelial cells

2200 | Nov 07 2016

Li W et al. revealed a fine regulation by EGF and TGF-β of sensitivity of human breast epithelial cells to TRAIL which may be relevant during morphogenesis. [Read the Full Post]

Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells

4360 | Oct 19 2016

[Read the Full Post]

Myocardial commitment from human pluripotent stem cells: Rapid production of human heart grafts

2431 | Oct 12 2016

Garreta E et al. provided a suitable platform for cardiac engineering and disease modeling in the human setting. [Read the Full Post]

Transforming growth factor-β-dependent Wnt secretion controls myofibroblast formation and myocardial fibrosis progression in experimental autoimmune myocarditis

2563 | Oct 08 2016

Blyszczuk P et al. identified TAK1-mediated rapid Wnt protein secretion as a novel downstream key mechanism of TGF-β-mediated myofibroblast differentiation and myocardial fibrosis progression in human and mouse myocarditis. [Read the Full Post]

Cell alignment induced by anisotropic electrospun fibrous scaffolds alone has limited effect on cardiomyocyte maturation

3079 | Sep 27 2016

Han J et al. suggested that electrospun anisotropic fibrous scaffolds, as a single method, have limited effect on improving the maturation of hPSC-CMs. [Read the Full Post]

High glucose-induced Matrilin-2 expression in mouse mesangial cells was mediated by transforming growth factor beta 1 (TGF-β1)

2182 | Sep 26 2016

Zhang S et al. found that high-glucose-induced Matrilin-2 expression that was mediated by the TGF-β1/Smad3 signaling pathway might play a role in Diabetic nephropathy (DN) pathogenesis. [Read the Full Post]

MAP3K19 Is a Novel Regulator of TGF-β Signaling That Impacts Bleomycin-Induced Lung Injury and Pulmonary Fibrosis

2386 | Sep 22 2016

Boehme SA et al. suggested that inhibition of MAP3K19 may have a beneficial therapeutic effect in the treatment of IPF and represents a novel strategy to target this disease. [Read the Full Post]

Developmental expression of STATs, nuclear factor-κB and inflammatory genes in the jejunum of piglets during weaning

7034 | Sep 20 2016

Yi H et al. found that weaning caused severe inflammation associated with activation of the NF-κB and STAT-3 pathways and suppression of STAT-1 and STAT-6 in the jejunum of piglets. [Read the Full Post]

CY190602, a novel DNA/HDAC dual-targeting drug with enhanced anti-cancer potency

9867 | Mar 19 2015

Liu et al. demonstrated a novel bendamustine-derived drug, CY190602, enhanced anticancer potency. [Read the Full Post]

ERK induces degradation of tumor suppressor FBW7 in pancreatic cancer

7552 | Mar 18 2015

Ji et al. demonstrated a correlation between low expression of FBW7 and ERK activation in pancreatic cancer. [Read the Full Post]

Inhibition of proteasome restores bortesomib-induced thrombocytopenia

10589 | Feb 10 2015

Shi et al. reported clinical proteasome inhibitor enable to block proplatelet formation by megakaryocytes in human and mouse model. [Read the Full Post]

A protocol for human pluripotent stem cell differentiation into endoderm related cells

7559 | Feb 02 2015

Diekmann et al. showed a detailed protocol started from a defined cell number of dispersed single cells of three different human ESC lines, and one human iPSC line. [Read the Full Post]

Unexpected role of Notch signaling on directing the trophectoderm lineage in the mouse blastocyst

6550 | Jan 30 2015

Rayon et al. showed that Notch signaling plays a key role in mediating TE-specific expression of Cdx2, though interaction with the transcription factor TEAD4. [Read the Full Post]

BUB1 plays a key role in promoting TGF-β signaling

7914 | Jan 20 2015

By using human kinome siRNA screen and a live-cell reporter for TGF-β receptor (TGFBR) activity, Nyati et al. identified the kinase budding uninhibited by benzimidazoles-1 (BUB1) plays a critical role in regulating TGF-β signaling. [Read the Full Post]

Tofacitinib promotes myeloid-derived suppressor cells expansion and reduces disease severity of arthritis SKG mice

6976 | Jan 14 2015

Nishimura et al. revealed that tofacitinib has effect on promoting MDSCs expansion and ameliorating arthritis in SKG mice. [Read the Full Post]

Generate hypothalamic neurons from hESCs and human iPSCs

4030 | Jan 08 2015

Wang et al. reported a protocol of differeiciating human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) into hypothalamic cells. [Read the Full Post]

The important role of HSF1 expressed by cancer-associated fibroblasts

4319 | Dec 29 2014

Scherz-Shouval et al. found cancer-associated fibroblasts (CAFs) frequently express heat shock factor 1 (HSF1), which acts as a strong enabler of tumorigenesis. [Read the Full Post]

Innate immunity-induced IRF3 signaling suppress TGF-β via Smad

5913 | Dec 23 2014

By investigating the innate host defense, Xu et al. found RIG-I-Like receptor (RLR) signaling suppress TGF-β via activation of Interferon regulatory factor 3 (IRF3). [Read the Full Post]

The inhibition of JAK signaling promotes the conversion from white to brown adipocytes

8609 | Dec 17 2014

By using a screening platform of small molecules identification, Moisan et al. found two inhibitors of JAK signaling were able to convert white adipocytes to brown adipocytes. [Read the Full Post]

The Notch signaling controls maintenance of memory CD4+ T cells

10136 | Dec 16 2014

Recently, Maekawa et al. demonstrated Notch signaling is important for the survival of memory CD4+ T cells by regulating glucose uptake. [Read the Full Post]

IncRNA BCAR4 regulates cancer development cooperated with chemokine signals

7495 | Dec 09 2014

Xing et al. demonstrated the mechanism of BCAR4, a disease-related Inc RNA, in regulation signaling pathways in breast cancer metastasis. [Read the Full Post]

MeCP2 S421 phosphorylation mediates neurogenesis via Notch signaling pathway

8782 | Dec 04 2014

Li et al. identified the Notch signaling is involved in the regulation of MeCP2 S421 phosphorylation other than neuronal activity. [Read the Full Post]

Retinoic acid and Wnt signaling are key regulators in development of hematopoietic stem cells

6611 | Dec 02 2014

Chanda et al. identified retinoic acid (RA) and Wnt signaling pathways as key mediators of HSC development. [Read the Full Post]

Mechanism of Cdo-induced Wnt suppression during neuronal differentication

4605 | Nov 28 2014

Jeong et al. found that Wnt signaling is negatively regulated by Cdo, a Shh multifunctional co-receptor which is highly expressed in the central nervous system, in order to promote neuronal differentiation. [Read the Full Post]

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

11424 | Nov 24 2014

Dechow et al. determined GP130/JAK/STAT3 signaling pathway is sufficient to induce MM generation in mice retroviral murine BM transduction-transplantation model. [Read the Full Post]

ERK/Cdk5 axis regulates diabetes-related PPARγ phosphorylation

8175 | Nov 21 2014

Recently, Banks et al. discovered that ERK/Cdk5 axis is involved in regulation PPARγ activities, and the inhibition of ERK and MEK leads to the improvement of insulin resistance. [Read the Full Post]

The mechanism of drug resistance in BRAF (V600E) mutant melanoma

9791 | Nov 19 2014

Sun et al. demonstrated the resistance of BRAF (V600E) is reversible and adaptive. The process involves several transduction factors, such as EGFR, PDGFRB, TGF-β, and SOX10. [Read the Full Post]

The activation of BMP and WNT signals specifies epicardial lineage from hESCs

7060 | Nov 12 2014

Witty et al. describe a new strategy of using human pluripotent stem cells (hESCs) to generate epicardial lineage cells by activation the BMP and WNT signaling pathways in a stage-specific way. [Read the Full Post]

Interactions between Slit-Robo and JAK-STAT signaling in regulation of stem cell-niche adhesion

8938 | Nov 10 2014

Rachel R. Stine et al. found Slit-Robo and JAK-STAT signaling pathways play key roles in stem cells competition within their niches. [Read the Full Post]

FGF21 is not required for CR-mediated IGF-1 reduction or cell proliferation inhibition

8222 | Nov 06 2014

Thompson et al. found that, in response to moderate CR, phosphorylated STAT5 may act as a key molecule, and FGF21 was not required for the down-regulation of IGF-1 expression level or cell proliferation rates. [Read the Full Post]

New platform of high efficiency iPSC reprogramming

8824 | Nov 05 2014

Vidal et al. found the inhibition of transforming growth factor β (TGF-β) or activation of Wnt signaling, or both, can provide a high efficient iPSC reprogramming in a cell-type-specific manner. [Read the Full Post]

JAK2 and MPL are two main regulators of TPO-induced megakaryopoiesis

7344 | Nov 03 2014

Megakaryopoiesis is regulated by TPO, which activates multiple signaling molecules. Besancenot et al. demonstrated that the protein levels of JAK2 and MPL determine TPO-induced megakaryopoiesis. [Read the Full Post]

Neural stem cells "heal" target cells via extracellular vesicles

4377 | Oct 29 2014

Cossetti et al. found NPCs communicate to the host via extracellular vesicles (EVs) and also investigated the cytokine-regulated pathways involved in the communication. It comes to a novel view in the understanding the mechanisms of stem cell therapy. [Read the Full Post]

The role of TGFβ target——LTBP4 in muscular dystrophy

4315 | Oct 24 2014

Ceco et al. found latent transforming growth factor-β (TGFβ) binding proteins 4 (LTBP4) play determinant roles in muscular dystrophy symptoms.Their data suggested that blocking LTBP4 results in reduced TGFβ release, and then leads to a reduction of muscle inflammation and damage in DMD. [Read the Full Post]

Notch signaling acts as a key regulator in generation of neurons from neural precursor cells

5727 | Oct 23 2014

Notch signaling plays a central role before asymmetric division and in the fate of Drosophila melanogaster neural precursor cells. It also acts as a critical factor in Numb distribution in neural precursor cells before cleavage. [Read the Full Post]

Two side roads toward conquest of HBV

2964 | May 05 2014

Vismodegib (GDC-0449) is a potent, novel and specific hedgehog inhibitor with IC50 of 3 nM and also inhibits P-gp with IC50 of 3.0 μM. [Read the Full Post]

How to survive the zombie apocalypse

2874 | Apr 02 2014

LDE225 (NVP-LDE225) is a Smoothened (Smo) antagonist, inhibiting Hedgehog (Hh) signaling with IC50 of 1.3 nM (mouse) and 2.5 nM (human), respectively. [Read the Full Post]

AZD1080 is a novel GSK3 inhibitor rescues synaptic plasticity deficits in rodent brain

3870 | Mar 06 2014

AZD1080 is a selective, orally active, brain permeable GSK3 inhibitor, inhibits human GSK3α and GSK3β with a Ki of 6.9 nM and 31 nM [Read the Full Post]

Y27632 is a biochemical tool used in the study of the ROCK

5872 | Mar 05 2014

Y-27632 2HCl inhibits ROCK-II while displaying little activity against PKC. [Read the Full Post]

SB431542 is a small molecule that acts as a specific inhibitor

4045 | Feb 13 2014

SB431542 is a potent and selective inhibitor of ALK5 with IC50 of 94 nM, 100-fold more selective for ALK5 than p38 MAPK and other kinases. [Read the Full Post]

SB525334 is a potent and selective inhibitor of TGFB

3923 | Feb 12 2014

SB 525334 (10 mg/kg/day) decreases the renal mRNA levels of PAI-1, procollagen α1(I), and procollagen α1(III) in a nephritis-induced renal fibrosis rat model. [Read the Full Post]

Y 27632 is available in a 5 mg format and has been optimized

5560 | Jan 17 2014

Y-27632 2HCl is a selective ROCK1 (p160ROCK) inhibitor with Ki of 140 nM, exhibits >200-fold selectivity over other kinases, including PKC, cAMP-dependent protein kinase, MLCK and PAK. [Read the Full Post]

WP1066 is a cell permeable AG 490 tyrphostin analog

6554 | Jan 15 2014

WP1066 is a novel inhibitor of JAK2 and STAT3 with IC50 of 2.30 μM and 2.43 μM in HEL cells; shows activity to JAK2, STAT3, STAT5, and ERK1/2 not JAK1 and JAK3. [Read the Full Post]

Y 27632 is a biochemical tool used in the study of the rho associated protein kinase

5643 | Jan 10 2014

Y-27632 2HCl is a selective ROCK1 inhibitor with Ki of 140 nM, exhibits >200-fold selectivity over other kinases, including PKC, cAMP-dependent protein kinase, MLCK and PAK. [Read the Full Post]

AZD1080 is a selective orally active brain permeable GSK3 inhibitor

0 | Jan 06 2014

AZD1080 reverses cognitive deficits and rescues dysfunctional synapses in mice. [Read the Full Post]

Wnt C59 was first disclosed in patent WO2010101849 as a potent

4125 | Dec 19 2013

Wnt-C59 is claimed to inhibit PORCN enzyme activity at nanomolar concentrations. [Read the Full Post]

XAV 939 is a small molecule and selective Wnt pathway

4431 | Dec 11 2013

XAV-939 specifically inhibits tankyrase PARP activity. [Read the Full Post]

SB 525334 is a selective inhibitor of transforming growth factor B

3612 | Dec 10 2013

SB525334 is a potent and selective inhibitor of TGFβ receptor I (ALK5) with IC50 of 14.3 nM, is 4-fold less potent to ALK4 than ALK5 and inactive to ALK2, 3, and 6. [Read the Full Post]

LDN193189 is a cell permeable

3446 | Dec 03 2013

LDN193189 is a selective BMP signaling inhibitor, inhibits the transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC50 of 5 nM and 30 nM, respectively, exhibits 200-fold selectivity for BMP versus TGF-β. [Read the Full Post]

Thiazovivin helps in promoting human embryonic stem cell

5364 | Nov 22 2013

Thiazovivin (Tzv) is a novel ROCK inhibitor with IC50 of 0.5 μM, promotes hESC survival after single-cell dissociation. [Read the Full Post]

AZD1080 is a selective orally active brain permeable GSK3 inhibitor

4448 | Nov 11 2013

AZD1080 is a selective, orally active, brain permeable GSK3 inhibitor, inhibits human GSK3α and GSK3β with a Ki of 6.9 nM and 31 nM, respectively, shows >14-fold selectivity against cdk2, cdk5, cdk1 and Erk2. [Read the Full Post]

Thiazovivin is a drug which dramatically improves the survival of hES

5733 | Nov 05 2013

Thiazovivin (Tzv) is a novel ROCK inhibitor with IC50 of 0.5 μM, promotes hESC survival after single-cell dissociation. [Read the Full Post]

This study is designed to evaluate the efficacy and safety of tofacitinib

7152 | Oct 30 2013

Tofacitinib citrate inhibits IL-2-mediated human T cell blast proliferation and IL-15-induced CD69 expression with IC50 of 11 nM and 48 nM, respectively. [Read the Full Post]

SANT1 is a potent inhibitor of Sonic hedgehog signaling

0 | Oct 16 2013

SANT-1 inhibits wild type and oncogenic Smo with equal potency. [Read the Full Post]

Y27632 is a selective inhibitor of the Rhoassociated kinase p160ROCK

5564 | Sep 12 2013

Y27632 2HCl inhibits ROCK-II while displaying little activity against PKC, cAMP-dependent protein kinase and myosin light-chain kinase (MLCK) with Ki of 26 μM, 25 μM and > 250 μM, respectively, as well as PKA activated by another Rho-family GTPase member, Cdc42. [Read the Full Post]

SANT1 is a potent inhibitor of Sonic hedgehog signaling

2698 | Sep 02 2013

SANT-1 inhibits wild type and oncogenic Smo with equal potency. SANT-1 counteracts SAG-induced pathway activation in Shh-LIGHT2 cells. [Read the Full Post]

Tideglusib might be useful for slowing atrophy rates

3905 | Aug 15 2013

Tideglusib (NP031112, NP-12) is an irreversible, non ATP-competitive GSK-3β inhibitor with IC50 of 60 nM; fails to inhibit kinases with a Cys homologous to Cys-199 located in the active site. Phase 1/2. [Read the Full Post]

TWS119 is thought to bind GSK with high affinity

4378 | Jul 11 2013

Treatment of a monolayer of P19 cells with 1 μM TWS119 causes 30–40% cells to differentiate specifically into neuronal lineages based on counting of TuJ1 positive cells with correct neuronal morphology (up to 60% neuronal differentiation occurred through the standard EB formation protocol with concomitant TWS119 treatment). [Read the Full Post]

y27632 is a biochemical tool used in the study of the rho associated protein kinase signaling pathways

5908 | Jun 07 2013

Oral administration of Y-27632 2HCl at 30 mg/kg significantly decreases the blood pressure in a dose-dependent manner in spontaneous hypertensive rats, renal hypertensive rats, as well as deoxycorticosterone acetate (DOCA)-salt hypertensive rats. [Read the Full Post]

Tideglusib may be useful for slowing atrophy rates

4290 | Jun 05 2013

Tideglusib (50 mg/kg) injected into the adult male Wistar rats hippocampus dramatically reduces kainic acid-induced inflammation and has a neuroprotective effect in the damaged areas of the hippocampus. [Read the Full Post]

Erismodegib is an orally bioavailable small molecule

3382 | Jan 07 2013

C Kit is a transmembrane receptor tyrosine kinase that binds stem cell factor SCF . CKit is encoded by the kit proto oncogene, localized to human chromosome and to mouse chromosome The c Kit SCF erismodegib interaction is critical for the survival and development of stem cells involved in hematopoiesis [Read the Full Post]

LY2109761 is a novel transforming growth factor

3250 | Jan 04 2013

The JAK2V617F mutated allele is present in virtually all patients with polycythemia vera (PV) and in about 60% of those with essential thrombocythemia (ET) and primary myelofibrosis (PMF), which are the other two main clinical entities included within the group of myeloproliferative LY2109761 neoplasms. [Read the Full Post]

ROCK Kinase is involved in cytokinesis

5920 | Dec 03 2012

The first evidence that the JNK pathway, the low level of expression in SMC Lon RGS4 ch Lt, then led end F F promotion from SMC contraction. Inhibition of tonic RGS4 expression by JNK pathway represents a novel mechanism for the contribution of the JNK pathway in the regulation of smooth muscle contraction. crosstalk between MAPK and JNK by other means NFkB not well ROCK Kinase understood. [Read the Full Post]

Gamma Secretase were grown in 5 ml of medium

5403 | Nov 28 2012

The cells were pelleted by centrifugation, the medium was Gamma Secretase removed with the drug, and the cells were washed washed with sterile PBS and centrifuged again. [Read the Full Post]

CP-690550: THE CURE FOR ARTHRITIS

6876 | Mar 20 2012

Introduction: JAK and its role in signaling pathways The protein kinase family plays an essential role in the government of the growth or death properties of mammalian tissues. These proteins form an interrelated, redundant system that is capable of selectively initiating the growth of certain cell types in response to the needs of the host system. To do this the protein kinase super family is subdivided into a series of related protein kinases which make up a signaling pathway, traveling from the extracellular matrix into the cell nucleus. The Janus kinase pathway is one which is activated in response to the action of cytokines on the cytokine transmembrane receptors. Since these receptors have no kinase ability themselves they are total dependant on the Janus kinases (JAK) for activity. [Read the Full Post]

INCB18424 – JACKING THE JAK2

7463 | Mar 20 2012

Introduction: JAK2 in relation to metabolic blood disorders The transmission of signals from extracellular factors through the cell membrane to effect actions within the cell cytosole and nucleus is conducted along pathways of protein to protein interactions. Many metabolic disorders have been associated with aberrations in these pathways causing a variety of destructive cellular actions. Many of these diseases possess no known cure and in response research has focused on the mechanisms behind the progression of these diseases. One area that has received a lot of attention is the possibility that the natural immune function can be detrimental to healthy growth patterns if over stimulated by mutations in the genetic information of individuals. A key series of proteins in the immune response is the Janus kinases (JAK), a series of four distinct but domain related kinases located in the cellular cytosole. These kinases form a distinct link between extracellular immune function ligands and a direct regulation of transcription of genetic information. However, a mutation of the JAK2 isoform has been associated with degenerative effects such as myeloproliferative neoplasms, thrombocythemia, polycythemia vera and psoriasis. [Read the Full Post]

RO4929097 – CHECKS NOTCH SIGNALING IN CANCERS

5854 | Mar 20 2012

RO4929097: A GAMMA SECRETASE INHIBITOR: Among well known proteases Gamma secretase is one which is made up of various subunits. This is present in the membrane hence is a protein in membrane which is also capable of cleaving certain transmembrane proteins therefore also known as the intramembrane protease. In case of Alzheimer’s disease amyloid plaques are formed in brain, these plaques are resulted due to the amyloid beta peptide and these peptides are produced due to the action of gamma secretase, this is one of the well known examples of this protease. Presently, we are focusing on the important role of gamma secretase in the Notch protein processing. In case of many cancers and tumors this Notch protein signaling is found to be abnormal, therefore the arresting of this pathway can be an authentic way to get rid of abnormal cell growth. In the light of this idea a novel RO4929097 gamma secretase inhibitor is discovered. The inhibitory effect of this inhibitor has been confirmed by various methods like western blotting. [Read the Full Post]

THIAZOVIVIN: THE PLURIPOTENCY INDUCER

4828 | Mar 20 2012

POTENTIAL OF EMBRYONIC STEM CELLS OF HUMAN (hESCs): The stem cells are not only known for their property of pluripotency in nature which means they have the potency to replicate in an indefinite manner but also famous for their capability of getting differentiate into all other kinds of cells and organelles from the three basic germinal layers named as ectoderm, mesoderm and endoderm. Embryonic stem cells of human (hESCs) have the ability of producing various numbers of types of cells in contrast to adult stem cells having the capability of producing only a limited cell types. Due to their pluripotency hESCs or human embryonic stem cells are of great interest and importance for the scientists and researchers as they are being used for detection and analysis of different genetic disorders of human in their research. The successful models of Human Embryonic Stem Cells are made for Fragile-X syndrome and Cystic fibrosis (CF) etc like genetic maladies and their will be many more in upcoming years. In olden years the usual practice was to use embryo to generate pluripotent stem cells which is brought down very significantly due to the process of insertion of various genes like Sox2, Oct4 and Klf4 etc into differentiated cells. These genes can enhance the pluripotency in differentiated cells and make them exactly like embryonic stem cells. A recent more advanced approach is to use molecules like Thiazovivin. [Read the Full Post]

TASOCITINIB: THE REVOLUTION IN ARTHRITIS MANAGEMENT

7248 | Mar 18 2012

Introduction: Inhibition of the JAK pathway The protein kinases are a super family of protein that govern the control of cellular growth, creation of vascular structure and many other processes the control the way in which cells and tissue regenerate. In is estimated that 30% of all cellular regulation is governed by protein kinases. Protein kinases are subdivided into 7 different classifications of which one is the tyrosine kinases. These kinases operate by phosphorylation of a tyrosine amino acid residue transferring a signal down a cascade of protein to regulate cellular processes. A further subdivision of the tyrosine kinases can be made into receptor based kinases and non receptor based kinases. The Janus kinases (JAK) are a sub family of the receptor based tyrosine kinases. Signals from the JAK regulate the cytokines, the GM-CSF family and the GP130 receptor family. JAK kinases exist in the 4 distinct isoforms with twinned phosphorylation domains. Inhibitors of the JAK kinases have been demonstrated to have a positive effect on cancerous cells both in vivo and in vitro. [Read the Full Post]

RUXOLITINIB: THE JACK FOR JAK INHIBITION

7571 | Mar 13 2012

Ruxolitinib: Inhibition of the Janus Kinases The janus kinases are a sub family of the protein kinases and are refer to as non receptor tyrosine kinases. Signals from the Janus kinases regulate several different types of proteins such as the cytokine receptor family (interferon), the GM-CSF family and the GP130 receptor family. The JAK kinases occur in four isoforms, with two matching phosphorylation domains, one for activity one for regulation. JAK2 in been shown to be mutated in several conditions including thrombocthemia and myeloprliferation disorders. In relation to haematological maliganacies the JAK2 mutation have been shown to essential for tumor growth and proliferation. Inhibiting the JAK2 kinase offers a potential mechanism for chemotherapeutic action. Ruxolitinib is a small, molecule inhibitor that has been established to inhibit the Janus kinases; early clinic work established that Ruxolitinib has sufficient anti-tumor activity to warrant further investigation. [Read the Full Post]

RO4929097 – TARGETING NOTCH SIGNALING IN CANCER

6681 | Mar 13 2012

RO4929097: INHIBIT GAMMA SECRETASE: Gamma secretase is famous protease consists of several subunits complex. This enzyme is also recognized as inter-membrane protease as it cuts trans-membrane proteins. The most eminent gamma secretase example is breakage of amyloid precursor, a protein to produce amyloid beta peptide which is involved in the formation of amyloid plaques in patient’s brain who suffer with Alzheimer’s disease. In the present situation though, we concentrate on the key role of gamma secretase in the Notch protein processing. It has been found as there is link between anomalous notch signaling and many cancers. Hence the idea of targeting those enzymes which are responsible for the processing of Notch protein became the reason of RO4929097 gamma secretase inhibitor discovery. The inhibiting Notch signaling by using RO4929097 GS inhibitor has been confirmed by protein estimation methods like Biuret method etc. [Read the Full Post]

RO4929097 – CONTROLLING NOTCH SIGNALING IN TUMORS

6759 | Mar 13 2012

Introduction: Gamma secretase Inhibition Gamma secretase is an internal protease enzyme that is a complex of a number of subunits. Its mode of action is to cleave proteins that lie within the membrane-spanning domain, these include the amyloid precursor protein (APP) and the Notch. The Notch signaling pathway processes four different Notch receptors (1, 2, 3 and 4) which span the cell membrane. Upon extracellular interaction with a substrate protein the internal domain is released. This section of the protein then induced a signaling cascade within the cell nucleus to alter gene expression. The function of the various NOTCH proteins is varied but in terms of cancer notch receptors have been demonstrated to be down regulated in basal cells carcinomas and cervical cancers. Notch 1 over-expression is associated with acute T cell leukemia and breast cancer, Notch 3 receptor is over-expressed in 20% of ovarian cancers [5-7] while overexpression of Notch 4 is evident in murine models of breast cancer. The field of research into NOTCH signaling is vast and beyond the scope of this document, simple put there existed evidence that inhibition of aberrant NOTCH over-expression would be an ideal target for chemotherapeutic activity. The development of inhibitors which would affect the action of NOTCH led to the targeting of the Gamma secretase enzyme. Developed by Roche the RO4929097 gamma secretase inhibitor represents a potent novel small molecule that is orally bioavailable. [Read the Full Post]

GSK3 and Alzheimer’s disease

6705 | Nov 24 2011

Glycogen synthase kinase 3 (GSK-3), as a serine/threonine protein kinase, can contribute to phosphorylating and thus inactivating glycogen synthase, and also been involved in the control of cellular response to damaged DNA. [Read the Full Post]

The hedgehog signaling pathway, as the target in cancer treatment

9142 | Nov 18 2011

The hedgehog(Hh) signaling pathway is one of the key regulators of animal development and is present in all bilaterians. The Hh family of proteins have since been recognized to involve in many fundamental processes in vertebrate embryonic development and play an important role in regulating cell fate, patterning, proliferation, survival and differentiation of many different regions. In the embryonic period, dysfunction in the Hh signaling pathway will lead to brain, facial and other midline defects such as holoprosencephaly, cyclopia, absent nose or cleft palate. [Read the Full Post]

Li, C., S. Chi, et al. (2011). "Hedgehog signaling in skin cancers." Cell Signal 23(8): 1235-1243.

3398 | Aug 20 2011

This article introduces the relationship between hedgehog signal transduction and cancer including Skin cancers linked to aberrant hedgehog pathway activity, models of Hh pathway activity in cancer and implications for therapy, and inhibitors and modulators of Hh pathway and their application in skin cancers. [Read the Full Post]

Yin, L., O. C. Velazquez, et al. (2010). "Notch signaling: emerging molecular targets for cancer therapy." Biochem Pharmacol 80(5): 690-701.

5737 | Jul 13 2011

This article is a review which give a presentation of Notch signal pathway and how the researchers target Notch signal pathway for a cancer therapy. [Read the Full Post]

Eldar-Finkelman, H., A. Licht-Murava, et al. (2010). "Substrate competitive GSK-3 inhibitors - strategy and implications." Biochim Biophys Acta 1804(3): 598-603.

4495 | Jul 11 2011

A short article introduces the substrates and inhibitors of GSK-3 and the relationship between substrates of GSK-3 and GSK-3. [Read the Full Post]

Narumiya, S., M. Tanji, et al. (2009). "Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion." Cancer Metastasis Rev 28(1-2): 65-76.

5726 | Jun 7 2011

This review summaries the Rho signaling in transformation, metastasis and invasion. It explains the relationship between Rho signaling and tumor cells, and it gives the perspectives in this review. [Read the Full Post]

Jacob, L. and L. Lum (2007). "Hedgehog signaling pathway." Sci STKE 2007(407): cm6.

3121 | May 12 2011

A brief introduction of hedgehog signal transduction with good hedgehog signal transduction map. [Read the Full Post]

Yardy, G. W. and S. F. Brewster (2005). "Wnt signalling and prostate cancer." Prostate Cancer Prostatic Dis 8(2): 119-126.

4854 | Apr 8 2011

This article introduce the wnt pathway and the relationship between wnt and cancer. It really give athe detail information of wnt signal pathway. [Read the Full Post]

Doble, B. W. and J. R. Woodgett (2003). "GSK-3: tricks of the trade for a multi-tasking kinase." J Cell Sci 116(Pt 7): 1175-1186.

4323 | Mar 20 2011

This article introduces the insights of GSK-3 phosphorylation from crystal structures. It also introduces the role of GSK-3 in human disease, the role of GSK-3 in the Hedgehog pathway, the role of GSK-3 in the Wnt/beta-catenin pathway, GSK-3-binding proteins, GSK-3 substrates, and small molecule inhibitors of GSK-3. [Read the Full Post]

Riento, K. and A. J. Ridley (2003). "Rocks: multifunctional kinases in cell behaviour." Nat Rev Mol Cell Biol 4(6): 446-456.

4944 | Mar 3 2011

This article introduces regulation of ROCK activity, ROCK function and ROCK inhibitors. This review concludes knowledge of ROCK in different ways. [Read the Full Post]