Rubus parvifolius L. root has been used to treat chronic hepatitis in Chinese medicine practice for generations. However, the in vivo hepatoprotective mechanisms of the Rubus parvifolius L. root extract (RRE) have not been systematically investigated. We established a mouse model of chronic liver injury induced by CCl4 and evaluated the protective effect of RRE on chronic liver injury by measuring serum liver function indicators (ALT, AST), hepatic oxidative stress markers (MDA, SOD), and liver pathological changes. Oral administration of RRE can significantly alleviate liver injury in a dose-dependent manner. Molecular analyses showed that RRE up-regulated the mRNA and protein expression of HO-1, nuclear red cell 2-associated factor 2 (Nrf-2) and B-cell lymphoma-2 (Bcl-2), while down-regulating Bcl-2 associated X protein (Bax), caspase-3, NLRP3, interleukin17a (IL-17A) and transforming growth factor β1(TGF-β1). These findings suggest that RRE alleviates chronic liver injury, an effect that may be associated with up-regulation of Nrf-2 and HO-1, increased Bcl-2 with decreased Bax and Caspase-3, and reduced NLRP3, IL-17A, TGF-β1 expression. This study provides a scientific basis for the potential clinical application of RRE.
Residents living near smelters and abandoned metal mines may experience chronic heavy metal exposure through multiple environmental pathways. Proteomic profiling provides a promising approach for identifying early biological responses and candidate biomarkers. This study investigated heavy metal exposure and associated proteomic alterations among residents living near smelters and abandoned metal mines to identify candidate proteomic biomarkers of early biological responses to metal exposure. Adults aged ≥19 years were recruited between June 2021 and September 2023 from smelter areas (n=243), abandoned metal mine areas (n=142), and control areas (n=204). Lead, cadmium, mercury, and arsenic concentrations were measured in blood and urine samples, and serum proteomic profiling was performed using liquid chromatography–mass spectrometry (LC–MS). Differentially expressed proteins (DEPs) associated with metal exposure were identified using sparse partial least-squares discriminant analysis (sPLS-DA) and functional analyses. Blood lead and both blood and urinary cadmium concentrations were significantly higher in residents of smelter and abandoned metal mine areas than in controls (p < 0.05). Blood cadmium concentrations were highest in the smelter area, whereas urinary cadmium and total arsenic concentrations were highest in the abandoned metal mine area. Confounder-adjusted proteomic analysis identified 153 DEPs in the smelter group and 187 DEPs in the abandoned metal mine group compared with controls, of which 124 DEPs were shared between the two exposed groups. The shared DEPs were mainly associated with complement and coagulation cascades, immune-related responses, lipid metabolism, and extracellular matrix and cell-adhesion processes. Reduced fibronectin, paraoxonase 1, and serum amyloid P-component levels, together with elevated hemopexin and prolow-density lipoprotein receptor-related protein 1, suggested enhanced oxidative stress and biological defense responses. These findings demonstrate that heavy metal exposure alters immune, inflammatory, metabolic, and coagulation pathways at the proteomic level and identify candidate biomarkers for early detection of metal exposure.
Micro- and nanoplastics are associated with metabolic toxicity, but their effects on hepatic cholesterol homeostasis and potential mitigating interventions remain insufficiently characterized. To characterize hepatic responses to 50-nm PS-NPs and determine whether Sal B modulates these responses. In a 28-day oral exposure model, PS-NPs consistently increased hepatic cholesterol and produced focal lipid deposition, localized histological alterations, F4/80-positive macrophage enrichment, and increased ROS. These changes were accompanied by increased SREBF1, p62/SQSTM1, NF-κB, and COX2 abundance and reduced PPARA and other PPAR-related proteins. In a separate 14-day intervention model, Sal B reduced hepatic cholesterol and focal lipid deposition and modulated CD36-, SREBF1-, and PPAR-related proteins, although aminotransferases and representative inflammatory lipid mediators were not broadly restored. Docking predicted favorable interactions of Sal B with CD36 and COX2. In THP-1-derived macrophages, Sal B reduced PS-NP-induced CD36 elevation and increased JC-1 red fluorescence without a significant change in the red/green ratio. PS-NPs produced a cholesterol-centered hepatic metabolic phenotype, and Sal B selectively attenuated lipid-related and associated molecular responses rather than uniformly normalizing the broader biochemical profile.
Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants that accumulate in human tissues and may cause prolonged cellular and organ damage. Ferroptosis, an iron-dependent form of regulated cell death driven by phospholipid peroxidation, has emerged as a potential mechanism linking PFAS exposure to toxicity. This critical narrative mini-review synthesised original studies directly investigating PFAS-regulated ferroptosis, with emphasis on molecular pathways, affected organs, causal strength, independent replication, disease relevance, and implications for human health risk assessment. The final evidence set comprised 18 direct empirical studies. The liver had the most developed mechanistic evidence, but confidence in several detailed perfluorooctane sulfonatehepatocyte pathways was downgraded because multiple reports originated from one research network and lackedindependent replication. Reported mechanisms included glutathione depletion, glutathione peroxidase 4 dysfunction, acyl-CoA synthetase long-chain family member 4-dependent lipid remodelling, nuclear receptor coactivator 4-mediated ferritinophagy, mitochondrial calcium and iron overload, and inter-organelle iron transfer. Ferroptosis-related injury wasalso reported in renal tubular, endothelial, bladder epithelial, oral mucosal, neural, oocyte, and embryonic models.Evidence outside the liver was generally moderate, preliminary, or hypothesis-generating. Perfluorooctanoic acid-mediated suppression of ferroptosis in hepatocellular carcinoma cells further indicated that PFAS effects vary by cellularand disease context. Ferroptosis is a credible but context-dependent contributor to PFAS toxicity, but no detailed PFAS–ferroptosis pathway canyet be considered high certainty without stronger external replication. Future studies require verified internal PFAS doses,environmentally relevant mixtures, multiple ferroptosis criteria, orthogonal rescue experiments, organ-relevant models,explicit consideration of sex as a biological variable, and prospective human validation.
L-theanine, a unique non-protein amino acid derived from tea, exhibits potent antioxidant and muscle-protective activities, but the mechanism underlying its protection against oxidative stress-induced muscle damage remains unclear, and elucidating this mechanism may provide experimental evidence for alleviating muscle damage. To investigate whether L-theanine alleviates muscle oxidative damage by regulating the hypoxia-inducible factor-1α (HIF-1α)/glucocorticoid receptor α (GRα) signaling pathway. C2C12 myotubes were treated with diquat to induce oxidative damage, with or without L-theanine, and with or without the HIF-1α inhibitor 2-methoxyestradiol (2ME) or the GRα inhibitor mifepristone (RU486). Cell viability, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) and malondialdehyde (MDA) levels, antioxidant enzyme activities, cytoskeletal protein and antioxidant gene expression, as well as HIF-1α and GRα expression and their interaction were detected. L-theanine significantly alleviated diquat-induced oxidative damage in C2C12 myotubes, as indicated by restored cell viability, reduced LDH release, and decreased ROS and MDA levels, along with enhanced antioxidant enzyme activities and nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant gene expression. L-theanine also maintained cytoskeletal protein homeostasis by downregulating desmin and upregulating integrin β1 and calpain 1 expression. Mechanistically, L-theanine inhibited HIF-1α and GRα expression and suppressed their protein interaction. Pharmacological inhibition of HIF-1α (2ME) or GRα (RU486) recapitulated the protective effects of L-theanine on antioxidant capacity and cytoskeletal protein homeostasis, supporting the involvement of the HIF-1α/GRα pathway. L-theanine alleviates diquat-induced oxidative damage in C2C12 myotubes, an effect that is associated with inhibition of the HIF-1α/GRα signaling pathways, and accompanied by enhanced antioxidant capacity and maintaining cytoskeletal protein homeostasis.
