PubMed

Sci Rep. 2025 Jan 19;15(1):2448. doi: 10.1038/s41598-025-86794-2.ABSTRACTThis study aimed to assess the causal relationship between lipidome and female reproductive diseases (FRDs) using an advanced series of Mendelian randomization (MR) methods. This study utilized genome-wide association study (GWAS) summary statistics encompassing 179 lipidomes and six prevalent FRDs, namely polycystic ovary syndrome (PCOS), endometriosis, uterine fibroid, female infertility, uterine endometrial cancer, and ovarian cancer. The two-sample MR (TSMR) approach was employed to investigate the causal relationships, with further validation using false discovery rate (FDR) and multivariable MR (MVMR) methods. Subsequently, a range of comprehensive evaluations were performed, including sensitivity analysis, mediation MR analysis, reverse MR analysis, and steiger test. Examining 179 lipidome traits as exposures and 6 FRDs as outcomes, this study identified significant causal effects of 56 lipids on FRDs. Following multiple testing correction and MVMR validation, sphingomyelin (d38:2) was found to have a protective effect against PCOS (β = -0.104, 95% CI: -0.199 ~ -0.010, P = 0.031). Phosphatidylcholine (18:0_22:6) was associated with a decreased risk of developing uterine fibroid (β = -0.111, 95% CI: -0.201~ -0.021, P = 0.016), and sterol ester (27:1/20:3) showed significance in uterine endometrial cancer (β = -0.248, 95% CI: -0.443 ~ -0.053, P = 0.013). Conversely, phosphatidylethanolamine (18:2_0:0) was associated with increased risk of endometriosis (β = 0.183, 95% CI: 0.015 ~ 0.350, P = 0.033), while sterol ester (27:1/18:1) posed a risk influence on uterine fibroid (β = 1.007, 95% CI: 0.925 ~ 1.089, P < 0.001), and phosphatidylcholine (16:0_22:6) on uterine endometrial cancer (β = 0.229, 95% CI: 0.039 ~ 0.420, P = 0.018). Furthermore, it was determined that the causal associations between these lipidome profiles and FRDs were independent of BMI, obesity, diabetes, smoking, alcohol use, physical activity, inflammation, depression, waist-hip ratio, vitamin D, dehydroepiandrosterone sulphate, sex hormone binding globulin, and testosterone levels. Most outcomes passed consistent tests without evidence of heterogeneity, pleiotropy, or reverse causality. The results indicated a close association between specific lipidomes, particularly sphingomyelin, lysophosphatidylethanolamine, cholesterol ester, and phosphatidylcholines, with FRDs. These lipid species may potentially serve as biomarkers and future drug targets for the treatment of FRDs.PMID:39828767 | DOI:10.1038/s41598-025-86794-2

N Biotechnol. 2025 Jan 17:S1871-6784(25)00006-8. doi: 10.1016/j.nbt.2025.01.005. Online ahead of print.ABSTRACTIn order to improve predictability of outcome and reduce costly rounds of trial-and-error, machine learning models have been of increasing importance in the field of synthetic biology. Besides applications in predicting genome annotation, process parameters and transcription initiation frequency, such models have also been of help for pathway optimization. The latter is a common strategy in metabolic engineering and improves the production of a desirable compound by optimizing enzyme expression levels of the production pathway. However, engineering steps might not lead to sufficient improvement, and bottlenecks may remain hidden among the hundreds of metabolic reactions occurring in a living cell, especially if the production pathway is highly interconnected with other parts of the cell's metabolism. Here, we use the synthesis of chitooligosaccharides (COS) to show that the production from such complex pathways can be improved by using machine learning models and feature importance analysis to find new compounds with an impact on COS production. We screened Escherichia coli libraries of engineered transcription regulators with an expected broad range of metabolic diversity and trained several machine learning models to predict COS production titers. Subsequent feature analysis led to the finding of iron, whose addition we could show improved COS production in vivo up to 2-fold. Additionally, the analysis revealed important clues for future engineering steps.PMID:39827984 | DOI:10.1016/j.nbt.2025.01.005

J Hazard Mater. 2025 Jan 14;487:137226. doi: 10.1016/j.jhazmat.2025.137226. Online ahead of print.ABSTRACTCadmium (Cd) is recognized as one of the most toxic heavy metal in the environment that causes pronounced phytotoxicity. This study investigated the physiological and biochemical responses and detoxification mechanisms of Hemarthria compressa under various concentrations of Cd stress (0, 30, 60, 90, and 270 mg·kg-1). Our research findings indicate that the growth and photosynthetic capacity of H. compressa reach their peak at a Cd concentration of 60 mg·kg-1. At this concentration, the Cd concentration in the shoots of H. compressa is 0.67 mg·kg-1, the total Cd accumulation is 0.25 μg, and the MDA content is 6.25 nmol·g-1, which represents the lowest values among all treatments.Metabolomics analysis reveals that sugar is related to Cd stress resistance, and the levels of organic acids involved in metabolic processes show only minor changes. H. compressa alters the composition of its root exudates by secreting substantial quantities of organic acids (such as citric acid, fumaric acid, and malic acid), sugars (such as trehalose, maltose, and glucose), and fatty acids (such as citraconic acid). These organic acids modulate the pH of the rhizosphere soil and recruit beneficial microorganisms, including Gp6, Sphingoaurantiacus, Devosia, and Neobacillus species, thereby enhancing plant growth and mitigating Cd accumulation.PMID:39827800 | DOI:10.1016/j.jhazmat.2025.137226

JACC Adv. 2025 Jan 17;4(2):101563. doi: 10.1016/j.jacadv.2024.101563. Online ahead of print.ABSTRACTBACKGROUND: Patients with Fontan circulation are frail and experience multisystem dysfunction including impaired exercise capacity, low resting and exercise-augmented cardiac output, and progressive liver fibrosis. However, common underlying biochemical abnormalities or disease-specific biomarkers have not been well-described.OBJECTIVES: We wish to investigate Fontan and their matched healthy subjects using a nontargeted, followed by targeted metabolomic analysis.METHODS: Patients with Fontan circulation were compared to age- and sex-matched healthy controls with regard to body composition, markers of frailty, cardiopulmonary exercise testing, and resting and exercise-augmented hemodynamics. Subsequently, the study participants underwent a nontargeted metabolomics assessment, followed by targeted plasma bile acid (BA) analysis.RESULTS: Twenty Fontan patients (28.8 ± 9.8 years of age; 35% women) and 20 healthy controls (29.7 ± 6.0 years of age; 30% women) were enrolled. Fontan patients had significantly lower skeletal muscle mass, took longer to complete the 5 times sit-to-stand test; achieved lower %VO2 max, and had lower resting and postexercise hemodynamic parameters. Nontargeted metabolomics assessment demonstrated elevated BAs, oxylipins, and leucine metabolites in Fontan patients. Total BA as well as 17 BA components were markedly elevated in the Fontan patients. Selective BAs were negatively associated with age, degree of frailty, cardiopulmonary function, and hemodynamic parameters.CONCLUSIONS: Elevated BAs are associated with worsening Fontan physiology. These findings warrant further exploration.PMID:39827765 | DOI:10.1016/j.jacadv.2024.101563

Plant Physiol Biochem. 2025 Jan 7;220:109480. doi: 10.1016/j.plaphy.2025.109480. Online ahead of print.ABSTRACTInfections caused by root-knot nematodes (RKNs) significantly impair vegetable growth and crop yield, posing a severe threat to global food security. Our previous study indicated that fungal-derived 2-furoic acid was a promising lead compound for the exploitation of eco-friendly nematicides. However, the exact molecular mechanism remains poorly understood. In this study, we observed behavioral changes in the nematodes following treatment with 100 μg/mL of 2-furoic acid. Subsequently, transcriptomics and metabolomics were combined to identify changes in differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs). Transcriptome analysis revealed 199 up-regulated and 109 down-regulated DEGs. Metabolomics analysis indicated that 140 metabolites (72 up-regulated and 68 down-regulated) exhibited significant differences. Notably, the integrated transcriptomics and metabolomics analysis identified a total of 72 DEGs and 54 DEMs annotated across 51 pathways, including lipid metabolism and amino acid metabolism. Intriguingly, 14 out of the 51 pathways were simultaneously annotated to the downregulated calmodulin gene (cam). RNA interference (RNAi) results demonstrated that the down-regulated cam, a potential drug target for controlling RKNs, significantly reduced the motility, infectivity, and pathogenicity of M. incognita. Our results provide insights into the molecular basis of 2-furoic acid against M. incognita and offer a valuable theoretical foundation for the design of eco-friendly nematicides.PMID:39827706 | DOI:10.1016/j.plaphy.2025.109480

Poult Sci. 2025 Jan 15;104(2):104818. doi: 10.1016/j.psj.2025.104818. Online ahead of print.ABSTRACTEggshells not only protect the contents of the egg from external damage but are also a key factor influencing consumer choice, second only to price. In the later stages of egg production, the incidence of pimpled eggs significantly increases, severely affecting the hatchability and food safety of the eggs. This study compares the differences in the uterine proteomes and metabolomes of hens producing pimpled eggs and those producing normal eggs, aiming to identify the proteins and metabolites that may play a crucial role in the formation of pimpled eggs. A total of 242 differentially expressed proteins (DEPs) were identified in uterine tissue, of which 116 were upregulated and 126 were downregulated. Enrichment analysis revealed that the DEPs were enriched in pathways related to ion transport, energy metabolism, and immune responses. The study found that in the normal eggs (NE) group, HCO₃⁻ was predominantly transported via SLC4A1, although other transport pathways may also play a role. In contrast, in the pimpled eggs (PE) group, bicarbonate ions (HCO₃⁻) was primarily transported through SLC4A4. Additionally, a total of 44 differentially metabolites (DMs) were identified in the uterus, with 5'-Adenylic acid (ATP) being significantly downregulated in the PE group. The ions and matrix proteins required for eggshell formation are transported from uterine cells to the uterine fluid against a concentration gradient, a process that consumes a substantial amount of energy. The decrease in ATP concentration in the PE group may be a significant factor influencing the formation of pimpled eggs. Subsequently, we found that the DEPs and DMs were jointly enriched in several signaling pathways, including the FoxO signaling pathway related to energy metabolism, nicotinate and nicotinamide metabolism, and tryptophan metabolism associated with immune response. Notably, the DMs involved in these signaling pathways were all downregulated in the PE group. Our research findings indicate that SLC4A1, SLC4A2, and ATP2B4 (DEPs), along with 5'-adenylic acid and trigonelline (DMs), influence the formation of eggshells through mechanisms related to energy metabolism, ion transport, and immune response. These DEPs and DMs may serve as potential biomarkers for the genetic improvement of eggshell quality.PMID:39827695 | DOI:10.1016/j.psj.2025.104818

Int Immunopharmacol. 2025 Jan 18;148:114101. doi: 10.1016/j.intimp.2025.114101. Online ahead of print.ABSTRACTAcute pulmonary inflammation is a severe lower respiratory tract infection. Sinensetin (SIN), a polymethoxyflavone with strong anti-inflammatory properties, is known to ameliorate LPS-induced acute inflammatory lung injury, but its molecular mechanisms are not fully understood. This study aimed to provide insight into the pharmacological mechanisms of SIN in attenuating acute pulmonary inflammation. In LPS-induced inflammation assays in vivo and in vitro, SIN significantly reduced the mRNA levels of inflammatory genes including MCP-1, ICAM1, Ccl3, Ccl4, Ccl5, Ccl7, Cxcl9, Cxcl10, IL1α, IL1β, IL6, IL11, IL18, IL27, TNF-α, IFN-γ, TLR4, MyD88, F4/80, COX2, iNOS, NLRP3, ASC, JAK2, STAT3, STAT4, and Bcl2l1, as well as increased the mRNA levels of anti-inflammatory genes such as IL4, IL10, and IL12α. Besides, SIN markedly decreased the expression of CD68, TLR4, MyD88, phospho-IκBα (S32/S36), phospho-NF-κB p65 (S536), MCP-1, ICAM1, phospho-JAK2 (Tyr1008), phospho-STAT1 (S727), phospho-STAT3 (Y705), and phospho-STAT4 (Y693), inhibited NF-κB p65 translocation into the nucleus, thereby blocking in combination with STAT transcription factors to induce target gene expression. Further GC-MS/MS and LC-MS/MS metabolomic analysis revealed that SIN significantly increased the abundance of anti-inflammatory metabolites, such as L-alanine, L-carnitine, L-glutamic acid, Glycine, and L-cysteine. In conclusion, the results indicated that SIN attenuated LPS-induced acute pulmonary inflammation by modulating NF-κB p65-mediated immune resistance and STAT3-mediated tissue resilience. All these favorable findings presented critical insights into the remarkable abilities and health benefits of SIN in ameliorating inflammatory lung disease.PMID:39827664 | DOI:10.1016/j.intimp.2025.114101

Ecotoxicol Environ Saf. 2025 Jan 18;290:117753. doi: 10.1016/j.ecoenv.2025.117753. Online ahead of print.ABSTRACTPlastics and pesticides are commonly used and often coexist in the environment. As pollinating insects, honeybees are simultaneously exposed to both these toxins. However, there has been no study on the toxic effects of nano-polystyrene plastics (nanoPS) and cyfluthrin (Cy) on the Apis cerana cerana Fabricius until now. This study found that nanoPS did not significantly impact the mortality of Apis cerana cerana but could reduce cyfluthrin-induced mortality. Additionally, nanoPS caused damage to the honeybee gut and hindered the development of the hypopharyngeal glands, whereas cyfluthrin did not produce these pathological changes. Concerning the detoxification-related genes, the two toxins alone and in combination significantly promoted the expression of P450 9E2 and Cyp9Q3 genes, and the upregulation trend was found more significant for the combination. Regarding immune gene expression, exposure to a single toxin or both toxins significantly down-regulated the abaecin gene, but only exposure to nanoPS significantly decreased apidaecin expression. The changes in metabolites and metabolic pathways in honeybees after ingesting nanoPS were also studied. This study highlights the toxicity of nano-microplastics and Cy alone and in combination to Apis cerana cerana Fabricius and provides new insights into the potential ecological risks of nanoPS.PMID:39827611 | DOI:10.1016/j.ecoenv.2025.117753

J Environ Manage. 2025 Jan 18;374:124075. doi: 10.1016/j.jenvman.2025.124075. Online ahead of print.ABSTRACTCrop diseases significantly threaten global food security, driving the need for innovative control strategies. This study explored using ZnO-TiO2@MSC, a novel nanomaterial synthesized using a corn stover template, to enhance disease resistance in tomato plants. In vitro assays demonstrated potent antimicrobial activity of ZnO-TiO2@MSC against the pathogen Pseudomonas syringae pv. tomato DC3000 (Pst. DC3000) by disrupting bacterial cell membranes and modulating oxidative stress-related gene expression. When applied to tomato leaves in pot trials, ZnO-TiO2@MSC achieved 79.83% control of bacterial leaf spot disease while promoting plant growth and photosynthesis. The nanomaterial triggered plant defense mechanisms, upregulating resistance genes and increasing the activities of key enzymes. Metabolomic profiling revealed elevated lipids, lipid-like molecules, and organic acid derivative levels in treated leaves, suggesting cell membrane remodeling as part of the defense response. These findings highlight the potential of biologically-templated nanomaterials like ZnO-TiO2@MSC as multifunctional tools for sustainable disease management in crops. The corn stover-based synthesis approach also provides a way to valorize agricultural waste. Further research is needed to understand the long-term impacts and viability of field-scale application of ZnO-TiO2@MSC as an alternative to conventional pesticides.PMID:39827603 | DOI:10.1016/j.jenvman.2025.124075

Food Chem. 2025 Jan 16;472:142936. doi: 10.1016/j.foodchem.2025.142936. Online ahead of print.ABSTRACTThe impacts of various aging techniques on meat quality and metabolism alterations over time were investigated. Meat tenderness improved with aging, whereas prolonged aging negatively impacted color and oxidative stability. Dry-aging (DA) group exhibited significantly higher (P < 0.05) weight loss, lipid oxidation, and carbonyl contents, along with significantly lower (P < 0.05) centrifugal loss, cooking loss, a* value, and sulfhydryl content compared to wet-aging (WA) group. Substantial amounts of small peptides, amino acids, and amino acid derivatives were detected in the 28 d aged samples. Higher abundances of benzenoids, lipids and lipid-like molecules, amino acids and their derivatives, and alkyl phosphates were found in the WA group, while dialkyl ethers, fatty acids, fatty acid metabolites, and hydroxy acids showed higher intensities in the DA and dry-aging in bag groups. These findings provide comprehensive metabolome information and their underlying relation with meat quality changes during aging under different aging methods.PMID:39827567 | DOI:10.1016/j.foodchem.2025.142936

J Agric Food Chem. 2025 Jan 19. doi: 10.1021/acs.jafc.4c09151. Online ahead of print.ABSTRACTAlteration of the gut microbiota and its metabolites plays a key role in the development of inflammatory bowel disease (IBD). Here, we investigated the mechanism of saponins, a byproduct from quinoa (SQ) processing, in regulating IBD. SQ ameliorated gut microbiota dysbiosis revealed by 16S rRNA sequencing and improved colonic antioxidant activities and barrier integrity in dextran sulfate sodium (DSS)-treated mice. Broad-spectrum antibiotics further proved that the gut-protective effects of SQ were mediated by gut microbiota. Next, fecal microbiota transplantation (FMT) of SQ-induced gut microbiota/metabolites to inoculate DSS-treated mice alleviated colitis significantly. Untargeted metabolomics and lipidomics revealed that ursodeoxycholic acid (UDCA) was enriched as a microbial metabolite after SQ supplementation. UDCA was then found to attenuate DSS-induced colitis in vivo by targeting the TLR4/NF-κB pathway, which was also verified in a Caco-2 cell model treated with a TLR4 agonist/antagonist. Overall, our findings established that gut microbiota-UDCA-TLR4/NF-κB signaling plays a key role in mediating the protective effects of SQ.PMID:39827465 | DOI:10.1021/acs.jafc.4c09151

Ecotoxicol Environ Saf. 2025 Jan 17;290:117754. doi: 10.1016/j.ecoenv.2025.117754. Online ahead of print.ABSTRACTCadmium (Cd) is a highly toxic agricultural pollutant that inhibits the growth and development of plants. Arbuscular mycorrhizal fungi (AMF) can enhance plant tolerance to Cd, but the regulatory mechanisms in Allium fistulosum (green onion) are unclear. This study used a Cd treatment concentration of 1.5 mg·kg-1, which corresponds to the risk control threshold for soil pollution in Chinese agricultural land, to examine the effects and molecular mechanisms of AMF inoculation on the growth and physiology of green onion under Cd stress. AMF formed an effective symbiotic relationship with green onion roots under Cd stress, increased plant biomass, improved root structure and enhanced root vitality. AMF-colonized green onion had reduced Cd content in roots and leaves by 63.00 % and 46.50 %, respectively, with Cd content being higher in the roots than in the leaves. The ameliorative effect of AMF on Cd toxicity was mainly due to a reduction in malondialdehyde content in leaves (30.12 %) and an enhancement of antioxidant enzyme activities (peroxidase, catalase, superoxide dismutase, glutathione reductase and reduced glutathione) that mitigated damage from excessive reactive oxygen species. In addition, AMF induced secretion of easily extractable glomalin soil protein and total glomalin-related soil protein and inhibited the translocation of Cd to the shoots. Transcriptomic and metabolomic correlation analyses revealed that differentially expressed genes and metabolites in AMF-inoculated green onion under Cd stress were predominantly enriched in the "phenylpropanoid biosynthesis" and "phenylalanine metabolism" pathways, upregulated the expression of the HCT, PRDX6, HPD, MIF, and HMA3 genes, and accumulation of the phenylalanine, L-tyrosine, and 1-O-sinapoyl-β-glucose metabolites. Thus, AMF enhance Cd tolerance in green onions by sequestering Cd in roots, restricting its translocation, modulating antioxidant defenses and inducing the expression of genes involved in the phenylpropanoid biosynthesis and phenylalanine metabolism pathways. Collectedly, we for the first time revealed the mechanism of AMF alleviating the toxicity of Cd to green onion, providing a theoretical foundation for the safe production and sustainable cultivation of green onion in Cd-contaminated soils.PMID:39826408 | DOI:10.1016/j.ecoenv.2025.117754

Sci Rep. 2025 Jan 18;15(1):2428. doi: 10.1038/s41598-025-86726-0.ABSTRACTWe hypothesized that daily exercise promotes joint health by upregulating anti-inflammatory mediators via adaptive molecular and metabolic changes in the infrapatellar fat pad (IFP). We tested this hypothesis by conducting time-resolved analyses between 1 and 14 days of voluntary wheel running exercise in C57BL/6J mice. IFP structure and cellularity were evaluated by histomorphology, picrosirius red collagen staining, and flow cytometry analysis of stromal vascular fraction cells. Joint inflammation and metabolism were evaluated by multiplex gene expression analysis of synovium-IFP tissue and synovial fluid metabolomics, respectively. Exercise transiently increased cytokine and chemokine gene expression in synovium-IFP tissue, resolving within the first 5 days of exercise. The acute inflammatory response was associated with decreased adipocyte size and elevated CD45+Gr1+ myeloid cells, increased collagen content, and oxidized phospholipids. Exercise acutely altered synovial fluid metabolites, characterized by increased amino acids, peptides, bile acids, sphingolipids, dicarboxylic acids, and straight medium chain fatty acids and decreased hydroxy fatty acids and diacylglycerols. Between 5 and 14 days of exercise, inflammation, collagen, and adipocyte size returned to pre-exercise levels, and CD206+ immuno-regulatory macrophages increased. Thus, although the onset of new daily exercise transiently induced synovium-IFP inflammation and altered tissue structure, sustained daily exercise promoted IFP homeostasis.PMID:39827311 | DOI:10.1038/s41598-025-86726-0

Sci Rep. 2025 Jan 18;15(1):2404. doi: 10.1038/s41598-025-86604-9.ABSTRACTEnvironmental stresses, particularly salinity, pose significant challenges to global crop production, notably impacting the growth and yield of rice. Integrating gene expression and metabolomics data offers valuable insights into the molecular mechanisms driving salt tolerance in plants. This study examined the effects of high salinity on the roots and shoots of rice genotypes with contrasting tolerances: CSR28 (tolerant) and IR28 (sensitive) at the seedling stage. Our phenotypic and physiological assessments indicated significant differences in response to prolonged salinity exposure between the two genotypes. Notably, osmoprotectants, including amino acids and sugars, exhibited increased accumulation, whereas most organic acids showed a decline. Linear regression analyses established significant correlations between the levels of proline, myoinositol, catalase (CAT), and superoxide dismutase (SOD) and their respective encoding genes: OsP5CS2, OsIMP, OsNCA1a, and OsSOD-Fe. Furthermore, a relationship was identified between H2O2 content and the expression of glycolate oxidase (GLO), highlighting its role in initiating defense mechanisms under salinity stress. Our findings indicated specific metabolites and genes associated with distinct organs, genotypes, and timepoints that can serve as biomarkers for the development of new salt-tolerant rice varieties.PMID:39827270 | DOI:10.1038/s41598-025-86604-9

Anim Microbiome. 2025 Jan 18;7(1):10. doi: 10.1186/s42523-024-00373-w.ABSTRACTBACKGROUND: As the pet population grows, there is increasing attention on the health and well-being of companion animals. Weaning, a common challenge for young mammals, often leads to issues such as diarrhea, growth retardation, and in severe cases, even mortality. However, the specific changes in gut microbiota and metabolites in kittens following weaning remain unclear. In this study, we conducted a comprehensive investigation of the dynamic changes in the gut microbiota, serum metabolism, antioxidant capacity, and immune function of kittens at various time points: days 0, 4, and 30 post-weaning.RESULTS: Significant changes in the immune response and gut microbiota were observed in kittens following weaning. Specifically, IgM levels increased significantly (P < 0.01, n = 20), while IgA and IgG levels showed a sustained elevation. Weaning also disrupted the intestinal microbiota, leading to notable changes in serum metabolism. On day 4 post-weaning, there was a decrease in beneficial bacteria such as Bacteroides vulgatus, Fusobacterium nucleatum, Anaerostipes caccae, and Butyricico-ccaceae. However, by day 30, beneficial bacteria including Candidatus Arthro-mitus, Holdemanella, and Bifidobacterium had increased (P < 0.05, n = 20). Serum metabolites showed clear separation across time points, with day 0 and day 4 exhibiting similar patterns. A total of 45 significantly altered metabolites (P < 0.05, n = 20) were identified, primarily related to vitamins, steroids, peptides, organic acids, lipids, and carbohydrates. Pathway analysis revealed significant enrichment in eight metabolic pathways, with key changes in arginine metabolism and biosynthesis. Additionally, bacteria such as Bacteroides fragilis, Bacteroides stercoris, Leuconostoc citreum, and Bifidobacterium adolescentis were positively correlated with serum metabolic changes, emphasizing the link between gut microbiota and systemic metabolism (P < 0.05, n = 20).CONCLUSION: Our study demonstrated that the composition and function of intestinal microorganisms as well as serum metabolic profiles of weaned kittens presented dynamic changes. These findings not only deepen our understanding of the effects of weaning on kitten health, but also provide valuable insights into post-weaning nutritional regulation strategies for kittens.PMID:39827164 | DOI:10.1186/s42523-024-00373-w

Cardiovasc Diabetol. 2025 Jan 18;24(1):21. doi: 10.1186/s12933-024-02566-8.ABSTRACTThe global increase in human life expectancy, coupled with an unprecedented rise in the prevalence of obesity, has led to a growing clinical and socioeconomic burden of heart failure with preserved ejection fraction (HFpEF). Mechanistically, the molecular and cellular hallmarks of aging are omnipresent in HFpEF and are further exacerbated by obesity and associated metabolic diseases. Conversely, weight loss strategies, particularly caloric restriction, have shown promise in improving health status in patients with HFpEF and are considered the gold standard for promoting longevity and healthspan (disease-free lifetime) in model organisms. In this review, we implicate fundamental mechanisms of aging in driving HFpEF and elucidate how caloric restriction mitigates the disease progression. Furthermore, we discuss the potential for pharmacologically mimicking the beneficial effects of caloric restriction in HFpEF using clinically approved and emerging caloric restriction mimetics. We surmise that these compounds could offer novel therapeutic avenues for HFpEF and alleviate the challenges associated with the implementation of caloric restriction and other lifestyle modifications to reduce the burden of HFpEF at a population level.PMID:39827109 | DOI:10.1186/s12933-024-02566-8

Chin J Traumatol. 2025 Jan 3:S1008-1275(24)00182-2. doi: 10.1016/j.cjtee.2024.08.011. Online ahead of print.ABSTRACTPURPOSE: Organ damage caused by electric shock has attracted great attention. Some animal investigations and clinical cases have suggested that electric shock can induce liver injury. This study aimed to investigate the potential mechanism of liver injury induced by electric shock.METHODS: Healthy male C57BL/6J mice aged 6-8 weeks were romandly divided into two groups: control group and electric shock group. Mice in the electric shock group were shocked on the top of the skull with an electric baton (20 kV) for 5 sec, while mice in the control group were exposed to only the acoustic and light stimulation produced by the electric baton. The effect of electric shock on liver function was evaluated by histological and biochemical analysis, and a metabolomics and transcriptomics study was performed to investigate how electric shock might induce liver damage. All data of this study were analyzed using a two-tailed unpaired Student's t-test in SPSS 22.0 Statistical Package.RESULTS: The electric shock group had significantly higher serum aspartate aminotransferase and alanine aminotransferase levels than the control group (p < 0.001), and the shock notably caused cytoplasmic swelling and vacuolization, mild inflammatory cell (mainly macrophages and monocytes) infiltration and acute focal necrosis in hepatocytes (p < 0.001). A total of 47 differential metabolites and 249 differentially expressed genes (DEGs) were detected using metabolomic and transcriptomic analyses. These differential metabolites were significantly enriched in primary bile acid biosynthesis (p < 0.05). Gene ontology functional analysis of the DEGs revealed that electric shock disturbed a key biological process involved in the inflammatory response in the mouse liver, and a significant number of DEGs were enriched in Kyoto Encyclopedia of Genes and Genomes-identified pathways related to inflammation, such as the interleukin-17, tumor necrosis factor and mitogen-activated protein kinase signalling pathway. Transcriptomic and metabolomic analyses revealed that bile acid metabolism disturbance including up-regulation of the taurochenodesoxycholic acid, chenodeoxycholic acid and taurocholic acid, and down-regulation of chenodeoxycholic acid clycine conjugate may contribute to the electric shock-induced inflammatory response.CONCLUSION: Electric shock can induce liver inflammatory injury through the interleukin-17, tumor necrosis factor, and mitogen-activated protein kinase signaling pathway, and the bile acid metabolism disturbance including up-regulation of the taurochenodesoxycholic acid, chenodeoxycholic acid and taurocholic acid, and down-regulation of chenodeoxycholic acid clycine conjugate may contribute to inflammatory liver injury following electric shock.PMID:39827045 | DOI:10.1016/j.cjtee.2024.08.011

Microb Pathog. 2025 Jan 16:107307. doi: 10.1016/j.micpath.2025.107307. Online ahead of print.ABSTRACTAntimicrobial resistance (AMR) poses significant challenges to global public health. The major cause of AMR development is previous use of antibiotics, hospitalization, and the lack of efficient methods for screening AMR pathogens. Mass spectrometry techniques offer rapid, sensitive, and early detection of AMR both on proteomics and metabolomics levels. Hence, a metabolomics analysis on clinical isolates of A. baumannii was conducted to understand the resistance patterns exhibited by these isolates. A. baumannii (ATCC strain) and its clinical isolates (n=26) were screened against five antibiotics i.e., ciprofloxacin, colistin, cefixime, gentamicin, and co-amoxiclav to obtain their resistance profile using antibiogram and MIC methods. After that, all the samples were analyzed in both positive and negative modes of Flow Injection-High Resolution-Electrospray Ionization Mass Spectrometry (FI-HR-ESI-MS) after 6 h of incubation. Data analysis revealed the identification of a total of 43 metabolites., The metabolites were then subjected to chemometric analysis to find any significant association of the metabolites with an increase in the MIC values. The chemometric analysis resulted in a total of eleven metabolites with p-values< 0.05 to be significantly associated with the resistance of A. baumannii isolates against the drugs. The concentrations of two metabolites, pyochelin, and L-serine, increased sequentially with the increase in MIC values (increase in resistance) of ciprofloxacin and cefixime, respectively. The study showed a significant association of metabolites with the resistance in A. baumannii isolates and can play a potential role in the development of new therapeutics against the arising antimicrobial resistance of A. baumannii towards various antibiotic drugs.PMID:39826862 | DOI:10.1016/j.micpath.2025.107307

J Ethnopharmacol. 2025 Jan 16:119338. doi: 10.1016/j.jep.2025.119338. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Di Dang Tang is a classic formula from Shang Han Lun, originally used to treat conditions such as blood stasis and heat accumulation. It is widely applied in the treatment of diabetes and its complications, but its effects on Type 2 Diabetes Mellitus-related Cognitive Dysfunction (T2DM-CD) remain unclear.AIM OF THE STUDY: The study aimed to investigate the metabolic characteristics of patients with T2DM-CD. Additionally, it sought to evaluate the effects of Di Dang Tang on cognitive function in T2DM-CD model rats by targeting the metabolic pathways identified in the clinical analysis, exploring the underlying mechanisms through animal experiments.METHODS: Fasting venous serum was collected from patients with Type 2 Diabetes Mellitus (T2DM) to detect metabolism-related products, and KEGG annotation analysis was performed. Separately, thirty rats were randomly divided using a random number table method, with six rats selected as the blank control group. Twenty-four successfully modeled rats were then randomly divided into the model group and three Di Dang Tang groups (low, medium, and high doses). After administering the medication, the relevant indicators in the rats were assessed.RESULTS: Clinical metabolomics detected 32 key differential metabolites between the T2DM-CD and the blank control groups. Between the T2DM-CD and T2DM groups, 29 key differential metabolites were identified. In animal experiments, blood glucose levels in the model group were significantly higher compared to the blank control group at the same time points, whereas the high dose groups of Di Dang Tang exhibited reduced blood glucose levels at weeks 6 and 8 relative to the model group. In the Morris water maze test, the model group had longer escape latencies than the blank control group. The medium and high dose groups of Di Dang Tang showed shorter latencies. Additionally, compared to the model group, the Di Dang Tang groups spent more time and covered more distance in the target quadrant but had reduced average proximity and fewer platform entries. HE staining observation of the hippocampal CA1 area showed no apparent pathological changes in the blank group, obvious pathological damage in the model group, and no significant pathological changes in the medium and high dose groups of Di Dang Tang. Compared to the blank control group, the model group showed significant increases in the levels of Arachidonic Acid (AA), Ceramide (Cer), Glutamate (Glu), TNF- α, IL-1β, TG, and LDL-C, and a significant decrease in HDL-C levels. Compared to the model group, the groups of Di Dang Tang significantly modulated the levels of the above indicators. In Western Blot (WB) assays, compared to the blank control group, the model group rats exhibited significantly higher levels of cPLA2, PKC, ERK, and JNK , and significantly lower levels of claudin-5, NMDA, CaMKII, CREB, and BDNF. The Di Dang Tang groups significantly altered the levels of the above indicators compared to the model group.CONCLUSION: Amino acid metabolism, sphingolipid signaling pathways, glycerophospholipid metabolism, and various signaling pathways play significant roles in the pathogenesis of T2DM-CD. Di Dang Tang can improve learning and memory abilities in T2DM model rats and ameliorate cognitive impairments, potentially by regulating metabolic levels and inflammatory responses.PMID:39826792 | DOI:10.1016/j.jep.2025.119338

J Ethnopharmacol. 2025 Jan 16:119371. doi: 10.1016/j.jep.2025.119371. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Emilia sonchifolia is a very widely used traditional Chinese medicine, with the efficacy of heat-clearing, detoxicating, dissipating blood stasis, reducing swelling and relieving pain. As a widely used traditional miao herb, Emilia sonchifolia is often used to treat upper respiratory tract infections, oral ulcer, pneumonia, mastitis, enteritis, bacillum, urinary tract infection, sores, eczema, falls and injuries, etc. In fact, many cases of liver injury caused by Emilia sonchifolia have been reported clinically. However, the mechanisms underlying hepatotoxicity induced by Emilia sonchifolia remain poorly understood.AIM OF THE STUDY: This study aimed to systematically evaluate the acute and chronic hepatotoxicity of water extract from Emilia sonchifolia, identify its hepatotoxic metabolites, and elucidate the potential mechanisms underlying Emilia sonchifolia-induced hepatotoxicity.MATERIAL AND METHOD: The chemical components in the water extract of Emilia sonchifolia were identified using mass spectrometry. The acute toxicity study was conducted by orally administering a gradient dose of water extract of Emilia sonchifolia ranging from 0 to 37.6 g/kg. Mice were orally administered a water extract of Emilia sonchifolia at a dose of 13.72 g/kg/d for 14 days to induce liver injury. The hepatotoxicity was evaluated using hematoxylin and eosin staining as well as enzyme-linked immunosorbent assay (ELISA). The mechanisms of hepatotoxicity were explored through transcriptomics, proteomics, and metabolomics analysis. Meanwhile, the core pathways related to the hepatotoxicity of Emilia sonchifolia were analyzed and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and ELISA.RESULT: The present study demonstrates that the water extract of Emilia sonchifolia can induce hepatotoxicity in mice. We found that the water extract of Emilia sonchifolia contained hepatotoxic pyrrolizidine alkaloids, such as seneciphyllin, senecionine, rinderine, echimidine, retrorsine and echimidine N-oxide. A dose of 19.20 g/kg or higher of the water extract of Emilia sonchifolia caused acute liver failure and death in mice. A dose of 13.72 g/kg or lower of the water extract of Emilia sonchifolia produced dose-dependent acute hepatotoxicity. Meanwhile, a dose of 13.72 g/kg of the water extract from Emilia sonchifolia induced chronic hepatotoxicity in mice. Furthermore, the results of liver transcriptomics, proteomics, and metabolomics indicate that the mechanism of hepatotoxicity induced by the water extract of Emilia sonchifolia is associated with ferroptosis caused by abnormalities in bile acid accumulation, lipid and bilirubin accumulation, and glutathione metabolism. The validation experiment results demonstrate that in mice treated with the water extract of Emilia sonchifolia, the gene levels of Cyp2c29, Cyp3a41a and Ugt2b1 decreased while the gene level of Hsd3b3 increased. In mice treated with a water extract of Emilia sonchifolia, the levels of total bilirubin, direct bilirubin, total bile acids, alkaline phosphatase, and γ-glutamyl transferase were significantly elevated. Additionally, in mice treated with a water extract of Emilia sonchifolia, the levels of malondialdehyde increased while the levels of catalase and superoxide dismutase decreased.CONCLUSION: In conclusion, our results suggest that the water extract of Emilia sonchifolia can cause hepatotoxicity in mice. The chronic hepatotoxicity of Emilia sonchifolia is associated with Cyp2c29, Cyp3a41a, Ugt2b1, and Hsd3b3-mediated cholestasis, oxidative stress, and ferroptosis.PMID:39826791 | DOI:10.1016/j.jep.2025.119371