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ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

Blog of Signaling Pathways

Vaccines prevent reinduction of rheumatoid arthritis symptoms in collagen-induced arthritis mouse model

170 views | Jun 02 2023

This study suggests that immune metabolic modulators such as paKG(PFK15 + bc2) microparticles may be a promising alternative or complementary treatment option for RA and paves the way for the development of flare-up mouse models and antigen-specific drug treatments. [Read the Full Post]

Dual mechanism: Epigenetic inhibitor apabetalone reduces SARS-CoV-2 Delta and Omicron variant spike binding and attenuates SARS-CoV-2 RNA induced inflammation

30 views | Jun 02 2023

The passage discusses the potential use of apabetalone, an inhibitor of epigenetic regulators, for the treatment of COVID-19 and post-COVID syndrome by reducing ACE2 expression and countering pro-inflammatory factors regardless of the SARS-CoV-2 variant. [Read the Full Post]

Epigenetics in Obesity and Diabetes Mellitus: New Insights

48 views | Jun 02 2023

Obesity-related diseases such as type 2 diabetes are associated with epigenetic modifications that can lead to stable changes in gene expression, and targeting these modifications with drugs like apabetalone holds promise as a potential treatment strategy. [Read the Full Post]

Discovery of Potent and Wild-Type-Sparing Fourth-Generation EGFR Inhibitors for Treatment of Osimertinib-Resistance NSCLC

127 views | Jun 02 2023

The development of Osimertinib derivatives as fourth-generation inhibitors for the treatment of Osimertinib-resistant NSCLC, particularly the top candidate D51, shows promising selectivity and antitumor activity with favorable in vivo druggability. [Read the Full Post]

PARP1 Activation Induces HMGB1 Secretion Promoting Intestinal Inflammation in Mice and Human Intestinal Organoids

67 views | Jun 02 2023

PARP1 promotes HMGB1 secretion in intestinal inflammation, and inhibiting PARP1 could be a novel approach to manage inflammatory bowel diseases. [Read the Full Post]

Blocking STAT3/5 through direct or upstream kinase targeting in leukemic cutaneous T-cell lymphoma

93 views | Jun 01 2023

The study found that copy number gains of loci containing the STAT3/5 oncogenes are present in 74% of L-CTCL cases and identified the STAT3/5 and PAK kinase interaction as a potential therapeutic target for L-CTCL. [Read the Full Post]

Crosstalk between activating transcription factor 6 and the inositol-requiring enzyme 1-X-box binding protein 1 pathway in oxygen-glucose deprivation/reoxygenation-injured HT22 cells

51 views | Jun 01 2023

The study investigated the crosstalk between the ATF6 and IRE1-XBP1 pathways in OGD/R-injured HT22 cells and found that activation of ATF6 inhibited the mRNA expression of XBP1s and XBP1u without affecting their downstream transcriptional response, while inhibition of IRE1 had no significant effect on the examined parameters. [Read the Full Post]

Loss of deubiquitylase USP2 triggers development of glioblastoma via TGF-β signaling

91 views | Jun 01 2023

This study suggests that USP2 is a major regulator of the TGF-β signaling pathway in glioblastoma, and its loss leads to poor prognosis in patients, while DNMT3A inhibitor SGI-1027 could be a potential treatment by inducing USP2 expression and suppressing TGF-β signaling. [Read the Full Post]

Dieting reverses histone methylation and hypothalamic AgRP regulation in obese rats

80 views | Jun 01 2023

The study suggests that KDM4D, a specific demethylase of residue H3K9, plays a key role in modulating the expression of AgRP, a key neuropeptide that regulates hunger response, and may offer a target to develop new treatments for obesity. [Read the Full Post]

Targeting endoplasmic reticulum associated degradation pathway combined with radiotherapy enhances the immunogenicity of esophageal cancer cells

43 views | Jun 01 2023

The study found that inhibiting ERAD pathways combined with moderate dose radiation therapy can enhance the immunogenicity of esophageal cancer cells, leading to an improved antitumor immune response and favorable clinical outcomes. [Read the Full Post]

Pharmacologic inhibition of PARP5, but not that of PARP1 or 2, promotes cytokine production and osteoclastogenesis through different pathways

100 views | May 31 2023

The study shows that pharmacologic inhibition of PARP5 unexpectedly induces adverse autoinflammatory side effects through activation of innate immunity, unlike inhibition of other PARPs. [Read the Full Post]

Differential requirement of Hippo cascade during CTNNB1 or AXIN1 mutation-driven hepatocarcinogenesis

118 views | May 31 2023

The study shows that targeting YAP/TAZ is an effective treatment against hepatocellular carcinoma (HCC) with loss-of-function mutations of AXIN1. [Read the Full Post]

Synergistic apoptotic effect of miR-183-5p and Polo-Like kinase 1 inhibitor NMS-P937 in breast cancer cells

60 views | May 31 2023

This research study explores the role of miRNAs in breast cancer and their impact on breast cancer cells' response to PLK1 inhibition, with miR-183-5p targeting the PLK1 gene and enhancing the effectiveness of NMS-P937 in inducing apoptosis. [Read the Full Post]

UPP1 Promotes Lung Adenocarcinoma Progression through Epigenetic Regulation of Glycolysis

55 views | May 31 2023

This study characterized the function and underlying mechanisms of Uridine phosphorylase 1 (UPP1) in mediating the progression of Lung Adenocarcinoma (LUAD) cells, confirming it as a novel oncogene and a potential therapeutic target for LUAD. [Read the Full Post]

Right Ventricular Dysfunction and Exercise Impairment in Patients with Heart Failure, Insulin Resistance, and Diabetes Mellitus: Insights from the T.O.S.CA. Registry (Cardiovascular Diabetology 2022)

73 views | May 31 2023

The study findings suggest that insulin resistance and type 2 diabetes mellitus have a negative impact on right ventricular function, exercise tolerance, and cardiovascular outcomes, highlighting the need for early detection and management of these conditions. [Read the Full Post]

Four-Component Strain-Release-Driven Synthesis of Functionalized Azetidines

94 views | May 30 2023

This passage describes a successful and rapid multicomponent [1,2]-Brook rearrangement/strain-release-driven anion relay sequence for the modular synthesis of substituted azetidines, which was demonstrated through the 4-step synthesis of the EP2 receptor antagonist PF-04418948. [Read the Full Post]

Examining anti-inflammatory therapies in the prevention of cardiovascular events: protocol for a systematic review and network meta-analysis of randomised controlled trials

71 views | May 30 2023

The proposed methodology for the systematic review appears appropriate for addressing the research question, with a comprehensive search strategy, independent review, network meta-analysis, and quality assessment tools. [Read the Full Post]

In vitro target validation and in vivo efficacy of p38 MAP kinase inhibition in established chronic collagen-induced arthritis model: a pre-clinical study

128 views | May 30 2023

The study found that p38 MAPK inhibitors, GW856553X and GSK678361, effectively suppressed murine collagen-induced arthritis, indicating potential therapeutic value for the treatment of RA. [Read the Full Post]

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

57 views | 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]

G9a/GLP Targeting Ameliorates Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

71 views | May 30 2023

This study suggests that inhibiting the histone methyltransferase G9a and its partner protein GLP may be a new therapeutic approach in pulmonary arterial hypertension. [Read the Full Post]