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Related Articles from SNS

O-GlcNAc transferase regulates H2O2 production via p38 MAPK

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by augmented transforming growth factor-{beta} (TGF-{beta}) signaling leading to excessive extracellular matrix (ECM) deposition. The fibroblast-to-myofibroblast-transition (FMT) and metabolic reprogramming of lung fibroblasts (HLFs) are essential to IPF pathogenesis, yet the connection between nutrient metabolism and fibrogenesis remains poorly defined. The O-linked N-acetylglucosamine (O-GlcNAc)...

bioRxiv 10d ago

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer

Abstract BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse1,2,3.

Nature 17h ago

p38 dependent IL-33 responses define a conserved inflammatory programme in mast cells

Interleukin-33 (IL-33) is a key cytokine in mast cell mediated immunity, promoting inflammatory cytokine production without inducing degranulation. Here, we compared IL-33 induced proteomic responses across three mast cell culture systems, Foetal Liver derived Mast Cells (FLMCs), Bone Marrow derived Mast Cells (BMMCs), and Peritoneal Mast Cells (PMCs), using quantitative data-independent acquisition mass spectrometry. Although baseline proteomes were largely conserved across all mast cell...

bioRxiv 9d ago

Radiosensitization of Glioblastoma by the K-ras Inhibitor RMC-6236

Purpose: Glioblastoma (GBM) is characterized by poor clinical outcomes and marked resistance to radiotherapy. Because effective radiosensitizing strategies for GBM remain limited, we investigated whether inhibition of KRAS/RAS signaling could enhance radiation response in GBM. In particular, we evaluated the radiosensitizing potential of RMC-6236, an RAS(ON) multiselective inhibitor that suppresses active RAS signaling across multiple RAS-dependent states.

bioRxiv 8d ago

A prognostic human brain network for diffuse midline glioma

Abstract Diffuse midline gliomas (DMGs) are near-universally lethal tumours of the childhood central nervous system1,2. In animal models, DMGs form brain-wide integrated networks through neuron-to-glioma synapses3,4,5,6 and glioma-to-glioma gap junctional coupling3. This extensive connectivity robustly promotes the growth and invasion of DMG3,4,5,6,7,8,9 and other glial malignancies10,11,12 through paracrine mechanisms and direct neuron-to-glioma synapses.

Nature 17h ago

Salivary microRNA Profiling of Long COVID Subjects Reveals Host-Encoded Regulators of Inflammation and Viral Persistence

Periodontal disease (PD) and SARS-CoV-2 infection converge upon shared immunoinflammatory axes, yet the molecular mechanisms underpinning their interplay remain insufficiently characterized. Herein, we delineate a comprehensive salivary microRNA (miRNA) repertoire from convalescent individuals with prior SARS-CoV-2 infection sampled 3-6 months post-diagnosis who fulfilled criteria for post-acute sequelae of COVID-19, yielding novel insights into the post-viral oral milieu. Salivary miRNA...

bioRxiv 2d ago

Genotype and methylation interact to reconfigure transcriptional regulation in colorectal cancer

Background Transcriptional regulation is shaped by both genomic variants and the environment. Yet, how the regulatory effects of genomic variants are reconfigured by dynamic epigenomic changes during tumorigenesis remains incompletely understood. Methods We investigated methylation context-dependent links between genotype and gene expression in colorectal cancer (CRC) using paired tumor and normal-adjacent tissue (NAT) from 80 patients, thereby controlling for germline genomic background.

bioRxiv 11d ago

From flat moss to forests and flowers: Protein discovery may explain how plants conquered land

From flat moss to forests and flowers: Protein discovery may explain how plants conquered land Sadie Harley Scientific Editor Robert Egan Associate Editor If plants had never learned to grow in multiple directions, our world would look very different. No trees, flowers, or other complex plants—and therefore no animals or humans. New research from the University of Copenhagen now suggests that a specific protein in moss may have been crucial for this key step in plant evolution—a step that...

Phys.org 8d ago