Nat Commun. 2026 Aug 29;17(1):10311. doi: 10.1038/s41467-026-77187-8.

ABSTRACT

Type 2 diabetes (T2D) subgroups defined by clinical variables differ in disease progression and treatment response. To uncover potential molecular drivers of this heterogeneity, we performed a multi-omics analysis of 826 drug-naïve T2D patients from two phase 3 trials of the insulin sensitizer chiglitazar. Here we show that severe insulin-resistant diabetes (SIRD) is characterized by distinct miRNA profiles (e.g., miR-122-5p) correlated with liver injury, and metabolic shifts in amino acids and primary bile acids. Mild obesity-related diabetes (MOD) showed the lowest level of phenylacetylglutamine, a metabolite known to promote cardiovascular disease. Severe insulin-deficient diabetes (SIDD) exhibited high pancreas-specific miR-7-5p, while mild age-related diabetes (MARD) presented the mildest abnormalities. Finally, integrating these multi-omics signatures into machine learning models enhanced prediction of insulin sensitizer efficacy over clinical data alone. Our findings define the distinct molecular signatures of T2D subgroups, facilitating the prediction of heterogeneous treatment responses and supporting personalized clinical management.

PMID:42805981 | PMC:PMC13620142 | DOI:10.1038/s41467-026-77187-8

Nat Commun. 2026 Mar 20;17(1):2655. doi: 10.1038/s41467-026-70193-w.

ABSTRACT

Pulmonary fibrosis represents a progressive interstitial lung disease marked by excessive extracellular matrix deposition and architectural distortion. Vascular endothelial cells critically contribute to fibrogenesis through paracrine secretion of pro-fibrotic mediators, yet their mechanobiological regulation remains elusive. Using integrated single-cell multi-omics profiling of human pulmonary fibrosis specimens and experimental fibrosis models induced by bleomycin or silica, we identify mechanosensitive Piezo1 upregulation in Endothelial cells as a hallmark of fibrotic progression. Endothelial-specific Piezo1 knockout significantly attenuates Bleomycin-induced fibrotic remodeling in male mice, establishing its pathogenic necessity. Mechanistically, PIEZO1 activation promotes pulmonary fibrosis development via CAPN2-mediated STAT3 phosphorylation, which may regulate the secretion of the pro-fibrotic molecule interleukin-33. These findings suggest that the endothelial PIEZO1-CAPN2-STAT3-IL33 axis is a potential therapeutic target for PF intervention.

PMID:41862476 | PMC:PMC13004862 | DOI:10.1038/s41467-026-70193-w

J Multidiscip Healthc. 2026 Mar 11;19:584071. doi: 10.2147/JMDH.S584071. eCollection 2026.

ABSTRACT

Non-small cell lung cancer (NSCLC) is one of the malignant tumors with the highest incidence and mortality rates. Zeqi Decoction has the functions of "promoting diuresis and reducing swelling, resolving phlegm and dispersing nodules", embodying the unique approach of traditional Chinese medicine in treating lung cancer by "strengthening the body's resistance and eliminating pathogenic factors". Modern research shows that Zeqi Decoction exerts anti-NSCLC effects through multiple pathways and targets. In terms of the material basis of its efficacy, its active ingredients (such as diterpene esters and flavonoids contained in Zeqi) have the ability to directly inhibit the proliferation, invasion and migration of tumor cells and induce apoptosis. In terms of the mechanism of action, basic experiments have revealed that Zeqi Decoction can down-regulate the S100A9/STAT3 signaling pathway, inhibit the immunosuppressive activity of myelium-derived suppressor cells (MDSCs), reshape the tumor microenvironment, thereby enhancing the cytotoxic function of CD8⁺T cells, and can also regulate the EGFR/PI3K/Akt pathway to affect PD-L1 expression. Intervene in tumor immune escape; In terms of clinical transformation, the combination of Zexi Decoction with chemotherapy and targeted therapy can improve patients' symptoms such as cough and pleural effusion, prolong progression-free survival, and alleviate the toxic and side effects of Western medical treatment. In addition, Zexi Decoction also shows potential value in reversing drug resistance such as gemcitabine. At present, there are still problems such as the lack of standardized protocols and unclear molecular mechanisms in the research. In the future, it is necessary to combine new technologies such as network pharmacology and multi-omics analysis to deepen the research on the pharmacological material basis, dose-effect relationship and evidence-based medicine of Zeqi Decoction, so as to promote the clinical application and transformation of the combination of traditional Chinese and Western medicine in the treatment of NSCLC.

PMID:41847115 | PMC:PMC12991379 | DOI:10.2147/JMDH.S584071