Red rice bran extract (RRBE) has been reported to have the potential for in vitro metabolic modulation and anti-inflammatory properties. However, little is known about the molecular mechanisms of these potentials in adipose tissue. This study aimed to evaluate the in vivo anti-adipogenic, anti-hypertrophic, and anti-inflammatory activities of RRBE and its major bioactive compounds in mice. After six weeks of consuming either a low-fat diet or a high-fat diet (HFD), 32 mice with initial body weights of 20.76 ± 0.24 g were randomly divided into four groups; the four groups were fed a low-fat diet, a HFD, a HFD plus 0.5 g/kg of RRBE, or a HFD plus 1 g/kg of RRBE, respectively. The 6-week treatment using RRBE reduced HFD-induced adipocyte hypertrophy, lipid accumulation, and inflammation in intra-abdominal epididymal white adipose tissue (p < 0.05) without causing significant changes in body and adipose tissue weight, which reductions were accompanied by the down-regulated expression of adipogenic and lipid metabolism genes, including CCAAT/enhancer-binding protein-alpha, sterol regulatory element-binding protein-1c, and hormone-sensitive lipase (p < 0.05), as well as inflammatory genes, including macrophage marker F4/80, nuclear factor-kappa B p65, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and inducible nitric oxide synthase (p < 0.05), in adipose tissue. Furthermore, RRBE significantly decreased serum tumor necrosis factor-alpha levels (p < 0.05). Bioactive compound analyses revealed the presence of phenolics, flavonoids, anthocyanins, and proanthocyanidins in these extracts. Collectively, this study demonstrates that RRBE effectively attenuates HFD-induced pathological adipose tissue remodeling by suppressing adipogenesis, lipid dysmetabolism, and inflammation. Therefore, RRBE may emerge as one of the alternative food products to be used against obesity-associated adipose tissue dysfunction.

Fine particulate matter (PM2.5; aerodynamic diameter ≤2.5 μm) is a leading contributor to the global burden of disease and is associated with substantial morbidity and mortality. However, its health effects are often evaluated within single-exposure frameworks, limiting causal inference and reducing the translational relevance of evidence for policy development. In this study, we reconceptualise PM2.5 within the exposome framework by integrating external exposures, internal biological responses, and structural determinants of health across the life course. PM2.5 comprises a complex and dynamic mixture of pollutants from ambient and household sources, including biomass combustion, traffic emissions, and industrial activities. After inhalation, PM2.5 particles can penetrate the respiratory tract, and finer fractions may enter the systemic circulation, where they induce oxidative stress, inflammation, epigenetic dysregulation, and endocrine disruption. These mechanisms contribute to a broad spectrum of adverse health outcomes, including cardiovascular, respiratory, metabolic, and neurodegenerative diseases as well as cancers. The multi-level and temporally accumulated nature of these effects highlights the limitations of reductionist exposure assessment and underscores the need for integrative, systems-based approaches. Integrating cumulative impact assessment with exposome-wide approaches that leverage satellite, clinical, land-use, urban planning, and socioeconomic data can improve the characterization of context-specific cumulative health effects. Positioning PM2.5 as a sentinel indicator of cumulative environmental risk provides a unifying framework for exposome-informed science and supports the development of more precise, equitable, and policy-relevant interventions.

Background: N-acetyl-p-aminophenol (APAP) overdose remains a leading cause of acute liver failure worldwide. The aril extracts derived from Gac (Momordica cochinchinensis) (MC) fruit contain diverse phytonutrients that exhibit a range of pharma-nutritional properties, including antioxidant and anti-hepatic damage properties. Despite the therapeutic potential, the molecular mechanisms underlying its hepatoprotective action, particularly in preventing drug-induced toxicity, remain unelucidated. Purpose: This study investigated the hepatoprotective potential of MC in a mouse model of APAP-induced acute liver injury and characterized its bioactive compounds. Methods: MC was prepared using aqueous extraction. Mice were pre-treated with either 500 or 1,000 mg/kg of MC for seven consecutive days prior to intraperitoneal administration of APAP 300 mg/kg to induce hepatotoxicity. Serum and liver samples were then collected to analyze biochemical changes, histopathological changes, oxidative stress markers, and/or mRNA expression. Standard chemical tests were used to identify bioactive compounds. Results: APAP administration caused a marked rise in liver enzymes, extensive histological necrosis, suppression of hepatocyte proliferation, infiltration of neutrophils and macrophages, and significant oxidative damage (p < 0.05). Studies revealed the constitution of MC as phenolic compounds, flavonoids, proanthocyanidins, and ascorbic acid, significantly attenuated the hepatotoxicity (p < 0.05). Mechanistically, MC ameliorated hepatic mRNA expression of CYP2E1, JNK, Ddit3, Bax, Casp3, NF-κB, and MCP-1, while increasing Bcl-2, IL-10, VEGF, Nrf2, SOD2, and GCLC mRNA (p < 0.05). Furthermore, MC prevented hyperglycemia by influencing the expression of AdipoR1, GLUT-2, and PEPCK (p < 0.05). Conclusion: MC exhibits hepatoprotective effects against APAP-induced liver injury through multifaceted modulation of toxic metabolism (CYP2E1), cell death and ER stress (JNK, Ddit3, Bax, Casp3, and Bcl-2), antioxidant response (Nrf2 pathway), inflammation (NF-κB pathway and IL-10), tissue repair (VEGF), and glucose metabolism (AdipoR1, GLUT-2, and PEPCK).