Search Results (1,087)

Background/Objectives: Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Despite advances in treatment, outcomes for advanced CRC remain unsatisfactory due to uncontrolled proliferation, metastasis, and recurrence. This study investigated the anti-cancer effects of KMU-11342, an indolin-2-one-based multi-protein kinase inhibitor with previously reported anti-inflammatory properties, in human colorectal cancer models. Methods: The anti-cancer effects of KMU-11342 were evaluated in colorectal cancer cells and further investigated in three-dimensional (3D) spheroid and patient-derived organoid models. Cell proliferation, migration, apoptosis, and cell cycle progression were assessed. Kinase activity profiling and molecular docking analyses were performed to identify potential targets and characterize the underlying signaling pathways. Results: KMU-11342 significantly inhibited the proliferation and migration of CRC cells. It reduced CRC cell density by 58.9% and 83.3% at 0.5 and 1 μM, respectively. These effects were accompanied by G2/M cell cycle arrest and apoptotic cell death. In 3D models, spheroid formation was markedly reduced and stemness-related characteristics were diminished. Patient-derived CRC organoids also showed decreased viability, exhibiting 38.6% and 77.4% reductions at 1 and 2 μM, respectively. These effects were observed in a dose-dependent manner in both two-dimensional (2D) and 3D colorectal cancer models. Kinase activity profiling and molecular docking analyses identified glycogen synthase kinase 3 beta (GSK3β) and cyclin-dependent kinase 1 (CDK1) as potential mediators of the anti-cancer effects of KMU-11342 through the p53/nuclear factor kappa B (NF-κB) and FoxO1 signaling axes, respectively. Conclusions: KMU-11342 exhibits potent anti-tumor activity against CRC through suppressing proliferation, migration, and stemness in both 2D and 3D models, including patient-derived organoids. Its effects may be mediated, at least in part, through modulation of GSK3β and CDK1 via the p53/NF-κB and FoxO1 signaling pathways. Full article

Lactate is increasingly recognized as a signaling molecule capable of modulating gene expression and vascular function. This descriptive pilot study investigated the effects of different lactate concentrations (0 mM, 10 mM, 20 mM, and 30 mM) and exposure times (1 h, 3 h, and 6 h) on the transcriptomic responses of human umbilical vein endothelial cells (HUVECs). Using next-generation RNA sequencing, an unbiased genome-wide analysis was performed, followed by focused examination of genes relevant to endothelial biology, calcium signaling, and glycocalyx integrity. Results showed that there was no statistically significant effect of lactate concentration on the expression of the examined genes. In contrast, prolonged incubation time was associated with differential expression of KLF2, KLF4, FOXO1, CD34, and VCAM1. These findings suggest that exposure time, rather than lactate concentration, may be associated with endothelial gene expression patterns under static conditions. This exploratory pilot study provides preliminary transcriptomic observations and highlights the need for further mechanistic investigations including functional and protein-level analyses. Full article

Diabetic nephropathy (DN) is a severe diabetic complication with substantial clinical burden. The complex pathogenesis of DN has hindered the development of targeted therapies, creating an urgent need to develop novel strategies that directly address its underlying inflammatory and fibrotic mechanisms. Coreopsis tinctoria (CE) is an edible plant rich in polyphenols, but its mechanism against DN remains understood. An integrated framework combining network pharmacology and machine learning was developed to prioritize active polyphenols and their targets. A multi-layer perceptron classifier, trained on 3.16 million compound–target pairs from Binding DB, predicted interactions between 36 CE polyphenols and 12,030 DN-associated genes. The top 100 targets were subjected to KEGG enrichment analysis, and the identified pathways were validated in a high-fat diet/STZ-induced DN rat model. The MLP model achieved superior performance (AUC-ROC = 0.9219, AP = 0.9592). Five lead polyphenols (flavonoids/chalcones) showed high predicted activity. KEGG analysis revealed enrichment in PI3K-Akt, calcium signaling, metabolic pathways, and cellular senescence. In vivo, CE treatment (150–600 mg/kg/day) dose-dependently improved glucose/lipid metabolism and renal function, and ameliorated histopathological damage, including glomerular hypertrophy, fibrosis, and mesangial expansion. Mechanistically, CE suppressed NFκB/TGFβ/Smad signaling, restored PPARγ and Nrf2/HO-1/FoxO1 antioxidant defenses, and inhibited apoptosis via Bcl-2/Bax regulation. CE exerts multi-target renoprotective effects through coordinated modulation of metabolic, inflammatory, fibrotic, and antioxidant pathways, supporting its potential as a functional food ingredient for DN management. Full article

Background: Sarcopenia and frailty are highly prevalent extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD) and are strongly associated with reduced exercise tolerance, exacerbation risk, hospitalizations, and mortality. Beyond inflammation, oxidative stress, and physical inactivity, emerging evidence highlights nutrition as a major modifiable driver of muscle deterioration in COPD. Nutritional deficits impair anabolic signaling, exacerbate proteolysis, worsen mitochondrial dysfunction, and contribute to frailty progression. Methods: This narrative review synthesizes evidence from PubMed, Embase, Scopus, and Web of Science up to 2025, integrating mechanistic, metabolic, nutritional, and biomarker-related pathways underlying muscle dysfunction in COPD. Studies examining inflammation, hypoxemia, oxidative stress, hormonal imbalance, nutrition, and emerging biomarkers were included. Results: COPD-related sarcopenia results from converging inflammatory (TNF-α, IL-6), catabolic (FOXO, UPS), metabolic, and vascular mechanisms, compounded by energy deficiency, protein insufficiency, and micronutrient deficits. Inadequate intake of protein, vitamin D, antioxidants, and omega-3 fatty acids increase anabolic resistance, enhance muscle catabolism, and worsen frailty. Nutritional interventions, particularly high-protein supplementation, leucine-enriched formulas, vitamin D repletion, omega-3 fatty acids, and multimodal nutrition–exercise programs, demonstrate benefits in muscle mass, strength, and physical performance. Biomarkers such as GDF-15, CAF22, and specific microRNAs reflect nutritional status and correlate with muscle health in COPD. Conclusions: Sarcopenia and frailty in COPD arise from a complex interplay of inflammatory, metabolic, nutritional, and lifestyle-related factors. Integrating nutritional assessment and targeted dietary interventions with exercise and pulmonary rehabilitation is essential to counteract anabolic resistance and improve functional outcomes. Advances in biomarker research may support earlier diagnosis and personalized nutrition-based therapeutic strategies. Full article

Skin aging is associated with oxidative stress, extracellular matrix degradation, and dysregulation of melanogenesis, leading to wrinkles, loss of elasticity, and hyperpigmentation. Natural plant-derived compounds have attracted increasing interest as multifunctional cosmetic ingredients due to their antioxidant and anti-aging properties. Mai-Kae-Den-Klong (MKDK), a traditional Thai longevity herbal formula composed of Albizia procera (Roxb.) Benth., Cyperus rotundus L., Diospyros rhodocalyx Kurz, Piper nigrum L., Streblus asper Lour., and Tinospora crispa (L.) Hook.f. & Thomson, has historically been used to promote vitality and healthy aging; however, its potential application as a cosmetic anti-aging ingredient remains scientifically unexplored. Therefore, this study investigated the anti-aging potential of MKDK extract using integrated enzyme-based bioassays and in silico approaches. Phytochemical profiling of the ethanolic extract was performed using LC-MS analysis, revealing diverse bioactive constituents, including flavonoids, phenolic glycosides, alkaloids, and terpenoids, with (−)-epicatechin, procyanidin B1, and piperine identified as major metabolites. Antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays, while inhibitory activities against tyrosinase, collagenase, elastase, and hyaluronidase were assessed to determine skin anti-aging potential. The extract exhibited strong antioxidant activity, with IC₅₀ values of 17.23 ± 2.11 µg/mL for DPPH and 11.87 ± 1.77 µg/mL for ABTS assays. In addition, the extract demonstrated inhibitory effects against tyrosinase (IC₅₀ = 41.25 ± 1.56 µg/mL), elastase (IC₅₀ = 49.51 ± 3.69 µg/mL), collagenase (IC₅₀ = 61.54 ± 2.88 µg/mL), and hyaluronidase (IC₅₀ = 63.74 ± 6.32 µg/mL), suggesting multifunctional anti-aging properties associated with skin brightening and extracellular matrix preservation. Network pharmacology analysis predicted multiple aging-related signaling pathways, particularly the FoxO signaling pathway, which is associated with oxidative stress regulation and longevity. Molecular docking analysis further demonstrated favorable binding affinities of procyanidin B1, epicatechin, and piperine toward skin-aging-related enzymes, supporting their potential contribution to the observed bioactivities. Overall, these findings suggest that MKDK possesses promising cosmeceutical potential as a natural multifunctional anti-aging ingredient and provides scientific support for the application of traditional Thai herbal formulations in cosmetic and skin health products. Full article

Prostate cancer progression and therapy response are strongly influenced by the tumor microenvironment (TME), particularly stromal fibroblasts that regulate survival signaling, metabolism, and drug resistance. In this study, we investigated whether extracts from three Lepidium meyenii (maca) morphotypes, yellow (MY), red (MR), and black (MB), modulate doxorubicin (DOX) responses in 22Rv1 prostate cancer cells under mono-culture and co-culture conditions with human dermal fibroblasts (HDFa). Cell viability, proliferation, apoptosis-related proteins, lipid droplets (LDs) accumulation, and selected signaling markers were analyzed. In mono-culture, maca extracts exhibited limited cytotoxicity, with MB showing the strongest but still moderate effect. Co-treatment with DOX did not enhance cytotoxicity and resulted in context-dependent modulation of caspase-3 and caspase-8. In co-culture, HDFa cells reduced DOX sensitivity, suggesting altered treatment responses under co-culture conditions. Morphometric analysis suggested fibroblast activation-like changes. Across models, maca reduced LDs accumulation, while increased adipose triglyceride lipase (ATGL) levels in co-culture suggested altered lipid utilization. Additionally, maca extracts modulated PI3K, PSMA, FOXO1, FAP, and HAT1 in a morphotype-dependent manner. Overall, maca extracts acted primarily as context-dependent modulators of signaling and lipid metabolism markers rather than direct cytotoxic agents with their effects strongly dependent on both extract type and microenvironmental context. Full article

The mechanisms by which ferulic acid (FA) improves meat quality and promotes muscle development in pigs remain unclear. This study evaluated the effects of dietary FA on meat quality and muscle development in Shaziling pigs. A total of 108 pigs (30 kg ± 0.71 kg) were selected and randomly assigned to three groups, with six replicates per group and six pigs per replicate. Pigs were fed a corn–soybean meal basal diet supplemented with 0 mg/kg, 250 mg/kg, or 500 mg/kg of FA for 120 days. Results showed that FA reduced fat percentage, increased lean meat percentage and loin-eye area, enhanced redness and pH, and elevated muscle crude protein content. It also increased muscle fiber diameter and improved antioxidant enzyme activities (p < 0.05). The FA increased the levels of capric acid and methionine in the muscle, while reducing the content of stearic acid (p < 0.05). Furthermore, analysis of muscle development-related genes showed that FA upregulated the expression of PI3K, AKT1, mTOR and downregulated the expression of FOXO1 and MSTN in the muscle (p < 0.05). Analysis of muscle fiber type and glucose metabolism-related genes revealed that FA upregulated the expression of PGC-1α, MYH IIa, MYH I, HK2, and PFK and downregulated the expression of PKM and MYH IIX in the muscle (p < 0.05). In conclusion, FA improves muscle development and meat quality in Shaziling pigs, possibly through modulation of genes associated with PI3K/AKT/mTOR signaling, enhancement of antioxidant capacity, and regulation of muscle fiber type and glucose metabolism. Full article

The red sea urchin Loxechinus albus is a species of high commercial importance in Chilean aquaculture, whose performance is strongly influenced by environmental conditions such as temperature. The gut microbiota plays a central role in host physiology; however, its interaction with stress-induced molecular responses remains poorly understood. This study evaluated the effects of thermal stress on food consumption, gut microbial composition, oxidative status, and immune- and stress-related gene expressions in L. albus gut. Sea urchins were exposed to control (16 °C) and elevated temperature (22 °C) conditions for 7 and 14 days. Gut microbiota was characterized using 16S rRNA sequencing, while oxidative damage to DNA and proteins was quantified. Gene expression analyses targeted markers of apoptosis (casp3, casp10, bak1), cellular growth (mtor, raptor), stress response (hsp70), and immune regulation (nfκb, foxo). Thermal stress induced a marked reduction in microbial alpha diversity and promoted a shift toward opportunistic taxa. Heat-stressed individuals exhibited significantly increased oxidative DNA damage, whereas protein oxidation remained unchanged. Gene expression analyses revealed early upregulation of casp3, casp10, nfκb, foxo, and hsp70, suggesting activation of apoptotic, immune, and stress-response pathways. In contrast, bak1, mtor, and raptor showed limited or no significant modulation. These findings demonstrate that thermal stress disrupts host–microbiota homeostasis and induces oxidative and molecular responses in L. albus. This integrative response provides insight into mechanisms underlying physiological performance under thermal stress, with important implications for aquaculture sustainability. Full article

Background/Objectives: Chronic obstructive pulmonary disease (COPD) is increasingly viewed as a disorder of impaired cellular adaptation to chronic stress, involving oxidative injury, mitochondrial dysfunction, and accelerated cellular senescence. We investigated whether genetic variation in these pathways contributes to disease susceptibility, lung function impairment, and polygenic risk prediction. Methods: Thirty-three single-nucleotide variants were analysed in 747 patients with COPD and 703 controls. Associations with disease susceptibility and lung function parameters were assessed using regression models with correction for multiple testing. Weighted and unweighted polygenic scores were constructed from associated variants and evaluated using receiver operating characteristic and net reclassification improvement analyses. Results: Significant associations were identified in genes involved in antioxidant defence (NFE2L2, HMOX1, GSR), PI3K/AKT/mTOR signalling (PIK3R1, PTEN), mitochondrial function (TOMM40), cellular stress responses (FOXO3A), and long non-coding RNA regulation (MEG3, CDKN2B-AS1). The strongest association was observed for PIK3R1 rs831125 (OR = 2.31, p = 2.53 × 10⁻¹⁰). Variants in NFE2L2, PIK3R1, MEG3, MALAT1, and SIRT3 were additionally associated with pulmonary function parameters. The weighted polygenic score demonstrated good discriminative ability (AUC 68.8%, 95% CI 65.9–71.7%) and substantially improved prediction when combined with age, sex, and smoking exposure (AUC 88.1%, 95% CI 86.3–89.8%; NRI = 0.62, p = 2.21 × 10⁻²⁸). Conclusions: The identified loci converge on interconnected pathways involved in cellular stress adaptation, mitochondrial homeostasis, and senescence, supporting their contribution to chronic obstructive pulmonary disease susceptibility and functional decline. Full article

Human ageing and longevity are increasingly understood as biologically integrated and heterogeneous processes shaped by interactions among genetic susceptibility, epigenetic remodelling, and environmental modulation. This narrative review examines these interconnections within a nutrigenomic framework, with particular emphasis on how inherited variation and epigenetic plasticity may influence responses to ageing-related interventions. A structured literature search was conducted in PubMed, Scopus, Web of Science, and Embase, focusing on English-language studies published during the last 10 years. The review was organized into three major domains: (i) genetic determinants of longevity, (ii) epigenetic mechanisms of ageing, and (iii) intervention-responsive pathways relevant to precision geroscience. Current evidence supports a polygenic model of longevity in which loci such as FOXO3 and APOE show the most consistent human associations, while telomere maintenance, insulin/IGF-1 and mTOR signalling, sirtuins, Klotho, inflammatory mediators, and DNA repair remain biologically important but variably supported at the variant level. Epigenetic mechanisms, including DNA methylation drift, epigenetic clocks, histone modifications, chromatin remodelling, heterochromatin loss, and non-coding RNA regulation, provide an environmentally responsive interface linking genetic background to ageing phenotypes. Nutritional, pharmacological, behavioural, and circadian interventions converge on overlapping molecular pathways involving AMPK, mTOR, FOXO, sirtuins, autophagy, mitochondrial maintenance, and inflammatory signalling, although human evidence remains heterogeneous and biomarker modulation should not be equated with clinically meaningful slowing of organismal ageing. Overall, this review highlights the value of integrating genetics, epigenetics, and intervention biology to support a more cautious and translationally relevant model of healthy ageing. It also underscores the need for precision nutrigeroscience approaches that account for tissue context, baseline physiology, and inter-individual molecular variability. Full article

Rhabdomyosarcoma (RMS) confined to the bone marrow represents an exceptionally rare and aggressive presentation that can mimic primary hematological malignancies, often leading to diagnostic delays and therapeutic challenges. We report the case of a 34-year-old woman who presented with clinical and laboratory findings highly suggestive of a hematological disorder, including cytopenias and diffuse bone marrow involvement. Initial evaluation raised suspicion for leukemia; however, comprehensive diagnostic work-up, including immunohistochemistry and molecular studies, ultimately confirmed the diagnosis of PAX3/FOXO1 gene-rearranged alveolar RMS isolated in the bone marrow, with no identifiable primary soft tissue mass. The patient was treated with an intensive multi-agent chemotherapy regimen, resulting in a marked hematological recovery and a significant radiological improvement after a limited number of cycles. We further reviewed the limited literature on bone-marrow-confined RMS, highlighting the proposed pathophysiological mechanisms, diagnostic pitfalls, and reported treatment strategies. Given the absence of standardized management guidelines for this rare entity, therapeutic approaches are often extrapolated from conventional RMS protocols or regimens used for high-grade sarcomas. Our experience supports the potential efficacy of intensive chemotherapy in achieving meaningful clinical responses. This case report emphasizes the challenges in the diagnosis of RMS confined to the bone marrow due to its atypical presentation. It also highlights the poor prognosis and aggressiveness of this entity compared to conventional RMS. Full article

Background: Hydroxysafflor Yellow A (HSYA), the major bioactive component from Carthamus tinctorius L., exerts significant protective effects against myocardial ischemia-reperfusion injury (MIRI). Mitophagy is pivotal in the pathological process of MIRI, yet the specific molecular mechanism underlying HSYA-mediated mitophagy regulation remains unclear. Objective: This study aimed to investigate the association between HSYA treatment and mitochondrial autophagy in murine MIRI and to explore the potential mechanistic role of the SIRT1-FOXO3-BNIP3 signaling pathway using functional loss-of-function and rescue experiments. These findings may provide preliminary evidence supporting the clinical translational potential in MIRI therapy. Methods: Mouse myocardial ischemia-reperfusion injury (MIRI) model and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced AC16 cardiomyocyte injury models were established. Metabolomics, molecular docking, and surface plasmon resonance (SPR) techniques were combined to screen the potential targets of HSYA. The SIRT1 inhibitor EX527 and SIRT1 siRNA were used to verify the underlying mechanism. Cardiac function, myocardial infarct size, mitochondrial function, the expression of autophagy-related proteins, and protein–protein interaction were detected and analyzed. Results: Compared with the MIRI group, HSYA significantly improved cardiac function in mice, as evidenced by increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (p < 0.01), attenuated ST-segment elevation, and improved myocardial perfusion. HSYA also markedly reduced myocardial infarct size (p < 0.01) and serum levels of CK-MB, LDH, and cTnI (all p < 0.01) and ameliorated myocardial histopathological damage and mitochondrial ultrastructural integrity. Mechanistic studies revealed that HSYA significantly upregulated the expression of SIRT1, FOXO3, BNIP3, Beclin-1, and the LC3II/I ratio while downregulating p62 expression (p < 0.01), consistent with enhanced mitophagy-related activity. Furthermore, these protective effects were markedly attenuated upon SIRT1 inhibition or siRNA-mediated silencing, whereas HSYA intervention partially reversed these alterations. Additionally, co-immunoprecipitation (Co-IP) and pull-down assays demonstrated that HSYA promoted protein–protein interactions between SIRT1-FOXO3, FOXO3-BNIP3, and BNIP3-LC3B. Conclusions: These findings highlight that HSYA is associated with improved cardiac function, enhanced mitophagy-related activity, and upregulated SIRT1-FOXO3-BNIP3 signaling, providing robust experimental evidence for its clinical translational application in MIRI treatment. Full article

Objectives: The study aimed to evaluate the effects of full-fat rice bran (FFRB; Tainung No. 81, Taiwan) at various doses on insulin resistance, muscle atrophy, and gut microbiota composition in middle-aged ovariectomized (OVX) mice fed a high-fat diet (HFD), using young sham-operated mice as a life-stage reference group. Methods: Thirty-six female ICR mice were assigned to six groups, including OVX mice fed HFD with or without 5%, 10%, or 20% FFRB. Results: Compared with HFD-fed OVX controls, 20% FFRB reduced body weight gain by 43%, decreased visceral fat mass, and improved insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR reduced by 65%, P_trend = 0.001). FFRB attenuated the decline in relative grip strength (forelimb, P_trend = 0.013; four-limb, P_trend < 0.001), and upregulated muscle protein synthesis genes, including insulin receptor substrate 1 (IRS-1), mammalian target of rapamycin (mTOR), eukaryotic translation initiation factor 4E binding protein 1 (eIF-4EBP1), while downregulating forkhead box protein O1 (FOXO1), muscle RING-finger protein-1 (MuRF-1), and interleukin (IL)-6. FFRB was also associated with higher fecal acetate levels (P_trend < 0.001), upregulated colonic tight junction genes (occludin and zonula occludens (ZO)-1), and greater relative abundance of g_Muribaculum. Correlation analyses revealed positive associations between short-chain fatty acids (SCFAs) and muscle strength, muscle anabolic markers, genus Lachnospiraceae_UCG_001, and Muribaculum. Conclusions: Dietary inclusion of FFRB was associated with favorable metabolic and muscle-related parameters in HFD-fed middle-aged OVX mice, with potential involvement of gut microbiota and SCFA alterations. Full article

Oxidative stress causes brain damage contributing to neurodegenerative and vascular diseases. In Alzheimer’s disease (AD), elevated oxidative stress and mitochondrial damage are closely linked to misfolded protein accumulation. ROS also plays a major role in ischemic brain injury, particularly during reperfusion, impairing the blood–brain barrier and highlighting the association between vascular pathology and AD. To investigate perturbations in brain cells occurring in mixed dementia (AD combined with vascular dementia components), we used a triple culture system comprising neurons, astrocytes, and microglia and induced neuronal injury by combining LPS and H₂O₂ exposures. Cell viability assays revealed that neuronal death occurred mainly through apoptosis and DNA damage. In neurons and astrocytes exposed to LPS+H₂O₂, the expression of NADPH oxidase isoform 2, a major source of ROS, increased, along with FOXO3 and SOD2, a key mitochondrial ROS scavenger. Indeed, these changes were accompanied by altered mitochondrial morphology and integrity, as well as reduced neurite extension and thickness. The treatment with extracellular vesicles (EVs) derived from amniotic fluid stem cells was tested due to their rich content of antioxidant molecules. Interestingly, EVs reversed the negative effects of LPS+H₂O₂, suggesting the protective role against neuronal injury in vitro may be mediated by the EV-cargo. Full article

Objectives: This study aimed to investigate the therapeutic effects and potential mechanisms of Lonicerae japonicae Flos (Jinyinhua, JYH) against respiratory syncytial virus (RSV)-induced pneumonia by integrating lung tissue metabolomics with gut microbiota analysis. Methods: An RSV-infected mouse model was established through intranasal inoculation. Lung pathological changes, viral RNA levels, lung index, and inflammatory cytokine levels were evaluated. Untargeted metabolomics and 16S rRNA gene amplicon sequencing were performed to characterize JYH-mediated alterations in pulmonary metabolites and the gut microbiota. Spearman correlation analysis was conducted to assess associations between differentially abundant bacterial genera and significantly altered metabolites. Results: JYH alleviated RSV-induced pulmonary histopathological injury, reduced viral RNA levels, decreased lung index and interleukin-6 (IL-6) levels, and increased interferon-γ (IFN-γ) levels. Metabolomic profiling identified 46 differential metabolites, among which 26 showed a reversal trend following JYH administration. These metabolites were mainly enriched in pathways associated with the synaptic vesicle cycle, lysosomal function, and Forkhead box O (FoxO) signaling. Gut microbiota analysis showed that JYH increased microbial richness and diversity, whereas KEGG-based functional prediction indicated that the differentially abundant taxa were primarily involved in amino acid, carbohydrate, and nucleotide metabolism. Moreover, correlation analysis revealed significant associations between key bacterial genera, including Gemella, Sutterella, and CC_115, and differential metabolites such as pyridoxamine, uridine monophosphate (UMP), and argininosuccinic acid. Conclusions: JYH may protect against RSV-induced pneumonia by restoring pulmonary metabolic homeostasis and modulating gut microbiota composition. These findings provide new insights into metabolite–microbiota interactions underlying the anti-RSV activity of JYH. Full article