Search Results (20,804)

Objectives: Preterm infants confront multiple coexistent health risks and may not receive human milk (HM), which contains human milk oligosaccharides (HMOs), among other biologically active, beneficial components. 2′-Fucosyllactose (2′-FL) is the most abundant HMO in most HM. Interventional studies of formula with added HMOs have demonstrated multiple beneficial outcomes in healthy, term infants. Methods: This double-blind, randomized, placebo-controlled pilot study (NCT03306316) evaluated the effect of a 2′-FL supplement on growth, tolerance, and neurobehavior, as assessed by the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS), in preterm infants. Eligible neonates born between 26 0/7 and 31 6/7 weeks gestational age (GA) were enrolled from three NICUs in the United States. Preterm infants consuming mother’s own milk or donor human milk were randomized to receive a supplement of 0.135 g/mL of 2′-FL or 0.05 g/mL dextrose (placebo) twice daily until 36 weeks corrected GA, NNNS assessment, or hospital discharge, whichever came first. Results: Of 42 participating preterm infants, 23 (55%) received 2′-FL and demonstrated no significant differences in growth in weight, length, or head circumference over 5 weeks. There were also no differences in stool frequency, adverse (AEs) or serious adverse events (SAEs), or neurobehavior (NNNS) between groups. Conclusions: This pilot study found that 2′-FL supplementation in preterm infants through 36 weeks corrected GA was safe and well-tolerated and supported adequate growth and neurobehavior. Full article

Population aging is a growing problem. This process is driven not only by genetic factors but also by environmental factors, such as diet. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide, characterized by cognitive decline, synaptic dysfunction, and neuronal loss. Despite extensive research, effective disease-modifying therapies remain limited. Increasing evidence indicates that oxidative stress plays a central role in AD pathogenesis, acting as a key link between β-amyloid accumulation, tau hyperphosphorylation, mitochondrial dysfunction, and neuroinflammation. Accordingly, dietary strategies have been proposed to mitigate these pathological processes and may represent an important component of Alzheimer’s disease prevention. Moreover, emerging evidence on the gut–brain axis highlights the critical role of gut microbiota in regulating neuroinflammation and oxidative stress. Dysbiosis has been associated with increased permeability of the intestinal barrier, systemic inflammation, and accelerated neurodegeneration. Dietary patterns such as the Mediterranean, DASH, and MIND diets may exert beneficial effects by simultaneously influencing antioxidant status and microbial composition. This review aims to provide a comprehensive overview of the role of oxidative stress in Alzheimer’s disease and evaluate the potential of dietary interventions in modulating mechanisms involved in Alzheimer’s disease pathogenesis and supporting cognitive health. Particular attention is given to the neuroprotective effects of dietary antioxidants, including vitamins, polyphenols, and polyunsaturated fatty acids, which act through the reduction in reactive oxygen species, modulation of inflammatory pathways, and support of neuronal survival. Although current findings are promising, inconsistencies in clinical data indicate the need for further well-designed studies. Future research should focus on personalized nutritional strategies integrating dietary, genetic, and microbiome-related factors. Targeting oxidative stress through diet and microbiota modulation represents a promising complementary strategy for Alzheimer’s disease prevention and supportive management, although further clinical studies are required to establish disease-modifying effects. Full article

Heat shock protein 70 (HSP70) regulates the stress tolerance and reproductive ability of insects. In this study, the SfHSP70-7 gene was cloned and identified from the rice pest Sogatella furcifera. SfHSP70-7 encodes a typical cytoplasmic HSP70 protein that has a conserved functional domain and is highly similar to the HSP70 homologous protein of Laodelphax striatellus. SfHSP70-7 was found to be widely expressed across all developmental stages, with the highest levels in nymphs and female adults. In terms of tissue distribution, it was particularly abundant in the gut and ovaries. Its expression was strongly induced by high/low temperatures and three insecticides (triflumezopyrim, sulfoxaflor, and imidacloprid), with the maximum induction under heat and triflumezopyrim stress. RNA interference (RNAi) efficiently silenced SfHSP70-7 and significantly increased the susceptibility of S. furcifera to triflumezopyrim and sulfoxaflor, but it had no effect on susceptibility to imidacloprid. RNAi knockdown of SfHSP70-7 markedly reduced survival by 45.5% (30 °C) and 38.9% (35 °C) under heat stress. In addition, gene knockdown can damage the reproductive performance of females by reducing oviposition and egg hatchability. These results indicate that SfHSP70-7 is involved in regulating the heat tolerance, insecticide adaptability, and reproductive regulation mechanism of S. furcifera, providing a potential target for pest control. Full article

(1) Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain and altered bowel habits, linked to dysbiosis and inflammation. Currently available treatments, focused on symptom management, displayed limited efficacy. Recent research highlights microbiota modulation as a potential therapeutic strategy to restore intestinal barrier integrity; (2) A dextran sulfate sodium (DSS)-induced mouse model of post-colitis IBS-like symptoms was performed to evaluate the effect of a novel mixture of Enterococcus lactis SF68^®, butyrate, and folate. Disease activity index and spleen weight were assessed. Markers of gut inflammation, intestinal barrier alterations, and gut butyrate bioavailability were measured. The activity of colonic mitochondria was also analyzed; (3) Supplementation with the novel mixture significantly reduced spleen weight and cytokine levels. The intestinal epithelial barrier was restored through an increase in claudin-1, occludin, and defensin 1–3 and a reduction in LBP plasma level. Treatment with the mixture enhanced the expression of butyrate transporters in mice. Mitochondrial activity markers, including citrate synthase and Cytochrome c oxidase, were improved by treatment; (4) The novel mixture containing Enterococcus lactis, butyrate, and folate exerted a protective effect against post-inflammatory IBS by reducing local inflammation, restoring intestinal barrier integrity, and enhancing butyrate bioavailability, suggesting its potential for managing post-inflammatory IBS symptoms effectively. Full article

The endocannabinoid system (ECS) is increasingly recognized as a central regulator of immune homeostasis, integrating neural, metabolic, and immune signaling to maintain physiological equilibrium. This Perspective examines the “therapeutic paradox” of endocannabinoid immunomodulation, whereby anti-inflammatory and tissue-protective effects are mechanistically linked to transient immunosuppression. Although cannabinoid receptor 2 (CB2) is the primary mediator of immune regulation, growing evidence indicates that cannabinoid receptor 1 (CB1) also contributes to inflammatory control in both the central nervous system and peripheral tissues. Activation of CB2 suppresses inflammatory signaling through Gi/o-mediated inhibition of adenylate cyclase, reduced cyclic adenosine monophosphate (cAMP) signaling, and repression of nuclear factor kappa B (NF-κB)-dependent transcription. While these mechanisms limit pathological inflammation and promote tissue protection, they simultaneously attenuate innate and adaptive immune functions required for effective pathogen clearance. Across neuroinflammatory disorders, inflammatory bowel disease, hepatic injury, sepsis, cancer, and systemic inflammatory syndromes, the ECS shifts immune responses toward resolution at the cost of reduced antimicrobial readiness. We synthesize the molecular mechanisms underlying this therapeutic paradox, including macrophage polarization, lymphocyte reprogramming, and tissue-specific immune adaptations, and discuss strategies for developing endocannabinoid-based therapeutics that preserve anti-inflammatory efficacy while minimizing immunosuppressive liabilities. Full article

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by progressive insulin resistance, impaired glucose regulation, and elevated cardiometabolic risk. Despite the availability of pharmacological therapies, long-term glycemic control remains suboptimal in many patients, highlighting the need for effective adjunctive nutritional strategies. Probiotic yogurt containing well-characterized bacterial consortia has been proposed as one such approach, given its potential to modulate gut microbiota composition, increase short-chain fatty acid (SCFA) production, improve intestinal barrier integrity, and attenuate low-grade systemic inflammation. A narrative review was conducted by searching PubMed, Scopus, and Google Scholar databases using terms related to probiotic yogurt, synbiotic yogurt, insulin sensitivity, T2DM, gut microbiota, Lactobacillus, and Bifidobacterium. Priority was given to randomized controlled trials (RCTs), meta-analyses, and systematic reviews, supplemented by mechanistically relevant preclinical studies. The reviewed evidence indicates that probiotic yogurt generally produces more consistent improvements in long-term metabolic markers, particularly glycated hemoglobin (HbA1c) and lipid profile, than in acute fasting glucose responses. Several trials also report reductions in fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR), combined with improvement in the quantitative insulin sensitivity check index (QUICKI), particularly when yogurt is enriched with prebiotic substrates such as inulin and konjac glucomannan. Probiotic yogurt formulated with well-selected microbial consortia may serve as a safe complementary intervention for improving insulin sensitivity and overall metabolic control in T2DM patients. Full article

Metabolic syndrome (MetS) is a multifactorial disorder characterized by central obesity, insulin resistance, dyslipidemia, hypertension, and impaired glucose metabolism, significantly increasing the risk of type 2 diabetes and cardiovascular disease. Recent evidence highlights the important role of the gut–brain axis in the pathogenesis of MetS through complex interactions between the gut microbiota, immune system, endocrine signaling, and host genetics. This narrative review provides an integrative overview of the mechanisms linking dysbiosis to metabolic dysfunction, with particular emphasis on gut microbiota alterations, intestinal permeability, chronic low-grade inflammation, and microbial metabolites such as short-chain fatty acids and lipopolysaccharides. The review also discusses the neural, endocrine, and immune pathways involved in gut–brain communication, including the role of gut-derived neurotransmitters in metabolic regulation. In addition, the contribution of host genetic susceptibility and epigenetic regulation is explored, highlighting how gene–microbiome interactions influence individual metabolic responses and disease risk. Recent advances in multi-omics technologies and precision medicine suggest that personalized approaches targeting both microbial and genetic factors may improve prevention and treatment strategies for MetS. Furthermore, microbiota-targeted interventions, including dietary modifications, probiotics, prebiotics, and fecal microbiota transplantation, are discussed as emerging therapeutic perspectives. Overall, this review emphasizes the importance of considering MetS as a systemic disorder driven by interconnected biological networks involving microbiota, metabolism, immunity, and genetics. Full article

Alzheimer’s disease (AD) is a complex, multifactorial neurodegenerative disorder whose core pathological hallmarks include Aβ aggregation, tau hyperphosphorylation, chronic neuroinflammation, oxidative stress, mitochondrial dysfunction, and gut microbiota dysbiosis. Lignans, a class of naturally occurring polyphenolic dimers widely distributed in medicinal plants and diet, exhibit multi-target neuroprotective effects with low toxicity. This review provides a systematic synthesis of the anti-AD pharmacological mechanisms underlying nine structurally distinct lignan subtypes—dibenzocyclooctadiene, tetrahydrofuran, bisepoxy, benzofuran, and biphenyl types—emphasizing scaffold-dependent structure–activity relationships. Key mechanistic pathways encompass direct inhibition of Aβ aggregation and tau phosphorylation, activation of the Nrf2 antioxidant signaling axis and PI3K/Akt pro-survival pathways, suppression of NF-κB-mediated neuroinflammation, restoration of cholinergic function, protection of mitochondria via SIRT3, inhibition of ferroptosis through Gsk3β/Nrf2/GPX4 signaling, and modulation of the gut–brain axis via microbiota-mediated conversion to enterolactone. This review addresses key pharmacokinetic limitations such as low oral bioavailability, rapid metabolism, and limited brain exposure, alongside strategies including structural modification, brain-targeted delivery systems, and gut microbiota modulation. Despite promising preclinical evidence, clinical translation remains limited. Future research priorities should focus on direct target validation, network pharmacology, optimized formulations, and well-designed clinical trials to develop lignans into next-generation anti-aging and anti-AD therapeutics. Full article

Plant-derived extracellular vesicles (PDEVs) have emerged as promising natural nanocarriers for biomedical applications owing to their distinctive ability to facilitate intercellular communication and transport bioactive molecules. In this review, we employ bibliometric analysis to identify research hotspots and trends, providing a comprehensive overview of these core themes. The bibliometric results reveal a sustained increase in annual publications in this field, with keyword analysis identifying drug delivery, cross-kingdom regulation, immunomodulation, engineering modification, and gut microbiota as five major research themes. The focus of research has evolved from early basic biological characteristics into engineered smart delivery platforms, with the application areas expanding from intestinal inflammation to neurological, metabolic, dermatological, and oncological diseases. This review systematically examines the core directions in this field. It compares the strengths and limitations of mainstream isolation methods and highlights the value of multi-omics integration, covering the molecular mechanisms of ferroptosis and gut microbiota regulation by PDEVs along with engineering strategies such as drug loading, surface modification, and membrane fusion. It also discusses the latest progress in frontier therapeutic applications of PDEVs, including cancer, inflammatory diseases, tissue regeneration and aesthetics, and neurological disorders. Finally, this review summarizes the key challenges confronting the field, including the lack of standardized protocols, production bottlenecks, and engineering obstacles. It also delineates future directions, including establishing international standardization definitions, advancing multi-omics and AI-driven mechanistic elucidation, developing scalable and efficient purification technologies, and executing systematic preclinical safety and pharmacokinetic evaluations to facilitate clinical translation. 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

The search for sustainable alternatives to fish oil (FO) in aquafeeds is imperative for the long-term sustainability of aquaculture. This study evaluated the effects of partially replacing FO with oils derived from Hermetia illucens (RH) and Musca domestica (RY) larvae at 10%, 30%, and 50% levels on growth, lipid metabolism, hepatic antioxidant capacity, and gut microbiota in juvenile Cyprinus carpio. Results showed distinct source- and dose-dependent responses. RY produced a consistent dose-dependent trend in growth parameters, whereas RH exhibited a biphasic pattern, with growth impairment at 30% replacement and recovery at 50%. Both oils significantly suppressed hepatic fatty acid synthase (FAS) activity, yet this suppression was accompanied by dose-dependent up-regulation of fas expression, particularly at high RH and RY levels, indicating complex post-transcriptional regulation. RH at higher replacement levels reduced digestive enzyme activities and antioxidant capacity, while higher RY caused minimal disruption. Both oils reshaped gut microbiota toward oil-specific community structures. Two-way ANOVA revealed significant synergistic interactions between oil source and replacement level for most serum biochemical and hepatic antioxidant parameters (ηp² > 0.90). These findings demonstrate that RY is a tolerable alternative across a wide replacement range, though all RY groups exhibited lower growth than the control, 30% is identified as the maximum tolerable level; whereas RH requires precise dosing at 10% to avoid the 30% impairment threshold. Full article

Background: Multiple sclerosis and periodontal disease are chronic inflammatory conditions that may share immune-mediated mechanisms, including cytokine activation, oral dysbiosis, oxidative stress, and systemic inflammatory burden. This systematic review aimed to synthesize recent evidence on common inflammatory pathways linking periodontal disease and multiple sclerosis. Methods: The review was conducted according to PRISMA 2020 guidelines. PubMed/MEDLINE, Cochrane Library, and Scopus were searched for English-language studies published between June 2020 and June 2026. Eligible studies addressed multiple sclerosis, periodontal disease, oral microbiome alterations, systemic inflammation, or neuroinflammatory outcomes. Study selection and data extraction were performed independently by three reviewers. Risk of bias was assessed using AMSTAR 2, the Newcastle–Ottawa Scale, and the Joanna Briggs Institute checklist, according to study design. Results: Seventeen studies were included in the qualitative synthesis. The main shared mechanisms were cytokine-mediated inflammation involving TNF-α, IL-1β, IL-6, and IL-17; NF-κB signaling; Th17/Treg imbalance; blood–brain barrier disruption; oxidative stress; matrix metalloproteinase activity; complement activation; and oral–gut–brain axis dysregulation. The evidence suggests that periodontal inflammation may contribute to systemic immune activation and may amplify neuroinflammatory processes in multiple sclerosis. Conclusions: Current evidence supports a biologically possible association between periodontal disease and multiple sclerosis through shared inflammatory and microbial pathways. However, causality remains unproven, and further longitudinal and interventional studies are needed. Full article

Allopolyploidy can generate rapid phenotypic change, yet its early transcriptomic consequences in a newly generated triploid hybrid remain poorly understood in animals. Here, we establish a sterile triploid hybrid between grass carp (Ctenopharyngodon idella) and yellowcheek (Elopichthys bambusa), designated CCE, using an optimized hydrostatic pressure protocol that achieved 100% triploidy with high embryonic viability. Whole-genome resequencing supported an approximately 2:1 maternal-to-paternal genomic dosage. Transcriptomes from seven tissues revealed that maternal expression-level dominance (ELD-Ci) was the predominant expression-inheritance pattern (63.7–84.2%), consistent with a passive, dosage-dependent mode of regulation. Paternal expression-level dominance (ELD-Eb) was detected in all tissues but with marked tissue specificity: most ELD-Eb genes in the liver and muscle showed expression levels similar to those of the paternal yellowcheek parent before hybridization (96.2% and 72.8%, respectively), whereas the brain and hypothalamus contained more ELD-Eb genes not directly explained by parental differences. Finally, in the gut, CCE had shorter villi than both parents, a thicker muscularis layer than both parents, and fewer goblet cells than Eb. Genes related to digestion, absorption, and nutrient transport were more highly expressed in Eb and retained an Eb-like expression pattern in CCE. By contrast, several smooth muscle-related genes, including myh14 and smtnl1, showed non-additive upregulation beyond the parental range, in parallel with the thickened muscularis layer. Together, these findings provide new insights into how parental genome dosage and tissue-specific regulation shape gene expression divergence in newly formed animal allopolyploids. Full article

Background/Objectives: Colorectal cancer (CRC) is complicated by cachexia, a wasting syndrome with muscle and fat loss that worsens survival and treatment outcomes. Evidence suggests that the gut microbiome may contribute to CRC cachexia, but its role remains unclear. This systematic review synthesizes evidence to identify microbial signatures linked to cachexia hallmarks in CRC. Methods: The protocol was pre-registered with PROSPERO and followed PRISMA guidelines. PubMed, Web of Science, and Scopus were searched for studies on CRC patients and preclinical models with cachexia. Eligible studies compared microbiota composition between cachectic and non-cachectic groups to identify alterations linked to cachexia progression. Study quality was assessed using the Newcastle–Ottawa Scale and CAMARADES checklist. Results: Of 2456 records, 15 studies met inclusion criteria, including 13 preclinical studies and 2 clinical studies. Study quality was moderate for preclinical studies and high for clinical cohort studies. Murine CRC cachexia models showed reduced alpha diversity and beta diversity shifts. Butyrate-producing taxa were depleted, whereas Enterobacteriaceae and other pathobionts were enriched. Some microbial changes were independent of food intake and linked to inflammation, metabolic dysregulation, and muscle wasting. Clinical evidence was limited to two reports from the same cohort, in which higher pre-surgical abundance of Fusobacterium nucleatum and lower Porphyromonas and Actinomyces spp. were associated with cachexia onset. Conclusions: Current evidence suggests an association between CRC-associated cachexia and gut microbiome alterations, but causality, directionality, and clinical relevance remain uncertain. Full article

Background and Objectives: The concept of the gut–muscle–brain axis encompasses the intricate, multidirectional interactions between the gut microbiota (GM), physical exercise (PE), and the central nervous system. Within this framework, gut dysbiosis has been implicated in the pathogenesis of Alzheimer’s disease (AD). Given that cognitive functions in AD appear to benefit from PE, it is plausible to hypothesize that these improvements may be partially mediated by PE-induced alterations in GM taxonomy. Therefore, the objective of this study is to evaluate the potential effects of PE in the GM and their implications for AD. Methods: A systematic review was conducted in PubMed, Web of Science and Scopus following the PRISMA guidelines up to July 2025 for preclinical controlled trials that assessed the effects of PE on the GM of AD animal models. A random-effects model meta-analysis was performed to estimate the pooled effect of PE on GM frequency or composition. This study received no external funding. Results: Eight studies were included in the systematic review (sample size, n = 126), of which two could be meta-analyzed. We found that PE significantly reduced Actinobacteria abundance (MD, −0.005%; 95% CI, −0.008 to −0.002; p = 0.001) with no statistically significant evidence of heterogeneity (I² = 89.60%, Q = 0.102, p = 0.950) or publication bias observed (Begg’s test, p = 0.296), but no significant effects were found for other phylums or genera. Conclusions: PE appears capable of modulating the GM of animal models with AD in a selective and heterogeneous manner. Further studies are needed to clarify the mechanisms by which this is possible and to determinate its impact on the pathogenesis of the disease. Full article