Search Results (188)

Melatonin has evolved from its classical role as a pineal-derived circadian regulator to a molecule increasingly recognized for its mitochondrial and cytoprotective functions. This review examines the molecular mechanisms and translational implications of melatonin within a mitochondria-centered framework, with particular emphasis on reproductive medicine. Available evidence suggests that melatonin may influence mitochondrial quality control (MQC) through multiple interconnected processes, including ROS regulation, mitochondrial dynamics, mitophagy, biogenesis, and mitochondrial inflammatory signaling. In mitochondria, melatonin can attenuate electron transport chain-derived oxidative stress through direct radical-scavenging reactions, antioxidant metabolite formation, and indirect activation of endogenous antioxidant systems. Experimental studies further suggest that melatonin may modulate Drp1-mediated fission, OPA1- and Mfn1/2-associated fusion, PINK1/Parkin-mediated mitophagy, and SIRT1/PGC-1α-related mitochondrial biogenesis. In reproductive medicine, melatonin has been investigated as a potential adjunctive strategy in assisted reproductive technology, endometriosis, and polycystic ovary syndrome. However, clinical evidence remains heterogeneous, and most human studies have evaluated reproductive or biochemical outcomes rather than direct MQC-related biomarkers. Therefore, although melatonin represents a promising mitochondria-targeted adjunct, standardized dosing strategies, tissue-level pharmacodynamic assessment, and validated mitochondrial biomarkers are needed to determine whether these mechanisms translate into reproducible clinical benefit. Full article

Reproductive activity imposes significant physiological demands on rams. This study evaluated metabolic and hormonal fluctuations in Sarda rams under semi-extensive management conditions, together with flock reproductive outcomes. Fourteen rams were isolated from ewes, subjected to nutritional flushing, and treated with melatonin implants (3 × 18 mg) before joining the flock. From June to December, body condition score (BCS), non-esterified fatty acids (NEFA), urea, triglycerides, cholesterol, testosterone, faecal thyroid hormone metabolites (FTMs), and faecal corticosteroid metabolites (FCMs) were measured every 45 days. Ewes’ pregnancy rates (PRs) and conception dates were determined by ultrasound scanning to estimate flock reproductive performance. BCS declined (p < 0.05) from June (3.11 ± 0.06) to November (2.80 ± 0.06). In November, NEFA, cholesterol and FCMs peaked (p < 0.05), whereas triglycerides and urea reached the lowest levels (p < 0.05). FTMs peaked in June and November (p < 0.05). Testosterone concentrations were three-fold higher in June than the rest of the mating season (p < 0.05), while overall PR was stable. Despite metabolic and endocrine changes in rams, overall flock reproductive performance remained stable. The final stage of mating season may represent a strategic period for targeted management strategies to sustain welfare and long-term performance. Full article

The circadian rhythm is an internal timing system formed by the body’s adaptation to the Earth’s rotation, which helps maintain homeostasis by regulating physiological, metabolic, and behavioral activities. The gut microbiota (GM), the largest microbial ecosystem in the human body, exhibits a bidirectional regulatory relationship with the host circadian clock. Emerging evidence indicates that circadian rhythm disruption (CRD) is linked to disturbances in the diurnal oscillations and compositional balance of the GM, accompanied by reduced short-chain fatty acid levels, increased lipopolysaccharide leakage, and altered tryptophan metabolism. These microbial abnormalities may be involved in anxiety-like behaviors through three major pathways: neuroendocrine (hyperactivation of the HPA axis), immune (microglia-mediated neuroinflammation), and neurotransmitter (imbalance of the serotonergic and dopaminergic systems). Conversely, microbial metabolites such as butyrate and secondary bile acids may reciprocally regulate peripheral clock gene expression, forming a complex “circadian rhythm–GM–anxiety” interaction network. This review summarizes the molecular basis of circadian–GM interactions, potential GM-mediated mechanisms linking CRD with anxiety, and emerging intervention strategies including chrononutrition (time-restricted feeding, sequential nutrient intake), microbiota-targeted therapies (probiotics/prebiotics, fecal microbiota transplantation), and light therapy and melatonin supplementation. Future directions should focus on cell-specific mechanisms using single-cell and spatial transcriptomics, developing personalized interventions that integrate chronotype and microbiome profiling, and conducting large-scale randomized controlled trials to facilitate clinical translation. This review provides a framework for understanding the integrative role of circadian biology and gut microbiota in anxiety and may help develop precision intervention paradigms. Full article

Atractylodes chinensis (DC.) Koidz is a pharmacologically significant medicinal plant that produces various bioactive metabolites, including β-eudesmol, which largely determines its medicinal quality and clinical efficacy. Treatment of A. chinensis hairy roots with 5-methoxyindole (5-MI), a chemical homolog of melatonin, revealed that 0.5 mmol·L⁻¹ 5-MI significantly enhanced β-eudesmol production. To investigate the underlying mechanism, we performed integrated transcriptomic and metabolomic analyses. Comprehensive targeted metabolomics identified ten upregulated terpenoids among the differentially expressed metabolites following 5-MI treatment in A. chinensis hairy roots, including β-eudesmol. The 5-MI treatment significantly influenced the expression levels of genes associated with metabolic regulation and secondary metabolite synthesis in A. chinensis hairy roots, particularly promoting the upregulation of genes involved in terpenoid biosynthesis. Notably, a putative sesquiterpene synthase gene, AcTPS1, was significantly upregulated after 5-MI treatment and was a strong candidate gene correlated with β-eudesmol. AcTPS1 belongs to the TPS-a subfamily and exhibits tissue-specific expression, with high transcript levels in root tissues, especially in one-year-old roots of A. chinensis. This study demonstrates that 5-MI serves as an effective elicitor, providing valuable insights for the production of medicinally active compounds and enhancing our understanding of the molecular mechanism by which 5-MI regulates plant secondary metabolism. Full article

The adoption of sustainable agricultural practices is essential to cope with climate change and to ensure soil health, efficient nutrient use, and food security. This study aims to delve into the effects of the use of different mulching techniques, both traditional and with an innovative ecological and sustainable mulch called hydromulch, on soil quality parameters, gas-exchange parameters and the final quality of the artichoke fruit (Cynara cardunculus subsp. scolymus L. (Heigi) cv. Symphony), as well as its impact on the metabolomics profile. The experimental design consisted of three blocks, each with three treatments: traditional polyethylene (PE) mulch, a rice husk-based hydromulch, and a bare soil control. The results show an increase in the physical quality of the artichokes grown with both mulches, as well as a direct impact on the primary and secondary metabolism, being more pronounced in the artichokes grown with hydromulch. In particular, hydromulch significantly up-regulated metabolites associated with the melatonin, serotonin, and polyamine pathways, suggesting a marked metabolic response compared with both polyethylene mulch and bare soil treatments. Furthermore, soil organic carbon (SOC) and soil organic matter (SOM) were increased in hydromulched soils. Gas exchange measurements revealed that hydromulched plants reduced stomatal conductance and transpiration, resulting in enhanced intrinsic water use efficiency. These improvements contribute to the production of high-quality, nutritionally enriched crops with direct relevance to food safety and sustainable agri-food systems. Full article

Cardiometabolic diseases are increasingly understood as disorders involving compartment-specific redox disruption rather than a uniform excess of reactive oxygen species. This narrative review synthesizes evidence for a proposed gut microbiota–mitochondria ferroptosis framework in which dysbiosis-derived lipopolysaccharide, trimethylamine N-oxide, short-chain fatty acids, bile acids, and tryptophan metabolites may modulate mitochondrial reactive species production, antioxidant defenses, iron handling, lipid peroxide detoxification, and inflammatory signaling. The reference set was assembled through searches of PubMed and Web of Science Core Collection, supplemented by targeted Google Scholar searches and citation chaining during manuscript preparation and revision through June 2026 and was organized around microbial metabolites, mitochondrial redox biology, ferroptosis pathways, disease-specific evidence, and redox-targeted interventions. Because this is a narrative synthesis rather than a systematic review, the framework should be interpreted as hypothesis-generating rather than as a systematically validated pathological model. Across atherosclerosis, diabetic cardiomyopathy, metabolic dysfunction-associated steatotic liver disease, obesity-associated insulin resistance, chronic kidney disease, and cardiorenal metabolic injury, the most consistent mechanistic links involve mtROS, impaired mitophagy, glutathione/GPX4 and SLC7A11 dysfunction, ACSL4-dependent lipid peroxidation, Nrf2 signaling, NLRP3 activation, and cGAS-STING-associated inflammation, although human causal evidence remains uneven. Importantly, much of the current literature supports local links within this sequence rather than a fully verified dysbiosis–metabolite–mitochondria ferroptosis–organ dysfunction chain in the same study. We therefore emphasize evidence tiers, terminology discipline, and biomarker requirements when interpreting ferroptosis-sensitive injury. Polyphenols, flavonoids, probiotics, postbiotics, melatonin, CoQ10-related strategies, mitochondria-targeted antioxidants, and ferroptosis-sensitive approaches may be most translatable when paired with microbiome, metabolomic, lipidomic, pharmacokinetic, and redox biomarkers. Full article

Shearing is a stressful procedure for sheep, combining isolation, restraint, and the mechanical action of shearing, which activates the hypothalamic–pituitary–adrenal axis and induces oxidative stress. This study investigated whether melatonin—a pleiotropic hormone with well-documented antioxidant properties—administration could modulate the stress response and oxidative stress in Sarda sheep during shearing. Forty lactating ewes (aged 3–5 years, mean body weight 41 ± 1.1 kg) were randomly assigned to four groups (n = 10 each): two groups received a subcutaneous melatonin implant (18 mg); two remained untreated as controls. Within each category, one group was shorn and the other subjected only to restraint. Blood samples were collected before, during, and after shearing to measure cortisol, glucose, reactive oxygen metabolites (ROMs), biological antioxidant potential (BAP), and oxidative stress index (OSI). Procedures elevated cortisol, glucose, ROMs, and OSI in all groups, but melatonin treatment significantly reduced these parameters and increased BAP relative to untreated animals at all sampling points (p < 0.05). No significant differences were observed between shorn and unshorn animals within the same treatment, suggesting that the handling, restraint, and isolation associated with the shearing procedure represent the major sources of stress, rather than the mechanical act of shearing itself. In conclusion, melatonin administration blunts the stress response and reduces oxidative stress in sheep during routine shearing-related handling procedures, suggesting its potential as a practical tool to improve animal welfare during routine management practices. Full article

Melatonin has been recognized as a regulator of plant growth and stress responses; however, its role in nitrogen metabolism, particularly in Capsicum chinense Jacq., remains poorly understood. In this study, we evaluated the effect of melatonin priming alone (chemopriming, CP) or in combination with substrate reinforcement (soil drench, SD) (CP + SD), at different doses, on physiological, biochemical, and molecular parameters in habanero pepper plants growing in non-stressed conditions. Growth traits, nitrogen-related metabolites, total carbohydrates, the expression of key genes involved in nitrogen metabolism, and glutamate dehydrogenase (GDH) activity were analyzed. The results showed that priming increased biomass mainly at 25 and 50 µM, whereas the combined treatment promoted improvements from early doses (5 µM). Additionally, the evaluated genes exhibited tissue-specific expression patterns. Most genes were downregulated in leaves, whereas proline and total carbohydrate levels correlated with fresh and dry weight. Our results provide new insights into the regulation of nitrogen metabolism according to the application method and dosage, establishing an application strategy to optimize nitrogen metabolism and growth in habanero peppers. The mechanism of melatonin in regulating the balance of C and N metabolites and its impact on the response of chili plants to growth and environmental signals should be addressed later. Full article

Chrysanthemum is one of the world’s four main cut flowers. However, postharvest drought stress severely disrupts water homeostasis, triggering reactive oxygen species burst and membrane lipid peroxidation, thereby reducing its ornamental quality and vase life. Melatonin serves as a multifunctional antioxidant and stress regulator. This study demonstrated that 200 μmol L⁻¹ melatonin effectively alleviated drought-induced leaf wilting, maintained relative water content, decreased the accumulation of MDA, H₂O₂, and O₂^•−, and enhanced the activities of SOD, CAT, POD, and APX. Concurrently, non-enzymatic antioxidants (proline, GSH, ASA) accumulated to high levels. RNA-seq analysis revealed that drought affects pathways closely related to the production of antioxidant and osmoprotectant metabolites, while melatonin initiated extensive transcriptional reprogramming and responded to drought stress through distinct pathways at the early (12 h) and late (24 h) treatment stages. Melatonin also modulated key transcription factor families, including bHLH, NAC, ERF, MYB, and bZIP. Collectively, exogenous MT mitigates drought damage in chrysanthemum cut flowers by coordinating antioxidant systems and complex transcriptional regulatory networks. This study provides a theoretical foundation for improving postharvest drought tolerance and prolonging the vase life of cut flowers. Full article

The discovery of melatonin as a multifunctional free radical scavenger and its possible synthesis in the mitochondrial matrix of peripheral eukaryotic somatic cells highlights a critical new perspective on the importance of this indole. Experimental evidence supporting these findings is substantial, but there are still lingering questions whether melatonin is a direct radical scavenger in vivo and whether it is synthesized in the mitochondrial matrix. We systematically analyze the innovative experimental approaches that support melatonin’s radical scavenging actions and assess the compelling data supporting its production in mitochondria. Melatonin concentrations are reportedly higher in this organelle than in other cellular compartments. Proteins for the enzymes required to convert serotonin to melatonin are present in the mitochondrial matrix and purified mitochondria synthesize melatonin. In the mitochondrial matrix, melatonin is likely located within the “damage radius” of highly reactive oxygen species. We also summarize novel actions of melatonin associated with its regulation of membrane fluidity, determine the molecular composition of membrane lipid rafts, and modulate liquid–liquid phase separation and biomolecular condensates intracellularly. If the findings discussed herein continue to be validated, melatonin would be in an optimal position to function as an antioxidant and may be a key driver in the context of preserving mitochondrial redox homeostasis and disease mitigation. Full article

Sprout vegetables have emerged as functional instant foods, with elevated concentrations of bioactive compounds compared with their mature counterparts. Chinese kale (Brassica oleracea var. alboglabra) is a cruciferous Brassica vegetable particularly rich in phenolic compounds, glucosinolates, and other nutrients, making it a suitable candidate for sprout production. This study aimed to explore the impact of melatonin (MT), calcium chloride (CaCl₂), and their combination on the quality and functional metabolism of Chinese kale. The results showed that MT treatment alone led to significantly higher ferric-reducing antioxidant power and concentrations of chlorophylls, carotenoids, soluble sugar, soluble protein, flavonoid, total phenolic compounds, and glucosinolates than those under CaCl₂ treatment alone. CaCl₂ treatment alone increased ascorbic acid content by 30.5%, but had limited effects on protein accumulation and secondary metabolites. However, the combined treatment did not exert a synergistic effect on ascorbic acid content, which decreased by 19.8% compared with that under the control treatment, significantly (p < 0.05). Overall, MT treatment was effective in boosting nutrient levels, thereby elevating the functional quality of Chinese kale sprouts. Full article

Cold stress (CS) represents a major environmental factor that adversely affects plant growth, development, and productivity. To cope with low-temperature conditions, plants have evolved sophisticated mechanisms for CS perception and response, mediated through complex cellular signaling networks and physiological processes. Central to these adaptive responses are phytohormones, which function either independently or through synergistic and antagonistic interactions to fine-tune CS tolerance. This review synthesizes current knowledge on the roles of major classical phytohormones and signaling metabolites in regulating CS tolerance in plants. We first outline the molecular mechanisms involved in CS sensing and signal transduction, highlighting the roles of membrane-associated sensors, calcium signaling, and downstream transcriptional networks. Then, we discuss the contributions of key classical phytohormones, including auxin, abscisic acid, ethylene, salicylic acid, cytokinin, jasmonic acid, brassinosteroids, gibberellic acid, strigolactones, and signaling metabolites, including melatonin and gamma-aminobutyric acid, to CS tolerance, highlighting their individual and interacting roles in modulating gene expression regulation, antioxidant defense and physiological adaptations. We also discuss the crosstalk between these hormones, emphasizing the dynamic and often context-dependent nature of their interactions in response to CS. Furthermore, the review highlights recent advances in CRISPR/Cas9-based genome editing strategies targeting phytohormone biosynthesis, signaling, and response pathways to improve CS tolerance in plants. By integrating hormonal signaling, molecular regulation, and modern biotechnological tools, this review provides a comprehensive framework for understanding phytohormone-mediated CS adaptation and offers perspectives for developing climate-resilient crops through genetic and agronomic approaches. Full article

Autism spectrum disorder (ASD) has been associated with alterations in the gut microbiota and its metabolites, particularly short-chain fatty acids (SCFAs) and microbiota-derived tryptophan catabolites, which may influence neurodevelopment through immune and epigenetic mechanisms. We investigated whether stool SCFAs and tryptophan-pathway metabolites differ between children with ASD and typically developing controls, and whether these metabolites associate with ASD severity and systemic biochemical signatures. In this cross-sectional study, we analyzed stool samples from 229 children (160 with ASD, 69 controls) with complete SCFA and tryptophan-metabolite data, while urine metabolomics data were available for a subset and were used for exploratory stool–urine integration analyses. Children with ASD and controls were similar in age, but the ASD group had a higher proportion of males. Absolute concentrations of individual SCFAs, total SCFAs, and derived indices were broadly comparable between groups; nominal differences in propionate/acetate ratio and caproate did not remain significant after false discovery rate correction. Similarly, stool tryptophan-pathway metabolites reported as ng/a.u. based on the NanoDrop-derived proxy (tryptophan, kynurenine, indole-3-acetic, indole-3-lactic, indole-3-propionic, indole-3-aldehyde, N-acetyl-tryptophan, serotonin, melatonin, tryptamine) and functional ratios (kynurenine/tryptophan, indole-derived/tryptophan, serotonin/tryptophan) showed no robust ASD–control differences; N-acetyl-tryptophan was nominally higher in ASD but did not survive multiple-testing correction. In the ASD subgroup with available Childhood Autism Rating Scale (CARS) data (n = 34), SCFA and tryptophan indices showed only weak, non-significant correlations with global ASD severity. In contrast, correlation analyses revealed two coherent metabolic modules, i.e., an SCFA block with very strong internal correlations among individual SCFAs and total SCFAs and a tryptophan block with strong correlations between metabolites and their normalized ratios, while cross-module correlations were modest. These results indicate that stool SCFA and microbiota-derived tryptophan profiles do not robustly distinguish ASD from controls in this cohort, but they form stable metabolic modules compatible with microbiome–epigenome frameworks. Full article

Melatonin plays a crucial role in modulating plant stress responses; however, its potential for mitigating salt–alkali stress remains incompletely understood. This study evaluates the efficacy of exogenous melatonin in alleviating moderate salt–alkali stress (120 mM) in poplar (Populus davidiana × P. bolleana ‘Baicheng Shanxinyang No. 1’) seedlings, investigating both pre- and post-stress treatments across a concentration range of 0–1000 μM. Physiological and morphological parameters, including chlorophyll content, antioxidant enzyme activities, and osmolyte accumulation, were analyzed to assess stress responses. Under salt–alkali stress, seedlings exhibited elevated stress markers and osmolyte levels, reflecting activated stress responses. Melatonin at concentrations of 200–400 μM was the most effective in mitigating stress, significantly enhancing antioxidant enzyme activities such as superoxide dismutase (SOD) and catalase (CAT), restoring chlorophyll content, and reducing oxidative damage markers such as malondialdehyde (MDA). It also regulated osmotic balance in leaves, indicating improved cellular stability under stress. Notably, post-stress application required slightly higher melatonin concentrations to achieve comparable recovery, highlighting the critical influence of application timing. These findings provide valuable insights for optimizing melatonin use to improve poplar growth in saline–alkali environments and support molecular breeding efforts aimed at developing salt–alkali-tolerant poplar varieties. Full article