Blog of Signaling Pathways

Circulating small extracellular vesicles promote proliferation and migration of vascular smooth muscle cells via AXL and MerTK activation

0 views | Sep 10 2023

This study demonstrates that circulating small extracellular vesicles (csEVs) enhance the proliferation and migration of vascular smooth muscle cells (VSMCs) via phosphatidylserine (PS) and activate AXL and MerTK signaling pathways, highlighting their crucial role in neointima formation and suggesting the potential of dual AXL/MerTK inhibitors as a therapeutic approach for vascular diseases. [Read the Full Post]

Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia

32 views | Sep 10 2023

This study utilizes automated chromatin profiling techniques to map fusion-specific targets of KMT2A oncofusion proteins, revealing aberrant chromatin regulation and potential therapeutic vulnerabilities in acute myeloid and lymphoid leukemias. [Read the Full Post]

Promotion of Knee Cartilage Degradation by IκB Kinase ε in the Pathogenesis of Osteoarthritis in Human and Murine Models

45 views | Sep 10 2023

The study demonstrates that IKKε regulates cartilage degradation in osteoarthritis through NF-κB signaling and suggests that IKKε inhibition, exemplified by BAY-985, may serve as an effective modulatory treatment for the disease. [Read the Full Post]

Phloretin Improves Ultrafiltration and Reduces Glucose Absorption during Peritoneal Dialysis in Rats

27 views | Sep 10 2023

The study found that blocking facilitative glucose channels with phloretin reduced glucose absorption and improved ultrafiltration efficiency in peritoneal dialysis, suggesting it as a promising approach for therapeutic interventions in this context. [Read the Full Post]

Phase II drugs under clinical investigation for the treatment of chronic constipation

110 views | Sep 10 2023

New investigational drugs for the treatment of chronic constipation show promise in terms of improved effectiveness and tolerability, but further clinical trials with larger sample sizes and longer durations are needed to establish their efficacy and safety. [Read the Full Post]

Start Selective and Rigidify: The Discovery Path toward a Next Generation of EGFR Tyrosine Kinase Inhibitors

54 views | Sep 09 2023

BI-4020, a noncovalent, wild-type EGFR sparing, macrocyclic TKI, demonstrates potent inhibition of EGFR variants including T790M and C797S, and induces tumor regressions in a cross-resistant EGFRdel19 T790M C797S xenograft model. [Read the Full Post]

Establishment and characterization of Yellow River carp (Cyprinus carpio haematopterus) muscle cell line and its application to fish virology and immunology

60 views | Sep 09 2023

This study presents the establishment of a novel Yellow River carp muscle cell line (CCM) and explores its immune response strategies to lipopolysaccharide (LPS) and poly (I:C), providing a valuable tool for fish immunology research. [Read the Full Post]

Efficient and Stable β-CsPbI3 Solar Cells through Solvent Engineering with Methylamine Acetate Ionic Liquid

60 views | Sep 09 2023

The utilization of MAAc solvent and the incorporation of strong C═O···Pb coordination enabled the controllable growth of β-CsPbI3 perovskite thin films with a compact morphology and facilitated the achievement of efficient and stable perovskite solar cells (PSCs) with an efficiency of 18.9% and improved stability even in humid environments. [Read the Full Post]

Dual inhibition of EZH1/2 induces cell cycle arrest of B cell acute lymphoblastic leukemia cells through upregulation of CDKN1C and TP53INP1

93 views | Sep 09 2023

The study demonstrates that the EZH1/2 dual inhibitor DS-3201 (valemetostat) shows significant antitumor effects against B cell acute lymphoblastic leukemia (B-ALL) by inhibiting cell growth, inducing cell cycle arrest and apoptosis, and upregulating CDKN1C and TP53INP1 expression, offering a potential treatment option for B-ALL. [Read the Full Post]

Activation of the integrated stress response (ISR) pathways in response to Ref-1 inhibition in human pancreatic cancer and its tumor microenvironment

37 views | Sep 09 2023

Inhibition of Ref-1 redox signaling and activation of the integrated stress response (ISR) pathway through eIF2 phosphorylation could represent a promising therapeutic approach for treating pancreatic ductal adenocarcinoma (PDAC). [Read the Full Post]

Degradation of MYC by the mutant p53 reactivator drug, COTI-2 in breast cancer cells

62 views | Sep 08 2023

The study demonstrated that the mutant p53 reactivating drug COTI-2 effectively degraded MYC protein and showed synergistic growth inhibition when combined with an MYC inhibitor, suggesting its potential as a broad-spectrum anticancer therapy. [Read the Full Post]

A randomized trial of eribulin monotherapy versus eribulin plus anlotinib in patients with locally recurrent or metastatic breast cancer

108 views | Sep 08 2023

The combination of eribulin and anlotinib demonstrated improved progression-free survival and disease control rates compared to eribulin monotherapy in patients with HER2-negative locally recurrent or metastatic breast cancer, suggesting it as a potential alternative treatment option. [Read the Full Post]

Targeting of SOS1: from SOS1 Activators to Proteolysis Targeting Chimeras

0 views | Sep 08 2023

Research has led to the development of targeted therapies, including KRAS G12C-directed drugs and SOS1 inhibitors, with potential for treating specific mutations in lung, pancreatic, and colon cancers. [Read the Full Post]

UHRF1/UBE2L6/UBR4-mediated ubiquitination regulates EZH2 abundance and thereby melanocytic differentiation phenotypes in melanoma

15 views | Sep 08 2023

The study identified EZH2 as a master regulator of cellular heterogeneity in melanoma, specifically in relation to melanin pigment content, and proposed targeting the UHRF1/UBE2L6/UBR4-mediated regulation of EZH2 as a potential strategy for modulating its activity in melanoma cells. [Read the Full Post]

Structural Mass Spectrometry Probes the Inhibitor-Induced Allosteric Activation of CDK12/CDK13-Cyclin K Dissociation

68 views | Sep 07 2023

The integration of lysine reactivity profiling (LRP) and native MS (nMS) enables the systematic investigation of dynamic molecular interactions and overall protein assembly in CDK12/CDK13-CycK complexes, providing valuable insights for the rational design of effective kinase inhibitors. [Read the Full Post]

[18F]ONO-8430506: A novel radioligand for PET imaging of autotaxin (ATX)

11 views | Sep 07 2023

The novel radioligand [18F]ONO-8430506 ([18F]8) showed promising inhibitory potency against ATX but exhibited relatively low tumor uptake and retention in PET imaging studies. [Read the Full Post]

Ziritaxestat, a Novel Autotaxin Inhibitor, and Lung Function in Idiopathic Pulmonary Fibrosis: The ISABELA 1 and 2 Randomized Clinical Trials

38 views | Sep 07 2023

The phase 3 clinical trials of ziritaxestat, an autotaxin inhibitor, showed no improvement in clinical outcomes compared to placebo in patients with idiopathic pulmonary fibrosis (IPF), regardless of whether they were receiving standard of care treatment or not. [Read the Full Post]

Integrating knowledge of protein sequence with protein function for the prediction and validation of new MALT1 substrates

133 views | Sep 07 2023

The bioinformatics-led substrate discovery workflow, GO-2-Substrates, successfully identified seven new MALT1 substrates, including TANK, TAB3, CASP10, ZC3H12D, ZC3H12B, CILK1, and ILDR2, expanding the known repertoire and providing valuable insights into the function of MALT1. [Read the Full Post]

Treg-targeted efficient-inducible platform for collagen-induced arthritis treatment

100 views | Sep 07 2023

The study successfully developed a chitosan-stabilized nanoparticle drug delivery system (NDDS) capable of efficiently inducing regulatory T cells (Tregs), which showed promising results in alleviating the severity and progression of rheumatoid arthritis (RA) by restoring the equilibrium of Treg/Th17 cells. [Read the Full Post]

RUNX1 isoform disequilibrium promotes the development of trisomy 21-associated myeloid leukemia

41 views | Sep 07 2023

The study proposes that an imbalance of RUNX1 isoforms, particularly elevated expression of RUNX1A, in combination with the Gata1s mutation, contributes to the development of myeloid leukemia associated with Down syndrome (ML-DS), and restoring the equilibrium between RUNX1A and RUNX1C holds potential for targeted therapies. [Read the Full Post]