Moh’d Khushman, MD, discusses the rationale for investigating INCA33890 plus FOLFOX/bevacizumab in the phase 3 setting in patients with MSS/pMMR mCRC.

Purpose This study aimed to evaluate the protective effects of Dioscin in an age-related macular degeneration (AMD) -like model and to explore its potential therapeutic mechanisms. Methods The therapeutic potential of Dioscin for AMD was investigated using D-galactose-induced senescence models in ARPE-19 cells (an in vitro preliminary screening model) and C57BL/6J mice using RT-qPCR, western blotting, immunofluorescence, and SA-β-gal staining. Bioinformatic analysis and molecular docking identified TGF-β2 as a computationally predicted potential target of Dioscin in AMD. Key mechanisms involving TGF-β2 and the PI3K/Akt/β-catenin signaling pathway were assessed in vitro using RT-qPCR, western blotting. Results In D-galactose-induced senescence models, Dioscin significantly alleviated RPE senescence and EMT. Single-cell transcriptome analysis revealed that TGF-β2 is highly expressed in choroidal vascular endothelial cells of AMD patients. Mechanistically, computational predictions (molecular docking and dynamics simulations) identified TGF-β2 as a computationally predicted potential target of Dioscin, and experimental data showed that Dioscin suppressed D-galactose-induced activation of the TGF-β2/PI3K/Akt/β-catenin pathway in RPE cells, suggesting a potential paracrine regulatory mechanism. Conclusion Dioscin alleviates RPE senescence and EMT through suppression of the TGF-β2/PI3K/Akt/β-catenin pathway. Single-cell transcriptomics reveals that TGF-β2 is specifically upregulated in choroidal vascular endothelial cells in AMD, suggesting a paracrine mechanism linking vascular pathology to RPE dysfunction. These findings suggest that Dioscin may have potential value in mitigating RPE senescence and EMT in an AMD‑like model, although further validation in more clinically relevant AMD models is required.

APOE4 causes a pericyte-to-myofibroblast transition that promotes cerebrovascular fibrosis and perivascular amyloid accumulation. TGF-β inhibition reverses this pathological remodeling and thus presen...

Using a broad panel of ciliopathy iPSC-retinal pigment epithelium (RPE) new approach models, Reichert et al. identified shared cellular endophenotypes across patients, including mesenchymal drift and loss of polarization. Mechanistic studies implicated mitochondrial dysfunction and aberrant TGF-β signaling in RPE pathology. Drug screening identified pioglitazone and galunisertib as candidate therapeutics.

APOE4 causes a pericyte-to-myofibroblast transition that promotes cerebrovascular fibrosis and perivascular amyloid accumulation. TGF-β inhibition reverses this pathological remodeling and thus presen...

Μπλοκάροντας την πρωτεΐνη TGF-β, οι επιστήμονες κατάφεραν να προστατεύσουν τα αιμοφόρα αγγεία του εγκεφάλου σε ποντίκια που έφεραν το γονίδιο APOE4.

Un estudio en Cell muestra cómo el gen APOE4 convierte en cicatriz los vasos cerebrales y cómo bloquear TGF-β lo revirtió en ratones.