Search Results (6,723)

Gypenoside XLIX is a bioactive saponin with reported diverse biological activities, including antioxidant, regulation of cell growth, immune responses, and metabolic regulatory properties. The increasing global prevalence of non-alcoholic fatty liver disease (NAFLD) underscores the importance of exploring novel therapeutic agents such as Gypenoside XLIX. NAFLD pathogenesis involves lipotoxicity, oxidative stress, and mitochondrial dysfunction, in which mitochondria-associated endoplasmic reticulum membranes (MAMs) play a critical role in organelle communication, calcium signaling, and lipid metabolism. This narrative review summarizes current evidence indicating that Gypenoside XLIX may modulate oxidative stress, restore mitochondrial membrane potential, and regulate calcium homeostasis, thereby indirectly influencing MAM integrity and function. These effects can reduce lipid accumulation, improve hepatocellular metabolism, and attenuate inflammatory responses. This review evaluates the mechanistic impact and function of Gypenoside XLIX on MAM integrity and its effects on NAFLD. However, there is limited direct experimental evidence linking Gypenoside XLIX to MAM regulation, and further studies are required to validate its mechanisms and therapeutic potential in clinical settings. Full article

Chronic oxidative stress and lipid imbalance drive metabolic disorders such as obesity and non-alcoholic fatty liver disease, yet few therapies target the upstream redox imbalance in key tissues. Human carbonic anhydrase III (hCA III), a redox-associated enzyme enriched in liver and adipose tissue, has long remained pharmacologically elusive due to its low catalytic activity and lack of modulators. Here, we identify fragment-like nicotinic acid derivatives as non-sulfonamide hCA III modulators and evaluate their associated cellular effects. Using an esterase activity assay, we screened 25 analogues and identified two fragment-like hits, compound 17 (2-thioethyl) and compound 22 (6-morpholino), with IC₅₀ values of 487 and 361 µM, respectively. Orthogonal thermal shift analysis supported compound-protein interaction, and selected hits were subsequently evaluated in HepG2 cells. Both compounds were associated with reduced CA3 mRNA expression after treatment at 1 µM, while their cellular phenotypes diverged, with compound 22 increasing ROS under oxidative stress conditions and compound 17 affecting mitochondrial membrane potential. Taken together, these findings identify tractable nicotinic acid-derived fragment hits and associated cellular phenotypes that warrant further mechanistic investigation. These fragment-like hits provide a practical starting point for studying the redox-linked biology of hCA III. Full article

Lignin is an abundant aromatic biopolymer, but its conversion into high-performance fibers remains challenging due to intrinsically poor spinnability, structural heterogeneity, and inefficient stress transfer in lignin-rich systems. In this study, a processing and structure strategy is demonstrated to overcome these limitations by transforming industrial black-liquor kraft lignin into a spinnable and load-bearing fiber component. Kraft lignin recovered from black-liquor waste was extracted and subsequently purified using a hot-water treatment to remove inorganic impurities and thermally unstable fractions, increasing lignin purity to 95.9% through extensive deionized water purification using a water-to-lignin ratio of 300:1. The purified lignin was then blended with poly(vinyl alcohol) (PVA), wet-spun into continuous filaments, and subjected to post-spinning hot drawing to induce molecular orientation. This sequential extraction, purification, blending, spinning, and drawing approach enables stable wet spinning and the continuous formation of lignin-rich lignin/PVA filaments without filament breakage, directly addressing the primary processing bottleneck of lignin-based fibers. Molecular-level miscibility between lignin and PVA is confirmed by the presence of a single glass transition temperature at 88.3 °C, indicating the formation of a homogeneous amorphous phase. SEM observations reveal composition-dependent surface roughness and non-circular cross-sectional morphologies arising from differential coagulation and shrinkage, demonstrating that lignin actively participates in the load-bearing fiber network rather than acting as a passive filler. As a result of purification-enabled spinnability, true blend miscibility, and post-spinning hot drawing, fibers with a lignin-to-PVA composition of 40:60 achieve a maximum tensile strength of 2.8 GPa, approaching the performance range of commercial high-strength polymer fibers. This work establishes a clear relationship between material structure, processing strategy, and resulting properties, highlighting the potential of industrial lignin waste as a sustainable precursor for advanced fiber applications. Full article

Poly(vinyl alcohol)/chitosan (PVA/CS) biodegradable films reinforced with acid-functionalized multi-walled carbon nanotubes (f-MWCNTs) were fabricated via solution casting to investigate the effects of nanotube incorporation on structural, mechanical, thermal, dielectric, and physicochemical properties. Unlike conventional CNT-reinforced systems, this study focuses on the role of acid functionalization in improving nanotube dispersion and interfacial interactions, enabling simultaneous enhancement of multiple performance characteristics. Fourier transform infrared spectroscopy (FTIR) analysis confirmed strong intermolecular interactions between PVA/CS functional groups and carboxyl groups on f-MWCNTs, while scanning electron microscopy (SEM) revealed homogeneous nanotube dispersion at low loadings and partial aggregation at higher contents. X-ray diffraction (XRD) indicated that crystallinity was modified in a non-monotonic manner with increasing nanotube concentration due to competing nucleation and chain-restriction effects, while dielectric measurements showed an increase in dielectric constant from 3.78 to 4.27 as a result of enhanced interfacial polarization. The thermal conductivity improved from 0.195 to 0.247 W·m⁻¹·K⁻¹, and tensile strength increased from 19.8 to 24.5 MPa at 0.2 wt.% f-MWCNT, with elongation at break decreasing from 37.9% to 25.1%, reflecting increased stiffness. The degree of swelling and water solubility decreased with higher nanotube content, indicating reduced hydrophilicity and enhanced structural compactness. The results provide new insights into how surface-functionalized nanofillers can be used to tailor the multifunctional performance of biodegradable polymer nanocomposite films, highlighting their potential in advanced applications such as sustainable packaging, flexible electronics, sensors, and membrane technologies. Full article

Inflammatory bowel disease (IBD)—including Crohn’s disease, ulcerative colitis, and indeterminate colitis—is a chronic immune-mediated condition that primarily affects the intestinal mucosa but often presents with extraintestinal digestive manifestations, which are important yet frequently underrecognized sources of morbidity. These heterogeneous manifestations reflect diverse genetic, microbial, immunologic, and environmental influences, highlighting the value of a personalized medicine approach. Hepatobiliary involvement affects IBD adults patients and is even more common in children, ranging from mild liver enzyme elevations to severe complications such as liver failure, with autoimmune disorders, cholelithiasis, portal vein thrombosis, and non-alcoholic fatty liver disease as key considerations. Pancreatic manifestations may include autoimmune or acute pancreatitis, often linked to gallstones, thiopurine exposure, or duodenal Crohn’s disease, while splenic abnormalities, such as granulomatous lesions, splenomegaly, or functional hyposplenism, reflect systemic immune dysregulation. Oral findings—including aphthous ulcers, periodontitis, pyostomatitis vegetans, and granulomatous cheilitis—can serve as early, patient-specific indicators of disease activity. Personalized approaches, encompassing investigations tailored to the individual profile and selected targeted therapies, are essential for improving diagnostic accuracy, preventing complications, and optimizing multidisciplinary care in patients with IBD. Full article

Glutinous rice huangjiu, a non-distilled wine variety unique to China, is rich in nutrients. However, systematic research on the differences in its non-volatile functional components remains scarce, despite these variations being key factors influencing its antioxidant effects. This study employed non-targeted metabolomics to systematically analyze the non-volatile metabolite profiles of 16 glutinous rice huangjiu brands, identifying 1450 metabolites. An alcohol-induced hepatocyte injury model was established, combining cell viability and reactive oxygen species (ROS) level assays to screen for samples (G10 and G11) exhibiting significant efficacy across varying alcohol concentrations. Differential metabolite analysis further identified key bioactive compounds including L-proline, dihydroferulic acid, chalcones, and multiple phenolic derivatives. Using molecular docking technology, we preliminarily revealed that these components may exert antioxidant and hepatoprotective effects either by directly scavenging free radicals or indirectly through mechanisms such as participating in glutathione metabolism and regulating the KEAP1-Nrf2 signaling pathway. This study elucidates the differences among glutinous rice huangjiu at the metabolomic and cellular model levels, providing a scientific basis for evaluating the health benefits and developing new products of huangjiu. Full article

During alcoholic fermentations, some non-Saccharomyces yeasts are often displaced by Saccharomyces cerevisiae. It remains unclear whether this displacement is mediated by metabolites produced by S. cerevisiae or depends on cell–cell contact. This study evaluated the effects of extracellular metabolites produced by S. cerevisiae on the growth and fermentative performance of Kluyveromyces marxianus isolated from mezcal fermentations. The development of both yeasts was evaluated in monocultures and in co-cultures with physical contact. Indirect interaction was also tested by exchanging cell-free fermented media. The growth and fermentative response of K. marxianus in cell-free S. cerevisiae-fermented medium showed modulation that depended on the growth phase during which the exchange was performed. The exchange performed at 6 h (exponential phase) limited the maximum growth of K. marxianus and resulted in lower fermentative performance. When the exchange was done during the stationary phase (17.5 h), K. marxianus exhibited a longer stationary phase and better fermentative performance. Finally, when the exchange was performed at 24 h (the beginning of the death phase), the effects on survival and fermentative performance were less pronounced. Furthermore, co-culture with cell–cell contact showed that direct competition and/or mechanisms dependent on physical contact intensify the displacement of K. marxianus. The results show that direct cell–cell contact promotes greater inhibition of K. marxianus by S. cerevisiae, which is relevant for the design of mixed fermentations aimed at achieving a greater contribution of non-Saccharomyces yeasts to the organoleptic characteristics of alcoholic beverages. Full article

Metabolic dysfunction-associated (non-alcoholic) steatotic liver disease (MASLD) is a chronic inflammatory liver disorder characterized by excessive hepatic lipid accumulation. Its progressive subtype, metabolic dysfunction-associated (non-alcoholic) steatohepatitis (MASH), is featured by enhanced inflammation and liver injury. Some MASH cases are accompanied by hepatic fibrosis, which may progress to cirrhosis and hepatocellular carcinoma (HCC). MASLD is also associated with comorbidities such as cardiovascular disease and chronic kidney disease. To date, only Resmetirom has been approved by the FDA for MASH treatment, highlighting the urgency of investigating MASH pathogenesis and developing effective therapeutic agents. Establishment of experimental animal models which can mimic the clinical symptom of MASLD are fundamental to explore therapeutic targets and advance clinical drugs development. Therefore, this review focus on the pathological features of MASLD/MASH and comprehensively summarizes the current MASH-related mouse models, which can be useful for researchers to select appropriate models in order to explore the underlying mechanisms and dig novel targets for MASH treatment. Full article

Adolescence is a metabolically vulnerable period, during which rapid physiological maturation coincides with the dynamic remodelling of the gut microbiome. This narrative review summarises evidence from 2015 to 2025 to clarify how disturbances to the gut–liver axis driven by dysbiosis contribute to the development and progression of non-alcoholic fatty liver disease (NAFLD) in young people. Based on a systematic search of the databases PubMed, Scopus and Web of Science, we outline the basis of bidirectional communication between the gut and liver and emphasise how microbial imbalance alters the handling of lipids in the liver by enhancing de novo lipogenesis, impairing fatty acid oxidation and disrupting AMPK signalling and mitochondrial function. Consistent findings from clinical and experimental studies show that adolescents with NAFLD exhibit reduced microbial diversity, the enrichment of ethanol- and LPS-producing taxa, and altered short-chain fatty acid profiles. Each of these is associated with hepatic inflammation and metabolic reprogramming. Microbial molecules, including LPS, secondary bile acids and branched-chain amino acid metabolites, activate TLR4–NF-κB pathways, promote Kupffer cell activation and intensify oxidative stress. These mechanisms intersect with factors specific to adolescence, such as increased adiposity, hormonal shifts and diet-induced metabolic strain. Dietary patterns emerge as key modulators of these processes. Westernised diets promote dysbiosis and endotoxemia, whereas Mediterranean, fibre-rich and plant-based diets enhance SCFA production, strengthen epithelial integrity and modulate adiponectin-dependent hepatic metabolism. Micronutrient-sensitive epigenetic regulation, particularly that involving folate, choline and polyphenols, also plays a role in shaping lipid homeostasis and inflammatory tone. We also highlight emerging evidence that the activation of cytoprotective pathways, especially Nrf2, is dependent on lifestyle factors and links antioxidant-rich functional foods and physical activity to improved mitochondrial resilience and microbiome stability. We evaluate therapies targeting the microbiome, including probiotics, prebiotics, synbiotics and postbiotics, which reduce endotoxemia, restore microbial balance and complement dietary strategies. Thus, these findings emphasise the importance of age-specific, mechanistically informed interventions that integrate diet quality, microbial ecology, and the molecular pathways that govern metabolic health in adolescents with NAFLD. Full article

Bactrocera dorsalis (Hendel) is a major fruit-feeding pest that poses a severe and persistent threat to the horticulture industry in tropical and subtropical regions. Methyl eugenol (ME) is a powerful male-specific attractant phytochemical and pheromone precursor that has been widely exploited in lure-and-kill pest management programs. Upon ingestion, ME is metabolized (E)-coniferyl alcohol (E-CF) and 2-allyl-4,5-dimethoxyphenol (DMP), which are stored in the male rectal glands and released during courtship to attract females. Despite its ecological significance, the fundamental molecular mechanism underlying ME perception remains poorly understood. Here, we performed a comparative transcriptomic analysis of ME-responsive and ME-non-responsive male B. dorsalis across four tissues (head, gut, midleg, and wing). A total of 15,727 genes were annotated, of which 970 were associated with odorant-binding proteins (OBPs), odorant receptors (ORs), gustatory receptors (GRs), ionotropic receptors (IRs), and chemosensory proteins (CSPs), as well as detoxification families comprising cytochrome P450s (CYPs), carboxylesterases (CaEs), glutathione S-transferases (GSTs), and uridine diphosphate (UDP)-glycosyltransferases (UGTs), and the stress-related heat shock proteins (HSPs) genes. Differential expression analysis identified 7222, 7763, and 6105 differentially expressed genes (DEGs) in the head, gut, and wings/midlegs, respectively, between ME-responsive and ME-non-responsive males. Notably, CYPs, UGTs, and HSPs involved in detoxification and stress response were significantly downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that CYPs were significantly enriched in metabolic detoxification pathways. These findings reveal a complex molecular interplay between olfaction and detoxification and suggest that ME induces coordinated genetic pathways supporting survival, reproduction, and environmental adaptability. This knowledge provides a foundation for the development of eco-friendly pest management strategies targeting these molecular mechanisms. Full article

Background: Alcohol-related liver disease is frequently associated with systemic vascular dysfunction and increased arterial stiffness. This may contribute to adverse clinical outcomes. Modulation of the gut microbiota through fecal microbiota transplantation (FMT) has emerged as a potential therapeutic strategy in liver cirrhosis, but its influence on vascular stiffness in humans remains insufficiently characterized. Methods: This prospective study evaluated arterial stiffness in patients with alcohol-related liver cirrhosis undergoing FMT. A control group received standard care. Vascular stiffness was assessed non-invasively using an oscillometric arteriograph based on pulse wave analysis. Measurements were performed at baseline and at one and three months after FMT under standardized conditions. The main indices assessed included aortic pulse wave velocity, augmentation index, ejection duration and return time. Direct microbiome sequencing and metabolomic profiling were not performed. Results: At baseline, the study and control groups had comparable vascular stiffness profiles. Only minor differences in selected hemodynamic parameters were observed. At one month after intervention, no statistically significant differences in arterial stiffness indices were observed between groups. Longitudinal analysis within the FMT group also showed no significant changes in direct markers of arterial stiffness across the three-month follow-up period. A non-significant tendency toward reduced ejection duration was noted. Conclusions: In patients with advanced alcohol-related liver cirrhosis, FMT did not produce measurable short-term improvements in arterial stiffness. These findings suggest that short-term vascular effects of microbiota modulation may be difficult to detect in patients with advanced alcohol-related liver cirrhosis. Larger studies including earlier-stage patients, longer follow-up and direct microbiome and metabolomic assessment are needed to clarify potential vascular effects of FMT. Full article

Atrial septal defect (ASD) has become increasingly common in the USA and now affects 1 in 11.3 children in some places, but space–time analysis has not been applied to this emerging trend. ASD rate (ASDR) data were obtained from the National Birth Defects Prevention Network 2003–2020. Substance (cigarettes, alcohol, cannabis, analgesics, cocaine) use data were obtained from the National Survey of Drug Use and Health. Income data were obtained from the US Census. Analysis was limited to the Non-Hispanic White population by technical factors. Time-sequential univariate and bivariate maps were prepared for both covariates and outcomes and their combinations. Spatial regression of the ASDR was performed using the R package splm. A total of 7.6% of data was interpolated by linear regression. A total of 110,107 ASD cases were identified amongst 17,751,437 live births in 27 US states across 10 reporting periods. Time series maps showed that ASDR showed concordant patterns with indices of cannabis use rather than other substances. This was confirmed by multivariate spatial regression where cannabis and cannabinoids alone were found to significantly relate to ASDR, with p = 0.00002 for cannabidiol. Cannabis legal status similarly tracked with ASDR. Compared to states where cannabis was not legal, ASDR was more prevalent in cannabis-legal states (OR = 2.73 (2.66, 2.80); E-Value 4.90 (lower C.I. 4.76)). Twenty-seven of 34 (79.4%) E-values were >9 (high range) and 34/34 were > 1.25 (causal threshold). Data show that cannabis, including cannabis legalization, is driving the US ASD epidemic. While most high-ASDR states have high rates of cannabis use, Midwestern states where cannabis is farmed, such as Kentucky, Tennessee and Missouri, do not, suggesting other routes of exposure, potentially implicating environmental contamination. ASD is a bellwether marker for cannabinoid teratogenicity, indicating that communities should carefully control cannabinoid exposure and limit transgenerational cannabinoid genotoxicity more generally. Full article

Background and Objectives: Diabetes is one of the most common chronic non-communicable diseases and represents a major public health problem. At the global level, the epidemic character of diabetes mellitus can be attributed to an extended life expectancy but also to lifestyle. The aim of this study was to examine the sociodemographic, health, and lifestyle characteristics of adults with type 2 diabetes mellitus in Serbia. Materials and Methods: The research is part of the Serbian Population Health Survey conducted in the period from October to December 2019 by the Republic Statistical Office, in cooperation with the Institute of Public Health of Serbia “Dr Milan Jovanović Batut” and the Ministry of Health of the Republic of Serbia. The research instrument was standardized questionnaires constructed in accordance with the European Health Interview Survey (EHIS—European Health Interview Survey, wave 3) questionnaire, which were adapted to the specifics of our area. The research was conducted as a cross-sectional study on a representative sample of the adult population of Serbia. Results: Among 1138 adults with type 2 diabetes in Serbia (52.8% female; mean age 66.0 ± 11.9 years), overweight and obesity were highly prevalent (40.1% and 34.4%, respectively), with Obesity I predominating. Significant gender differences were observed: female more often reported obesity, multimorbidity, and depressive symptoms, whereas men were more physically active and more frequently overweight. Most participants were physically inactive, consumed breakfast and bread daily, and had low engagement in cycling and sports. Alcohol consumption was significantly higher in men, while dietary habits differed by gender for bread intake. These findings highlight substantial gender- and lifestyle-related disparities among adults with type 2 diabetes in Serbia. Conclusions: Targeted interventions promoting healthy lifestyle, physical activity, psychosocial support, and chronic disease management are urgently needed to address gender- and lifestyle-related disparities in adults with type 2 diabetes in Serbia. Full article

Inflammation is associated with metabolic alterations that can lead to the release of volatile organic compounds (VOCs) reflecting cellular biochemical activity. Profiling these volatile metabolites may provide insight into cellular responses to inflammatory stimuli, although their characterization in skin-derived cells remains limited. In this exploratory proof-of-concept study, we investigated the volatile metabolite profiles of human skin fibroblasts exposed to different inflammatory stimuli. Fibroblast cell lines were stimulated with polyinosinic:polycytidylic acid (Poly I:C), tumor necrosis factor-alpha (TNF-α), and lipopolysaccharide (LPS) to model viral-, cytokine-, and bacterial-associated stress conditions. Headspace solid-phase microextraction coupled with comprehensive two-dimensional gas chromatography and time-of-flight mass spectrometry (HS-SPME-GC×GC-TOFMS) was applied to analyze volatile metabolites released from the cell cultures, enabling exploratory profiling of the fibroblast volatilome. A data-processing workflow including pairwise comparisons between experimental groups and statistical filtering was implemented to identify volatile features associated with the different conditions. Several VOCs were tentatively identified, mainly belonging to alcohol, ester, and hydrocarbon classes, and showed differential abundance patterns between stimulated and control samples. Multivariate analysis indicated a separation between stimulated and non-stimulated groups, suggesting stimulus-associated differences in the volatile profiles of fibroblast cultures. While these observations may reflect metabolic responses occurring under inflammatory stimulation, the chemical identity and biochemical origins of several detected features remain to be confirmed. All in all, this study demonstrates the feasibility of applying HS-SPME-GC×GC-TOFMS-based volatilome profiling to investigate stimulus-associated changes in fibroblast cultures. The detected VOC patterns should therefore be considered preliminary observations requiring further chemical characterization and independent validation. Future studies including larger sample numbers, complementary biological verification of the inflammatory response, and more physiologically relevant experimental models will be necessary to further assess the robustness and potential relevance of these volatile signatures in the context of inflammatory processes. Full article

Social determinants of health (SDoH) are non-medical factors shaped by the socioeconomic status of individuals or communities that influence the onset and progression of diseases and affect their outcomes. We have narratively analyzed the most important findings relating chronic kidney disease (CKD) and SDoH, evaluating the following items: (i) medical care and social determinants of health, (ii) socioeconomic risk for kidney disease at the individual level and (iii) socioeconomic risk for kidney disease at the population level. SDoH can be categorized by how they influence a person’s daily life. Individual factors include personal lifestyle choices such as smoking habits, alcohol consumption, and how a patient spends their non-working time. Community factors include structural elements such as average household income, educational attainment, employment rates, and the quality of the surrounding physical environment. Research consistently shows that a low socioeconomic status is a primary driver of poor clinical outcomes. While healthcare systems vary globally, the negative impact of socioeconomic deprivation on CKD patients remains a constant. Disadvantaged patients experience a faster loss of renal function, and there is a significantly higher incidence of cardiovascular events and mortality compared to those with financial stability. Financial hardship often leads to a “double burden,” where the struggle to afford care triggers a decline in both physical health and mental well-being. To improve patient care, it is essential to raise awareness among healthcare providers regarding the profound impact of these social factors. More precise data and thorough research are needed to fully understand these associations and develop targeted interventions. Full article