Various stresses derived from both internal and external oxidative environments lead to the excessive production of reactive oxygen species (ROS) causing progressive intracellular oxidative damage and ultimately cell death. The objective of this study was to evaluate the protective effects of Citrus junos Tanaka peel extract (CE) against oxidative-stress induced the apoptosis of lung cells and the associated mechanisms of action using in vitro and in vivo models. The protective effect of CE was evaluated in vitro in NCI-H460 human lung cells exposed to pro-oxidant H₂O₂. The preventive effect of CE (200 mg/kg/day, 10 days) against pulmonary injuries following acrolein inhalation (10 ppm for 12 h) was investigated using an in vivo mouse model. Herein, we demonstrated the inhibitory effect of CE against the oxidative stress-induced apoptosis of lung cells under a highly oxidative environment. The function of CE is linked with its ability to suppress ROS-dependent, p53-mediated apoptotic signaling. Furthermore, we evaluated the protective role of CE against apoptotic pulmonary injuries associated with the inhalation of acrolein, a ubiquitous and highly oxidizing environmental respiratory pollutant, through the attenuation of oxidative stress. The results indicated that CE exhibits a protective effect against the oxidative stress-induced apoptosis of lung cells in both in vitro and in vivo models.

Airborne particulate matter less than 10 µm in diameter (PM10) is recognized as a significant environmental risk factor for hemorrhagic stroke (HS), as evidenced by epidemiological studies that link PM10 with the heightened cerebrovascular mortality related to HS. Nonetheless, the molecular mechanisms underlying this association remain unknown. Cerebral aneurysm (CA), an etiological factor of HS, is characterized by a bulge resulting from the abnormal loss of the muscular layer of a cerebral artery, comprising brain vascular endothelial cell (BVEC) and vascular smooth muscle cell (VSMC). BVEC exhibiting an inflammatory phenotype is critical for VSMC death within the cerebrovasculature. Here, we elucidate a molecular mechanism by which PM10 augments necroptotic death of VSMC as a consequence of intercellular effects arising from FasL inflammatory cytokine, which is derived from BVEC. Notably, BVEC exposed to PM10 upregulates FasL through ATM-NF-κB signaling, in response to oxidative DNA damage. This genotoxic stress is attributed to pro-oxidant action of aluminum, the prevalent element in PM10. Furthermore, respiratory exposure to PM10 in mice precipitates early onset of CA development through necroptotic VSMC death in cerebral artery, by activating FasL expression in BVEC. In conclusion, this study provides molecular evidence establishing a direct association between PM10 pollution and an elevated risk of stroke, particularly HS.

Obesity, characterized by excessive fat accumulation, poses global health risks due to its association with metabolic diseases. Beyond conventional treatments, the gut microbiome has emerged as a promising therapeutic target. Given the critical role of microbiome alterations in obesity, modifying its composition through probiotics, prebiotics, or synbiotics offers a novel strategy for mitigating obesity and related conditions. In this study, we demonstrate the dose-dependent anti-obesity effects of a novel strain, Bifidobacterium longum subsp. longum HN001 (HN001), in a high-fat diet (HFD)-induced mouse model. Among the doses tested (100, 200, and 400 mg/kg), the 200 mg/kg dose showed the most pronounced effect, significantly reducing body weight gain, serum triglyceride (TG), and total cholesterol (TC) levels. These effects were associated with reductions in fat mass and adipocyte hypertrophy in white adipose tissue (WAT), suppression of lipogenesis, and enhanced energy expenditure through WAT browning and thermogenesis in brown adipose tissue (BAT). Microbiome analysis revealed that HN001 increased the abundance of beneficial, SCFA-producing microbes while reducing taxa linked to metabolic dysfunction. Importantly, HN001 restored serum short-chain fatty acid (SCFA) levels, and its lipid-lowering effect in adipocytes was attenuated by a GPR43 antagonist, supporting an SCFA–GPR43–mediated pathway that links microbiome modulation with reduced adipogenesis and enhanced thermogenesis. These findings suggest that HN001 may represent a promising therapeutic strategy for obesity via SCFA-driven modulation of host metabolism and gut microbiome composition.

Nuclear factor erythroid 2-related factor 2 (Nrf2) coordinates detoxification and antioxidant programs that protect the liver from chemical and metabolic stress. Nrf2 is restrained by Kelch-like ECH-associated protein 1 (Keap1), which can be removed through p62-mediated selective autophagy; however, nutritional cues that engage this pathway remain incompletely understood. This study provides evidence that betaine (trimethylglycine; BET) can regulate the Keap1-Nrf2 axis through modulation of Keap1. In biochemical and cellular assays, betaine was associated with methylation of Keap1 at Cys513 and Cys518 within the Kelch domain, which was linked to enhanced p62-dependent autophagic degradation of Keap1 and Nrf2 stabilization. In AML12 hepatocytes and in mice, betaine enhanced Nrf2 activity, induced canonical Nrf2 target genes, and increased cellular glutathione (GSH), consistent with improved GSH-dependent redox capacity. In an acetaminophen (AAP) overdose model, betaine attenuated hepatic injury, consistent with improved redox capacity under acute toxic stress. In an MCD diet-induced steatotic liver disease model, betaine was associated with reduced steatohepatitis-like histopathology, inflammatory signaling, and lipogenic markers. Finally, RNA-seq analysis of a large human metabolic dysfunction-associated steatotic liver disease (MASLD) cohort revealed Nrf2-related transcriptomic signatures associated with disease severity, providing correlative support for the disease relevance of this pathway. Collectively, these findings suggest that Keap1 cysteine methylation may represent a regulatory node linking betaine to p62-mediated autophagy, Nrf2 stabilization, and GSH homeostasis, while further studies are required to establish the causal and translational relevance of this mechanism in human liver disease.