PubMed

Kidney360. 2024 Nov 12. doi: 10.34067/KID.0000000630. Online ahead of print.ABSTRACTBACKGROUND: In acute kidney injury, macrophages play a major role in regulating inflammation. Classically activated macrophages (M1) undergo drastic metabolic reprogramming during their differentiation and upregulate the aerobic glycolysis pathway to fulfill their pro-inflammatory functions. NAD+ regeneration is crucial for the maintenance of glycolysis and the most direct pathway by which this occurs is via the fermentation of pyruvate to lactate, catalyzed by lactate dehydrogenase A (LDHA). Our previous study determined that LDHA is predominantly expressed in the proximal segments of the nephron in the mouse kidney and increases with hypoxia. This study investigates the potential of LDHA as a therapeutic target for inflammation by exploring its role in macrophage function in vitro.METHODS: Bone-marrow-derived macrophages (BMDMs) were isolated from myeloid-specific LDHA knockout mice derived from crossbreeding LysM-Cre transgenic mice and LDHA floxed mice. RNA sequencing and LC-MS/MS metabolomics analyses were used in this study to determine the effect of LDHA deletion on BMDM following stimulation with IFN-γ.RESULTS: LDHA deletion in IFN-γ BMDMs resulted in a significant alteration of the macrophage activation and functional pathways, and change in glycolytic, cytokine, and chemokine gene expression. Metabolite concentrations associated with pro-inflammatory macrophage profiles were diminished while anti-inflammatory-associated ones were increased in LDHA KO BMDMs. Glutamate and amino sugars metabolic pathways were significantly affected by the LDHA deletion. A combined muti-omics analysis highlighted changes in Rap1 signaling, cytokine-cytokine receptor interaction, focal adhesion, and MAPK signaling metabolism pathways.CONCLUSIONS: Deletion of LDHA in macrophages results in a notable reduction in the pro-inflammatory profile and concurrent upregulation of anti-inflammatory pathways. These findings suggest that LDHA could serve as a promising therapeutic target for inflammation, a key contributor to the pathogenesis of acute kidney injury.PMID:39531318 | DOI:10.34067/KID.0000000630

Anal Chem. 2024 Nov 12. doi: 10.1021/acs.analchem.4c04400. Online ahead of print.ABSTRACTVarious polarity chemicals exist in complex samples, such as plasma; nontargeted comprehensive analysis naturally requires multiple polar-extracted solvents; consequently, the polarity of the solvent plays a crucial role in the extraction efficiency of analytes from complex samples. In the present study, based on the diffusion behavior and nanoconfinement effect of solvents in the nanoconfined space, the polarity gradient solvent confinement liquid-phase nanoextraction (PGSC-NLPNE) protocol aimed to perform a one-step nontargeted analysis of a wide range of metabolites in plasma was established. The continuously wide range of extracted solvent polarities on carbon nanofibers/carbon fiber (CNFs/CF) membranes was achieved using a mixture of hexane, dichloromethane, methanol, and water as nanoconfined solvents. The polarities (Log P) of gradient solvents ranged from -1.38 to 3.94. Correlational analyses indicated that metabolites with Log P values ranging from -1.90 to 3.84 were closely related according to similarity-intermiscibility theory. Coupled with a homemade modified guard column device, CNFs/CF membrane cartridge (CCMC), a PGSC-NLPNE-UHPLC-MS online protocol was established and applied in plasma untargeted analysis. By comparing metabolome coverage, reproducibility, and extraction recovery with protein precipitation and two-step liquid-liquid extraction commonly used in untargeted analysis, the PGSC-NLPNE-CCMC protocol demonstrated higher reproducibility and recovery. This protocol has shown great potential for ultrafast analysis of plasma untargeted metabolomics with broader metabolome coverage. It could be a potential tool to rapidly screen out valuable biomarkers related to diseases in the clinic.PMID:39531215 | DOI:10.1021/acs.analchem.4c04400

Inflammation. 2024 Nov 12. doi: 10.1007/s10753-024-02184-2. Online ahead of print.ABSTRACTChanges in gut flora are associated with liver fibrosis. The interactions of host with intestinal flora are still unknown, with little research investigating such interactions with comprehensive multi-omics data. The present work analyzed and integrated large-scale multi-omics transcriptomics, microbiome, metabolome, and single-cell RNA-sequencing datasets from Kaempferol-treated and untreated control groups by advanced bioinformatics methods. This study concludes that kaempferol dose-dependently improved serum markers (like AST, ALT, TBil, Alb, and PT) and suppressed fibrosis markers (including HA, PC III, LN, α-SMA, and Collagen I), while kaempferol also increased body weight. Mechanistically, kaempferol improved the metabolic levels of intestinal flora dysbiosis and associated lipids. This was achieved by increasing the abundance of g__Robinsoniella, g__Erysipelotrichaceae_UCG-003, g__Coriobacteriaceae_UCG-002, and 5-Methylcytidine, all-trans-5,6- Epoxyretinoic acid, LPI (18:0), LPI (20:4), etc. to achieve this. Kaemferol exerts anti-inflammatory and immune-enhancing effects by down-regulating the Th17/IL-17 signaling pathway in PDGF-induced LX2 cells. In addition, kaempferol administration remarkably elevated CD4 + T and CD8 + T cellular proportions, thereby activating immune cells for protecting the body and controlling inflammatory conditions. The combined interaction of multiple data may explain how Kaempferol modulates the intestinal flora thereby remodeling the hepatocyte population and alleviating liver fibrosis.PMID:39531210 | DOI:10.1007/s10753-024-02184-2

Appl Microbiol Biotechnol. 2024 Nov 12;108(1):512. doi: 10.1007/s00253-024-13341-w.ABSTRACTSalmonella, a common pathogenic bacterium in food, can have a severe impact on food safety and consumer health. At present, Salmonella infection is controlled primarily by the use of antibiotics, which creates unsafe factors for food safety. Thus, finding a natural antibacterial agent is highly practical. In this study, resveratrol was screened from 17 kinds of polyphenols, and its inhibitory mechanism and effects on metabolites of Salmonella typhimurium were investigated to occur through cell wall and membrane damage and metabolomics analysis. The results revealed that the minimum inhibitory concentration of resveratrol against S. typhimurium was 250 μg/mL. After treatment with resveratrol, the lag period of the strain was prolonged, and the cell wall and membrane structure were destroyed. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) further confirmed that resveratrol induced damage to the cell walls and cell membrane. The metabolic profile of S. typhimurium following resveratrol treatment was analysed by gas chromatography‒mass spectrometry. In the metabolome evaluation, we screened 23 differentially abundant metabolites, including 11 upregulated and 12 downregulated metabolites. Eight metabolic pathways of S. typhimurium, including pathways important for amino acid metabolism and the tricarboxylic acid (TCA) cycle, exhibited significant changes after resveratrol treatment. The verification results of the citric acid content, cis-aconitase activity, and ATP content further revealed that the tricarboxylic acid cycle and other related metabolic pathways of S. typhimurium were affected. These results could provide a theoretical possibility for the use of resveratrol as a plant-derived bacteriostatic for food safety problems caused by S. typhimurium. KEY POINTS: • The mechanism of bacteriostasis was studied via metabolomics • Resveratrol causes the death of Salmonella by disrupting the cell wall and membrane.PMID:39531061 | DOI:10.1007/s00253-024-13341-w

Physiol Res. 2024 Nov 12;73(5):687-702.ABSTRACTOver recent decades, advancements in omics technologies, such as proteomics, genomics, epigenomics, metabolomics, transcriptomics, and microbiomics, have significantly enhanced our understanding of the molecular mechanisms underlying various physiological and pathological processes. Nonetheless, the analysis and interpretation of vast omics data concerning reproductive diseases are complicated by the cyclic regulation of hormones and multiple other factors, which, in conjunction with a genetic makeup of an individual, lead to diverse biological responses. Reproductomics investigates the interplay between a hormonal regulation of an individual, environmental factors, genetic predisposition (DNA composition and epigenome), health effects, and resulting biological outcomes. It is a rapidly emerging field that utilizes computational tools to analyze and interpret reproductive data, with the aim of improving reproductive health outcomes. It is time to explore the applications of reproductomics in understanding the molecular mechanisms underlying infertility, identification of potential biomarkers for diagnosis and treatment, and in improving assisted reproductive technologies (ARTs). Reproductomics tools include machine learning algorithms for predicting fertility outcomes, gene editing technologies for correcting genetic abnormalities, and single cell sequencing techniques for analyzing gene expression patterns at the individual cell level. However, there are several challenges, limitations and ethical issues involved with the use of reproductomics, such as the applications of gene editing technologies and their potential impact on future generations are discussed. The review comprehensively covers the applications and advancements of reproductomics, highlighting its potential to improve reproductive health outcomes and deepen our understanding of reproductive molecular mechanisms.PMID:39530905

Food Funct. 2024 Nov 12. doi: 10.1039/d4fo90094d. Online ahead of print.ABSTRACTCorrection for 'Using integrated transcriptomics and metabolomics to explore the effects of infant formula on the growth and development of small intestinal organoids' by Xianli Wang et al., Food Funct., 2024, 15, 9191-9209, https://doi.org/10.1039/d4fo01723d.PMID:39530838 | DOI:10.1039/d4fo90094d

J Exp Bot. 2024 Nov 12:erae457. doi: 10.1093/jxb/erae457. Online ahead of print.ABSTRACTPriming modulates plant stress responses before the stress appears, increasing the ability of the primed plant to endure adverse conditions and thrive. In this context, we investigated the effect of biological (i.e., arbuscular mycorrhizal fungi, AMF) agents and natural compounds (i.e., salicylic acid applied alone or combined with chitosan) against water deficit and salinity on a commercial tomato genotype (cv. Moneymaker). Effects of seed treatments on AMF colonization were evaluated, demonstrating the possibility of using them in combination. Responses to water and salt stresses were analysed on primed plants alone or in combination with the AMF inoculum in soil. Trials were conducted on potted plants by subjecting them to water deficit or salt stress. The effectiveness of chemical seed treatments, both alone and in combination with post-germination AM fungal inoculation, was investigated using a multidisciplinary approach that included eco-physiology, biochemistry, transcriptomics, and untargeted metabolomics. Results showed that chemical seed treatment and AM symbiosis modified the tomato response to water deficit and salinity triggering a remodelling of both transcriptome and metabolome, which ultimately elicited the plant antioxidant and osmoprotective machinery. The plant physiological adaptation to both stress conditions improved, confirming the success of the adopted approaches in enhancing stress tolerance.PMID:39530649 | DOI:10.1093/jxb/erae457

Mov Disord. 2024 Nov 12. doi: 10.1002/mds.30054. Online ahead of print.ABSTRACTBACKGROUND: Alterations in gut microbiota are observed in Parkinson's disease (PD). Previous studies on microbiota-derived metabolites in PD were small-scale and post-diagnosis, raising concerns about reverse causality.OBJECTIVES: Our goal was to prospectively investigate the association between plasma microbial metabolites and PD risk within a metabolomics framework.METHODS: A nested case-control study within the prospective EPIC4PD cohort, measured pre-diagnostic plasma microbial metabolites using untargeted metabolomics.RESULTS: Thirteen microbial metabolites were identified nominally associated with PD risk (P-value < 0.05), including amino acids, bile acid, indoles, and hydroxy acid, although none remained significant after multiple testing correction. Three pathways were implicated in PD risk: valine, leucine, and isoleucine degradation, butanoate metabolism, and propanoate metabolism. PD-associated microbial pathways were more pronounced in men, smokers, and overweight/obese individuals.CONCLUSION: Changes in microbial metabolites may represent a pre-diagnostic feature of PD. We observed biologically plausible associations between microbial pathways and PD, potentially influenced by individual characteristics. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.PMID:39530417 | DOI:10.1002/mds.30054

Pediatr Allergy Immunol. 2024 Nov;35(11):e14267. doi: 10.1111/pai.14267.ABSTRACTBACKGROUND: The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown.OBJECTIVE: To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multiethnic cohorts and responses to OIT.METHODS: Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N = 384), a Costa Rican cohort of children with asthma (N = 1040), and a peanut OIT trial (N = 20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterward). Generalized linear regression modeling and pathway enrichment analysis identified metabolites associated with food allergy and OIT outcomes.RESULTS: Compared with unaffected children, those with food allergy were more likely to have metabolomic profiles with altered histidines and increased bile acids. Eicosanoids (e.g., arachidonic acid derivatives) (q = 2.4 × 10-20) and linoleic acid derivatives (q = 3.8 × 10-5) pathways decreased over time on OIT. Comparing SU versus TD revealed differing concentrations of bile acids (q = 4.1 × 10-8), eicosanoids (q = 7.9 × 10-7), and histidine pathways (q = .015). In particular, the bile acid lithocholate (4.97 [1.93, 16.14], p = .0027), the eicosanoid leukotriene B4 (3.21 [1.38, 8.38], p = .01), and the histidine metabolite urocanic acid (22.13 [3.98, 194.67], p = .0015) were higher in SU.CONCLUSIONS: We observed distinct profiles of bile acids, histidines, and eicosanoids that vary among patients with food allergy, over time on OIT and between SU and TD. Participants with SU had higher levels of metabolites such as lithocholate and urocanic acid, which have immunomodulatory roles in key T-cell subsets, suggesting potential mechanisms of tolerance in immunotherapy.PMID:39530396 | DOI:10.1111/pai.14267

Onco Targets Ther. 2024 Nov 6;17:933-948. doi: 10.2147/OTT.S482767. eCollection 2024.ABSTRACTPURPOSE: Gastric cancer (GC) is a disease with high prevalence and mortality, but we lack convenient and accurate methods to screen for this disease. Thus, we aimed to search for some salivary biomarkers and explore changes in metabolites in patients' saliva after radical gastrectomy.PATIENTS AND METHODS: A total of 152 subjects were divided into three groups (healthy group, GC group, and one-week postoperative group). After simple processing, saliva samples were analyzed by liquid chromatography-mass spectrometry. First, we used total ion chromatography and principal component analysis to determine the metabolite profiles. Next, t-test, partial least squares discriminant analysis, support vector machine, and receiver operating characteristics curve analysis were performed to identify biomarkers. Then, Fisher discriminant analysis and hierarchical clustering analysis were performed to determine the discriminating ability of biomarkers. Finally, we established a generalized linear model to predict GC based on biomarkers, and used bootstrapping for internal validation.RESULTS: Between the healthy and GC groups, we identified four biomarkers: lactic acid, kynurenic acid, 3-hydroxystachydrine, and S-(1,2,2-trichlorovinyl)-L-cysteine. We used stepwise regression to select five metabolites and develop a model with areas under the curve equal to 0.973 in the training dataset and 0.924 in the validation dataset. Between the GC and one-week postoperative groups, we found two differential metabolites: 19-hydroxyprostaglandin E2 and DG (14:0/0:0/18:2n6).CONCLUSION: Differential metabolites were observed among the three groups. GC could be initially diagnosed on the basis of detection of these biomarkers. Moreover, changes in salivary metabolites in postoperative patients could provide important insights for basic studies.PMID:39530041 | PMC:PMC11551007 | DOI:10.2147/OTT.S482767

Arch Endocrinol Metab. 2024 Oct 17;68:e230527. doi: 10.20945/2359-4292-2023-0527. eCollection 2024.ABSTRACTOBJECTIVE: This pilot study investigated whether single nucleotide polymorphisms (SNP) in the NOX5 gene (NADPH oxidase 5) are associated with the type 2 diabetes (T2D) risk.SUBJECTS AND METHODS: A total of 1579 patients with T2D and 1627 age- and sex-matched healthy subjects were recruited for this study. Genotyping of common SNPs, namely rs35672233, rs3743093, rs2036343, rs311886, and rs438866, was performed using the MassArray-4 system.RESULTS: SNP rs35672233 was associated with an increased risk of T2D (OR = 1.67, 95% CI 1.29-2.17, FDR = 0.003). The H3 haplotype (rs35672233T-rs3743093G-rs2036343A-rs311886C-rs438866C) increased T2D risk (OR = 1.65, 95% CI 1.27-2.13, FDR = 0.001). The rs35672233 polymorphism and H3 haplotype were found to have an association with T2D risk only in subjects with a body mass index greater than 25 kg/m2 (FDR < 0.01). Environmental risk factors, such as chronic psycho-emotional stress, sedentary lifestyle, high-calorie diet and SNP rs35672233 were jointly associated with T2D susceptibility. A haplotype comprising the allele rs35672233-C and conferring protection against T2D, was associated with elevated levels of antioxidants such as total glutathione and uric acid, as well as reduced levels of two-hour postprandial glucose in the plasma of patients. The NOX5 polymorphisms showed no associations with diabetic complications.CONCLUSION: The present study is the first to establish associations between polymorphisms in NOX5 and the risk of type 2 diabetes mellitus, and provides a new line of evidence for the crucial role of oxidative stress-related genes in disease susceptibility.PMID:39529984 | PMC:PMC11554360 | DOI:10.20945/2359-4292-2023-0527

Front Plant Sci. 2024 Oct 28;15:1425815. doi: 10.3389/fpls.2024.1425815. eCollection 2024.ABSTRACTINTRODUCTION: Microplastic pollution has emerged as a significant global change factor, with the potential to alter the biological, physicochemical properties of soil and to subsequently affect plant growth. Despite growing recognition of the impacts of microplastic pollution, the mechanisms by which microplastics modify plant leaf chemistry and influence allelopathic interactions among co-existing plant species remain unclear.METHODS: We used the native perennial forb Achyranthes bidentata and the invasive annual forb Amaranthus spinosus as focal species. We grew the two species with and without competition with each other. This setup was further combined with a treatment involving the addition of polyethylene (PE). We then testd the effects of aqueous extract on seed germination and seedling growth for five invasive and five native species. Subsequently, metabolomic analysis was conducted on the aqueous extracts, in which significant allelopathic effects were observed on test species.RESULTS AND DISCUSSION: The presence of PE microplastics enhanced the biomass of both Achyranthes and Amaranthus under competitive and non-competitive growth conditions. Furthermore, PE microplastics were found to induce a negative allelopathic effect for the native plant Achyranthes on co-occurring plants, which appeared to be mediated through changes in leaf chemistry. Bisdemethoxycurcumin, ethylparaben, salicin 6'-sulfate and 5-hydroxy-3',4',7-trimethoxyflavone glucoside were proven important compounds for allelopathic enhancement. Overall, these results suggest that microplastic pollution has the capability to influence the co-existence of invasive and native plants by altering their allelopathic potential. This insight into the interactions between microplastics and plant allelopathy provides a novel perspective on how microplastic pollution could modify plant species interactions and ecosystem dynamics. Future studies could aim to answer how microplastics might affect plant root exudates and whether this process would mediate biological invasion.PMID:39529932 | PMC:PMC11551022 | DOI:10.3389/fpls.2024.1425815

Front Pharmacol. 2024 Oct 28;15:1447077. doi: 10.3389/fphar.2024.1447077. eCollection 2024.ABSTRACTINTRODUCTION: This study aimed to establish a fermentation system based on Lactobacillus casei (LC) and Arctium lappa L. root (AR) to investigate its effects. The objectives included comparing metabolite profiles pre- and post-fermentation using untargeted metabolomics and evaluating the impact of LC-AR in high-fat diet-induced hyperlipidemic mice.METHODS: Untargeted metabolomics was used to analyze differences in metabolites before and after fermentation. In vitro antioxidant activity, liver injury, lipid levels, pro-inflammatory cytokine levels, and cholesterol-related mRNA expression were assessed. 16S rRNA sequencing was conducted to evaluate changes in gut microbiota composition.RESULTS: LC-AR exhibited stronger antioxidant activity and higher metabolite levels than AR. It also improved liver injury as well as better regulation of lipid levels, pro-inflammatory cytokine levels, and cholesterol-related mRNA. 16S rRNA analysis revealed that LC-AR decreased the Firmicutes/Bacteroidetes ratio, which correlated negatively with triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels.DISCUSSION: These findings suggest that LC-AR may serve as a promising functional food and drug raw material for improving hyperlipidemia, particularly through its beneficial effects on gut microbiota and lipid regulation.PMID:39529876 | PMC:PMC11551023 | DOI:10.3389/fphar.2024.1447077

Front Microbiol. 2024 Oct 28;15:1478330. doi: 10.3389/fmicb.2024.1478330. eCollection 2024.ABSTRACTBACKGROUND: Tian-ma (Gastrodia elata) is a traditional medicinal herb found in China. It is used in healthy food and to treat various diseases, therefore cultivated extensively in southwest China. However, continuous cropping of this species has led to various obstacles, such as microbial disease and pest infestation, significantly affecting the production and development of valuable medicinal and food resources. As per the growth habit, soil is presumed to be the primary factor contributing to these obstacles, despite the known issues of continuous cropping obstacles in Gastrodia elata, such as microbial disease, there is a lack of comprehensive understanding of the specific soil bacterial communities and metabolites involved in these processes.METHODS: We analyzed soil samples collected during the year of Tian-ma cultivation (0 Year), after the Tian-ma harvest (1 Year), after two years (2 Year), and three years (3 Year) of fallowing post-cultivation using soil 16S rRNA metabarcoding sequencing by illumina platform and metabolomics (GC-MS/MS). Soil sample collected from the uncultivated field was used as the control (CK).RESULTS: Metabarcoding sequencing showed high bacterial alpha diversity during the cultivation of Tian-ma (0 Year) and the period of deterioration of soil bacterial community. (1 Year), with decreased anaerobic bacterial abundance and increased copiotrophic bacterial abundance. Bacteria associated with sulfur metabolism also showed increased abundance during the year of cropping obstacles. Further metabolomics approach identified 4-hydroxy-benzenemethanol as an indicator of Tian-ma continuous cropping obstacles. Besides, metabolites of the carbohydrate class were found to be the most abundant during the occurrence of continuous cropping obstacles of Gastrodia elata, suggesting that regulation of soil microbial diversity may be a critical factor in addressing these obstacles. Finally, the correlation analysis indicated a positive association between the abundance of some metabolite, e.g., carbamic acid, N-(2-butyl)-N-octadecyl-, ethyl ester detected after Tian-ma cultivation and the abundance of bacteria capable of degrading toxic metabolites, such as Massilia, Burkholderia-Caballeronia-Paraburkholderia, and Dyella.CONCLUSION: This study has revealed the specific soil bacteria and metabolic factors related to the continuous cropping obstacles of Gastrodia elata. These findings not only deepen our understanding of the continuous cropping issues but also pave the way for developing effective strategies to overcome them.PMID:39529674 | PMC:PMC11550952 | DOI:10.3389/fmicb.2024.1478330

Front Cell Dev Biol. 2024 Oct 28;12:1473616. doi: 10.3389/fcell.2024.1473616. eCollection 2024.ABSTRACTType 2 innate lymphoid cells (ILC2s) have emerged as pivotal regulators in the pathogenesis of diseases, with their roles in inflammation, metabolism, and tissue homeostasis becoming increasingly recognized. This review provides an overview of the current understanding of ILC2s in inflammation and metabolic disorders, including their functional contributions. Moreover, we will discuss how these cells adapt their metabolic processes to support their function and survival and how their metabolic requirements change under different physiological and pathological conditions. Lastly, we will review recent omics studies that have provided insights into the molecular and cellular characteristics of ILC2s. This includes transcriptomic, proteomic, and metabolomic analyses that have elucidated the gene expression profiles, protein interactions, and metabolic networks, respectively, associated with ILC2s. These studies have advanced our understanding of the functional diversity of ILC2s and their involvement in metabolic disease.PMID:39529633 | PMC:PMC11551558 | DOI:10.3389/fcell.2024.1473616

J Anim Sci. 2024 Nov 12:skae350. doi: 10.1093/jas/skae350. Online ahead of print.ABSTRACTThe in-utero environment is key to both fetal and postnatal growth and development. The objective of this study was to determine if administration of an acute low-dose lipopolysaccharide (LPS) to gestating sows during mid to late gestation and post-weaning would alter the offsprings metabolomic profile of the longissimus dorsi (LD) and muscle ultrastructure. Pregnant Camborough sows were randomly assigned to receive LPS (LPS; n= 7) at a dose of 2.5 μg/kg or saline (CON; n = 7) on 78 ± 1.8 d of gestation. At weaning (21 ± 1.3 d of age), barrows (CON n = 17; LPS n = 17) from each treatment were selected to receive a secondary LPS. Barrows were administered the secondary LPS challenge at a dose of 10 μg/kg 7 d post weaning. Twenty-four h after the postnatal LPS dose, barrows (31 ± 1.3 d of age) were euthanized, and each LD was removed. The left LD was utilized for morphometric measurements. Two samples from the medial section of the right LD were preserved for immunohistochemical measurements and metabolomic analyses. Mass spectral data were deconvoluted, aligned, and annotated using MS-DIAL. Univariate and multivariate analyses were conducted using MetaboAnalyst. Pathway analysis was conducted and compared to the Homo sapiens pathway library. Morphometric and immunohistochemical measurements were analyzed using the MIXED procedure of SAS version 9.4. Significance for all analyses was declared at P ≤ 0.05 and tendencies were considered at P ≤ 0.10. Average diameter of myosin heavy chain (MHC) type I and IIB/X fibers was increased (P ≤ 0.048) in LPS offspring compared with CON. Average cross-sectional area was increased (P = 0.030) in MHC IIB/X fibers and tended to be increased (P = 0.080) in MHC I fibers of LPS offspring. There were no differences (P ≥ 0.186) between treatment groups for total nuclei or nuclei positive for MYF5, PAX7, or MYF5 and PAX7 nuclei. Metabolomic analyses identified 14 differentially expressed (P < 0.05) metabolites in the LD between treatment groups. There were 10 metabolites within the LD that tended (P ≤ 0.096) to differ between treatment groups. Thus, this study shows that in-utero immune stimulation using LPS in gestating sows and a subsequent LPS challenge postnatally alters the metabolomic profile and muscle ultrastructure of the LD in weaned pigs.PMID:39529455 | DOI:10.1093/jas/skae350

Diabetes Obes Metab. 2024 Nov 11. doi: 10.1111/dom.16053. Online ahead of print.ABSTRACTAIMS: Obesity always leads to profound perturbation of metabolome. Metabolome studies enrich the knowledge on associations between endogenous metabolites and obesity, potentially providing innovative strategies for the development of novel anti-obesity pharmacotherapy. This study aims to identify an endogenous metabolite that regulates energy expenditure and to explore its application for obesity treatment.MATERIALS AND METHODS: C57BL/6 mice were fed with a high-fat and high-cholesterol (HFC) diet, comprising 60% fat and 1.2% cholesterol, for 12 weeks to induce obesity. Significant metabolites were identified in the livers of both health and obese mice through comparative hepatic metabolomics analysis. Correlation between serum or adipose L-aspartate level and body weight in obese mice, as well as human body mass index (BMI), was evaluated. In addition, saline or 200 mg/kg L-aspartate was orally administrated to HFC diet mice and HFC diet-induced obese mice for 6-7 weeks. Body weight, adipose tissue weight, glucose tolerance and liver damage were assessed to evaluate the effect on obesity prevention and treatment. Comprehensive lab animal monitoring system (CLAMS) and seahorse assay were employed to investigate the regulatory effect of L-aspartate on energy metabolism in vivo and in vitro, respectively. 3T3-L1 preadipocytes and murine white adipose tissue (WAT) were utilized to examine the impact of L-aspartate on adipocyte adipogenesis and lipogenesis and cellular signalling pathway in vitro and in vivo.RESULTS: L-aspartate, an approved drug for liver injury and chronic fatigue, was identified as an endogenous inducer of energy expenditure. Serum or adipose L-aspartate levels were found to be negatively correlated with the severity of obesity in both humans and mice. Administration of L-aspartate to HFC diet mice led to a significant reduction in body weight, with decreases of 14.5% in HFC diet mice and 8.5% in HFC diet-induced obese mice, respectively. In addition, the treatment improved related metabolic syndrome (Figure 2 and Figure S3). These therapeutics were associated with enhancements in whole-body energy expenditure and suppression of adipocyte adipogenesis along with activation of Adenosine 5'-monophosphate-activated protein kinase (AMPK) signalling pathway.CONCLUSION: L-aspartate may serve as a novel endogenous inducer of energy expenditure and suppressor of adipogenesis and lipogenesis along with activation of AMPK, thereby offering a promising therapeutic strategy for obesity prevention and treatment.PMID:39529440 | DOI:10.1111/dom.16053

Gut Microbes. 2024 Jan-Dec;16(1):2426623. doi: 10.1080/19490976.2024.2426623. Epub 2024 Nov 11.ABSTRACTGut microbiome plays a pivotal role in combating diseases and facilitating healthy aging, and natural products derived from biosynthetic gene clusters (BGCs) of the human microbiome exhibit significant biological activities. However, the natural products of the gut microbiome in long-lived populations remain poorly understood. Here, we integrated six cohorts of long-lived populations, encompassing a total of 1029 fecal metagenomic samples, and employed the metagenomic single sample assembled BGCs (MSSA-BGCs) analysis pipeline to investigate the natural products and their associated species. Our findings reveal that the BGC composition of the extremely long-lived group differed significantly from that of younger elderly and young individuals across five cohorts. Terpene and Type I PKS BGCs were enriched in the extremely long-lived, whereas cyclic-lactone-autoinducer BGCs were more prevalent in the young. Association analysis indicated that terpene BGCs were strongly associated with the abundance of Akkermansia muciniphila, which was also more abundant in the long-lived elderly across at least three cohorts. We assembled 18 A. muciniphila draft genomes using metagenomic data from the extremely long-lived group across six cohorts and discovered that they all harbor two classes of terpene BGCs, which aligns with the 97 complete genomes of A. muciniphila strains retrieved from the NCBI database. The core domains of these two BGC classes are squalene/phytoene synthases involved in the biosynthesis of tri- and tetraterpenes. Furthermore, the abundance of fecal A. muciniphila was significantly associated with eight types of triterpenoids. Targeted terpenoid metabolomic analysis revealed that two triterpenoids, Holstinone C and colubrinic acid, were enriched in the A. muciniphila culture solution compared to the medium, thereby confirming the production of triterpenoids by A. muciniphila. The natural products derived from the gut of long-lived populations provide intriguing indications of their potential beneficial roles in regulating health.PMID:39529240 | DOI:10.1080/19490976.2024.2426623

Int J Biol Macromol. 2024 Nov 9;282(Pt 6):137429. doi: 10.1016/j.ijbiomac.2024.137429. Online ahead of print.ABSTRACTRapid postharvest senescence and quality deterioration severely limit logistics of cowpeas. Melatonin (MEL) is a pivotal bioactive molecule that can modulate multiple physiological attributes in plants. In this study, physiological, transcriptomic and metabolomic analyses were conducted to explore the effects of exogenous MEL on cowpea senescence and its underlying mechanisms. Physiological results showed that 100 μM MEL treatment maintained sensory quality (greeness, firmness and soluble solids content), reduced weight loss as well as inhibited the degradation of chlorophyll (Chl) and protopectin. Preservation of color and firmness in cowpeas was greatly attributed to inhibition of expression of genes related to Chl and cell wall metabolism, which was based on a transcriptomic analysis. Integrated transcriptomic and metabolomic analyses revealed that MEL promoted transcription of genes associated with amino acid and carbohydrate metabolism, resulting in the accumulation of amino acid and sugar metabolites. Additionally, by integrating transcription factor-binding site analysis with cis-acting element analysis, we constructed a regulatory network of transcription factors underlying MEL-mediated antisenescence. The present study found a series of potential candidate genes and metabolites involved in regulating senescence process and provided an insight into improving postharvest quality of cowpeas.PMID:39528182 | DOI:10.1016/j.ijbiomac.2024.137429

Heliyon. 2024 Oct 9;10(21):e39126. doi: 10.1016/j.heliyon.2024.e39126. eCollection 2024 Nov 15.ABSTRACTBACKGROUND: Guillain-Barre syndrome (GBS), an autoimmune disease of the peripheral nervous system, is hallmarked by demyelination and immune cellular infiltration. Experimental autoimmune neuritis (EAN), considered a GBS prototype model, has been studied for its potential therapeutic benefits from lactobacilli. This study evaluated the protective role of Lactobacillus rhamnosus GG (GG) for treatment in EAN. T cell ratio, inflammation factors, sciatic nerve pathology, intestinal permeability, and gut inflammation were assessed on day 19 post-immunization to evaluate GG's effect on EAN. Fecal metabolomics and 16s rRNA microbiome analysis were conducted to elucidate its mechanism.RESULTS: GG dynamically balanced CD4+/CD8+T cell ratio, reduced serum IL-1β and TNF-α expression, improved sciatic nerve demyelination and inflammation, and enhanced neurological scores during peak disease period. Intestinal mucosal damage was evident in EAN rats, with downregulated Occludin and ZO-1 and upregulated IL-1β, TNF-α, and Reg3γ. GG treatment restored intestinal mucosal integrity, upregulated Occludin and ZO-1, and downregulated IL-1, TNF-α, and Reg3γ. GG partially rectified the gut microbiota and metabolite imbalance in EAN rats.CONCLUSION: GG mitigates EAN through immune response modulation and inflammation reduction via the gut microbiota and metabolites.PMID:39524841 | PMC:PMC11550083 | DOI:10.1016/j.heliyon.2024.e39126