Search Results (1,449)

With the acceleration of the pace of life, increased stress levels, and changes in lifestyle factors such as diet and exercise, the incidence of diseases such as cancer and immunodeficiency has been on the rise, which is closely associated with the impaired antioxidant capacity of the body. Polypeptides and polysaccharides derived from edible fungi demonstrate significant strong antioxidant activity and immunomodulatory effects. Auricularia auricula, the second most cultivated mushroom in China, is not only nutritionally rich but also offers considerable health benefits. In particular, its polysaccharides have been widely recognized for their immunomodulatory activities, while its abundant protein content holds great promise as a raw material for developing immunomodulatory peptides. To meet the demand for high-value utilization of Auricularia auricula resources, this study developed a key technology for the stepwise extraction of polypeptides (AAPP1) and polysaccharides (AAPS3) using a composite enzymatic hydrolysis process. Their antioxidant and immunomodulatory effects were assessed using cyclophosphamide (CTX)-induced immune-suppressed mice. The results showed that both AAPP1 and AAPS3 significantly reversed CTX-induced decreases in thymus and spleen indices (p < 0.05); upregulated serum levels of cytokines (e.g., IL-4, TNF-α) and immunoglobulins (e.g., IgA, IgG); enhanced the activities of hepatic antioxidant enzymes SOD and CAT (p < 0.05); and reduced the content of MDA, a marker of oxidative damage. Intestinal microbiota analysis revealed that these compounds restored CTX-induced reductions in microbial α-diversity, increased the abundance of beneficial bacteria (Paramuribaculum, Prevotella; p < 0.05), decreased the proportion of pro-inflammatory Duncaniella, and reshaped the balance of the Bacteroidota/Firmicutes phyla. This study represents the first instance of synergistic extraction of polypeptides and polysaccharides from Auricularia auricula using a single process. It demonstrates their immune-enhancing effects through multiple mechanisms, including “antioxidation-immune organ repair-intestinal microbiota regulation.” The findings offer a theoretical and technical foundation for the deep processing of Auricularia auricula and the development of functional foods. Full article

Androgenetic alopecia (AGA) is a common progressive hair loss disorder driven by elevated dihydrotestosterone (DHT) levels, leading to follicular miniaturization. This study investigated sulforaphane-rich broccoli sprout extract (BSE) as a potential oral therapy for AGA. BSE exhibited dose-dependent proliferative and migratory effects on keratinocytes, dermal fibroblasts, and dermal papilla cells, showing greater in vitro activity than sulforaphane (SFN) and minoxidil under the tested conditions, while maintaining low cytotoxicity. In a testosterone-induced AGA mouse model, oral BSE significantly accelerated hair regrowth, with 20 mg/kg achieving 99% recovery by day 15, alongside increased follicle length, density, and hair weight. Mechanistically, BSE upregulated hepatic and dermal DHT-metabolizing enzymes (Akr1c21, Dhrs9) and activated Wnt/β-catenin signaling in the skin, suggesting dual actions via androgen metabolism modulation and follicular regeneration. Pharmacokinetic analysis revealed prolonged SFN plasma exposure following BSE administration, and in silico docking showed strong binding affinities of key BSE constituents to Akr1c2 and β-catenin. No systemic toxicity was observed in liver histology. These findings indicate that BSE may serve as a safe, effective, and multitargeted natural therapy for AGA. Further clinical studies are needed to validate its efficacy in human populations. Full article

Barium chloride (BaCl₂), a known environmental pollutant, induces organ-specific oxidative stress through disruption of redox homeostasis. This study evaluated the protective effects and safety profile of sodium copper chlorophyllin (SCC) and ascorbic acid (ASC) against BaCl₂-induced oxidative damage in the liver and brain of mice using a two-phase experimental protocol. Animals received either SCC (40 mg/kg), ASC (160 mg/kg), or their combination for 14 days prior to BaCl₂ exposure (150 mg/L in drinking water for 7 days), allowing evaluation of both preventive and therapeutic effects. Toxicological and behavioral assessments confirmed the absence of systemic toxicity or neurobehavioral alterations following supplementation. Body weight, liver and kidney indices, and biochemical markers (Aspartate Aminotransferase (ASAT), Alanine Aminotransferase (ALAT), creatinine) remained within physiological ranges, and no anxiogenic or locomotor effects were observed. In the brain, BaCl₂ exposure significantly increased SOD (+49%), CAT (+66%), GPx (+24%), and GSH (+26%) compared to controls, reflecting a robust compensatory antioxidant response. Although lipid peroxidation (MDA) showed a non-significant increase, SCC, ASC, and their combination reduced MDA levels by 42%, 37%, and 55%, respectively. These treatments normalized antioxidant enzyme activities and GSH, indicating an effective neuroprotective effect. In contrast, the liver exhibited a different oxidative profile. BaCl₂ exposure increased MDA levels by 80% and GSH by 34%, with no activation of SOD, CAT, or GPx. Histological analysis revealed extensive hepatocellular necrosis, vacuolization, and inflammatory infiltration. SCC significantly reduced hepatic MDA by 39% and preserved tissue architecture, while ASC alone or combined with SCC exacerbated inflammation and depleted hepatic GSH by 71% and 78%, respectively, relative to BaCl₂-exposed controls. Collectively, these results highlight a differential, organ-specific response to BaCl₂-induced oxidative stress and the therapeutic potential of SCC and ASC. SCC emerged as a safer and more effective agent, particularly in hepatic protection, while both antioxidants demonstrated neuroprotective effects when used individually or in combination. Full article

Reactive oxygen species (ROS) play a dual role as both essential signaling molecules and harmful mediators of damage. Imbalances in the redox state of the liver can overwhelm antioxidant defenses and promote mitochondrial dysfunction, oxidative damage, and inflammation. Complex feedback loops between ROS and immune signaling pathways are a hallmark of pathological liver conditions, such as hepatic ischemia–reperfusion injury (IRI). This is a major cause of liver transplant failure and is of increasing significance due to the increased use of marginally discarded livers for transplantation. This review outlines the major enzymatic and metabolic sources of ROS in hepatic IRI, including mitochondrial reverse electron transport, NADPH oxidases, cytochrome P450 enzymes, and endoplasmic reticulum stress. Hepatocyte injury activates redox feedback loops that initiate immune cascades through DAMP release, toll-like receptor signaling, and cytokine production. Emerging regulatory mechanisms, such as succinate accumulation and cytosolic calcium–CAMKII signaling, further shape oxidative dynamics. Pharmacological therapies and the use of antioxidant and immunomodulatory approaches, including nanoparticles and redox-sensitive therapeutics, are discussed as protective strategies. A deeper understanding of how redox and immune feedback loops interact is an exciting and active area of research that warrants further clinical investigation. Full article

Background/Objectives: Antimicrobial resistance (AMR) is a health related threat world-wide. Biosynthesized gold nanoparticles (AuNPs) using plant extracts have been reported to exhibit certain biological activity. This study aimed to biosynthesize AuNPs using an aqueous extract of Eruca sativa leaves and to evaluate their biocompatibility, antimicrobial activity, and antioxidant properties. Methods: AuNPs were biosynthesized using an aqueous extract of Eruca sativa leaves. Their biocompatibility was evaluated through hemolytic activity and assessments of hepatic and renal functions in rats. AuNPs were biologically evaluated as antimicrobial and antioxidant agents. Results: The AuNPs exhibited particle sizes of 27.78 nm (XRD) and 69.41 nm (AFM). Hemolysis assays on red blood cells revealed negligible hemolytic activity (<1%). Hepatic enzyme levels, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were studied. ALT, AST, and ALP levels showed no significant changes compared to the negative control. However, LDH levels were elevated at higher concentration (52.8 µg/mL), while the lower concentration (26.4 µg/mL) appeared to be safer. Renal biomarkers, urea and creatinine, showed no significant changes at either concentration, indicating minimal nephrotoxicity. The antimicrobial activity of AuNPs, plant extract, and gold salt was tested against five microorganisms: two Gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae), two Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), and a fungal strain (Candida albicans). The AuNPs exhibited minimum inhibition concentrations (MICs) of 13.2 µg/mL against S. aureus and S. pneumoniae, 26.4 µg/mL against E. coli and C. albicans, and 39.6 µg/mL against P. aeruginosa, suggesting selectivity towards Gram-positive bacteria. Furthermore, the AuNPs demonstrated strong antioxidant activity, surpassing that of vitamin C. Conclusions: The biosynthesized AuNPs exhibited promising biocompatibility, selective antimicrobial properties, and potent antioxidant activity, supporting their potential application in combating the AMR. Full article

Volatile organic compounds (VOCs) are highly volatile chemicals in natural and anthropogenic environments, significantly affecting indoor air quality. Major sources of indoor VOCs include emissions from building materials, furnishings, and consumer products. Natural wood products release VOCs, including terpenes and aldehydes, which exert diverse health effects ranging from mild respiratory irritation to severe outcomes, such as formaldehyde-induced carcinogenicity. The temporal dynamics of VOC emissions were investigated, and the toxicological and physiological effects of the VOCs emitted by two types of natural wood, Korean Red Pine (Pinus densiflora) and Japanese Cypress (Chamaecyparis obtusa), were evaluated. Using female C57BL/6 mice as an animal model, the exposure setups included phytoncides, formaldehyde, and intact wood samples over short- and long-term durations. The exposure effects were assessed using oxidative stress markers, antioxidant enzyme activity, hepatic and renal biomarkers, and inflammatory cytokine profiles. Long-term exposure to Korean Red Pine and Japanese Cypress wood VOCs did not induce significant pathological changes. Japanese Cypress exhibited more distinct benefits, including enhanced oxidative stress mitigation, reduced systemic toxicity, and lower pro-inflammatory cytokine levels compared to the negative control group, attributable to its more favorable VOC emission profile. These findings highlight the potential health and environmental benefits of natural wood VOCs and offer valuable insights for optimizing timber use, improving indoor air quality, and informing public health policies. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition globally, strongly linked to obesity, insulin resistance, and type 2 diabetes (T2D). Tirzepatide (TZP), a dual GIP/GLP-1 receptor agonist, improves glycemic control and reduces body weight and the liver fat content in patients with obesity and T2D. However, its effect on liver-specific outcomes such as steatosis and fibrosis remains incompletely characterized. Low-energy ketogenic therapy (LEKT), a nutritional strategy characterized by carbohydrate restriction and nutritional ketosis, may enhance hepatic β-oxidation and reduce hepatic lipogenesis. To date, however, the combination of TZP and LEKT has not been studied in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to compare the hepatic and metabolic effects of TZP combined with either LEKT or a conventional low-calorie diet (LCD) over a 12-week period. Methods: Sixty adult patients with MASLD undergoing TZP therapy were prospectively assigned to either an LEKT or a conventional LCD, with 30 participants per group. As primary endpoints, the controlled attenuation parameter (CAP, an index of hepatic steatosis) and liver stiffness measurement (LSM, an index of liver fibrosis) were assessed at the baseline and after 12 weeks using FibroScan^®. Secondary outcomes included changes in body mass index (BMI), glycated hemoglobin (HbA1c), and liver enzymes. Adherence to both diet and pharmacological treatment, as well as tolerability, were systematically monitored throughout the intervention period. Results: Both groups showed significant reductions in body weight (TZP + LEKT, p = 0.0289; TZP + LCD, p = 0.0278), with no significant intergroup difference (p = 0.665). CAP and LSM improved significantly in both groups, but reductions were greater in the TZP + LEKT group (CAP −12.5%, p < 0.001; LSM −22.7%, p < 0.001) versus LCD (CAP −6.7%, p = 0.014; LSM −9.2%, p = 0.022). Between-group differences were statistically significant for both CAP (p = 0.01) and LSM (p = 0.03). Conclusions: Based on these preliminary findings, we support the hypothesis that the combination of TZP and LEKT may be superior to TZP with an LCD in reducing hepatic steatosis and stiffness in individuals with obesity. Full article

Background: Vaccines that stimulate systemic and mucosal immunity to a level required to prevent SARS-CoV-2 infection and transmission are an unmet need. Highly protective hepatitis B and human papillomavirus nanoparticle vaccines highlight the potential of multivalent nanoparticle vaccine platforms to provide enhanced immunity. Here, we report the construction and characterization of self-assembling 60-subunit icosahedral nanoparticle SARS-CoV-2 vaccines using the bacterial enzyme lumazine synthase (LuS). Methods and Results: Nanoparticles displaying prefusion-stabilized SARS-CoV-2 spike ectodomains fused to the surface-exposed amino terminus of LuS were designed using structure-guided approaches. Negative stain-electron microscopy studies of purified nanoparticles were consistent with self assembly into 60-mer nanoparticles displaying 20 spike trimers. After two intramuscular doses, these purified spike-LuS nanoparticles elicited significantly higher SARS-CoV-2 neutralizing activity than spike trimers in vaccinated mice. Furthermore, intramuscular DNA priming and intranasal boosting with a SARS-CoV-2 LuS nanoparticle vaccine stimulated mucosal IgA responses. Conclusion: These data identify LuS nanoparticles as highly immunogenic SARS-CoV-2 vaccine candidates and support the further development of this platform against SARS-CoV-2 and its emerging variants. Full article

Hypoxia represents a critical environmental stressor in aquaculture, significantly disrupting aquatic organisms’ physiological homeostasis and thereby constraining the sustainable development of aquaculture industries. To elucidate the mechanisms underlying hypoxia-induced metabolic regulation in aquatic species, this study employed hybrid yellow catfish (Pelteobagrus vachelli ♀ × Leiocassis longirostris ♂) as a model organism to systematically investigate the multidimensional physiological responses in brain, liver, and muscle tissues under hypoxia (0.7 mg/L) and reoxygenation (7.0 mg/L) conditions. Through qRT-PCR and enzymatic activity analyses, we comprehensively assessed molecular alterations associated with oxygen sensing (HIF-1α gene), respiratory metabolism (PFKL, HK1, PK, CS, and LDHA genes and corresponding enzyme activities), oxidative stress (SOD1, SOD2, GSH-PX, and CAT genes, along with LPO, MDA, PCO, T-SOD, GSH-PX, and CAT levels), apoptosis (Caspase-3, Bax/Bcl-2), inflammatory response (IL-1β, IKKβ), and mitochondrial function (COXIV, PGC-1α, ATP5A1). Key findings demonstrated pronounced HIF-1α activation across all examined tissues. Hepatic tissues exhibited adaptive metabolic reprogramming from aerobic to anaerobic metabolism, whereas cerebral tissues displayed suppressed anaerobic glycolysis during prolonged hypoxia, and muscular tissues manifested concurrent inhibition of both glycolytic and aerobic metabolic pathways. Notably, skeletal muscle exhibited marked oxidative stress accompanied by mitochondrial dysfunction, exacerbated inflammation, and apoptosis activation during hypoxia/reoxygenation cycles. This study delineates tissue-specific adaptive mechanisms to hypoxia in yellow catfish, providing theoretical foundations for both piscine hypoxia physiology research and aquaculture practices. Full article

In modern society, obesity and its associated complications have emerged as serious public health concerns, primarily stemming from sedentary lifestyles and carbohydrate-rich diets. Due to the severe side effects often associated with pharmacological anti-obesity agents, emerging global efforts focus on preventive strategies, e.g., dietary modifications and weight gain-suppressing functional foods. In this context, plant-derived metabolites are extensively investigated for their beneficial anti-obesity effects. In this study, we evaluated how Rosa rugosa Thunb. flower bud extract affects fat metabolism in 3T3-L1 preadipocyte cells. The extract significantly inhibited adipocyte differentiation and intracellular triglyceride accumulation in 3T3-L1 cells, enhanced lipolysis, suppressed lipogenesis, and promoted energy metabolism in differentiated adipocytes. In vivo, it reduced body and organ weights and fat mass in high-fat diet-induced obese rats, along with marked adipocyte size and hepatic lipid accumulation reductions. In the epididymal adipose tissue, the extract similarly enhanced lipolytic activity, suppressed lipogenic enzyme expression, and stimulated energy expenditure. Taken together, our results demonstrate the potential of R. rugosa Thunb. flower bud extract in reducing fat accumulation through lipid metabolism modulation both in cellular and animal models. Further studies are warranted to identify the active constituents and evaluate the safety and efficacy of the extract in clinical applications. Full article

Obesity and related metabolic disorders are closely linked to dysregulated lipid metabolism, where the metabolic balance of diacylglycerol (DAG) played a pivotal role. Although cis-palmitoleic acid (cPOA) exhibits anti-obesity effects, its efficacy varies across dietary conditions, and its molecular mechanisms remains unclear. In this study, we investigated the dose-dependent regulatory effects of cPOA on DAG metabolic shunting in db/db mice, employing lipidomics, pathway analysis, and gene/protein expression assays. Under a basal diet, low-dose cPOA (75 mg/kg) inhibited DAG-to-triglyceride (TAG) conversion, reducing hepatic lipid accumulation, while medium-to-high doses (150–300 mg/kg) redirected DAG flux toward phospholipid metabolism pathways (e.g., phosphatidylcholine [PC] and phosphatidylethanolamine [PE]), significantly lowering body weight and adiposity index. In high-fat diet (HFD)-fed mice, cPOA failed to reduce body weight but alleviated HFD-induced hepatic pathological damage by suppressing DAG-to-TAG conversion and remodeling phospholipid metabolism (e.g., inhibiting PE-to-PC conversion). Genetic and protein analyses revealed that cPOA downregulated lipogenic genes (SREBP-1c, SCD-1, FAS) and upregulated fatty acid β-oxidation enzymes (CPT1A, ACOX1), while dose-dependently modulating DGAT1, CHPT1, and PEMT expression to drive DAG metabolic shunting. Notably, DAG(36:3, 18:1–18:2) emerged as a potential biomarker for HFD-aggravated metabolic dysregulation. This study elucidated cPOA as a bidirectional regulator of lipid synthesis and oxidation, improving lipid homeostasis through dose-dependent DAG metabolic reprogramming. These findings provide novel insights and strategies for precision intervention in obesity and related metabolic diseases. Full article

Obesity and pediatric fatty liver disease are increasingly prevalent, yet the underlying mechanisms linking these conditions to heightened inflammatory and immune responses remain poorly understood. Using a murine model reflecting early-life obesity and hepatic steatosis, we tested the hypothesis that obesity-driven hepatic inflammation intensifies systemic immune responses and exacerbates vascular dysfunction following innate immune activation. Newly weaned C57BL/6 mice were fed either a high-saturated-fat, high-cholesterol diet (HFD) or a control diet (CD) for four weeks, modeling adolescence in humans. HFD-fed mice exhibited hepatic and splenic enlargement, elevated plasma cholesterol levels, increased activity levels of liver enzymes (alanine and aspartate aminotransferases), and higher plasma serum amyloid A (SAA) concentrations. Following a sublethal dose of lipopolysaccharide (LPS), the expression of hepatic inflammatory genes (VCAM-1 and iNOS) was significantly elevated in HFD-fed mice, indicating an exaggerated local immune response. Mice fed an HFD also showed significant impairment in endothelium-dependent vasorelaxation compared to CD mice and saline-treated controls, while endothelium-independent responses remained intact. These vascular changes occurred in the context of hepatic inflammation, suggesting that early-life diet-induced steatosis sensitizes the vasculature to inflammatory insult. These findings suggest that obesity-driven hepatic inflammation primes exaggerated systemic immune responses to innate immune stimuli, potentially contributing to the vascular dysfunction and variable clinical morbidity observed in pediatric inflammatory conditions. Full article

Acetaminophen (APAP) overdose is a major cause of drug-induced liver injury (DILI) globally, which necessitates effective therapies. Gallic acid (GA), a naturally abundant polyphenol, possesses potent antioxidant and anti-inflammatory properties that may overcome the limitations of N-acetylcysteine (NAC), such as its narrow therapeutic window. This study systematically investigated the hepatoprotective effects and underlying molecular mechanisms of GA against APAP-induced acute liver injury (ALI). Mice received an intraperitoneal injection of APAP (300 mg/kg), followed by an oral administration of GA (50 or 100 mg/kg) or NAC (150 mg/kg) 1 h post-intoxication. Both GA and NAC significantly ameliorated hypertrophy and histopathological damage, as evidenced by reduced serum ALT/AST levels and inflammatory cytokines. TUNEL staining revealed a marked suppression of apoptotic and necrotic cell death, further supported by the downregulation of pro-apoptotic Bax and the upregulation of anti-apoptotic Bcl-2 mRNA expression. GA and NAC treatment restored hepatic glutathione (GSH) content, enhanced antioxidant enzyme gene expression, and reduced malondialdehyde (MDA) accumulation. Mechanistically, GA and NAC inhibited MAPK phosphorylation while activating AMPK signaling. Taken together, these findings demonstrate that GA mitigates APAP-induced ALI by modulating oxidative stress and inflammation through the regulation of MAPK/AMPK signaling proteins. Full article

Sulfotransferase (SULT) enzymes contribute significantly to drug metabolism in pediatric patients. The purpose of this study was to develop a PBPK model for acetaminophen (APAP) in pediatric populations that accounts for the ontogeny of SULT isozymes that play a critical role in APAP metabolism. PBPK modeling and simulation were performed using the Simcyp^® Simulator. The model incorporated the developmental ontogeny of three key hepatic SULT enzymes: SULT1A1, SULT1A3, and SULT2A1 using “best-fit” ontogeny equations for each isozyme as determined by nonlinear regression analysis of enzyme abundance versus age. PBPK model-simulated pharmacokinetic profiles for APAP captured observed clinical data for systemic exposure (Cmax, AUC) in neonates, infants, and children. SULTS accounted for ~60% APAP metabolism in neonates, with decreased contributions to infants and children. Model sensitivity analysis highlighted the potential for APAP metabolic DDIs, primarily through SULT1A1. The study demonstrates that the impact of SULT enzymes on drug metabolism is significant in neonates, which is an important clinical consideration for APAP. A PBPK model that incorporates SULT ontogeny has the potential to help inform dosing decisions in this special patient population. Full article

Bothus podas (wide-eyed flounder) is a benthic flatfish likely exposed to microplastic (MP) pollution. We investigated MP ingestion and associated physiological effects in wild B. podas collected from Mallorca (Balearic Islands), Spain. Markers of oxidative stress, detoxification, and immunity were quantified in intestinal, hepatic, and splenic tissues. MPs were observed in the gastrointestinal tracts of 87.5% of the 24 specimens analyzed, with an average of 3.8 ± 0.6 items per fish. Fiber-type MPs predominated in both the gastrointestinal tract (69.6%) and sediment samples (97%). Additionally, micro-Fourier transform infrared spectroscopy analysis confirmed that the majority of ingested MPs were composed of polyethylene, polypropylene, and polyester. Fish were categorized into low (<3 items) and high (≥3 items) MP groups based on the median number of plastic items found in the gastrointestinal tract to assess sublethal impacts. In the gut, high-MP fish exhibited significantly elevated activities of detoxification enzymes: ethoxyresorufin-O-deethylase (phase I) and glutathione s-transferase (phase II), along with increased antioxidant enzyme superoxide dismutase and inflammatory myeloperoxidase. Gut catalase and malondialdehyde (MDA) were not significantly different between groups. In liver tissues, no biomarkers differed significantly with MP exposure. In the spleen, lysozyme and alkaline phosphatase activities were significantly higher in high-MP fish, while splenic MDA remained unchanged. These results indicate that gastrointestinal MP exposure triggers local oxidative stress responses and systemic immune activation in B. podas. Overall, ingestion of environmentally relevant MP levels elicited detoxification and inflammatory responses without significant increases in MDA, an indicator of oxidative damage, highlighting the physiological stress imposed by plastic pollution on benthic fish. Full article