Search Results (13,690)

Endometriosis is characterized by enhanced cellular proliferation, migration, and resistance to apoptosis, contributing to lesion persistence and progression. Targeting cellular plasticity and mesenchymal-associated functions may therefore represent a promising therapeutic strategy. Here, we investigated the effects of Pelargonium graveolens essential oil (PGEO) on proliferation, apoptosis, migration, cytoskeletal organization, transcriptional regulation, and metabolic alterations in human endometriotic 12Z cells. PGEO treatment suppressed proliferative capacity in a concentration-dependent manner and significantly impaired cell migration, accompanied by reduced β-tubulin expression and decreased levels of mesenchymal-associated markers CD73 and CD105. Increased GRP78 expression together with ultrastructural alterations, including cytoplasmic vacuolization and mitochondrial and endoplasmic reticulum changes, indicated activation of cellular stress responses. Although transcriptional analysis revealed increased CCND1 and PIK3CA mRNA levels, these changes did not parallel the observed suppression of proliferation, suggesting compensatory regulatory responses. Untargeted metabolomic profiling revealed alterations in energy metabolism characterized by increased levels of glycolysis-related metabolites, reduced levels of several amino acids including glutamine and histidine, and changes in lipid-associated metabolites. Collectively, these findings demonstrate that PGEO suppresses proliferative and migratory behavior in endometriotic cells while modulating cytoskeletal, transcriptional, and metabolic pathways, highlighting its potential as a candidate for further investigation in endometriosis-targeted therapeutic strategies. Full article

Risk stratification of impaired glycemic control remains a major challenge in biomedical data analysis due to heterogeneous metabolic, behavioral, and therapeutic factors observed in large-scale populations. This study proposes a calibrated and interpretable decision–support framework, termed Calibrated Multi-Task Stacking Ensemble (CMSE), for joint modeling of clinically related glycemic outcomes. The framework integrates demographic variables, lipid profiles, renal and inflammatory biomarkers, dietary and smoking indicators, and therapy-related features within a unified predictive architecture. Robust modeling is ensured through leakage-aware preprocessing, quantile-based Winsorization, out-of-fold stacking, and isotonic calibration of probabilistic outputs. The physiological coherence between short-term and long-term glycemic markers is investigated using an explicit intertask coupling mechanism based on the estimated average glucose (eAG) ratio. Model interpretability is supported using SHAP analysis, mutual information, distance correlation, and feature importance metrics. In the primary medication-free screening configuration, the framework is evaluated on the NHANES 2017–March 2020 dataset, achieving ROC-AUC of 0.865 for diabetes classification and R² values of 0.385 and 0.366 for plasma glucose and HbA1c prediction, respectively. These results indicate that CMSE provides a reliable and explainable approach for calibrated glycemic risk assessment and clinical decision support. Full article

Long-chain polyunsaturated fatty acids (LC-PUFAs) of omega-3 family, particularly docosahexaenoic acid and eicosapentaenoic acid, are essential nutrients that play a critical role in children’s growth and health. This review examines the evidence on the effects of omega-3 supplements and omega-3-enhanced foods on children’s development, as well as on neurological and metabolic disorders. Research consistently highlights the importance of DHA in brain and visual development, especially during early childhood, when rapid neural growth occurs. PubMed, Web of Science, Scopus and the Cochrane Library databases were searched for relevant articles published up to January 2026. Adequate omega-3 intake has been associated with improvements in cognitive performance, attention, and learning outcomes. In children with neurodevelopmental conditions such as attention-deficit/hyperactivity disorder and autism spectrum disorder, omega-3 supplementation shows modest but potential benefits in reducing behavioral symptoms and supporting executive function, although results remain mixed. Additionally, omega-3 fatty acids exhibit anti-inflammatory properties that may positively influence metabolic health, including lipid profiles, insulin sensitivity, and obesity-related risk factors in children. Omega-3-enhanced foods provide an alternative to supplements and may improve adherence and overall dietary quality. However, variability in dosage, study design, and baseline nutritional status limits definitive conclusions. Overall, omega-3 fatty acids appear to support healthy development and may aid in managing certain neurological and metabolic disorders in children. Full article

Background. Cardiometabolic diseases (CMDs) have become a major health concern among adults living with HIV (ALWH) as antiretroviral therapy (ART) extends life expectancy. Metabolic syndrome (MetS)—a cluster of abdominal obesity, hypertension, hyperglycemia, hypertriglyceridemia, and hypoalphalipoproteinemia—is a key predictor of CMD risk. Despite high HIV prevalence in Panama, data on MetS among ALWH are scarce. Thus, the Colón C3 Study aimed to estimate the prevalence of MetS and its criteria in a large cohort of ALWH in Colón, Panama. Methods. Between April–December 2024, 659 ALWH aged ≥18 years were enrolled at the province’s sole ART Clinic (78.1% of active patients). Participants completed a computer-assisted survey on demographics and social determinants of health (SDoH), underwent anthropometry and body composition assessment, and provided ≥8 h fasting blood samples for glucose, lipid profiles, HbA1c, and high-sensitivity C-reactive protein (hsCRP). MetS was defined using NCEP-R ATP-III criteria, and analyses were stratified by sex. Results. Mean age was 43.9 (range 18–79) years; 55% were female, and 51% identified as Black/Afro-Caribbean. The overall prevalence of MetS was 38.6% (binomial 95% CI 34.5%, 42.9%), exceeding pooled estimates for ALWH in the Americas (30.4%). Among individual criteria, hypoalphalipoproteinemia (59.6%) and hypertension (52.6%) were most prevalent, followed by abdominal obesity (45.2%), hyperglycemia (33.5%), and hypertriglyceridemia (22.5%). Women exhibited significantly higher body fat mass and BMI than men. Mean hsCRP was 7.2 mg/L, indicating persistent inflammation despite virologic suppression. Socioeconomic vulnerabilities, food insecurity (30%), and housing instability (>40%) were common. Conclusions. Findings reveal a substantial cardiometabolic burden among ALWH in Colón and underscore the need for integrated HIV–CMD care models, earlier screening, and natal sex–responsive interventions. The results provide foundational evidence for improving long-term, equitable cardiometabolic outcomes in HIV care across Panama and the broader Latin American region. Full article

Personalized transdermal drug delivery systems (TDDS) represent a transformative approach in precision medicine by enabling patient-specific, non-invasive, and controlled therapeutic administration. Conventional transdermal patches are limited by fixed dosing, passive diffusion, and interindividual variability in skin permeability and metabolism, often leading to suboptimal therapeutic outcomes. Recent advances in materials science, nanotechnology, microneedle engineering, and digital health have enabled the development of next-generation personalized TDDS capable of programmable, adaptive, and feedback-controlled drug release. Smart wearable patches integrating biosensors, microfluidics, microneedles, and wireless connectivity allow real-time monitoring of physiological and biochemical parameters, enabling closed-loop drug delivery tailored to individual metabolic profiles. Nanocarriers such as lipid nanoparticles, polymeric nanoparticles, and stimuli-responsive hydrogels further enhance drug stability, penetration, and controlled release, while 3D-printing technologies facilitate patient-specific customization of patch geometry, drug loading, and release kinetics. Artificial intelligence (AI) and machine learning tools are increasingly being employed to predict drug permeation behavior, optimize enhancer combinations, and personalize dosing regimens based on pharmacogenomic and pharmacokinetic data. Despite these advances, regulatory complexity, manufacturing standardization, long-term biocompatibility, and cybersecurity considerations remain critical challenges for clinical translation. This review highlights recent innovations in personalized TDDS, discusses their clinical potential, and examines regulatory and technological barriers. Collectively, these emerging smart transdermal platforms offer a promising pathway toward adaptive, patient-centered therapeutics that can significantly improve treatment efficacy, safety, and compliance. Future research should focus on integrating multimodal biosensing, advanced biomaterials, scalable manufacturing strategies, and robust regulatory frameworks to enable clinically validated, fully autonomous transdermal systems that can dynamically adapt to real-time patient needs in diverse therapeutic settings. Full article

This study evaluated the fermentative potential of eight industrial strains of Saccharomyces cerevisiae for producing mead from honeys originating from the Caatinga Biome in the semi-arid region of Pernambuco, Brazil. Despite presenting similar ethanol yields around 0.38 g/g, the strains differed in fermentation rate, residual sugar profile, and metabolic composition of the final products. Saccharomyces cerevisiae strains Renaissance TR313 and Fermol Distiller JP1 were selected for more detailed analyses, with JP1 standing out for its higher volumetric productivity (0.23 g/L/h) and shorter fermentation time of 20 days. Further fermentations demonstrated that increasing biomass, supplementing with the inorganic nitrogen source ammonium sulphate, or cell immobilization accelerates fermentation without compromising yield. Thus, the JP1 strain shows promise as a ferment for producing regionally identified mead from honeys typical of the Caatinga biome of the semi-arid Northeast of Brazil. The use of this strain with the honey of the Sertão can characterize the regional product and increase its value. Full article

Dictyophora rubrovolvata is highly regarded and increasingly cultivated in China for its nutritional value, unique taste, and medicinal properties. However, the chemical composition of fresh D. rubrovolvata is unclear. This study applied a comprehensive metabolomic analysis of D. rubrovolvata to characterize and compare the metabolite profiles and identify significantly differential metabolites from three geographical origins in China. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) combined with chemometrics was employed to conduct untargeted metabolomics analysis of fresh D. rubrovolvata samples collected from the Sichuan, Fujian, and Guizhou provinces in China. Among the 383 identified metabolites, lipids and organic acids were the predominant classes. There were notable variations in metabolite composition across the three geographical areas. The Sichuan (SC) group showed a high concentration of phospholipids, the Guizhou (GZ) group was characterized by specific oxidized lipids and bioactive benzenoids, and the Fujian (FJ) group showed elevated levels of the antioxidant ergothioneine. We identified 17 unique metabolites, including tryptophol, 12-oxophytodienoic acid, and various fatty acid derivatives, which may act as significantly differential metabolites for different origins. Analysis of KEGG enrichment indicated that the main metabolic pathways involved were tryptophan metabolism, glycerophospholipid metabolism, and phenylpropanoid biosynthesis. Full article

Soil salinization poses an escalating threat to global crop production. Extracellular polysaccharides (EPSs) secreted by plant growth-promoting rhizobacteria have the potential to improve the salt tolerance of crops. Here, we tested the effects of Pantoea alhagi NX-11 EPSs on the growth, physiological traits, and root proteomic profiles of rice under salt stress. We found that NX-11 EPSs effectively increased the salt tolerance of rice in soil, with 50 mg/kg EPS exhibiting the strongest plant growth-promoting effect. This effect was associated with increased the K⁺/Na⁺ ratio and soluble protein content in roots induced by NX-11 EPSs as well as reduced stomatal aperture and transpiration rate in leaves. Proteomic analyses revealed that NX-11 EPSs markedly changed the protein profiles of roots. Specifically, proteins associated with cyanoamino acid metabolism, glycolysis/gluconeogenesis, and fatty acid degradation were downregulated. Together, these results suggest that NX-11 EPSs improve rice performance under salt stress, accompanied by changes in physiological traits and root protein profiles. Full article

Heat stress (HS) affects female reproductive efficiency by disrupting redox homeostasis and activating inflammatory responses in the corpus luteum (CL), a metabolically active tissue essential for pregnancy maintenance. This study reveals the protective effect of resveratrol against HS-induced luteal injury in pregnant mice through the regulation of oxidative stress and cytokine–chemokine-mediated inflammatory and immune responses. The pregnant mice were divided into three groups: control, HS, and resveratrol +HS. Heat stress was applied at 40 ± 0.5 °C for 7 days, with resveratrol (10 mg/kg) given orally 2 h before exposure to HS. The results showed that heat exposure reduced serum total superoxide dismutase activity and increased malondialdehyde level, causing significant disruption of luteal morphology with cellular disorder and vacuolization, which was partially overcome by resveratrol pretreatment. Transcriptomic profiling showed that HS induced a strong immunological and inflammatory response, involving cytokine–cytokine receptor interaction and chemokine signaling. Resveratrol significantly attenuated HS-induced transcriptional changes. The RT-qPCR results showed that HS increased chemokine ligands (Ccl11, Cxcl13, Tslp) and cytokine receptors (Ccr3, Ccr4, Ccr5), which were suppressed by resveratrol. The chemokine-based inflammatory module is one of the most important regulatory properties of the HS response, according to the network analysis. Stable binding of resveratrol with major chemokine receptors was supported by molecular docking and molecular dynamics simulations. Collectively, HS induces oxidative, structural, and inflammatory alterations in luteal tissue, while resveratrol attenuates these changes by being associated with improved antioxidant status and suppression of cytokine–chemokine-mediated responses. Full article

Benign prostatic hyperplasia (BPH) is an age-related disorder increasingly linked to chronic inflammation and redox imbalance, yet its systemic oxidative and nitrosative profile remains insufficiently characterized. In this cross-sectional study, fasting serum samples were collected from 47 men with clinically confirmed BPH scheduled for transurethral resection of the prostate and 40 healthy controls. We assessed antioxidant status (thiols, total antioxidant capacity), lipid peroxidation (malondialdehyde, 4-hydroxynonenal), protein nitration (3-nitrotyrosine), glycoxidation markers (Amadori products, advanced glycation end products (AGE)-associated fluorescence), and tryptophan metabolism indices (tryptophan, kynurenine, N′-formylkynurenine). Compared with controls, BPH patients showed significantly lower antioxidant capacity and thiol levels, together with increased lipid peroxidation and protein nitration. AGE-associated fluorescence was modestly elevated, whereas Amadori products and advanced oxidation protein products did not differ significantly. Tryptophan metabolism was markedly altered, with lower tryptophan and higher kynurenine and N′-formylkynurenine, indicating activation of the kynurenine pathway. After false discovery rate correction, most redox biomarkers remained significant. Multivariable logistic regression confirmed independent associations of lipid peroxidation, nitrosative stress, and kynurenine pathway activation with BPH after adjustment for age and metabolic parameters. These findings support a role for systemic oxidative and inflammatory mechanisms in BPH pathophysiology, although confirmation in age-matched and longitudinal studies is needed. Full article

Lentinula edodes (Berk.) Pegler, also known as Shiitake, is one of the most popular edible mushroom species containing high contents of polysaccharides, proteins and unique aroma, widely cultivated in China, Japan and Korea. A series of studies has been carried out on the extraction and active effect of the L. edodes polysaccharides, but the molecular mechanisms involved in the protein expression profiles during the whole life cycle are relatively unclear. This study employed an iTRAQ-MS/MS proteomic approach, combined with real-time quantitative PCR (qRT-PCR) and enzyme activity assays, to systematically analyze the protein expression profiles and their relationship with lignocellulose degradation in L. edodes across four key developmental stages: mycelia (SF), brown film formation (BF), primordia (YF), and fruiting bodies (MF). A total of 2043 proteins were identified, with 1188 being differentially expressed proteins (DEPs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that metabolic processes, carbohydrate metabolism, and related pathways were significantly active during development. The study specifically focused on carbohydrate-active enzymes (CAZymes), identifying 197 CAZyme proteins classified into 78 families. Key families such as glycoside hydrolases (GHs) and carbohydrate esterases (CEs) played crucial roles in lignocellulose degradation. The enzymatic activities of major lignin-degrading enzymes (laccase, manganese peroxidase, and lignin peroxidase) were dynamically regulated across the developmental stages. qRT-PCR results largely corroborated the proteomic data, confirming the reliability of the protein expression profiles. This study provides a comprehensive, stage-resolved proteomic landscape of lignocellulose degradation during L. edodes development, revealing species-specific temporal dynamics, offering a valuable basis for understanding its growth and development, with implications for edible fungus cultivation and biomass conversion applications. Full article

Nitrogen metabolism is fundamental to all organisms, with ammonium transporters (Amt) playing a pivotal role in transmembrane ammonium transport. Brachiopods, as “living fossils”, offer unique insights into the evolutionary adaptation of marine invertebrates. This study systematically identified and characterized the Amt gene family in the brachiopod Lingula anatina. Five canonical Amt genes were identified, with nonrandom chromosomal distribution and evidence of lineage-specific duplication events. Phylogenetic analysis revealed that these Amt proteins cluster into three well-supported clades, showing closer affinity to Caenorhabditis elegans, reflecting conserved ancestral features predating protostome radiation. Structural predictions showed that LanAmtA and LanAmtB retain the canonical 11-transmembrane helix (TMH) topology with an extracellular N-terminus, while LanAmtC features a unique 12-TMH architecture with an intracellular N-terminus, resembling certain vertebrate Amt-related proteins. Critical functional residues involved in ammonium selectivity and transport were preserved across all paralogs. Expression profiling revealed non-redundant spatiotemporal patterns: LanAmtA1 and LanAmtB2 dominate early embryogenesis, with LanAmtB2 becoming the major isoform in late developmental stages; LanAmtC exhibits constitutive high expression across adult tissues. Collectively, our findings demonstrate that the L. anatina Amt family expanded via local duplications, evolving structural stability, regulatory diversity, and functional specificity. This study provides a comprehensive molecular framework for understanding the evolutionary adaptation of nitrogen-handling mechanisms in basal lophotrochozoans and sheds light on how intertidal organisms cope with dynamic environmental conditions. Full article

Rice–crab coculture, as China’s third-largest integrated farming model, is pivotal for sustainable Chinese mitten crab aquaculture. This study conducted untargeted metabolomics and 16S rRNA gene sequencing on gut contents of crabs from rice fields and ponds, integrating metabolic and microbial profiles. We aimed to reveal the chemical traits of rice-field Chinese mitten crab linked to gut microbiota, providing scientific guidance for optimizing culture practices and developing microbial additives. Both groups were dominated by the phyla Firmicutes, Proteobacteria, and Bacteroidota, but the phylum Bdellovibrionota was not detected in group R. A total of 1271 distinct amplicon sequence variants (ASVs) were identified, which were annotated to 649 genera. At the ASV level, the Chao1 index for the R group (197.12 ± 17.88) was notably lower compared to the P group (288.75 ± 30.59) (p < 0.01). In contrast, the Shannon index for the R group (3.90 ± 0.06) was significantly greater than that of the P group (3.70 ± 0.06) (p < 0.01). The PCA plot demonstrated a distinct discrimination between the groups. The P group had more microbial species but was dominated by Candidatus_Bacilloplasma, resulting in uneven distribution. In contrast, the R group had fewer species but a more balanced distribution. Among 3531 metabolites identified in both groups, 865 differed significantly. Compared to P, 736 metabolites were significantly upregulated and 129 were significantly downregulated in R. Key metabolic pathways included amino acid, carbohydrate, cofactor and vitamin metabolism, signaling, and xenobiotics biodegradation. Group R had higher levels of L-leucine, L-phenylalanine, L-tyrosine, 2-amino-1-phenylethanol, choline, and pyrophaeophorbide a, which correlated with genera like Candidatus_Hepatoplasma and Aeromonas (p < 0.05), suggesting better nutritional value, flavor, and metabolic health in rice-field crabs. 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

Objectives: This study aims to identify the reactive metabolite of acetaminophen (AAP) and the cyanopyrrolidine metabolite of saxagliptin in human induced pluripotent stem cell-derived hepatic organoids (HHOs) and to compare them with human liver microsomes (HLMs) and plateable cryopreserved human hepatocytes (CHHs) to evaluate the feasibility of HHOs for reactive metabolite screening and metabolite profiling. Methods: AAP (50 μM) or sax-agliptin (50 μM) was incubated for 1 h at 37 °C in HLMs with or without NADPH-generating solution and 0.5 mM reduced glutathione (GSH). AAP (50 μM) was incubated for 24 h in HHOs and CHHs at 37 °C in a CO₂ incubator. AAP and saxagliptin metabolites in the reaction mixtures were analyzed using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Results: N-acetyl-p-benzoquinone imine (NAPQI) was identified in the incubation mixture of HLMs with AAP, and its levels were reduced in the presence of GSH, accompanied by increased formation of AAP–GSH adduct. Incubation of AAP with HHOs for 24 h resulted in the formation of NAPQI, AAP–GSH, AAP–glucuronide, and AAP–sulfate. Moreover, CYP1A2 induction using omeprazole treatment increased the formation of AAP and AAP–GSH conjugate from phenacetin, reflecting enhanced CYP1A2 activity in both CHHs and HHOs. The findings indicate that HHOs are a suitable platform for reactive metabolites, such as NAPQI and AAP–GSH adducts, under chronic exposure and metabolic modulator intervention. Additionally, CHHs and HHOs exhibited similar saxagliptin metabolite profiles after incubation with saxagliptin and generated cysteine conjugates of saxagliptin and its hydroxylated metabolite. Conclusions: HHOs system can be used as an in vitro model for screening reactive metabolites, comparable to those obtained with CHHs. Full article