J Pharm Biomed Anal. 2026 Mar 29;276:117486. doi: 10.1016/j.jpba.2026.117486. Online ahead of print.

ABSTRACT

Patients with polycystic ovary syndrome (PCOS) are at an elevated risk of depression, yet the underlying mechanisms remain elusive. Emerging evidence implicates the gut-brain axis and systemic lipid homeostasis alterations as potential key contributors. We profiled untargeted plasma lipidomes of PCOS patients with and without comorbid depression (PCOS-DP) and integrated these data with our prior gut microbial and host transcriptomic datasets to construct multi-omics interaction networks. The causal role of the candidate gut microbial was preliminary explored in a germ-free PCOS mouse model using fecal microbiota transplantation, followed by behavioral phenotyping and ELISA-based protein quantification. We identified a distinct plasma lipidomic signature differentiating PCOS-DP from PCOS alone, characterized primarily by the downregulation of 26 lipid species. Most of these altered lipids were triacylglycerols (TAGs) enriched with FA18:1 and FA18:2, whose levels correlated with coagulation dysfunction. Multi-omics network analysis revealed significant interconnections between depression-associated gut microbiota (including Bacteroides eggerthii), specific altered lipids such as TAG (60:12/FA22:6), and host genes involved in inflammation (e.g., IL22, NLRP7), metabolism, and neural processes. Animal validation demonstrated that B. eggerthii colonization in PCOS mice specifically exacerbated anhedonia and hyperlocomotion, alongside modulating plasma IL-22 expression, suggesting its context-dependent neurobehavioral effect role. This study delineates a TAG-downregulated lipid signature with diagnostic potential and reveals a novel "gut microbiota-lipid-host gene" interaction network underpinning PCOS-DP, with B. eggerthii as a key microbial modulator of neurobehavioral phenotypes in the context of PCOS. These findings provide new pathophysiological insights and highlights potential diagnostic biomarkers for PCOS-DP.

PMID:41924769 | DOI:10.1016/j.jpba.2026.117486

Tissue Cell. 2026 Mar 10;101:103409. doi: 10.1016/j.tice.2026.103409. Online ahead of print.

ABSTRACT

Gastric cancer (GC) remains a major global health burden, with high incidence and mortality rates, particularly in East Asia, driven by factors such as Helicobacter pylori infection, dietary risks, and genetic predispositions. Conventional treatments like surgery and chemotherapy are limited by resistance, toxicity, and poor outcomes in advanced stages. The PI3K/Akt/mTOR and MAPK signaling pathways are central to GC pathogenesis, promoting proliferation, survival, metabolic reprogramming, epithelial-mesenchymal transition (EMT), and metastasis through aberrations like PIK3CA mutations, PTEN loss, and KRAS alterations. These pathways exhibit extensive crosstalk, contributing to therapeutic resistance. This review explores the regulatory effects of Traditional Chinese Medicine (TCM) on these pathways in GC, grounded in TCM principles such as Qi deficiency, Damp-Heat, and disharmony of the Spleen and Stomach. Single herbal monomers (e.g., curcumin, berberine, resveratrol) inhibit PI3K/Akt/mTOR by upregulating PTEN and suppressing mTOR, inducing autophagy and apoptosis. Classical herbs like Huangqin and Huanglian modulate Akt and ERK phosphorylation, while compound formulas (e.g., Banxia Xiexin Decoction, Sijunzi Decoction) synergistically target both pathways, reversing EMT and chemoresistance. TCM addresses crosstalk by disrupting feedback loops and reducing inflammation, enhancing efficacy in combination with Western therapies like chemotherapy and immunotherapy. Network pharmacology and multi-omics analyses reveal TCM's multitarget mechanisms, aligning with ZHENG-based personalization. Challenges include research variability, standardization issues, and incomplete mechanistic validation. Future directions emphasize high-quality trials, omics integration, and precision TCM for clinical translation. TCM offers low-toxicity, holistic options for integrative GC management, potentially improving survival and quality of life.

PMID:41825157 | DOI:10.1016/j.tice.2026.103409