Search Results (1,612)

Over the past two decades, immune–inflammatory dysregulation has emerged as a central paradigm in the biology of mood disorders. Patients with major depression (MDD) and bipolar disorder (BD) frequently display low-grade systemic inflammation. Elevated C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) identify clinically relevant subgroups of patients characterized by greater severity, cognitive impairment, and poor treatment response. Changes in the gut microbiota and disruptions of the blood–brain barrier (BBB) act as important gateways through which systemic immune activity can influence the brain. At the intracellular level, pattern-recognition receptors activate convergent hubs including NF-κB, JAK/STAT, and MAPK cascades, while the NLRP3 inflammasome integrates mitochondrial dysfunction and oxidative stress with IL-1β release and pyroptosis. These pathways converge on glial dysregulation, impaired BDNF/TrkB signaling, and kynurenine pathway (KP) alterations, fostering excitotoxicity and synaptic deficits. Translational studies demonstrate that elevated CRP and IL-6 predict poor antidepressant outcomes. Anti-inflammatory agents such as infliximab and celecoxib show efficacy in specific subgroups of patients. Emerging multi-omics approaches identify immuno-metabolic biotypes, supporting the rationale for biomarker-guided stratification. These findings define an ‘inflammatory biotype’ of mood disorders and highlight the need for biomarkers and precision-based trials to guide treatment. Full article

Mammalian metallomics, an advanced interdisciplinary field, explores the dynamic roles of metal elements within biological systems and their significance to life processes. While prior reviews have broadly covered metallomics across different systems, this review narrows the focus to mammals, offering new insights into the physiological roles of metal elements, their complex absorption and transport mechanisms, and their intricate associations with diseases. We summarize the characteristics and applications of common metal detection technologies and elaborate on the dynamic landscape of the mammalian metallomics across different tissues and life stages. Furthermore, we elaborate on the physiological functions of the metals from three perspectives, metal-binding proteins, metal ions, and gut microorganisms, and highlight the potential of metallomics in clinical translation, including its diagnostic and therapeutic implications, alongside future directions centered on multi-omics integration. Overall, this review introduces several common metallomics technologies and synthesizes the findings of mammalian metallomics research from multiple perspectives, offering new insights for future related studies. Full article

This study evaluated the antibacterial efficacy and growth-promoting potential of Moringa oleifera and Thymus vulgaris methanolic extracts in broiler chickens challenged with Escherichia coli O78. In vitro antibacterial screening using agar well diffusion and disc diffusion assays revealed that ciprofloxacin exhibited the strongest inhibitory effect, followed by tetracycline and enrofloxacin, whereas among plant extracts, T. vulgaris was more effective than M. oleifera. The optimal combination (M100T150; 100 mg M. oleifera + 150 mg T. vulgaris) produced the largest inhibition zones against E. coli strains. For the in vivo trial, 540 Ross-308 broiler chicks were distributed into six treatment groups in a completely randomized design and reared for 42 days. Parameters assessed included growth performance, carcass traits, gut pH, ileal microbial counts, and intestinal histomorphology. Results showed that E. coli challenge significantly reduced feed intake, weight gain, carcass yield, and villus integrity while increasing FCR and E. coli counts (p < 0.05). Addition of plant extracts, particularly M100T150, significantly improved weight gain, FCR, Broiler Performance Efficiency Factor (BPEF), and Broiler Farm Economy Index (BFEI) compared to the positive control (p < 0.05). Extracts reduced duodenal and jejunal pH (p < 0.001), suppressed E. coli counts (p = 0.003), and enhanced Lactobacillus populations (p = 0.0004). Histological analysis revealed that extract-supplemented groups had greater villus height and surface area with shallower crypts than the positive control, indicating restoration of gut integrity. These findings suggest that methanolic extracts of M. oleifera and T. vulgaris, particularly in combination, can serve as natural alternatives to antibiotics in broiler production under pathogenic challenge. Full article

Chronic inflammatory bowel disease, ulcerative colitis (UC), currently lacks specific drugs for clinical treatment, and screening effective therapeutic agents from natural plants represents a critical research strategy. This study aimed to investigate the therapeutic potential of the flavonoid extract of Polygonum viviparum L. (TFPV) against UC. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical components of TFPV, while cell and animal models were employed to evaluate its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation. The mechanism of anti-inflammatory action was further investigated using a mouse model of UC induced by dextran sulfate sodium (DSS). The results revealed the identification of 32 bioactive components in TFPV, with major compounds such as kaempferol, luteolin, galangin, and quercetin. TFPV effectively mitigated inflammatory damage induced by LPS in IPEC-J2 cells and C57BL/6 mice. In the UC modeled by DSS, TFPV attenuated intestinal inflammation by reducing pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; increasing the anti-inflammatory cytokine IL-10; up-regulating tight junction protein expression such as Claudin-1, Occludin, and ZO-1; and inhibiting the expression of PI3K, AKT, NF-κB, and IL-17 proteins. Analysis of mice fecal samples through 16S rRNA gene sequencing demonstrated that TFPV adjusted the equilibrium of gut microbiota by boosting the abundance of Dubosiella and diminishing that of Enterococcus, Romboutsia, and Enterobacter. Untargeted metabolomics analysis further revealed that TFPV reduced inosine and ADP levels while increasing dGMP levels by the regulation of purine metabolism, ultimately resulting in decreased uric acid levels and thereby alleviating intestinal inflammation. Additionally, TFPV safeguarded the intestinal mucosal barrier by enhancing the expression of tight junctions. In conclusion, TFPV alleviates UC by blocking the PI3K/AKT/NF-κB and IL-17 signaling pathways, lessening intestinal inflammation and injury, safeguarding intestinal barrier integrity, balancing gut microbiota, and lowering uric acid levels, suggesting its promise as a therapeutic agent for UC. Full article

Background/Objectives: Polygonatum sibiricum (PS), possessing both medicinal and edible dual functions, boasts a long history of application in Chinese traditional practices. As a component of its effectiveness, Polygonatum sibiricum polysaccharides (PSPs) have been reported to exert neuroprotective effects. However, the protective effects of PS on the cognitive deficits induced by simulated weightlessness remain unclear. This study evaluated the therapeutic potential of PSPs to counteract the cognitive deficits induced by simulated weightlessness using the Hindlimb Unloading (HU) method. Methods: Mice were subjected to HU to establish cognitive impairment, and PSP was administered for four weeks. The Morris water maze test (MWMT) and passive avoidance test (PAT) were used to evaluate the cognitive abilities of mice, followed by an analysis of molecular mechanisms. Results: PSP treatment increased learning and memory in mice. PSP treatment partially restored gut microbial diversity and composition towards beneficial taxa, including Lactobacillus and Firmicutes, while inhibiting proinflammatory genera, including Alistipes and Proteus. At the same time, PSP upregulated Claudin-5 and Zonula Occludens-1 (ZO-1) levels in the colon, suggesting improved intestinal barrier integrity, and decreased neuroinflammatory response by inhibiting NLRP3 inflammasome activation and NF-κB phosphorylation in the hippocampus. It also modulated neurotransmitter homeostasis along the microbiota–gut–brain (MGB) axis by increasing the levels of gamma-aminobutyric acid (GABA) and serotonin (5-HT) while reducing the levels of excitotoxic metabolites, including Glutamate (Glu) and 3-hydroxykynurenine (3-HK). Conclusions: These results indicate that PSP may have beneficial effects on HU-induced cognitive impairment by regulating gut microbiota, enhancing barrier function, suppressing neuroimmune signaling, and restoring neurotransmitter balance. Full article

Background/Objectives: Aging and metabolic disorders are associated with a decline in muscle function, referred to as age-related sarcopenia. The underlying mechanisms of sarcopenia include cellular senescence, imbalanced protein homeostasis, accumulation of oxidative and inflammatory stressors, and mitochondrial dysfunction. Probiotic supplementation improves the gut microbiome and enhances muscle function via the gut–muscle axis. However, details of molecular mechanisms and the development of an appropriate treatment are under active investigation. Methods: We have examined the effects of Lactiplantibacillus plantarum LM1001, a probiotic that reportedly improves the digestibility of branched-chain amino acids in myocyte cultures, but exactly how it contributes to muscle structure and function remains unclear. Results: We show that aged mice (male C57BL6/J) fed a high-fat diet (HFD) exhibit weak muscle strength, as reflected by a reduction in grip strength. LM1001 supplementation increases muscle strength and restores myofibril size, which has been altered by HFD in aged mice. Expression of myogenic proteins is increased, while protein markers for muscle atrophy are downregulated by LM1001 treatment via the IGF-1/Akt/FoxO3a pathway. LM1001 improves gut microbiota that are altered in aged HFD-fed mice, by increasing their abundance in beneficial bacteria, and efficiently maintains the epithelial lining integrity of the large intestine. Conclusions: We conclude that LM1001 supplementation serves a beneficial role in patients suffering from sarcopenia and metabolic disorders, improving their muscle function, gut microbiota, and intestinal integrity. Full article

Bone immunity represents a dynamic interface where skeletal homeostasis intersects with systemic immune regulation. We synthesize emerging paradigms by contrasting two functionally distinct microenvironments: the marrow cavity, a hematopoietic and immune cell reservoir, and cancellous bone, a metabolically active hub orchestrating osteoimmune interactions. The marrow cavity not only generates innate and adaptive immune cells but also preserves long-term immune memory through stromal-derived chemokines and survival factors, while cancellous bone regulates bone remodeling via macrophage-osteoclast crosstalk and cytokine gradients. Breakthroughs in lymphatic vasculature identification challenge traditional views, revealing cortical and lymphatic networks in cancellous bone that mediate immune surveillance and pathological processes such as cancer metastasis. Central to bone immunity is the neuro–immune–endocrine axis, where sympathetic and parasympathetic signaling bidirectionally modulate osteoclastogenesis and macrophage polarization. Gut microbiota-derived metabolites, including short-chain fatty acids and polyamines, reshape bone immunity through epigenetic and receptor-mediated pathways, bridging systemic metabolism with local immune responses. In disease contexts, dysregulated immune dynamics drive osteoporosis via RANKL/IL-17 hyperactivity and promote leukemic evasion through microenvironmental immunosuppression. We further propose the “brain–gut–bone axis” as a systemic regulatory framework, wherein vagus nerve-mediated gut signaling enhances osteogenic pathways, while leptin and adipokine circuits link marrow adiposity to inflammatory bone loss. These insights redefine bone as a multidimensional immunometabolic organ, integrating neural, endocrine, and microbial inputs to maintain homeostasis. By elucidating the mechanisms of immune-driven bone pathologies, this work highlights therapeutic opportunities through biomaterial-mediated immunomodulation and microbiota-targeted interventions, paving the way for next-generation treatments in osteoimmune disorders. Full article

Inflammatory bowel disease (IBD) demonstrates chronic relapsing inflammation extending beyond adaptive immunity dysfunction. “Trained immunity”—the reprogramming of innate immune memory in myeloid cells and hematopoietic progenitors—maintains intestinal inflammation; however, the mechanism by which gut microbiome orchestration determines protective versus pathological outcomes remains unclear. Microbial metabolites demonstrate context-dependent dual effects along the gut–bone marrow axis. Short-chain fatty acids typically induce tolerogenic immune memory, whereas metabolites like succinate and polyamines exhibit dual roles: promoting inflammation in certain contexts while enhancing barrier integrity in others, influenced by cell-specific receptors and microenvironmental factors. Interventions include precision probiotics and postbiotics delivering specific metabolites, fecal microbiota transplantation addressing dysbiotic trained immunity, targeted metabolite supplementation, and pharmacologic reprogramming of pathological myeloid training states. Patient stratification based on microbiome composition and host genetics enhances therapeutic precision. Future research requires integration of non-coding RNAs regulating trained immunity, microbiome–immune–neuronal axis interactions, and host genetic variants modulating microbiome–immunity crosstalk. Priorities include developing companion diagnostics, establishing regulatory frameworks for microbiome therapeutics, and defining mechanistic switches for personalized interventions. Full article

Healthcare-associated infections (HAIs) in the elderly represent a growing clinical and public health concern, primarily driven by age-related biological remodeling. Key mechanisms include immunosenescence, inflammaging, gut microbiota dysbiosis, and profound metabolic and epigenetic alterations, all of which progressively weaken host defense and resilience to pathogens. In this review, we delineate the molecular pathways underlying these processes, with particular attention to impaired innate and adaptive immune responses, dysfunctional cellular signaling, and disrupted immunometabolic networks that increase susceptibility to multidrug-resistant organisms and aggravate clinical outcomes in older patients. We also address the synergistic impact of frailty-related factors such as malnutrition, multimorbidity, and polypharmacy on infection risk. Finally, we discuss emerging translational perspectives, including nutritional interventions and microbiota-targeted strategies aimed at restoring immune competence and reducing infection burden. By integrating molecular mechanisms with clinical implications, this review highlights innovative opportunities for personalized prevention and management of HAIs in the aging population. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), have become the leading causes of chronic liver disease worldwide, with increasing rates of cirrhosis, hepatocellular carcinoma, and cardiovascular complications. Pathogenesis involves a complex interplay of dietary excess, sedentary lifestyle, insulin resistance, adipose tissue dysfunction, and alterations in the gut microbiome, which collectively lead to hepatocellular stress, inflammation, and fibrogenesis. Despite ongoing advances in pharmacotherapy, lifestyle intervention remains the cornerstone of management. Evidence shows that sustained weight loss of ≥5% reduces hepatic steatosis, ≥7% improves necroinflammation, and ≥10% stabilizes or reverses fibrosis. Dietary strategies, including Mediterranean-style patterns, high-protein approaches, and intermittent fasting, have been shown to be effective in improving insulin sensitivity and reducing intrahepatic triglycerides. Exercise interventions, focusing on both aerobic fitness and resistance training, enhance metabolic flexibility and combat sarcopenia, thereby improving hepatic and systemic outcomes. Equally important are behavioral support, digital health tools, and multidisciplinary approaches that enhance adherence and address barriers such as socioeconomic disparities, limited access, and patient engagement issues. Personalized nutrition plans, integrating physical activity, and ongoing support for behavioral change are essential for long-term disease management. This review synthesizes current evidence on the roles of macronutrients, micronutrients, dietary quality, physical activity, and adjunctive behavioral strategies in managing MASLD. By translating mechanistic insights into practical, evidence-based recommendations, we aim to provide clinicians, dietitians, and exercise professionals with effective frameworks to slow disease progression and improve outcomes across diverse patient populations. Full article

Quinoa (Chenopodium quinoa Willd.) is an ancient Andean crop renowned for its exceptional nutritional profile and diverse bioactive compounds, including polysaccharides, polyphenols, saponins, and essential fatty acids. As global incidence of colonic diseases such as inflammatory bowel disease (IBD), colorectal cancer (CRC), and celiac disease continues to rise, the therapeutic potential of quinoa has garnered increasing scientific attention. This review systematically examines the role of quinoa, with focus on quinoa polysaccharides (QPs), in maintaining and improving colonic health. It summarizes the molecular structure, functional properties, and gut microbiota-modulating effects of QPs, alongside emerging findings on their anti-inflammatory, antioxidant, immunomodulatory, and anticancer activities. Furthermore, the review explores quinoa’s auxiliary effects in mitigating CRC progression and chemotherapy resistance, alleviating intestinal inflammation, and supporting gastrointestinal integrity in celiac patients. By integrating evidence from multi-omics technologies, cell and animal models, and limited clinical studies with mechanistic insights, this review provides a focused synthesis of quinoa bioactive compounds in relation to colonic health. It highlights how precision nutrition and multi-omics approaches could guide future applications of quinoa as a novel functional food-based intervention for colonic diseases. Full article

Antlers are unique mammalian organs that grow rapidly through extensive cartilage proliferation. Vitamin A (VA), via retinoic acid, is known to influence skeletal development, yet its contribution to antler growth remains unclear. We investigated whether rumen-protected VA supplementation modulates antler biology in sika deer by integrating gut microbiota profiling, fecal and serum metabolomics, antler cartilage transcriptomics, and in vitro chondrocyte assays. VA was associated with compositional shifts in the gut microbiota and altered metabolic profiles in feces and serum. Notably, the melatonin-derived metabolite AMFK increased in both matrices and showed strong associations with antler weight and cartilage-related gene expression. VA-supplemented deer exhibited higher antler weight, and antler transcriptomes indicated changes in pathways consistent with cartilage extracellular matrix and growth signaling. In chondrocytes, AMFK promoted proliferation and upregulated chondrogenic markers. Together, these findings suggest that VA may promote antler growth through a microbiota–metabolite–gene axis rather than by altering systemic retinol alone. Full article

Globally, Parkinson’s disease (PD) is the neurodegenerative condition with the most rapidly increasing prevalence, and a growing body of evidence associates its pathology with impairments in the gut–brain axis. Traditionally viewed as a disease marked by the loss of dopaminergic neurons, emerging evidence emphasizes that chronic neuroinflammation is a driver of neurodegeneration, with gut-originating inflammation playing a crucial role. Increased intestinal permeability, often called “leaky gut,” allows harmful substances, toxins, and misfolded α-synuclein into the systemic circulation, potentially exacerbating neuroinflammation and spreading α-synuclein pathology to the brain through the vagus nerve or compromised blood–brain barrier (BBB). This review synthesizes current insights into the relationship between gut health and PD, emphasizing the importance of gut permeability in disrupting intestinal barrier function. This paper highlights innovative therapeutic approaches, particularly personalized therapies involving gut microbiome engineering, as promising strategies for restoring gut integrity and improving neurological outcomes. Modulating specific gut bacteria to enhance the synthesis of certain metabolites, notably short-chain fatty acids (SCFAs), represents a promising strategy for reducing inflammatory responses and decelerating neurodegeneration in Parkinson’s disease. Full article

The morphogenesis of the primordial gut relies on signaling pathways such as Wnt, FGF, Notch, Hedgehog, and Hippo. Reciprocal crosstalk between the endoderm and mesoderm is integrated into the signaling pathways, resulting in craniocaudal patterning. These pathways are also involved in adult intestinal homeostasis including cell proliferation and specification of cell fate. Perturbations in this process can cause growth disturbances manifesting as adenomas, serrated lesions, and cancer. Significant differences have been observed between right and left colon cancers in the hindgut, and between the jejunoileum, appendix, and right colon in the midgut. The question is to what extent the embryology of the mid- and hindgut contributes to differences in the underlying tumor biology. This review examines the precursor lesions and consensus molecular subtypes (CMS) of colorectal cancer (CRC) to highlight the significance of embryology and tumor microenvironment (TME) in CRC. The three main precursor lesions, i.e., adenomas, serrated lesions, and inflammatory bowel disease-associated dysplasia, are linked to the CMS classification, which is based on transcriptomic profiling and clinical features. Both embryologic and micro-environmental underpinnings of the mid- and hindgut contribute to the differences in the tumors arising from them, and they may do so by recapitulating embryonic signaling cascades. This manifests in the range of CRC CMS and histologic cancer subtypes and in tumors that show multidirectional differentiation, the so-called stem cell carcinomas. Emerging evidence shows the limitations of CMS particularly in patients on systemic therapy who develop drug resistance. The focus is thus transitioning from CMS to specific components of the TME. Full article

Traumatic brain injury (TBI) remains a major global health problem, contributing significantly to morbidity and mortality worldwide. Despite advances in understanding its complex pathophysiology, current therapeutic strategies are insufficient in addressing the long-term cognitive, emotional, and neurological impairments. While the primary mechanical injury is immediate and unavoidable, the secondary phase involves a cascade of biological processes leading to neuroinflammation, blood–brain barrier (BBB) disruption, and systemic immune activation. The heterogeneity of patient responses underscores the urgent need for reliable biomarkers and targeted interventions. Emerging evidence highlights the gut–brain axis as a critical modulator of the secondary phase, with microbiota-derived extracellular vesicles (MEVs) representing a promising avenue for both diagnosis and therapy. MEVs can cross the intestinal barrier and BBB, carrying biomolecules that influence neuronal survival, synaptic plasticity, and inflammatory signaling. These properties make MEVs promising biomarkers for early detection, severity classification, and prognosis in TBI, while also offering therapeutic potential through modulation of neuroinflammation and promotion of neural repair. MEV-based strategies could enable tailored interventions based on the individual’s microbiome profile, immune status, and injury characteristics. The integration of multi-omics with artificial intelligence is expected to fully unlock the diagnostic and therapeutic potential of MEVs. These approaches can identify molecular subtypes, predict outcomes, and facilitate real-time clinical decision-making. By bridging microbiology, neuroscience, and precision medicine, MEVs hold transformative potential to advance TBI diagnosis, monitoring, and treatment. This review also identifies key research gaps and proposes future directions for MEVs in precision diagnostics and gut microbiota-based therapeutics in neurotrauma care. Full article