Zhongguo Zhong Yao Za Zhi. 2026 Aug;51(15):4401-4409. doi: 10.19540/j.cnki.cjcmm.20260421.801.

ABSTRACT

Based on the gut-liver axis, this study integrated multi-omics and network pharmacology strategies to explore the mechanism of Biejia-Ruangan Compound Tablets(BRC), a preferred Chinese patent medicine for anti-hepatic fibrosis, in alleviating alcoholic liver disease(ALD). The Lieber-DeCarli ethanol liquid diet was used to establish the ALD model, and the pharmacodynamic effects of BRC were evaluated. Non-targeted metabolomics and network pharmacology were employed to screen key metabolites and pathways, while multiple technical methods such as immunohistochemistry were used to verify key molecules in the gut-liver axis. The results showed that BRC significantly improved liver morphology and pathological damage in mice, reduced organ indices, and decreased serum levels of aspartate aminotransferase(AST) and alanine aminotransferase(ALT). BRC also alleviated hepatocellular steatosis, inflammatory infiltration, and fibrosis, and reduced the levels of reactive oxygen species(ROS) and partially restored superoxide dismutase(SOD) activity. Metabolomic analysis indicated that BRC could significantly reverse the disordered metabolic profiles of the intestine and liver, and increase the level of the differential metabolite prostaglandin E_2(PGE_2), which may be closely related to the adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway. Compared with the model group, BRC effectively upregulated the expression of prostaglandin G/H synthase-2(COX-2) in the small intestine, inhibited the levels of inflammatory factors such as lipopolysaccharide(LPS), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) in the liver, and promoted the expression of phosphorylated AMP-activated protein kinase catalytic subunit α2(p-AMPKα2), forkhead box protein O1(FOXO1), and peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α) in the liver, as well as the activity of cytoplasmic phosphoenolpyruvate carboxykinase 1(PCK1). In conclusion, BRC may alleviate ALD by alleviating hepatic inflammation, oxidative stress, and metabolic disorders through the gut-liver axis via the COX-2/AMPK/FOXO1/PGC-1α/PCK1 signaling pathway. This study provides a scientific basis and new insights for the clinical application of BRC and the prevention and treatment of ALD with TCM.

PMID:42693054 | DOI:10.19540/j.cnki.cjcmm.20260421.801

Immunity. 2026 Apr 8:S1074-7613(26)00075-0. doi: 10.1016/j.immuni.2026.02.005. Online ahead of print.

ABSTRACT

DNA mutations are a well-characterized source of neoepitopes in immunotherapy. Here, we examined the contribution of dysregulated RNA processing to neoantigen production. Leveraging multi-omics and checkpoint inhibitor (CPI) response data from >1,000 patients, we identified reduced activity of the nonsense-mediated mRNA decay (NMD) pathway kinase SMG1 as a predictor of improved CPI response. NMD inhibition through SMG1 targeting stabilized transcripts containing premature termination codons, most of which were of non-mutational origin. This reshaped the major histocompatibility complex class I (MHC class I)-bound immunopeptidome and increased neoantigen abundance to levels comparable to high mutation burden tumors. Functionally, NMD inhibition drove antigen-dependent T cell-mediated tumor cell killing in vitro, promoted activation of tissue-resident T cells in patient-derived models ex vivo, and improved CPI efficacy in vivo. Our findings establish NMD inhibition as a strategy to harness a previously inaccessible source of canonical and non-canonical neoantigens, with the potential to increase tumor immunogenicity across cancers.

PMID:41956098 | DOI:10.1016/j.immuni.2026.02.005

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