Search Results (3,319)

Pogostemon cablin (Blanco) Benth. cv. ‘Jing Huoxiang’, is a valuable medicinal plant widely studied for its aboveground tissues, which are rich in bioactive compounds such as patchouli alcohol. However, systematic investigations into the biosynthesis of sesquiterpenes in its underground parts (roots) remain limited, with several critical knowledge gaps: (1) the metabolic basis of root-specific accumulation of polycyclic sesquiterpenes is unclear; (2) key terpene synthase (TPS) gene resources remain underexplored; and (3) the regulatory network of terpenoid biosynthesis is poorly understood. Addressing these questions is essential for the rational design and efficient production of terpene synthases. In this study, we integrated metabolomic and transcriptomic approaches to systematically characterize terpenoid profiles across different tissues of P. cablin and elucidate their biosynthetic regulation. Using GC-MS analysis, we identified distinct terpenoid compositions in roots, stems, leaves, flowers, and glandular trichomes. Notably, patchouli alcohol and pogostone accounted for over 60% of the total volatile oil content, while roots specifically accumulated polycyclic sesquiterpenes such as β-caryophyllene and α-humulene. Through transcriptome sequencing and bioinformatic analysis, we comprehensively annotated the TPS gene family, revealing that the TPS-a subfamily (34 genes) was the most abundant in P. cablin, with several members exhibiting root-predominant expression. Co-expression network analysis further identified candidate genes encoding potential high-efficiency polycyclic sesquiterpene synthases and uncovered a β-caryophyllene/α-humulene-regulated tertiary metabolic pathway. Our findings not only fill a critical gap in understanding sesquiterpene biosynthesis in the underground tissues of P. cablin but also provide a foundation for synthetic biology-based optimization of terpenoid production. This research paves the way for the efficient biosynthesis of sesquiterpenes to meet industrial demands in pharmaceuticals, fragrances, and biofuels. Full article

Tea, derived from the leaves of Camellia sinensis, is a non-alcoholic beverage rich in pharmacologically active bioactive components. This plant contains many bioactive components, such as xanthine alkaloids, tea polyphenols, L-theanine, theaflavins, tea polysaccharides, and volatile oils. Evidence indicates that these bioactive constituents contribute to various physiological benefits, including body weight regulation, anti-fatigue properties, hypoglycemic action, antitumor and neuroprotective potentials, improvement of vascular function, and attenuation of airway-induced organ obstruction. Up to now, research has systematically confirmed and summarized the functions of xanthine alkaloids, tea polyphenols, and L-theanine. However, much less attention has been given to theaflavins and tea polysaccharides. This review therefore focuses on how theaflavins and tea polysaccharides work in the human body and what they do, as well as how these two types of compounds are metabolized in tea plants. Overall, this work provides a new perspective on the study of bioactive components in tea and builds a useful foundation for a deeper understanding of how these components act in the human body. Full article

An abnormality of Ca²⁺ signaling may aggravate lipid accumulation in steatotic hepatocytes, leading to non-alcoholic fatty liver disease. However, the molecular identity of Ca²⁺-permeable channels and the mechanism of involvement of these channels in steatotic hepatocytes are not well-studied. In the present study, we investigated the role of a Ca²⁺-permeable channel TRPM2 in lipid metabolism in steatotic hepatocytes. A mouse model of non-alcoholic fatty liver disease was established by high-fat-diet feeding. Fat accumulation, fibrosis, lipophagic indexes, TFEB and lysosomal acid lipase in the liver tissue and/or hepatocytes were compared between TRPM2-knockout mice and wild-type mice. Knockout of the TRPM2 gene aggravated liver fat accumulation and fibrosis. Mechanistically, the TRPM2 knockout impaired the lipophagic process, decreased lysosomal abundance and attenuated lysosomal/autolysosomal acidification in mouse hepatocytes. Furthermore, the TRPM2 knockout reduced TFEB expression and its nuclear translation and also reduced the expression/activity of lysosomal acid lipase. These data demonstrate that TRPM2 deficiency may reduce lipophagy via its action on TFEB and lysosomal acid lipase, consequently contributing to liver steatosis and NAFLD under high-fat feeding conditions. Full article

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. In the U.S., HCC incidence is highest among Hispanic populations. With the exception of well-known PNPLA3 variants, the genetic risk factors underlying HCC in Hispanic individuals, particularly rare germline variants, are largely unexplored. Methods: We performed whole-exome sequencing in 719 Hispanic Americans, including 455 HCC cases and 264 controls. We analyzed rare to low frequency, putatively deleterious variants in 86 genes previously implicated in HCC susceptibility. Genetic associations were assessed at single-variant, gene, and cumulative multi-variant burden levels using Fisher’s exact tests and weighted burden tests. Results: We identified 29 rare deleterious variants across 16 genes enriched in HCC cases compared with controls. Single-variant tests identified statistically robust associations in pathways related to lipids metabolism, TM6SF2 R138W, immune regulation, HLA-DRB1 W38X, and Wnt signaling pathway, WNT9A R375H. Exploratory analyses showed that TM6SF2 R138W was further enriched among cases with alcohol and metabolic dysfunction-associated steatotic liver disease. Gene-based burden tests revealed five associated genes, including TM6SF2 and HLA-DRB1. A strong dose-effect relationship was observed, with HCC risk increasing ~4-fold per candidate variant carried (odds ratio, 3.84; 95% confidence interval, 2.40–6.53). Conclusions: Rare deleterious germline variants across lipid metabolism and immune pathways contribute to increased HCC risk in Hispanic individuals. These findings provide a genetic framework for understanding HCC disparities and support future mechanistic and epidemiologic studies in this high-risk population. Full article

Background and Aims: The glucose metabolism pattern of the liver is closely related to liver diseases. In recent years, alcoholic hepatitis, viral hepatitis, fatty liver and other diseases have become important liver diseases that impact people’s lives. IL-33 (interleukin-33), as a member of the IL-1 cytokine family, and “alarmin” play a multi-dimensional regulatory role in various physiological and pathological processes of the liver. Methods: This study, by integrating transcriptomic data analysis and in vitro and in vivo experiments, expounds on new insights into the regulation of hepatocyte fate by IL-33 through metabolic reprogramming and reveals the potential, new role of IL-33 as a regulatory factor of metabolism. Conclusions: Our research further confirmed that IL-33, in addition to serving as an alarm hormone, is also a key checkpoint for liver metabolism, capable of promoting oxidative phosphorylation in hepatocytes and antagonizing acute liver injury induced by CCl₄. Full article

Volatile fingerprints provide useful information for characterizing Astragali Radix (AR), a food–medicine homologous plant material, but differences among wild, wild-simulated, and cultivated samples remain unclear. In this study, headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry (HS-SPME-GC–MS) and headspace gas chromatography–ion mobility spectrometry (HS-GC–IMS) were integrated with multivariate analysis and interpretable machine learning to characterize volatile profiles and identify candidate discriminatory compounds in 117 AR samples from different cultivation patterns. HS-SPME-GC–MS tentatively identified 29, 34, and 45 volatile compounds in wild, wild-simulated, and cultivated samples, respectively. Esters were the predominant class in all groups, although the relative abundance of esters and the overall chemical-class composition varied among cultivation patterns. HS-GC–IMS tentatively identified 57, 50, and 55 compounds, respectively, comprising mainly low-molecular-weight aldehydes, alcohols, and ketones and thereby providing complementary volatile fingerprint information. Partial least squares discriminant analysis (PLS-DA) showed that the volatile fingerprints captured cultivation-pattern-associated differences, with the HS-GC–IMS model showing clearer group separation. Random forest, support vector machine, and CatBoost models were further constructed using the HS-SPME-GC–MS profiling results. By integrating variable importance in projection (VIP) and SHapley Additive exPlanations (SHAP) values, γ-hexalactone, methyl eugenol, methyl (9Z,11E)-octadeca-9,11-dienoate, eugenol, and ethyl linoleate were selected as candidate discriminatory compounds. Based on the HS-GC–IMS results, 1-octen-3-one, pentyl acetate, (Z)-2-penten-1-ol, 2-heptanone, and the monomeric signal of 2-ethyl-6-methylpyrazine were also identified as candidate discriminatory compounds. These compounds may be related to fatty acid-derived metabolism, aromatic secondary metabolism, and terpenoid-related processes. The integration of two complementary volatile-analysis platforms with VIP- and SHAP-based interpretation provided broader coverage of volatile features and improved the interpretability of candidate-compound screening. These findings provide an interpretable analytical workflow and candidate discriminatory compounds that may support future rapid screening, cultivation-pattern authentication, and volatile-profile-based differentiation of AR, pending independent external validation. Full article

Historically framed as a behavioral addiction, gambling disorder (GD) has had its somatic dimension neglected by standard clinical evaluation. This is a narrative, hypothesis-generating review focusing on the somatic aspects of GD. Cross-sectional and prospective evidence increasingly shows a somatic phenotype distributed across four axes: cardiovascular (hypertension, angina, stroke, acute stress-induced cardiac events), metabolic (obesity, type 2 diabetes, chronic liver disease), sleep-related (insomnia, poor sleep quality, daytime sleepiness), and—as an emerging and insufficiently characterized dimension—neurological (clustering with seizures and frontal lobe epilepsy). Three candidate biological systems may translate this exposure into multi-system physiology: (i) a hyperreactive mesostriatal reward circuit hypothesized to sustain a behavioral cluster of smoking, hazardous alcohol use, low physical activity, and unhealthy diet; (ii) an integrated stress response postulated to shift from acute hyperreactivity to chronic basal cortisol blunting and reduced vagal tone; and (iii) putative alterations in peripheral neurotrophic signaling and frontal-callosal structure, marked by elevated peripheral brain-derived neurotrophic factor and by frontal-callosal white-matter alterations—with cumulative allostatic load serving as a conceptual integrating frame. We propose that GD can be a behaviorally driven systemic medical condition, warranting internal medicine involvement alongside addiction psychiatry. Within this framework, glucagon-like peptide-1 receptor agonists emerge as an exploratory therapeutic hypothesis warranting dedicated evaluation in GD, given their action on the mesolimbic reward substrate and phase 3 evidence in adjacent cardiometabolic, hepatic, and sleep conditions. Full article

Secondary fermentation is a critical stage in the production of traditional method sparkling wines, during which yeast metabolism drives major changes in wine composition. However, the biochemical processes occurring during this phase and the influence of bottle closure systems remain poorly understood. This study evaluated the evolution of basic oenological parameters, free amino acids and volatile compounds during the first 90 days of secondary fermentation under two bottle closure systems: crown cap and tirage-cork. Fermentation time was the principal factor governing wine composition, with the most pronounced metabolic changes occurring between 30 and 45 days after bottling. Active nitrogen metabolism was evidenced by substantial amino acid redistribution, particularly involving ASN, ORN, AAA, GLU and ASP, while the accumulation of higher alcohols and other fermentation-derived volatiles reflected intense yeast metabolic activity during bottle fermentation. Although both closure systems successfully completed fermentation, tirage-cork-fermented wines showed a tendency towards faster fermentation progression and distinct patterns of amino acid and volatile compound development. Pearson correlation analysis revealed generally weak to moderate associations between amino acids and their corresponding volatile compounds, supporting the view that aroma formation results from the integration of multiple metabolic processes rather than from precursor availability alone. Overall, the results suggest that closure-associated metabolic divergence becomes detectable during the active phase of secondary fermentation and may contribute to differences in nitrogenous and aroma-related compounds. These findings suggest that bottle closure may represent an important technological variable associated with differences in the metabolic and compositional trajectories observed during the active phase of secondary fermentation. Given the limited biological replication of the present study, these observations should be interpreted with caution and warrant confirmation through studies incorporating biological replication and direct measurements of oxygen transfer. Full article

Patchouli alcohol, a natural tricyclic sesquiterpene isolated from Pogostemon cablin, exhibits promising antimicrobial properties, yet its activity against Streptococcus mutans (S. mutans), a major cariogenic bacterium associated with dental caries, has not been characterized. This study determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of patchouli alcohol against S. mutans to be 40 and 80 μg/mL, respectively. A series of phenotypic assays showed that patchouli alcohol delayed bacterial growth and culture acidification, reduced extracellular polysaccharide production, and decreased the biomass and metabolic activity of established S. mutans biofilms. Scanning electron microscopy showed treatment-associated changes in the surface morphology of S. mutans, with more evident deformation at MIC and 2MIC. Real-time quantitative PCR showed that sub-MIC treatment (20 μg/mL) significantly downregulated virulence genes associated with adhesion (gbpB and spaP), EPS synthesis (gtfB, gtfC, gtfD, and ftf), acid production (ldh, atpF, and atpD), and the two-component regulatory and quorum sensing systems (vicK, vicR, and luxS). These results suggest that patchouli alcohol may serve as a potential natural anti-cariogenic candidate targeting S. mutans-associated virulence traits under in vitro conditions. Full article

Alcohol-related liver disease (ALD) and metabolic dysfunction and alcohol-related liver disease (MetALD) are increasingly recognised as biologically heterogeneous conditions, but circulating novel adipokines have not been systematically synthesised in this setting. We searched PubMed/MEDLINE, Embase, Web of Science, Scopus and Cochrane CENTRAL from inception to 31 December 2025 for studies measuring chemerin, visfatin/nicotinamide phosphoribosyltransferase (NAMPT), vaspin, omentin-1 or retinol-binding protein 4 (RBP-4) in adults with ALD or MetALD; data were synthesised narratively using Synthesis Without Meta-Analysis (SWiM). Grey literature and non-English databases were not searched, which may have led to incomplete retrieval of small single-centre studies. Five studies were included. Direct ALD evidence came mainly from three cross-sectional alcoholic cirrhosis cohorts, while one population cohort linked baseline RBP-4 to incident MetALD/ALD. RBP-4 showed a phase-dependent pattern, increasing before incident MetALD/ALD but decreasing in established cirrhosis with impaired synthetic function. Chemerin was reduced, omentin-1 was markedly elevated, vaspin was nonspecific and historical visfatin/NAMPT assays were difficult to interpret. Current evidence supports a hypothesis-generating three-axis framework: hepatic source failure, impaired hepatic clearance/portal-systemic shunting and alcohol-driven adipose-liver inflammation. The available evidence chiefly reflects chronic alcohol-related cirrhosis together with limited incident MetALD/ALD risk data, rather than the full ALD/MetALD spectrum. Prospective MetALD-stratified cohorts with isoform-specific assays and objective alcohol biomarkers are required. Full article

Background: Alcohol-associated fatty liver disease (AFLD) is a major public health concern and remains one of the leading causes of chronic liver disease in the United States. Understanding the interplay between obesity, metabolic dysfunction, and lifestyle factors may help identify populations at increased risk for AFLD. Methods: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2013–2018. AFLD was operationally defined using elevated liver enzyme levels combined with risky alcohol consumption. Metabolic obesity phenotypes (MOPs) were characterized by combining body mass index categories with either metabolic health status or metabolic syndrome (MS). Results: The weighted prevalence of AFLD was 14% (95%CI: 12–16%). AFLD prevalence was significantly higher among males than females (17% vs. 10% respectively, p < 0.0001), and among Hispanics compared to Non-Hispanic Black participants (20% vs. 9% respectively, p < 0.0001). Compared with metabolically healthy normal-weight individuals, obese participants with MS demonstrated the strongest association overall AFLD association (adjusted PR: 6.73; 95% CI: 4.51–10.05). Furthermore, obese males with MS showed the highest odds of AFLD under both MOP schemes (MOP 1: OR: 8.19; 95% CI: 4.41–15.23; MOP 2: OR: 10.92; 95% CI: 6.86–17.37). Conclusions: Individuals with obesity and metabolic dysfunction demonstrated significantly higher AFLD prevalence compared with metabolically healthy normal-weight individuals. MOPs incorporating MS demonstrated stronger associations with AFLD than classifications based on metabolic health status alone. These findings support the importance of screening strategies that address both obesity and metabolic dysfunction in addition to alcohol use to better identify high-risk populations. Full article

Semaglutide and tirzepatide, glucagon-like peptide-1 (GLP-1) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists, respectively, have revolutionized the management of type 2 diabetes mellitus and obesity. Beyond their established metabolic indications, emerging preclinical and clinical evidence suggests these incretin-based therapies exert pleiotropic effects across multiple organ systems through mechanisms extending beyond glycemic control and weight reduction. This comprehensive review synthesizes current evidence for unconventional applications of semaglutide and tirzepatide across five distinct therapeutic domains: oncology, psychiatry and addiction medicine, orthopedics, aesthetic medicine, and human reproduction. In oncology, both agents demonstrate antitumor activity primarily through immune and metabolic reprogramming rather than direct cytotoxicity, with promising signals in pancreatic, thyroid, breast, and colorectal cancers. In psychiatry, modulation of mesolimbic dopamine reward pathways and GABAergic neurotransmission underlies robust preclinical and observational evidence for reducing alcohol use disorder, substance use, and binge-eating behaviors. Orthopedic applications include clinically meaningful improvements in knee osteoarthritis pain and function, though bone health signals remain mixed. Aesthetic medicine faces the dual challenge of managing GLP-1 receptor agonist-associated facial volume loss while exploring therapeutic potential in inflammatory dermatoses. In reproductive medicine, metabolic improvements translate to benefits in polycystic ovary syndrome and male fertility, though periconception safety concerns persist. Across all domains, evidence derives predominantly from preclinical models, observational cohorts, and pharmacoepidemiologic studies, with randomized controlled trials remaining limited. This review critically evaluates mechanisms, efficacy signals, safety considerations, and research priorities for each application domain, providing a roadmap for translating unconventional uses of semaglutide and tirzepatide into evidence-based clinical practice. Full article

Alcohol exposure during pregnancy leads to fetal alcohol spectrum disorders (FASD), yet the mechanisms through which alcohol disrupts the developing cerebrovasculature remain poorly defined. Acetaldehyde, the first oxidative metabolite of alcohol, can alter vascular function, but whether developing cerebral arteries possess intrinsic capacity to generate acetaldehyde is unknown. Alcohol is primarily oxidized by alcohol dehydrogenase (ADH), cytochrome P450 2E1 (CYP2E1), and catalase (CAT), and their local metabolic activity may contribute to cerebrovascular vulnerability. In this study, cerebral arteries were isolated from postnatal day (PND) 10 C57BL/6J mouse offspring (third trimester-equivalent to human pregnancy), and incubated ex vivo with physiologically relevant alcohol concentrations (13 or 50 mM). Acetaldehyde generation, transcript expression, protein abundance, and catalase-dependent metabolism were evaluated. Alcohol exposure produced a concentration-dependent increase in acetaldehyde generation within developing cerebral arteries, with comparable responses between males and females. Transcript analysis revealed that Adh1, Cyp2e1, and Cat were expressed across developing tissues; however, Western blotting showed that catalase was the only alcohol-metabolizing enzyme detectable at the protein level within developing cerebral arteries. Accordingly, catalase inhibition by sodium azide altered acetaldehyde production, revealing a significant blocker–sex interaction at the higher inhibitor concentration (0.06 mM). In summary, our ex vivo findings demonstrate that developing cerebral arteries possess intrinsic metabolic capacity to oxidize alcohol to acetaldehyde and that catalase plays an essential role in supporting this process at this developmental stage. These results point to a previously unrecognized metabolic pathway within the developing cerebrovasculature that may potentially contribute to early-life vulnerability to alcohol exposure. Full article

Cleft lip and palate (CL/P) are among the most common congenital craniofacial anomalies, arising from disruptions in facial development during early embryogenesis. These conditions show significant clinical and genetic heterogeneity and are broadly classified into syndromic and nonsyndromic forms. The objective of this review is to summarize current knowledge on the embryological, genetic, and molecular mechanisms underlying CL/P and to highlight their clinical implications. A comprehensive review of the literature was conducted, focusing on studies in developmental biology, human genetics, and genomics related to CL/P. Emphasis was placed on both syndromic and nonsyndromic forms, including findings from genome-wide association studies, gene mutation analyses, and investigations of gene–environment interactions. Syndromic clefting is frequently associated with pathogenic variants in genes such as IRF6, TP63, and TBX22, which play key roles in epithelial differentiation, transcriptional regulation, and palatal development. In contrast, nonsyndromic CL/P results from complex interactions between multiple genetic variants and environmental factors. Genome-wide association studies have identified numerous susceptibility loci, many located in noncoding regulatory regions active during craniofacial development. Environmental influences, including maternal nutrition, smoking, alcohol exposure, and folate metabolism, have been shown to significantly modify risk. CL/P is a multifactorial condition involving intricate interactions between genetic and environmental factors. Advances in genomics and developmental biology have enhanced understanding of its etiology and are contributing to improved risk assessment, diagnosis, and the development of future precision medicine approaches. Full article

Iodine-based antimicrobial materials are widely considered for biomedical applications due to their broad-spectrum antimicrobial activity; however, their potential genotoxicity requires systematic evaluation prior to clinical use. The aim of this study was to assess the genotoxic potential of a dextrin–polyvinyl alcohol–iodine (D/PVA/I-1) complex in accordance with OECD guidelines. Genotoxicity was evaluated in vitro using two complementary assays: the mammalian cell micronucleus test (OECD TG 487) in L5178Y TK^+/− cells and the bacterial reverse mutation assay (Ames test, OECD TG 471) using Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and Escherichia coli WP2 uvrA, both in the presence and absence of metabolic activation (S9). In the micronucleus assay, no statistically significant increase in micronucleus frequency was observed at concentrations ranging from 0.039 to 0.625 mg/mL compared with the negative control. In the Ames test, no increase in revertant colony numbers was detected in any tested bacterial strain at concentrations up to 1250 μg/plate. At higher concentrations, pronounced cytotoxic and bactericidal effects were observed without evidence of mutagenic activity. Overall, the results demonstrate that the D/PVA/I-1 complex does not exhibit genotoxic or mutagenic potential under the tested in vitro conditions, indicating a favorable genetic safety profile and supporting further preclinical evaluation for potential biomedical applications. Full article