ACTA2 (Actin Alpha 2 Smooth Muscle)

Within the perivascular microenvironment, EV-mediated interactions between glioblastoma cells and astrocytes support the induction of stemness and the differentiation of GBM cells toward a pericyte-like phenotype, promoting perivascular niche formation and microvascular proliferation. The hydrogel-based co-culture model thus provides a simple and effective platform for dissecting tumor-stroma communication in the glioblastoma microenvironment.

What Are the Clinical Implications? Cancer therapies involving radiotherapy are associated with increased long-term risk of atherosclerotic cardiovascular disease.Our findings identify a potential cellular mechanism underlying this risk, in which irradiation-induced smooth muscle cell loss is not functionally compensated by endothelial-to-mesenchymal transition toward a SMC-like state.This dual lineage-tracing model provides a tool to evaluate how cancer therapies and other vascular stressors may alter arterial wall cell fate and indices of plaque stability in atherosclerosis and other vascular diseases.

In vivo, both PDGFRα antibody neutralization and pharmacological inhibition with imatinib significantly attenuated DBP-induced hepatic fibrosis and inflammatory gene expression, confirming PDGFRα's central role in DBP toxicity...Collectively, these findings identify PDGFRα as a mechanistic nexus linking DBP and PS-NPs exposure to hepatic fibrosis and highlight its potential as a therapeutic target for environmentally induced liver disease. The results further underscore the importance of co-exposure paradigms in evaluating the health risks of complex contaminant mixtures.

HHSY effectively treats liver fibrosis, likely by inhibiting HSC activation through the NOX4/ROS/NLRP3 pathway. This underscores HHSY's clinical relevance as a potential therapeutic option for liver fibrosis.

This study demonstrates a role of platinum-based chemotherapy on HSC activation in liver cancer. Selective targeting of PI3K p110α may provide a novel strategy to inhibit chemotherapy-induced HSC activation and improve treatment response.

Given the prognostic value of this spatial pattern, we additionally applied transfer learning based on an ImageNet pre-trained ResNet-50 model to develop a machine learning framework that can accurately recognize the macrophage-fibroblast-malignant cell co-infiltration pattern, called Gastric-Discovery. Potentially, Gastric-Discovery could be a tool for precise patient stratification and provides novel insights into the dynamic architecture of the TME.

Mechanistically, ACSP-I suppressed HSCs activation through inhibition of pyruvate kinase M2 (PKM2)-mediated glycolysis, which suppressed the expression of proliferation-related genes (MYC and CCND1), and inhibited histone lactylation to downregulate fibrotic genes (ACTA2 and COL1A1). These results identify ACSP-I as a PKM2 inhibitor for HF treatment and reveal new mechanisms of polysaccharide-mediated hepatoprotection.

This study highlights the critical role of CAFs and SMCs heterogeneity and their interactions within the GC TME (Tumor microenvironment). Targeting stromal pathways such as PDGF, TGF-β, and NF-κB signaling, immunomodulating CAFs, and disrupting SMC-derived vascular niches may improve therapeutic responses. Further experimental validation of ligand-receptor pairs and spatial determinants is warranted.

Drug prediction and molecular docking identified chlorendic acid, idarubicin, PHA-848,125, and tosedostat as potential activators of the OAS family due to their strong binding affinity. Conversely, GW842166, NSC 23,766, and metolazone showed high binding affinity for OASL and may inhibit its expression. In summary, The OAS gene family, associated with poor prognosis in gastric cancer, promotes tumour progression and represents a promising therapeutic target.

In TGFβ-stimulated LX2 hepatic stellate cells, it downregulates profibrotic signaling as assessed by the reduced expression of ACTA2, COL1A2, and FN1. These findings implicate compound 11 as a promising candidate for further preclinical development in the context of fibrotic disease.

By integrating a large amount of RNA sequencing data, we identified VCL, FLNA, TAGLN, ACTA2, COL6A2, and CALD1 as potential biomarkers for B-cell-associated bladder cancer, and experimentally verified that these markers were significantly lower in bladder cancer patients than in the normal group, and were effective in predicting the survival rate of the patients and the status of the tumor immune microenvironment. Using a combination of transcriptomic and experimental validation at single-cell and batch levels, this study provides insights into the key gene signatures of B cells from patients with bladder cancer and their roles in regulating the tumor immune microenvironment, providing new biomarkers and potential therapeutic targets for predicting patient' prognosis and immunotherapy response.

These findings reveal a previously unrecognized role for hepatic ADRA1B in restraining inflammatory responses in MASLD. Loss of Adra1b signaling promotes hepatic inflammation, highlighting a neuroimmune mechanism that may be targeted to prevent disease progression.