Search Results (15,562)

Background: Testosterone deficiency is highly prevalent in men with obesity and type 2 diabetes mellitus and often reflects functional suppression of the hypothalamic–pituitary–gonadal (HPG) axis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used in these conditions, but their effects on male reproductive endocrinology remain incompletely defined. Objective: To systematically review the effects of GLP-1 receptor agonists on testosterone, HPG axis hormones, and male reproductive outcomes. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed/MEDLINE, Cochrane, and Google Scholar were searched (January 2021–January 2026) for studies evaluating GLP-1 RA therapy in adult men with reported endocrine or reproductive outcomes. Results: Eight studies met inclusion criteria, including one randomised placebo-controlled crossover trial and six observational or interventional studies. In men with obesity, type 2 diabetes, or functional hypogonadism, GLP-1 RAs were associated with modest increases in testosterone and improvements in erectile function or selected semen parameters. In contrast, a placebo-controlled trial in healthy eugonadal men showed no significant endocrine or reproductive effects. Responses appeared dependent on baseline metabolic status. Conclusions: GLP-1 RAs are associated with improvements in male reproductive endocrinology in metabolically compromised populations with metabolic hypogonadism while remaining neutral in healthy individuals. Larger prospective studies are needed. Full article

Chronic kidney disease (CKD) is a major public health problem worldwide, affecting over 10% of the global population, and its prevalence continues to increase. In addition to classic comorbidities, including cardiovascular and metabolic disorders, cognitive impairment (CI) has recently been recognized as a serious complication of CKD. CI can be observed across the entire spectrum of CKD, from G1 to G5 stages, independent of age-related changes. The kidney–brain axis seems to provide a conceptual framework in which microvascular disease, blood–brain barrier disruption, uremic toxins, oxidative stress, systemic inflammation, and consequent neuroinflammation converge to promote CI. This narrative review aims to synthesize the existing evidence on stage-dependent molecular mechanisms of CI in CKD, integrating clinical observations with proposed molecular and pathophysiological mechanisms. Because most studies investigating CI in CKD rely primarily on eGFR-based staging, our analysis was structured around GFR categories, assessing early-to-moderate CKD, defined according to KDIGO as G1–G3 stages, advanced CKD stages, including G4–G5 not yet requiring kidney replacement therapies, and kidney failure treated with different modalities of kidney replacement therapy, such as peritoneal dialysis, hemodialysis, and kidney transplantation. In addition to clinical observations and the burden of CI in CKD, we describe the potential stage-dependent pathomechanisms underlying vascular-executive, uremic-toxic, inflammatory, dialysis-hemodynamic, and post-transplant medication-related profiles as a continuum of cognitive disorders in individuals with CKD. Full article

Background/Objectives: Menopause is a complex physiological transition characterized by progressive estrogen deficiency and systemic biological changes that can affect multiple organs and tissues, including the oral cavity. Growing evidence suggests that hormonal fluctuations during the menopausal transition may influence periodontal health, salivary function, oral sensory perception, and overall oral health-related quality of life. Objective: This narrative review aims to provide a comprehensive overview of the biological mechanisms and clinical manifestations associated with the relationship between menopause and oral health, with particular attention to periodontal outcomes, salivary changes, oral discomfort, dental status, and the potential role of hormone replacement therapy (HRT). Methods: This narrative review was based on a structured literature search conducted in PubMed/MEDLINE and Scopus to identify studies published between January 2005 and May 2026. Predefined eligibility criteria were applied to identify relevant human studies. The retrieved evidence was synthesized narratively according to major oral health domains and menopausal phenotypes. Results: Fifty studies met the inclusion criteria. Overall, menopause was associated with poorer periodontal parameters, including increased probing depth, clinical attachment loss, and periodontal inflammation. Reduced salivary flow, dry mouth, altered salivary composition, burning symptoms, and taste disturbances were frequently reported in peri- and postmenopausal women. A higher prevalence of caries and tooth loss was also reported, although the contribution of age and other confounding factors varied across studies. New evidence suggests that estrogen deficiency may influence oral health through interconnected pathways involving immune regulation, bone metabolism, salivary gland function, and host–microbiome interactions. Evidence regarding the effects of HRT has been mixed, although several studies have reported improvements in salivary function and periodontal outcomes among treated women. Conclusions: Menopause appears to act as an important systemic modifier of oral health through multifactorial biological mechanisms. Menopause-associated oral manifestations go beyond local tissue changes and reflect broader interactions between hormonal status, inflammation, bone metabolism, and microbial ecology. Increased awareness among dental and medical professionals and a multidisciplinary approach could improve the prevention, diagnosis, and management of oral diseases in postmenopausal women. Further, well-designed longitudinal studies are needed to clarify causal relationships and identify effective therapeutic strategies. Full article

Antibiotic resistance genes (ARGs) have been widely recognized as emerging environmental contaminants due to their potential threats to public health and ecosystems. Owing to the extensive use of antibiotics in clinical, agricultural, and aquaculture settings, large quantities of ARGs are continuously introduced into the natural environment. As a result, aquatic environments—particularly surface waters—act as important reservoirs and transmission pathways for ARGs. However, despite the Yellow River being a major surface river in northern China, the occurrence and sources of ARGs in this river remain poorly understood. In this study, shotgun metagenomic sequencing was applied to investigate the composition of ARGs, mobile genetic elements (MGEs), and virulence factors (VFs) in three water sources in the Baotou section of the Yellow River. A total of 35 types of ARGs, 3 types of MGEs, and 14 categories of VFs were identified across all samples. Among them, multidrug resistance genes, peptide resistance genes and glycopeptide resistance genes exhibited relatively high abundances, indicating their widespread distribution in the study area. In terms of MGEs, recombinases and transposases were dominant, suggesting their important roles in gene mobilization. Meanwhile, VFs were mainly associated with metabolic functions, immune modulation, and adherence, reflecting the potential pathogenic risks in the aquatic environment. Co-occurrence networks revealed extensive associations between ARGs and MGEs, as well as ARGs and VFs. Many positive correlations were observed, suggesting possible ecological associations between ARGs and MGEs and potential co-selection between ARGs and VFs. Overall, this study provides valuable insights into the distribution patterns and co-occurrence patterns of ARGs, MGEs, and VFs in the Yellow River and offers a scientific basis for the management and control of antibiotic resistance pollution in large river systems. Full article

Background/Objectives: Major depressive disorder (MDD) has been increasingly associated with alterations of the gut microbiome through the microbiota–gut–brain axis. However, published findings remain highly heterogeneous, limiting identification of reproducible microbial signatures associated with depression. This systematic review aimed to evaluate reproducible taxonomic and functional gut microbiome alterations in patients with MDD compared with healthy controls. Methods: A systematic literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science Core Collection, and the Cochrane Library for studies published between January 2016 and December 2025. Observational human studies evaluating gut microbiome composition in adults with clinically diagnosed MDD and healthy control groups were included. Methodological quality was assessed using the Newcastle-Ottawa Scale. Due to substantial methodological heterogeneity, findings were synthesized using structured qualitative narrative analysis. Results: Sixteen observational studies were included in the qualitative synthesis. Findings related to alpha diversity were inconsistent across studies, whereas beta diversity alterations demonstrated greater reproducibility across independent cohorts. The most recurrent microbiome pattern involved depletion of short-chain fatty acid (SCFA)-producing bacteria, particularly Faecalibacterium and Roseburia, together with recurrent alterations affecting members of the Ruminococcaceae, Lachnospiraceae, and Clostridia groups. Functional microbiome alterations demonstrated greater consistency than higher-level taxonomic findings and included reduced butyrate synthesis pathways, dysregulated amino acid and tryptophan metabolism, increased lipopolysaccharide biosynthesis, and enrichment of pro-inflammatory microbial signatures. Antidepressant-naïve cohorts generally demonstrated more homogeneous dysbiosis patterns than mixed-treated populations. Conclusions: Current evidence suggests that functional gut microbiome dysregulation may represent a more reproducible biological feature of MDD than isolated taxonomic alterations alone. However, substantial heterogeneity in study design, participant characteristics, sequencing methodologies, and analytical approaches continues to limit clinical translation. Large-scale longitudinal multi-omics studies using standardized methodologies are required to clarify the role of the gut microbiome in depressive disorders and to evaluate the potential utility of microbiome-based biomarkers and interventions in mental health and public health practice. Full article

Rutin is a flavonoid glycoside with well-documented antioxidant and anti-inflammatory activities in preclinical models, but its oral bioavailability is poor due to extensive presystemic metabolism. Following oral administration, intact rutin reaches the colon largely unabsorbed, where gut microbiota convert it to quercetin aglycone, which is further metabolized to circulating conjugated metabolites and local phenolic acid derivatives. Accumulating evidence, derived predominantly from preclinical studies, suggests this metabolic activation can be usefully conceptualized as a microbiota-activated prodrug system. This challenges conventional formulation strategies that only increase parent compound exposure. In this review, we propose a metabolism-oriented conceptual framework for oral rutin delivery design. We compare nano-delivery systems and structural modifications strategies across pharmacokinetics, metabolic regulation, safety, manufacturability, and translational feasibility. Nano-delivery systems are functionally reclassified into four absorption, distribution, metabolism, excretion (ADME) -oriented categories based on their primary pharmacokinetic objectives. While numerous preclinical studies report improved bioavailability and efficacy, human metabolite-resolved pharmacokinetic data remain extremely limited, and no European Food Safety Authority (EFSA) -authorized health claims exist for rutin. This review provides a new conceptual framework for selecting oral rutin delivery strategies based on metabolic objectives rather than solely on improving solubility or systemic exposure. Full article

Background: We compared biochemical, micronutrient-related and complete blood count (CBC)-derived inflammatory profiles among children with obesity, undernutrition and normal weight, and explored the discriminatory performance of selected routine laboratory markers for the obesity phenotype. Methods: In this single-centre retrospective comparative study, medical records of children aged 2–17 years evaluated between January 2023 and December 2025 were reviewed. Participants were classified as obese, undernourished or normal weight using World Health Organization (WHO) body mass index-for-age (BMI-for-age) references. Liver enzymes, lipid parameters, iron-related indices, micronutrient levels, zinc, insulin and CBC-derived inflammatory indices were compared across groups using non-parametric omnibus tests. Exploratory receiver operating characteristic (ROC) analyses were performed for selected markers. Results: A total of 690 children were included: 100 with obesity, 90 with undernutrition and 500 with normal weight. The obesity group was significantly older than the normal-weight group (median 11.0 vs. 7.5 years; p < 0.001). Obesity was characterised by higher alanine aminotransferase (ALT), insulin, triglycerides, neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI), together with lower high-density lipoprotein (HDL) cholesterol, 25-hydroxyvitamin D [25(OH)D] and aspartate aminotransferase-to-alanine aminotransferase (AST/ALT) ratio (all p < 0.05). In exploratory, age-unadjusted ROC analyses, the AST/ALT ratio yielded the highest AUC among the evaluated biomarkers (AUC 0.859; 95% CI 0.823–0.895; optimal cut-off ≤ 1.52; sensitivity 77.0%; specificity 77.6%), followed by SIRI (AUC 0.751; 95% CI 0.700–0.802). Conclusions: Pediatric obesity was associated with a distinct liver enzyme-metabolic-inflammatory laboratory profile, whereas undernutrition exhibited a different micronutrient-biochemical pattern. Because the study was retrospective and age-unadjusted, these findings should be interpreted as exploratory and hypothesis-generating. Prospective studies with age-balanced sampling, pubertal staging and liver imaging are required before clinical implementation. Full article

Background/Objectives: Flavonoids are a diverse group of dietary polyphenolic compounds associated with a range of important biological activities. However, their low systemic bioavailability and extensive metabolism raise questions about how they exert their purported benefits. Methods: A comprehensive survey of literature published over the past 10 years was conducted, focusing on human, animal, and in vitro studies addressing the metabolic fate of major flavonoid subclasses. Results: Original research articles (n = 159) were selected following predetermined inclusion criteria. Data from diverse experimental models—including intestinal and hepatic systems—demonstrate that flavonoids undergo substantial transformation by Phase I and Phase II enzymes, alongside extensive biotransformation by the gut microbiota. In this critical narrative review we summarize dietary sources, bioavailability patterns, metabolic pathways, and analytical strategies, emphasizing advances enabled by high-resolution mass spectrometry. Recent findings indicate that enterohepatic recirculation and the biological activities of circulating and tissue-associated metabolites contribute significantly to the observed health effects, despite limited levels of parent compounds. Conclusions: Flavonoids exhibit limited oral bioavailability and undergo complex metabolic processing, yet growing evidence indicates that their metabolites play key roles in mediating beneficial effects. Understanding these metabolic pathways is essential for interpreting epidemiological associations and designing more effective intervention studies. Full article

Chickpea (Cicer arietinum L.) is a highly nutritious legume with significant potential as a food plant. With the advent of climate change and the challenge of feeding a growing population, strategies to produce high-nutrient crops are of utmost importance. In this context, this study describes how light intensity and wavelength affect the embryonic axis of chickpea sprout metabolism, using untargeted metabolomics. Chickpea sprouts were grown under varying light wavelengths (red—650, green—550, and blue—450 nm) at two intensities (75 and 275 µmol·m⁻²·s⁻¹). Analyses were restricted to the embryonic axis (hypocotyl), excluding the cotyledons, which are a reserve-rich tissue. Results showed that high-intensity red light (RH) increased phenolic content by more than 300% compared to controls. Green and blue light treatments significantly increased the protein content by more than twice that of the dark control. Antioxidant activity was significantly higher in sprouts grown under high-intensity blue light (BH). Additionally, the results suggested that pathway regulation is affected not only by wavelength but also by light intensity, with greater significance and effect under BH and RH treatments in isoflavonoid biosynthesis. High quercetin concentration found under BH is hypothesized to explain the high antioxidant activity when compared to the rest. For instance, these findings highlight the potential of light manipulation to modulate and enhance the nutritional and functional qualities of chickpea sprouts’ embryonic axis, contributing to food security and human health. Further studies need to be conducted to answer whether these metabolite changes directly translate to the nutritional quality of the whole edible sprouts. Full article

Iron (Fe) and selenium (Se) deficiencies are global health concerns associated with adverse health outcomes. Plants constitute a dietary source of these elements, particularly for individuals following plant-based diets. However, plant Fe availability is limited by soil processes that reduce Fe mobility and uptake, whereas Se accumulation is constrained by the low abundance of Se in soils. Increasing Fe and Se concentrations in edible plant parts through biofortification represents a sustainable strategy to alleviate micronutrient deficiency. This review examines the mechanisms governing Fe and Se uptake, translocation, metabolism, and genetic regulation, and discusses current biofortification strategies, including agronomic practices, natural and microbial-based approaches, conventional breeding and marker-assisted selection, transgenic technologies, and nanoparticles. While cereals remain the principal targets of large-scale biofortification programs, recent advances in horticultural crops are also highlighted because of their growing nutritional and commercial importance. Current evidence indicates that integrated agronomic and genetic approaches are more effective than single interventions, although simultaneous Fe and Se biofortification remains largely underexplored. Successful biofortification is also strongly influenced by soil properties, nutrient interactions, and crop genotype. Emerging tools, including plant–microbe interactions and synthetic biology, offer promising opportunities to enhance micronutrient accumulation and bioavailability. Further research should optimize integrated Fe–Se biofortification strategies while addressing agronomic and socioeconomic constraints to support their large-scale adoption and contribute to sustainable food systems. Full article

Improving the nutritional quality of food through advanced and sustainable agricultural practices has become a key objective of modern vegetable crop production. Emphasis is placed on increasing the content of health-promoting bioactive compounds, such as vitamins and polyphenols, particularly flavonoids whose accumulation is strongly affected by various biotic and abiotic stress factors. To mitigate stress-induced limitations and enhance plant performance, biostimulants are increasingly applied. Among them, Trichoderma spp. are widely recognized for their ability to promote plant growth and resilience, primarily through enzymatic activity and the production of bioactive metabolites. The aim of this study was to evaluate the potential of the native Trichoderma sp. strain STP8 to enhance the production of bioactive compounds through seed and soil applications at planting and 26 days after planting (DAP), applied individually or in combination. A spore suspension (4 × 10⁶ spores mL⁻¹) was used. The experiment was arranged in a randomized complete block design with five replicates. At harvest (43 DAP), dry matter, ascorbic acid, chlorophyll, and carotenoid contents were determined. Additionally, flavonoids and non-flavonoids, total phenolics, individual phenolic compounds, and antioxidant capacity were analyzed. Achieved results demonstrate that the effects of the native Trichoderma sp. strain STP8 on lettuce secondary metabolism and antioxidant properties are strongly dependent on the developmental stage at which inoculation is performed, providing further insight into the stage-specific interactions between plans and Trichoderma. Practically, a single application at planting proved to be the most effective strategy for enhancing the accumulation of bioactive compounds, indicating that optimized application timing may improve the efficacy of Trichoderma-based biostimulants, while avoiding unnecessary repeated applications. These findings support the potential use of native Trichoderma strains as sustainable tools for improving the nutritional and functional quality of lettuce. Further research integrating physiological, biochemical, and molecular analyses is required to elucidate the mechanisms by which the native Trichoderma sp. strain STP8 regulates the biosynthesis of bioactive compounds in lettuce. Full article

Recovery in elite athletes represents a critical determinant of performance and health outcomes. The gut microbiota has been proposed as a modulating factor for recovery through anti-inflammatory mechanisms, oxidative stress management, sleep regulation, and biosynthetic potential for essential micronutrients. This review examines the mechanisms linking gut microbiota composition and function to athletic recovery and critically evaluates the evidence supporting its application in sports medicine. Athletes appear to harbor a more enriched microbial biosynthetic potential, with substantially greater numbers of high-biological-impact synthases involved in the production of vitamins, amino acids, and bioactive metabolites. Short-chain fatty acids, particularly butyrate and propionate, have demonstrated anti-inflammatory effects in preclinical studies, with emerging evidence in humans. The gut–brain axis has been proposed to modulate recovery by regulating neurotransmitter production and controlling circadian rhythms. Sport-associated microbial signatures seem to reflect metabolic demands, with endurance athletes showing enrichment for Prevotella and Veillonella, while strength athletes tend to harbor higher levels of proteolytic bacteria. Probiotic interventions with multi-strain Lactobacillus and Bifidobacterium formulations have reported reductions in inflammatory markers, improvements in oxidative stress biomarkers, and enhanced sleep quality in small-scale randomized controlled trials involving athletic populations, and improvements in self-reported sleep quality in a controlled, non-randomized study in elite athletes. Optimizing gut microbiota composition and function offers a promising complementary strategy for enhancing recovery in elite athletes. Potential applications that require prospective validation include sport-specific probiotic interventions, nutritional strategies to enhance short-chain fatty acid production, and the integration of microbiota assessment with traditional recovery monitoring. Further research is needed to establish standardized protocols and identify predictive biomarkers of individual response to microbiota-targeted interventions. Full article

Functional meals are emerging, encompassing complete meal systems designed to deliver physiological benefits through food synergy, interactions with the food matrix, and optimized release of bioactive compounds. This narrative review examines the role of bioactive compounds in functional meals, with particular emphasis on bioavailability, food matrix effects, technological approaches, and health implications. Bioactive compounds can contribute to cardiometabolic, anti-inflammatory, gastrointestinal, and neuroprotective effects. However, their biological efficacy depends not only on their concentration in foods but also on their release from the food matrix, stability during processing and digestion, intestinal absorption, microbiota-mediated transformation, and post-absorptive metabolism. Therefore, functional meals represent complex systems in which food structure, culinary preparation, processing intensity, co-ingested nutrients, and host-related factors determine the final physiological response. Emerging technologies, including microencapsulation and nanoencapsulation, offer promising strategies to improve the stability, bioaccessibility, targeted release, and sensory acceptability of bioactives. Future research should prioritize well-designed human studies, standardized methodologies, clinically relevant outcomes, personalized nutritional approaches, and sustainable food system integration to support the development of effective, evidence-based functional meal strategies. Full article

As obesity, diabetes and other diet-related metabolic disorders continue to rise, non-nutritive artificial sweeteners (NASs) are widely used as sugar substitutes in free-sugar reduction and weight-management strategies, but their effects on the gut microbiota, host metabolism and related health outcomes remain debated. To clarify this evidence landscape, this review synthesizes current knowledge on the effects of major NAS on the gut microbiota and host metabolic and health-related outcome. A bibliometric analysis was conducted to characterize the development, knowledge structure and thematic evolution of this research area. For the eight NAS exposure categories included in this review (saccharin, cyclamate, aspartame, acesulfame potassium, sucralose, neotame, neohesperidin dihydrochalcone and mixed NAS), we performed a compound-specific analysis integrating physicochemical characteristics, regulatory status, and research findings from in vitro, ex vivo, animal and human studies on gut microbiota alterations, host metabolic and health-related outcomes. These findings were further compared through four interpretive dimensions: exposure conditions, research model background, outcome assessment and interpretation of discordant results. Current research evidence does not support a class-wide conclusion that NAS are uniformly harmful or safe. To make research findings searchable, we developed the NAS-MAP knowledge graph, an interactive non-nutritive artificial sweetener–microbiota-associated phenotype knowledge graph. Overall, this review consolidates current knowledge, clarifies the sources of inconsistent findings, and provides a framework for more mechanistically informative studies, standardized evidence reporting, and more precise sweetener-, exposure- and population-specific dietary and public health guidance. Full article