ACTA2 (Actin Alpha 2 Smooth Muscle)

In conclusion, stromal transgelin expression in colon cancer strongly correlated with distant metastasis and served as a prognostic factor for colon cancer. Mechanistically, transgelin in cancer-associated fibroblasts promotes tumor growth by regulating stromal contractility, suggesting transgelin as a potential therapeutic target.

In parallel, circSMAD4 formed a specific ribonucleoprotein complex with the m6A reader IGF2BP2, facilitating IGF2BP2 association with COL4A1, ACTA2, and SPI1 transcripts and enhancing their m6A-dependent stability. Together, these dual branches converge on a matrix-remodeling output, positioning circSMAD4 as a post-transcriptional hub that reinforces protumor TAM programs in LUAD and a potential target for microenvironment-directed therapy.

Finally, we demonstrate that multiscale spatial analysis provides a quantitative readout of stromal-immune-epithelial remodeling following therapy. These findings establish a simplified, translationally relevant CAF framework and highlight spatially resolved stromal dynamics as measurable indicators of therapeutic response in CRC.

Clinically, higher CCL21 expression, elevated CCL21+ CAF signature scores, and stronger CCL21-CCR7 signatures in B cells were associated with favourable outcomes. Together, these data suggest that CCL21+ CAFs or CCL21 are potential prognostic biomarkers for risk stratification and immune microenvironment profiling and highlight the CCL21-CCR7 axis as a candidate pathway for therapeutic modulation of TLS maturity in PSCC.

In parallel, the expression of apoptosis-related genes was altered, as evidenced by the upregulation of the B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) and Caspase-3 and the downregulation of Bcl-2. Overall, these findings indicate that Hes enhances DOX efficacy by simultaneously engaging apoptotic and migration-associated molecular processes, supporting its potential role as a preclinical chemosensitizing agent that warrants further investigation in advanced experimental models.

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.