PURPOSE Currently, no universally effective treatment exists to stop or reverse the development of liver fibrosis. Saxagliptin (SAX), a dipeptidyl peptidase-4 (DPP-4) inhibitor, has demonstrated extra-glycemic benefits, including anti-inflammatory and anti-apoptotic properties, but its role in hepatic fibrogenesis has not been characterized. This study examined the protective potential and underlying mechanisms of saxagliptin against thioacetamide (TAA)-induced hepatic fibrogenesis in rats. METHODS Twenty-four male Wistar rats were randomly allocated to four groups: control, TAA-induced fibrosis, TAA + saxagliptin (5 mg/kg), and TAA + saxagliptin (10 mg/kg). Biochemical, molecular, and histopathological analyses were conducted to assess liver injury, lipid profile, oxidative stress, inflammatory and fibrotic markers, apoptosis, and key cytoprotective signaling pathways. RESULTS TAA induced significant liver injury, oxidative stress, inflammation, apoptosis, and fibrosis, together with suppression of SIRT1 and Nrf2/HO-1 pathways. Saxagliptin was associated with improvements in hepatotoxicity, dyslipidemia, oxidative-stress, inflammatory, apoptotic, and fibrosis-related parameters, together with increased SIRT1 and Nrf2/HO-1 protein levels. The higher dose generally produced greater numerical improvement across several endpoints. Histopathological and immunohistochemical analyses showed reduced fibrosis-related changes and α-SMA immunoreactivity, with the higher dose (10 mg/kg) associated with hepatic architecture and fibrosis scores approaching the control findings. CONCLUSION Saxagliptin was associated with attenuation of TAA-induced hepatic fibrosis and improvements in oxidative stress, inflammation, apoptosis, and fibrosis-related signaling. These findings are consistent with involvement of SIRT1- and Nrf2/HO-1-associated cytoprotective responses but do not establish pathway causality. Further mechanistic studies are required to determine whether these pathways are necessary for the observed effects.
Hyperbaric oxygen (HBO) therapy has shown potential to improve sperm quality and reproductive outcomes, but the mechanisms underlying its protective effects remain unclear. This study investigated whether HBO ameliorates cyclophosphamide (CYP)-induced spermatogenic impairmentand whether Rhoa/Rock signaling is involved. Male BALB/c mice were assigned to control, CYP, and CYP + HBO groups. CYP was administered intraperitoneally for five consecutive days, followed by HBO treatment at 2.5 ATA for 60 min/day, 5 days/week for 2 weeks. Sperm parameters, serum sex hormones, testicular histopathology, oxidative stress indices, and Rhoa/Rock-related proteins were assessed. Rhoa knockout (KO) mice were additionally used for mechanistic evaluation. Compared with CYP treatment alone, HBO treatment increased sperm count by 80.95% (P < 0.0001) and progressive motility by 160.96% (P < 0.0001), while decreasing the sperm abnormality rate by 38.88% (P < 0.0001). HBO also reduced testicular MDA levels by 40.90% (P < 0.0001) and increased SOD activity by 69.53% (P = 0.0005). These changes were accompanied by reduced Rhoa and Rock1 protein expression and increased Nrf2 and Ho-1 expression. In Rhoa KO mice, the beneficial effects of HBO on serum hormone levels, sperm parameters, testicular indices, oxidative stress markers, and Nrf2/Ho-1 expression were largely abolished. These findings indicate that HBO therapy alleviates CYP-induced testicular oxidative stress injury and spermatogenic impairment, with Rhoa/Rock signaling contributing to the protective response.
Microplastics (MPs) have emerged as pervasive environmental contaminants with increasing relevance to human health. Beyond their role as inert particulate pollutants, accumulating evidence suggests that MPs may act as biologically active modulators of the gastrointestinal ecosystem. The gut represents a major interface for MP exposure, where ingested particles interact with intestinal epithelial cells, mucus layers, immune components, and resident microbial communities. This review summarizes current evidence on MPs' capacity to alter gut microbiota composition, impair intestinal barrier integrity, disrupt microbial metabolite production, and promote inflammatory and metabolic disturbances.Experimental studies indicate that MP exposure may reduce microbial diversity, shift the abundance of key bacterial taxa, impair tight junction proteins, and increase intestinal permeability. These changes may facilitate the translocation of bacterial products such as lipopolysaccharide, thereby activating inflammatory pathways including TLR4/NF-κB signaling. In parallel, MP-associated dysbiosis may alter short-chain fatty acids, bile acid metabolism, and tryptophan-derived metabolites, suggesting plausible biological pathways relevant to insulin resistance, hepatic lipid dysregulation, cardiometabolic risk, and gut-brain axis disruption. However, most available evidence is derived from animal and in vitro models, and causal relationships in humans remain insufficiently established. Major limitations include heterogeneous exposure protocols, non-standardized particle characterization, limited human longitudinal data, and difficulty separating particle-specific effects from those of associated chemical contaminants.Future studies integrating environmentally realistic exposure models, standardized microbiome analyses, multi-omics approaches, and human cohort designs are needed. Overall, the gut microbiota may represent a critical biological interface through which MPs interact with host physiology; however, further evidence is required before definitive conclusions can be drawn regarding their role in human chronic disease susceptibility.
OBJECTIVE To observe the inhibition of resveratrol on coal dust-induced pulmonary fibrosis and explore the possible mechanism. METHODS A mouse model of pneumoconiosis was established by coal dust inhalation, and resveratrol was administered as treatment. Lung inflammation and fibrosis were observed using hematoxylin/eosin (HE) and Masson staining, and hydroxyproline content was measured by colorimetric assay. In vitro, lung epithelial cells were exposed with coal dust alone or in combination with resveratrol. Cell migration and invasion abilities were assessed using wound healing assay and Transwell assay. The key molecules of epithelial-mesenchymal transition (EMT) were detected by western blotting and ELISA. Additionally, the effects of resveratrol on proliferation and collagen production in TGF-β1-stimulated fibroblasts were examined using EDU, CCK-8, and western blotting. Results: The coal dust group showed marked inflammatory cell infiltration, collagen deposition, and elevated hydroxyproline levels in lung tissue, all of which were significantly improved in the resveratrol-treated group. In vitro, coal dust increased the migration rate, invasive ability, downregulated E-cadherin, and upregulated N-cadherin, vimentin, and Snail of lung epithelial cells, whereas these cellular changes were markedly attenuated in the resveratrol-treated group. Moreover, the levels of TGF-β1 and TNF-α were significantly lower in the resveratrol-treated group than in the coal dust group. In fibroblasts, the cell proliferation rate and collagen (COL-1, COL-3, α-SMA) were lower in the resveratrol-treated group than in the TGF-β1-stimulated group. CONCLUSION Resveratrol inhibited EMT in lung epithelial cells, reduced TGF-β1 and TNF-α release, suppressed fibroblast-to-myofibroblast transformation (FMT), and alleviated coal dust-induced pulmonary fibrosis.
