Search Results (3,613)

Adipose tissue thermogenesis is a promising strategy to counter obesity and metabolic disease, but sustained activation of thermogenic adipocytes elevates oxidative and lipid-peroxidation stress, increasing susceptibility to ferroptotic cell death. Existing models often treat redox buffering, hypoxia signaling and ferroptosis as separate processes, which cannot explain why similar interventions—such as antioxidants, β-adrenergic agonists or iron modulators—alternately enhance thermogenesis or precipitate tissue failure. Here, we propose the Redox–Thermogenesis–Ferroptosis Compass (RTF-Compass) as a framework that maps adipose depots within a space defined by ferroptosis resistance capacity (FRC), ferroptosis signaling intensity (FSI) and HIF-1α-dependent hypoxic tone. Within this space, thermogenic output follows a hormetic, inverted-U trajectory, with a Thermogenic Ferroptosis Window (TFW) bounded by two failure states: a Reductive-Blunted state with excessive antioxidant buffering and weak signaling, and a Cytotoxic state with high ferroptotic pressure and inadequate defense. We use this model to reinterpret genetic, nutritional and pharmacological studies as state-dependent vectors that move depots through FRC–FSI–HIF space and to outline principles for precision redox medicine. Although the TFW is represented as coordinates in FRC–FSI–HIF space, we use ‘Compass’ to denote a coordinate framework in which perturbations act as vectors that orient depots toward thermogenic or cytotoxic outcomes. Finally, we highlight priorities for testing the model in vivo, including defining lipid species that encode ferroptotic tone, resolving spatial heterogeneity within depots and determining how metabolic memory constrains reversibility of pathological states. Full article

Several studies have demonstrated that methionine supplementation in fish diets enhances immune status, inflammatory response, and resistance to bacterial infections by modulating for DNA methylation, aminopropylation, and transsulfuration pathways. However, the immunomodulatory effects of methionine in viral infections remain unexplored. This study aimed to evaluate the effect of methionine supplementation on immune modulation and resistance to the viral haemorrhagic septicaemia virus (VHSV) in rainbow trout (Oncorhynchus mykiss). Two diets were formulated and fed to juvenile rainbow trout for four weeks: a control diet (CTRL) with all nutritional requirements, including the amino acid profile required for the species, and a methionine-supplemented diet (MET), containing twice the normal requirement of DL-methionine. After feeding, fish were bath-infected with VHSV, while control fish were exposed to a virus-free bath. Samples were collected at 0 (after feeding trial), 24, 72, and 120 h post-infection for the haematological profile, humoral immune response, oxidative stress, viral load, RNAseq, and gene expression analysis. In both diets, results showed a peak in viral activity at 72 h, followed by a reduction in viral load at 120 h, indicating immune recovery. During the peak of infection, leukocytes, thrombocytes, and monocytes migrated to the infection site, while oxidative stress biomarkers (superoxide dismutase glutathione S-transferase, and glutathione redox ratio) suggested a compromised ability to manage cellular imbalance due to intense viral activity. At 120 h, immune recovery and homeostasis were observed due to an increase in the amount of nitric oxide, GSH/GSSG levels, leukocyte replacement, monocyte influx, and a reduction in the viral load. When focusing on the infection peak, gene ontology (GO) analysis showed several exclusively enriched pathways in the skin and gills of MET-fed fish, driven by the upregulation of several key genes. Genes involved in recognition/signalling, inflammatory response, and other genes with direct antiviral activity, such as TLR3, MYD88, TRAF2, NF-κB, STING, IRF3, -7, VIG1, caspases, cathepsins, and TNF, were observed. Notably, VIG1 (viperin), a key antiviral protein, was significantly upregulated in gills, confirming the modulatory role of methionine in inducing its transcription. Viperin, which harbours an S-adenosyl-L-methionine (SAM) radical domain, is directly related to methionine biosynthesis and plays a critical role in the innate immune response to VHSV infection in rainbow trout. In summary, this study suggests that dietary methionine supplementation can enhance a more robust fish immune response to viral infections, with viperin as a crucial mediator. The improved antiviral readiness observed in MET-fed fish underscores the potential of targeted nutritional adjustments to sustain fish health and welfare in aquaculture. Full article

Plants from the Zingiberaceae family, particularly Zingiber officinale, Curcuma longa, and Alpinia galanga, are rich sources of bioactive compounds with documented antidiabetic and anti-inflammatory properties. This review summarizes current evidence on their phytochemical profiles and pathways relevant to metabolic regulation. Key compounds, including gingerols, shogaols, curcuminoids, and phenylpropanoids, support glucose homeostasis by enhancing insulin sensitivity, promoting Glucose Transporter Type 4 (GLUT4)-mediated glucose uptake, improving β-cell function, and modulating metabolic signaling pathways such as PI3K/Akt, AMPK, PPARγ, and NF-κB. Their potent antioxidant and anti-inflammatory activities further reduce oxidative stress and chronic low-grade inflammation, both central to the progression of type 2 diabetes and its complications. Evidence from selected clinical and experimental studies suggests that dietary supplementation with whole-rhizome preparations or standardized extracts (including formulation-enhanced products) may improve fasting blood glucose (FBG), glycated hemoglobin (HbA1c), lipid metabolism, and oxidative stress markers. Recent advances in delivery systems, including nanoemulsions, liposomes, and curcumin–piperine complexes, substantially enhance the bioavailability of poorly soluble phytochemicals, strengthening their therapeutic potential. Overall, Zingiberaceae plants emerge as promising natural supplements in nutritional and pharmacological strategies targeting diabetes. Further clinical research is required to refine dosage, confirm long-term efficacy, and support their integration into evidence-based metabolic interventions. Full article

Background: Bipolar disorder (BD) is a chronic psychiatric condition characterized by recurrent mood episodes and substantial functional impairment. Emerging evidence highlights the role of nutrition in modulating neurobiological pathways and influencing the course of BD. However, systematic recommendations for dietetic prescriptions remain limited. Methods: This narrative review was conducted by searching PubMed, Scopus, and Web of Science up to October 2025. Keywords included “bipolar disorder,” “nutrition,” “dietary interventions,” and “nutritional psychiatry.” Studies focusing on nutritional patterns, dietary components, and dietetic recommendations relevant to BD were included. Evidence was synthesized narratively to identify potential dietary strategies and gaps in current knowledge. Results: The available literature suggests that nutritional interventions may influence mood stabilization, metabolic comorbidities, and treatment response in BD. Key findings highlight the potential benefits of Mediterranean-style diets, omega-3 fatty acids, micronutrients (including magnesium, zinc, and vitamins D and B-complex), and dietary approaches targeting inflammation and oxidative stress. Conversely, Western-style diets, rich in saturated fats and refined sugars, appear to exacerbate mood instability and metabolic burden. Despite promising findings, heterogeneity across studies and the scarcity of randomized controlled trials limit firm conclusions. Conclusions: Nutrition represents a promising adjunctive strategy in the management of BD. Dietetic prescriptions may contribute to improved outcomes by addressing both psychiatric symptoms and physical health comorbidities. Future research should prioritize well-designed clinical trials to establish evidence-based guidelines for integrating nutrition into BD management. Full article

Climate change poses a threat to global rice production by increasing the frequency and intensity of extreme weather events. The widespread cultivation of genetically uniform modern varieties has narrowed the genetic base of rice, increasing its vulnerability to these increased pressures. Rice landraces are traditional rice varieties that have been cultivated by farming communities for centuries and are considered crucial resources of genetic diversity. These landraces are adapted to a wide range of agro-ecological environments and exhibit valuable traits that provide tolerance to various biotic stresses, including drought, salinity, nutrient-deficient soils, and the increasing severity of climate-related temperature extremes. In addition, many landraces possess diverse alleles associated with resistance to biotic stresses, including pests and diseases. In addition, rice landraces exhibit great grain quality characters including high levels of essential amino acids, antioxidants, flavonoids, vitamins, and micronutrients. Hence, their preservation is vital for maintaining agricultural biodiversity and enhancing nutritional security, especially in vulnerable and resource-limited regions. However, rice landraces are increasingly threatened by genetic erosion due to widespread adoption of modern high-yielding varieties, habitat loss, and changing farming practices. This review discusses the roles of rice landraces in developing resilient and climate-smart rice cultivars. Moreover, the Pantiange Heigu landrace, cultivated at one of the highest altitudes globally in Yunnan Province, China, has been used as a case study for integrated conservation by demonstrating the successful combination of in situ and ex situ strategies, community engagement, policy support, and value-added development to sustainably preserve genetic diversity under challenging environmental and socio-economic challenges. Finally, this study explores the importance of employing advanced genomic technologies with supportive policies and economic encouragements to enhance conservation and sustainable development of rice landraces as a strategic imperative for global food security. By preserving and enhancing the utilization of rice landraces, the agricultural community can strengthen the genetic base of rice, improve crop resilience, and contribute substantially to global food security and sustainable agricultural development in the face of environmental and socio-economic challenges. Full article

This study was conducted to evaluate the effect of rumen-protected γ-aminobutyric acid (GABA) supplementation on milk productivity of lactating Holstein cows. Eighteen Holstein dairy cows (mean parity, 2.2 ± 1.0 year; mean milk yield, 34.3 ± 5.5 kg) were selected in a commercial dairy farm for the experiment. The experiment was conducted from 17 July 2024 to 11 September 2024 (56 days). Generally, THI 72 is set as a threshold since the productivity of Holstein cows starts to decrease. Animals were exposed to heat stress conditions (THI ≥ 72) during the experimental period. The basal diet was fed as a total mixed ration (TMR), and GABA was top-dressed onto the TMR. The treatments were basal diet (Control), basal diet supplemented with rumen-protected GABA 3 g/d (Treatment 1), and basal diet supplemented with rumen-protected GABA 6 g/d (Treatment 2) as a completely randomized design. Statistical significance was compared between the control and GABA treatment groups using the method of repeated measurement. Increased levels of rumen-protected GABA supplementation tended to mitigate the decline in milk yield associated with heat stress (p = 0.083). Milk fat content in the GABA supplementation groups was significantly greater than that in the control group (p = 0.036). Milk lactose content was significantly increased by GABA supplementation (p = 0.017). Blood metabolic profiles and cortisol did not differ significantly between the control and GABA supplementation groups. Activities in the GABA supplementation groups were significantly greater than those in the control group (p < 0.05). Rest and rumination times in the GABA supplementation group were significantly lower than those in the control group (p < 0.05). These results suggest that rumen-protected GABA can be a practical nutritional intervention for minimizing productivity losses in Holstein cows during periods of elevated ambient temperature. Full article

Sustainable food production for a growing population requires farming practices that reduce chemical inputs while maintaining soil as a living, renewable foundation for productivity. This review synthesizes current advances in understanding how endophytic fungi (EFs) interact with the soil microbiome and contribute to the physicochemical and biological dimensions of soil health in arable ecosystems. We examine evidence showing that EFs enhance plant nutrition through phosphate solubilization, siderophore-mediated micronutrient acquisition, and improved nitrogen use efficiency while also modulating plant hormones and stress-responsive pathways. EFs further increase crop resilience to drought, salinity, and heat; suppress pathogens; and influence key soil properties including aggregation, organic matter turnover, and microbial network stability. Recent integration of multi-omics, metabolomics, and community-level analyses has shifted the field from descriptive surveys toward mechanistic insight, revealing how EFs regulate nutrient cycling and remodel rhizosphere communities toward disease-suppressive and nutrient-efficient states. A central contribution of this review is the linkage of EF-mediated plant functions with soil microbiome dynamics and soil structural processes framed within a translational pipeline encompassing strain selection, formulation, delivery, and field scale monitoring. We also highlight current challenges, including context-dependent performance, competition with native microbiota, and formulation and deployment constraints that limit consistent outcomes under field conditions. By bridging microbial ecology with agronomy, this review positions EFs as biocontrol agents, biofertilizers, and ecosystem engineers with strong potential for resilient, low-input, and climate-adaptive cropping systems. Full article

Oxidative stress contributes significantly to chronic disease burden, necessitating identification of accessible dietary antioxidant sources. Pigeon peas (Cajanus cajan L.) contain substantial bioactive compounds, yet most exist in bound forms with limited bioavailability. This study evaluated wild fermentation combined with systematic extraction optimization to enhance antioxidant recovery from pigeon peas. Seeds underwent wild fermentation in brine solution, followed by extraction under varying conditions (seven solvent systems, three temperatures, and three-time durations). Multiple complementary assays assessed antioxidant capacity (total phenolic content, DPPH radical scavenging, ferric reducing power, and ABTS activity). Fermentation substantially improved antioxidant properties across all parameters, with particularly pronounced effects on radical scavenging activities. Extraction optimization identified 70% methanol at 40 °C for 24 h as optimal, demonstrating marked improvements over conventional protocols. Strong intercorrelations among assays confirmed coordinated enhancement of multiple antioxidant mechanisms rather than isolated changes. The findings demonstrate that both biotechnological processing and analytical methodology critically influence antioxidant characterization in pigeon peas. This integrated approach offers practical guidance for developing antioxidant-rich functional foods, particularly relevant for resource-limited settings where pigeon peas serve as dietary staples. The study establishes foundation for translating fermentation technology into nutritional interventions, though further research addressing bioavailability, microbiological characterization, and bioactive compound identification remains essential. Full article

Background: Chronic kidney disease (CKD) represents a state of persistent, sterile low-grade inflammation in which sustained innate immune activation accelerates renal decline and cardiovascular complications. Diet-induced gut dysbiosis and intestinal barrier dysfunction lower mucosal immune tolerance, promote metabolic endotoxemia, and position the gut as an upstream modulator of systemic inflammatory signaling along the gut–kidney axis. Scope: Most studies address microbiota-derived metabolites, food-derived bioactive peptides, or omega-3 fatty acids separately. This review integrates evidence across these domains and examines their convergent actions on epithelial barrier integrity, immune polarization, oxidative-inflammatory stress, and inflammasome-dependent pathways relevant to CKD progression. Key mechanisms: CKD-associated dysbiosis is characterized by reduced short-chain fatty acid (SCFA) production and increased generation and accumulation of uremic toxins and co-metabolites, including indoxyl sulfate, p-cresyl sulfate, trimethylamine N-oxide, and altered bile acids. Reduced SCFA availability weakens tight junction-dependent barrier function and regulatory immune programs, favoring Th17-skewed inflammation and endotoxin translocation. Bioactive peptides modulate inflammatory mediator networks and barrier-related pathways through effects on NF-κB/MAPK signaling and redox balance, while omega-3 fatty acids and specialized pro-resolving mediators support resolution-phase immune responses. Across these modalities, shared control points include barrier integrity, metabolic endotoxemia, oxidative stress, and NLRP3 inflammasome activation. Conclusions: Although evidence remains heterogeneous and largely preclinical, combined nutritional modulation targeting these convergent pathways may offer greater immunomodulatory benefit than isolated interventions. Future multi-omics-guided, factorial trials are required to define responder phenotypes and translate precision immunonutrition strategies into clinical CKD care. Full article

Osteoporosis and chronic conditions such as type 2 diabetes mellitus, cardiovascular disease, heart failure, and chronic kidney disease share several common biological mechanisms, including chronic inflammation, oxidative stress, hormonal dysregulation, and metabolic alterations. In this context, multimorbidity presents an increasing clinical challenge, particularly in older populations, where osteoporosis remains frequently underdiagnosed and undertreated. This review aims to explore the complex interplay between skeletal fragility and cardiometabolic diseases, emphasizing the role of nutritional deficiencies (such as iron and vitamin C), shared molecular pathways (advanced glycation end-products, Renin–Angiotensin–Aldosterone System, RANK Ligand, RANK), and the systemic impact of chronic inflammation and tissue hypoperfusion. The review also addresses the effects of various drug classes—antidiabetics, antihypertensives, anticoagulants, and anti-osteoporotic agents—on bone metabolism and cardiovascular risk. Special focus is given to the implementation of integrated and personalized care models, particularly multidisciplinary team-based approaches, which have demonstrated significant reductions in mortality and refracture rates, despite their still limited adoption in clinical practice. In conclusion, this review highlights the shared mechanisms between osteoporosis and cardiometabolic conditions in the context of multimorbidity, underscoring persistent clinical challenges related to diagnosis, drug interactions, and care fragmentation that warrant further research into integrated care models. Full article

Zinc (Zn) in excess is very toxic for plants and can limit agriculture. Carbon-based engineered nanomaterials with high electron mobility and electron-accepting capability may be essential for mitigating heavy metal stress. In the present study, the protective role of some fullerene C₆₀ derivatives (fullerenol [C₆₀(OH)_22–24] and the arginine C₆₀ [C₆₀(C₆H₁₃N₄O₂)₈H₈]) were tested for the first time against Zn toxicity in Cucumis sativus L. (cucumber). Plants were grown hydroponically at three concentrations of fullerenes (0, 2, and 10 mg L⁻¹) without or with 40 µM Zn for 17 days. Plant growth, leaf chlorosis, and nutritional imbalances in combination with a metabolomics approach were analyzed. The Zn-treated plants show chlorotic leaves, the retarded growth of shoots (−20%), and roots (−49%) and nutrient imbalance. Addition of fullerene C₆₀ derivatives suppressed loss in the dry biomass of leaves (15%) and roots (40%; fullerenol only) induced by high Zn. However, they did not alter leaf chlorophyll, shoot dry biomass, and elemental composition, including leaf Zn. Moreover, the Zn of xylem sup from roots remained unchanged by fullerenes. In an adsorption experiment, the amounts of Zn adsorbed by tested C₆₀ were below the detection limits. The addition of C₆₀ derivatives slightly changed the metabolite profiling in stressed plants. Nevertheless, in fullerene-treated plants, the abundance of some Zn-responsible metabolites tended to be altered in the opposite direction as compared with the metabolic responses to excessive Zn alone. There were several up-regulated metabolites protecting plants under oxidative stress. We speculate that fullerene C₆₀ derivatives have the ability to increase antioxidant non-enzyme activity at least, improving some growth parameters. However, fullerenes did not reduce Zn transport from the root to the shoots. We concluded that the low capacity of these compounds to buffer Zn in the root zone might limit the efficiency of fullerene derivatives against Zn toxicity. Our results provide new evidence for the crucial role of Zn–fullerene interactions in the amelioration of Zn toxicity in plants. Full article

Background: The interplay between neuronutrition, physical activity, and mental health for enhancing brain resilience to stress and overall human health is widely recognized. The use of brain mapping via quantitative-EEG (qEEG) comparative analysis enables researchers to identify deviations or abnormalities and track the changes in neurological patterns when a targeted drug or specific nutrition is administered over time. High-functioning mild-to-borderline intellectual disorders (MBID) and autism spectrum disorder (ASD) constitute leading global public health challenges due to their high prevalence, chronicity, and profound cognitive and functional impact. Objective: The objectives of the present study were twofold: first, to characterize an extremely vulnerable group of children with functioning autism symptoms, disclosing their overall pattern of cognitive abilities and areas of difficulty, and second, to investigate the relevance of the effects of a mushroom (Hericium erinaceus) biomass dietary supplement on improvement on neurocognitive behavior. Methods: This study used qEEG to compare raw data with a normative database to track the changes in neurological brain patterns in 147 children with high-functioning autistic attributes when mushroom H. erinaceus biomass supplement was consumed over 6 and 12 months. Conclusions: H. erinaceus biomass in children with pervasive developmental disorders significantly improved the maturation of the CNS after 6 to 12 months of oral use, decreased the dominant slow-wave activity, and converted slow-wave activity to optimal beta1 frequency. Therefore, despite the lack of randomization, blinding, and risk of bias, due to a limited number of observations, it may be concluded that the H. erinaceus biomass may generate a complex effect on the deficits of the autism spectrum when applied to high-functioning MBID children, representing a safe and effective adjunctive strategy for supporting neurodevelopment in children. Full article

Acetaminophen (APAP) overdose is a major cause of acute liver failure and can be fatal, often without early symptoms. Protein deficiency, arising from illness or inadequate diet, impairs growth, immunity, and tissue repair. Both conditions can harm the kidneys, yet the impact of energy imbalance on renal physiology remains unclear. In this study, APAP toxicity and a low-protein diet induced behavioral suppression and tissue damage, as evidenced by reduced whole-body, liver, and kidney weights in rats. In kidney mitochondria of rats exposed to only toxic APAP doses, ATP levels declined sharply while ADP and AMP increased. AMP deaminase and ATPases’ activities rose about twofold and 1.5-fold, respectively, whereas cytosolic 5′-nucleotidase activity fell nearly threefold, suggesting compensatory responses to disrupted energy balance. The strongest reductions in ATP and the greatest increases in AMP and ATPase activity occurred in APAP-intoxicated rats fed a low-protein diet. This combination also intensified lipid peroxidation and oxidative protein damage, evidenced by elevated TBARS, reduced protein SH-groups, and increased protein carbonyls. Overall, APAP intoxication with protein deficiency disrupts renal energy metabolism, leading to mitochondrial dysfunction and structural kidney injury. Nutritional status therefore critically influences drug-induced nephrotoxicity, and antioxidant strategies may help prevent damage under metabolic stress. Full article

Training adaptation involves muscular–metabolic remodeling and personality-linked traits such as motivation, self-regulation, and resilience. This narrative review examines how training load oscillation (TLO)—the deliberate variation in exercise intensity, volume, and substrate availability—may function as a systemic epigenetic stimulus capable of shaping both physiological and psychological adaptation. Fluctuating energetic states reconfigure key energy-sensing pathways (AMPK, mTOR, CaMKII, and SIRT1), thereby potentially influencing DNA methylation, histone acetylation, and microRNA programs linked to PGC-1α and BDNF. This review synthesizes converging evidence suggesting links between these molecular responses and behavioral consistency, cognitive control, and stress tolerance. Building on this literature, a systems model of molecular–behavioral coupling is proposed, in which TLO is hypothesized to entrain phase-shifted AMPK/SIRT1 and mTOR windows, alongside CaMKII intensity pulses and a delayed BDNF crest. The model generates testable predictions—such as amplitude-dependent PGC-1α demethylation, BDNF promoter acetylation, and NR3C1 recalibration under recovery-weighted cycles—and highlights practical implications for timing nutritional, cognitive, and recovery inputs to molecular windows. Understanding TLO as an entrainment signal may help integrate physiology and psychology within a coherent, durable performance strategy. This framework is conceptual in scope and intended to generate testable hypotheses rather than assert definitive mechanisms, providing a structured basis for future empirical investigations integrating molecular, physiological, and behavioral outcomes. Full article

Osteoarthritis (OA) is a leading cause of chronic pain worldwide. This is driven by progressive cartilage degradation, inflammation, oxidative stress, and metabolic dysfunction. Current pharmacologic interventions mostly lead to symptomatic relief without actually affecting disease progression. Thus, there is a growing interest in the development of new interventional methods. Our review seeks to synthesize preclinical, translational, and clinical evidence on the impact nutritional methods have on OA management. Whole-diet approaches, such as Mediterranean and plant-based, have been linked to reduced pain, increased physical function, and positive biomarker changes. Bioactive compounds, including curcumin, polyphenols, omega-3 fatty acids, and select herbal extracts, have shown anti-inflammatory, antioxidant, and chondroprotective effects via NF-κB, Nrf2, AMPK, and SIRT1 pathways. This review particularly focuses on plant-derived substances. Emerging nanoparticle technology with regard to advanced delivery systems shows initial promise in nutraceutical pharmacokinetics and tissue targeting. Overall, nutritional interventions are adjunct interventions to OA management. Although these are not full treatment replacements, dietary modifications and targeted nutraceutical strategies with improved delivery systems may lead to more preventive, personalized, and holistic OA management and care. Full article