Search Results (672)

The continued rise in fishmeal prices and the scarcity of fishery resources have led to an increase in the use of plant-based protein sources in compound feed, making mold contamination in compound feed a frequent occurrence. Aflatoxin B1 (AFB1) contamination in aquaculture feed can seriously harm fish growth and liver health; it is extremely toxic, posing an even greater risk to carnivorous fish such as grouper. Lycopene, a natural carotenoid, has antioxidant and anti-inflammatory physiological functions and may act as a functional feed additive to mitigate damage induced by mycotoxins. This study utilized hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂) as the experimental model. An 8-week feeding trial was performed to systematically assess the impact of lycopene supplementation at levels of 0, 200, 400, 600, and 800 mg/kg to a basal diet containing 800 μg/kg AFB1 on the fish’s growth performance, antioxidant capacity, liver health, inflammation-related gene expression, and hepatic transcriptome. The results showed that adding 200 mg/kg lycopene to the feed significantly increased the FWB and SGR (p < 0.05) of hybrid grouper. An appropriate amount of lycopene could enhance the antioxidant capacity of serum and liver, significantly increase the activities of catalase (CAT) and superoxide dismutase (SOD), and significantly decrease serum alanine aminotransferase (ALT) activity while increasing albumin (ALB) levels (p < 0.05). An amount of 200 mg/kg lycopene significantly alleviated AFB1-induced hepatocyte vacuolation, steatosis, and inflammatory cell infiltration, while the protective effect of higher doses was weakened. The gene expression results showed that 200 mg/kg lycopene significantly upregulated the expression of antioxidant-related genes such as cat, sod, and nrf-2, and increased the expression level of the anti-inflammatory factor il10 (p < 0.05). The transcriptome analysis identified a total of 621 differentially expressed genes, which were mainly enriched in metabolic pathways, fatty acid metabolism, PPAR signaling pathway, redox process, ferroptosis, NF-κB signaling pathway, and Toll-like receptor signaling pathway. In summary, the addition of 200 mg/kg lycopene to the feed can effectively alleviate the growth inhibition and liver damage caused by AFB1 in hybrid grouper. Its mechanism of action may be related to enhancing antioxidant defenses, improving liver tissue structure, regulating lipid metabolism, and maintaining immune homeostasis. The research results indicate that lycopene can be used as a natural functional feed additive to alleviate AFB1 toxicity in hybrid grouper aquaculture. Full article

Hyperlipidemia is a chronic metabolic disorder driven by impaired lipid homeostasis. In this study, the steam explosion (SE)-assisted extraction was applied to obtain soluble dietary fiber (SDF) from ginger peel residue. Based on single-factor and orthogonal optimization experiments, SE treatment at a material-to-cavity ratio of 2:5 and a pressure of 1.5 MPa for 300 s achieved an SDF extraction yield of 8.20%, representing a 210.60% increase. Structural and physicochemical analyses showed that both SDF and SE-SDF were mainly composed of glucose, galactose and mannose. SE treatment generated a looser and more porous structure and significantly improved the thermal stability, water holding capacity (WHC) and swelling capacity (SC) of SE-SDF increasing by 38.89% and 30.77%, respectively (p < 0.05). In oleic acid/palmitic acid (OA/PA)-stimulated HepG2 cells, both SDF and SE-SDF reduced triglyceride (TG) and total cholesterol (TC) levels in a dose-dependent manner, with SE-SDF showing a stronger hypolipidemic activity. Zebrafish experiments further confirmed that 200 µg/mL SE-SDF significantly reduced TG and TC levels by 30.58% and 24.89%, respectively, and decreased lipid deposition in the caudal vasculature and liver by 65.59% and 33.86%, respectively. These findings indicate that SE-SDF from ginger peel residue is a promising functional food ingredient for hyperlipidemia prevention. Full article

Interactions among the gut, brain, and skin are increasingly understood as a systemic regulatory network connecting intestinal activity, neuroimmune communication, and cutaneous homeostasis. Microbiota-derived metabolites, immune mediators, and neuroendocrine pathways can influence central nervous system activity and subsequently regulate skin homeostasis. This review summarizes current evidence on how functional ingredients modulate the gut–brain–skin axis in the context of aging and skin health. Polyphenols, probiotics, and omega-3 fatty acids appear to act through overlapping biological routes, including reshaping microbial communities, supporting epithelial barrier function, regulating immune activity, and limiting oxidative stress. These gut-derived signals may affect the brain through neural, endocrine, and immune pathways, thereby modulating neuroinflammation, hypothalamic–pituitary–adrenal (HPA) axis activity, and neurotransmitter balance. Through brain–skin communication, these changes may influence inflammation, epidermal barrier integrity, collagen remodeling, and skin aging processes. Emerging clinical evidence suggests potential improvements in skin-related outcomes and systemic inflammatory markers; however, studies remain heterogeneous, and integrated assessments of gut, brain, and skin endpoints are limited. Further studies that integrate multi-omics profiling with carefully designed clinical trials will be required to define causal pathways and support the development of evidence-based nutritional approaches targeting this axis. Full article

Obesity is a multifactorial condition characterized by profound metabolic and inflammatory dysregulation that alters the adipose tissue-central nervous system (CNS) relationship. This paper critically summarizes the biochemical and cellular mechanisms governing this bidirectional crosstalk, moving beyond a descriptive perspective to propose an integrated model of peripheral-central interaction. White adipose tissue (WAT) and brown adipose tissue (BAT), modulated by the sympathetic nervous system (SNS), communicate with hypothalamic circuits (POMC and AgRP neurons) both through traditional endocrine signals (leptin, adiponectin, resistin, apelin) and through lipid mediators and extracellular vesicles (EVs) capable of crossing the blood–brain barrier (BBB). Under conditions of nutritional excess, the accumulation of lipotoxic lipid species (such as palmitate and ceramides) and the inflammatory polarization of brain macrophages (M1/BAMs) induce mitochondrial stress and central resistance to leptin and insulin, altering the adiposity set point. In parallel, we review emerging nutritional strategies based on polyunsaturated fatty acids (PUFAs), polyphenols, and short-chain fatty acids (SCFAs), and critically evaluate innovative technological platforms (nanoencapsulation, precision fermentation, and 3D food printing) designed to optimize nutrient bioaccessibility and restore adipose-CNS axis homeostasis, discussing current challenges for clinical translation. Full article

The gut–immune–metabolic axis has emerged as a central regulator of human health, with growing evidence indicating that microbiota-derived metabolites improve gut microbial ecology, enhance intestinal barrier integrity, reduce systemic inflammation, and maintain metabolic homeostasis. This review synthesizes current mechanistic and clinical evidence on the role of postbiotics in regulating intestinal barrier integrity, immune responses, oxidative stress, and metabolic–endocrine homeostasis. The literature was identified through the PubMed/MEDLINE, Scopus, and Web of Science, integrating evidence from experimental, mechanistic, animal and clinical studies on the therapeutic potential of postbiotics to modulate the gut–immune–metabolic axis. Preclinical studies suggest that postbiotics may enhance epithelial barrier function by improving tight junction integrity through multiple pathways such as PI3K/Akt signaling, stimulating mucin-2 (MUC2) production, and reducing intestinal permeability. They modulate immune responses through interactions with Toll-like receptors, nucleotide-binding oligomerization domain receptors, and G-protein-coupled receptors (GPR41/43), influencing key signaling pathways, including NF-κB and Nrf2, and altering cytokine profiles, such as IL-10, TNF-α, and IFN-γ. Similarly, preclinical investigations have demonstrated that short-chain fatty acids (SCFAs) and other microbial metabolites may improve insulin sensitivity, regulate hepatic gluconeogenesis, stimulate glucagon-like peptide 1 (GLP-1) secretion, and modulate lipid metabolism through the FXR and TGR5 signaling pathways. Emerging human studies suggest potential benefits of postbiotics in regulating gut, immune, and metabolic health; nevertheless, clinical evidence remains limited and is influenced by variability in postbiotic composition, dosage, formulation, and metabolite profiles. Therefore, standardized production approaches and well-designed large-scale randomized clinical trials are required to confirm therapeutic efficacy and establish evidence-based applications of postbiotics. Full article

Aging-related decline involves changes in oxidative stress, inflammation, mitochondrial function, telomere maintenance, metabolic regulation, and extracellular matrix homeostasis. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement and searched PubMed, Scopus, Embase, and Web of Science for English-language studies published from 1993 to 2025. Twelve primary studies met the eligibility criteria: four randomized clinical studies, four animal studies, one in vitro mechanistic study, and three delivery-system/formulation studies. Risk of bias was assessed using Cochrane Risk of Bias 2 (RoB 2), the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool, and a review-specific domain-based checklist informed by the National Toxicology Program/Office of Health Assessment and Translation framework. Representative compounds, including resveratrol, astragaloside IV, Ganoderma lucidum polysaccharide, epigallocatechin-3-gallate (EGCG) and betulinic acid, were associated with mitochondrial regulation, antioxidant defense, cytoskeletal stability, gut–brain signaling, extracellular-matrix protection, and longevity-related signaling. Nanoliposomes and poly(lactic-co-glycolic acid) (PLGA) nanoparticles improved selected stability, penetration, and pharmacokinetic outcomes. However, the evidence base was heterogeneous and predominantly preclinical; human evidence was limited to four relatively small studies, and certainty ranged from moderate to very low. The findings support mechanistic and translational potential but do not establish definitive anti-aging efficacy in humans. Full article

Post-myocardial infarction (MI) remodeling is accompanied by metabolic stress, but the myocardial genes associated with copper handling are poorly defined. We sought to prioritize a tissue-derived candidate rather than establish a copper-dependent mechanism. Regional MI transcriptomes and an in-house left anterior descending coronary artery ligation mouse RNA-sequencing cohort were integrated with protein quantitative trait locus-based Mendelian randomization (MR). Follow-up comprised local and external tissue validation, cardiac single-cell RNA sequencing, Genotype-Tissue Expression co-expression, computational perturbation, and CRIP2 knockdown or overexpression in H9c2 cells exposed to hypoxia/reoxygenation (H/R). CRIP2 showed a nominal protective-direction MR association (odds ratio 0.831, 95% confidence interval 0.735–0.939; p = 0.0031), but did not pass the Bonferroni threshold. Crip2 was lower in the local MI model (p = 0.0168; n = 5 per group) and in an independent dataset. A prespecified lipoylated-tricarboxylic-acid module was negatively enriched after MI (normalized enrichment score −1.63; false discovery rate 0.012), whereas the broader copper-homeostasis set was not significant. Single-cell data localized Crip2 mainly to cardiomyocytes, but were not adequately replicated for condition-level inference. Under H/R, Atp7a was the only copper-handling transcript whose knockdown-by-oxygen interaction remained significant after adjustment (q = 0.0405). CRIP2 overexpression was associated with higher Cell Counting Kit-8 metabolic activity during H/R (interaction p = 0.00551), whereas the knockdown interaction was not significant. Copper abundance, mitochondrial function, and cuproptosis markers were not measured. The data prioritize CRIP2 for mechanistic study, but do not show that it regulates copper flux or post-MI remodeling. Full article

This study investigated how defatted silkworm pupae meal (DSPM) modulates flesh quality in pearl gentian grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂). A total of 360 size-uniform fish were randomly assigned to four dietary treatments for 8 weeks: D0, the fishmeal (FM) based control diet; and D1, D2, and D3, in which DSPM substituted 25%, 50%, and 100% of dietary FM, respectively, with three replicates per treatment and 30 fish per replicate. Compared with D0, D1 and D2 improved final body weight, weight gain rate, specific growth rate, and feed conversion ratio, whereas D3 reduced survival and feed utilization. For flesh quality, D2 showed the most favorable phenotype, characterized by higher crude protein, collagen, flavor-associated amino acids, pH, texture attributes, and muscle fiber density, together with lower ether extract, cooking loss, freezing loss, and shear force. DSPM substitution also increased unsaturated and polyunsaturated fatty acid proportions and improved lipid health indices. Moderate substitution, especially D2, enhanced oxidative stability by increasing SOD and CAT activities and reducing MDA accumulation. Non-targeted metabolomics combined with qPCR analysis of selected flesh quality-related genes suggested that these improvements were associated with osmotic regulation, collagen remodeling, purine metabolism, membrane lipid homeostasis, nutrient sensing, myogenesis, and antioxidant defense. Complete FM substitution impaired muscle structure, water retention, and redox balance. Thus, 50% FM substitution with DSPM effectively optimized grouper flesh quality in this study. Full article

Background/Objectives: Triple-negative breast cancer remains a major therapeutic challenge due to its aggressive behavior and limited treatment options. Methods: In this study, an integrated multi-omics strategy combining SILAC-based quantitative proteomics, shotgun lipidomics, and targeted metabolomics was applied to characterize the biomolecular response of MDA-MB-231 cells following exposure to the Ag@MSN-Tf-SeNPs nanosystem. Results and Conclusions: The complementary analytical platforms provided a comprehensive and system-level view of the cytotoxic effects induced by the nanosystem, highlighting its potential as an antitumoral nanotherapeutic approach. Exposure resulted in reduced cell growth and metastatic potential, associated with DNA damage-induced cell-cycle arrest, disruption of protein biosynthesis, and impaired protein quality control linked to Ca²⁺ homeostasis imbalance. In addition, significant alterations in lipid metabolism were observed, including disruption of cholesterol biosynthesis. These changes, together with disturbances in glycolysis and the tricarboxylic acid cycle, and alterations in NAD⁺/NADH balance, indicate the induction of oxidative stress driven by reactive oxygen species accumulation. Furthermore, the integration of multi-omics data revealed the activation of compensatory mechanisms aimed at restoring cellular homeostasis, including metabolic rewiring and stress-response pathways, although these responses were insufficient to counteract nanosystem-induced cytotoxicity. Full article

Hemorrhagic shock is a leading cause of preventable death following multiple trauma, driven by a cascade of interacting cellular and molecular disturbances that extend well beyond simple volume loss. Acute blood loss initiates tissue hypoperfusion and cellular hypoxia, setting in motion the lethal triad of hypothermia, acidosis, and coagulopathy through several converging pathways: complement activation with excessive C3a and C5a production; neutrophil-mediated tissue injury; NADPH-oxidase-driven reactive oxygen species (ROS) overproduction that overwhelms superoxide dismutase defenses; mitochondrial respiratory chain impairment; dysregulation of the pro-inflammatory cytokine network; and endothelial apoptosis with degradation of the endothelial glycocalyx and disruption of interendothelial junctions, with consequent vascular hyperpermeability. These mechanisms provide the biological rationale for the resuscitation strategy. Each class of fluid acts on these pathways in a distinct way: crystalloids modulate acid–base homeostasis, chloride-mediated renal vasoconstriction, and coagulation factor activity; colloids influence oncotic pressure, endothelial integrity, and microvascular perfusion; and blood products, particularly plasma and whole blood, actively modulate mitochondrial metabolism, endothelial permeability, and pro-apoptotic signaling beyond their volume-expanding role. Translating this biology to the bedside requires a multimodal monitoring framework that converts molecular endpoints into real-time therapeutic targets, integrating lactate and base excess as markers of cellular oxygen debt, dynamic preload indices such as pulse pressure and stroke volume variation, advanced hemodynamic platforms, point-of-care ultrasonography, viscoelastic coagulation testing, and near-infrared spectroscopy of tissue oxygenation. This review synthesizes the biological basis of hemorrhagic shock and its translation into an individualized, goal-directed resuscitation strategy for the critically ill polytrauma patient. Full article

Background/Objectives: Postbiotics are increasingly recognized as biologically active products of microorganisms with emerging potential as microbiome-inspired therapeutic interventions. While most microbiome-based strategies focus on modifying microbial composition, restoration of microbial signaling has received comparatively less attention. This review examines postbiotics through the lens of microbial signaling restoration and proposes a unified Metabolite–Immune–Redox (MIR) axis linking microbial-derived signals with immune regulation, redox homeostasis, endothelial integrity, and host resilience. Methods: This narrative review synthesizes current evidence on postbiotics, microbial metabolites, structural microbial components, and extracellular vesicles, with emphasis on their roles in immunometabolic regulation, redox biology, endothelial function, and host-directed interventions. Results: Current evidence suggests that short-chain fatty acids, indole derivatives, bile acid metabolites, and microbial extracellular vesicles are important mediators of host–microbe communication. These signals influence interconnected pathways involving mitochondrial function, inflammasome activity, immune calibration, endothelial and glycocalyx homeostasis, and disease tolerance. The review highlights the endothelium as an underrecognized therapeutic target and discusses biomarkers, including soluble thrombomodulin, von Willebrand factor, and D-dimer, as potential tools for identifying patients most likely to benefit from host-directed interventions. Major translational challenges include product heterogeneity, incomplete mechanistic characterization, uncertain exposure–response relationships, and unresolved regulatory considerations. Conclusions: The proposed MIR axis provides a hypothesis-generating framework for understanding how restoration of microbial signaling may contribute to precision host-directed therapeutic strategies. Further mechanistic and clinical studies are needed to validate this concept and define its translational potential in inflammatory, infectious, and critical illness settings. Full article

Background/Objectives: Uterine dysfunction contributes to infertility in PCOS. Jiawei Qi Gong Wan (JQGW) is used to improve endometrial homeostasis, but its mechanism is unclear. This study investigated whether JQGW improves uterine function via gut microbiota and metabolites. Methods: Letrozole-induced PCOS mice received JQGW (low/high dose), metformin, or vehicle for 35 days. Endometrial morphology, receptivity genes, Akt2/NF-κB signaling, gut microbiota (16S rRNA), and serum metabolites (LC-MS) were assessed. Results: PCOS mice showed reduced endometrial thickness (126.4 ± 10.8 μm vs. 215.6 ± 12.3 μm in controls, p < 0.001) and fewer glands (12.6 ± 1.8 vs. 28.4 ± 2.1, p < 0.001). JQGW-H increased endometrial thickness (189.3 ± 11.2 μm, p < 0.01 vs. PCOS) and gland number (23.1 ± 1.9, p < 0.01 vs. PCOS), restored the receptivity markers (Nr2f2, Pc6, Ptch, and Hbegf) toward normal levels, suppressed Akt2/NF-κB activation, and reduced inflammatory cytokines. JQGW shifted the β-diversity structure of the gut microbiota toward the control pattern, with Oscillospira enrichment (LDA > 4). Four metabolites (PA(20:0/16:1(9Z)), 7-methylguanosine, methoxyacetic acid, 8.11-eicosadiynoic acid) showed nominal elevation in PCOS and negative correlations with endometrial thickness (r = −0.73 to −0.89, unadjusted p < 0.01), although none survived FDR correction. Conclusions: JQGW ameliorates PCOS-associated uterine dysfunction, potentially via gut microbiota and metabolite modulation. Future studies should validate causality using fertility-based outcomes and microbiota transplantation. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and is characterized by excessive hepatic lipid accumulation and metabolic dysfunction. Although microRNA-34a (miR-34a) has been implicated in hepatic lipid metabolism, the molecular mechanisms underlying its contribution to MASLD remain incompletely understood. Here, we investigated the role of miR-34a in FFA-induced hepatic steatosis using HepG2 cells and explored RXR-associated signaling as a potential therapeutic strategy. RT-qPCR quantified miR-34a expression; direct target interactions were validated using dual-luciferase reporter assays; proteomic alterations were characterized by iTRAQ-based proteomics followed by Ingenuity Pathway Analysis (IPA); and transcriptomic responses to 9-cis-retinoic acid (9-cis-RA) were analyzed by RNA sequencing. FFA treatment significantly increased miR-34a expression, and dual-luciferase assays confirmed that miR-34a directly targets the 3′-UTRs of RXRα, PPARα, and SIRT1. Integrated proteomic and transcriptomic analyses consistently identified LXR/RXR signaling as one of the principal pathways associated with miR-34a dysregulation and 9-cis-RA treatment. Pharmacological activation of RXR-associated signaling with the pan-RXR agonist 9-cis-RA attenuated intracellular lipid accumulation and reduced the expression of key regulators of lipogenesis and fatty acid uptake, including FASN, SCD1, FABP4, and CD36. Collectively, these findings support the miR-34a–RXRα axis as one regulatory component within a broader nuclear receptor network associated with hepatic lipid homeostasis and support further investigation of RXR-associated signaling as a potential therapeutic strategy for MASLD. Nevertheless, confirmation of receptor-specific mechanisms and validation in more physiologically relevant experimental models will be required. Full article

Salinity stress severely limits growth, physiological function, and metabolic balance in the black calla lily (Arum palaestinum Boiss.), a medicinal and ornamental species native to Mediterranean regions. This study evaluated the effectiveness of selected plant growth regulators (PGRs) in enhancing black calla lily recovery following salinity stress. Seedlings were exposed to severe salinity (25 dS m⁻¹) and subsequently treated with abscisic acid (ABA; 1.0–2.0 mM), salicylic acid (SA; 1.0–2.0 mM), fusicoccin (FC; 0.01–0.03 mM), or ethephon (E; 5–20 mM). Recovery was assessed using morphological, physiological, and biochemical indicators, including leaf color, leaf area, chlorophyll content, plant quality, K⁺/Na⁺ ratio, total nonstructural carbohydrates, reducing sugars, and proline content. All PGRs significantly improved recovery relative to untreated salt-stressed plants, with clear differences in efficacy. ABA was the most effective regulator, followed by ethephon, while SA and FC showed moderate benefits. Optimal ABA treatment (2.0 mM) resulted in near-complete recovery, characterized by improved leaf greenness and expansion, enhanced ionic homeostasis, increased carbohydrate reserves, and reduced accumulation of stress-related metabolites, particularly proline and reducing sugars, indicating alleviation of salinity stress and restoration of normal metabolic activity. These findings demonstrate that post-salinity recovery in A. palaestinum is strongly hormone-dependent and highlight the potential of ABA- and ethylene-based strategies to enhance salinity resilience. Full article

The composition and balance of the gut microbiota are important for human health, as they are involved in metabolic processes, immune regulation, intestinal barrier function, and gut–brain communication. This narrative review summarizes current evidence on dietary and supplementation-based strategies for modulating the gut microbiota, with particular attention to dietary fiber, fermented foods, prebiotics, probiotics, synbiotics, and postbiotics. The review discusses their potential mechanisms of action, including effects on microbial composition, short-chain fatty acid production, intestinal barrier integrity, immune responses, and metabolic homeostasis. Particular emphasis is placed on the context-dependent nature of microbiota modulation, as the effects of dietary and supplementation strategies may vary according to baseline microbiota composition, health status, habitual diet, probiotic strain, dose, and intervention duration. Overall, current evidence suggests that microbiota-targeted nutritional strategies may support gut homeostasis and selected health-related outcomes; however, their effects are not universal and require more personalized and better-controlled approaches in future research. Full article