Cyclophosphamide (CTX) is an anticancer medication that suppresses host immunity as well as adversely affects mucosal inflammation and gut microflora dysbiosis. The gut microflora is recognized as a substantial factor in host metabolism and immunological homeostasis. To improve immunity and inhibit cytotoxic and homeostatic imbalances triggered by CTX, it is essential to monitor immunoregulators. In this research, we assessed the impact of Octopus peptide hydrolysate (OPH) on immune modulation, intestinal integrity, and gut microbial composition in CTX-induced immune-deficient mice. The results revealed that OPH increased body weight, and immunological organ indices, and improved the histological changes in the colon, thymus, and spleen. The OPH stimulated the secretion of cytokines (IL-1β, IL-6, and TNF-α) and antibodies (IgM and IgA) while reducing the ratio of lipopolysaccharide (LPS) and diamine oxidase (DAO) in the serum. OPH further enhanced goblet cell and mucus production, upregulated the expression of gut tight-junction proteins (Occludin, Zonula Occludin-1, Mucin-2, and Claudin-1), and activated the TLR4/NF-κB cascade (p-IκBα, P65/p-p65). In addition, OPH treatment declined the Bacteroidetes/Firmicutes ratio, enhanced the relative ratio of Alistipes/Lachnospiraceae, and reversed the ecological equilibrium of the gut microflora. The findings revealed that OPH serves as a prebiotic to prevent CTX-mediated disruption in the intestinal barrier and boosts gut mucosal immunity by attenuating gut microflora imbalance, implying that OPH could be used as an immunological ingredient in nutritious foods to regulate the immune system and protect the gut from inflammatory diseases.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease driven by immune dysregulation, microbiota imbalance, and intestinal barrier dysfunction. Despite its global burden, effective therapies remain limited. This study explores the therapeutic potential of Agrocybe cylindracea polysaccharides (ACP) in a dextran sulfate sodium (DSS)-induced murine colitis model. High-performance liquid chromatography (HPLC)-characterized ACP was administered orally to BALB/c mice following colitis induction. ACP treatment significantly reduced Disease Activity Index (DAI) scores, preserved colon length, and restored intestinal barrier integrity by upregulating tight junction proteins. Mechanistically, ACP modulated immune homeostasis, suppressing pro-inflammatory cytokines (IL-17, IL-23, CRP) while enhancing anti-inflammatory mediators (IL-4, TGF-β). Furthermore, ACP inhibited hepatic TLR4/MyD88/NF-κB signaling, attenuated systemic inflammation, and reshaped gut microbiota composition by enriching beneficial taxa and reducing pathogenic Bacteroides. These findings demonstrate ACP multi-target efficacy in colitis, positioning it as a promising natural therapeutic for UC.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia, progressive β-cell dysfunction, and insulin resistance. While numerous chemically induced and transgenic rodent models exist, spontaneous models recapitulating natural type 2 diabetes mellitus (T2DM) progression remain scarce. Here, we characterize Myodes rufocanus as a novel spontaneous T2DM model through comprehensive assessments of 18-week-old male F6 voles, demonstrating hallmark diabetic features including weight gain, hyperphagia, polydipsia, hyperglycemia, insulin resistance, and dyslipidemia. Pancreatic transcriptomic profiling revealed pronounced COX14 (cytochrome c oxidase assembly factor 14) downregulation, as validated by qPCR and Western blotting in pancreatic tissue and MIN6 β-cells. MIN6 cells under chronic high-glucose conditions (30 mM) exhibited diminished mitochondrial membrane potential, impaired ATP biosynthesis, elevated reactive oxygen species, and attenuated glucose-stimulated insulin secretion, with consistent COX14 downregulation suggesting potential association with mitochondrial dysfunction. Additionally, suppressed Nrf2–HO-1 antioxidant signaling appeared to compound cellular injury, with intrinsic apoptotic pathway activation indicated by elevated Bax/Bcl-2 ratios and caspase-3 activity. These findings establish M. rufocanus as a valuable spontaneous T2DM model and implicate COX14 downregulation as a potential correlate of mitochondrial impairment and β-cell failure in diabetes pathogenesis.