PubMed

bioRxiv [Preprint]. 2024 Jul 31:2024.07.30.605945. doi: 10.1101/2024.07.30.605945.ABSTRACTMethods for assessing compound identification confidence in metabolomics and related studies have been debated and actively researched for the past two decades. The earliest effort in 2007 focused primarily on mass spectrometry and nuclear magnetic resonance spectroscopy and resulted in four recommended levels of metabolite identification confidence - the Metabolite Standards Initiative (MSI) Levels. In 2014, the original MSI Levels were expanded to five levels (including two sublevels) to facilitate communication of compound identification confidence in high resolution mass spectrometry studies. Further refinement in identification levels have occurred, for example to accommodate use of ion mobility spectrometry in metabolomics workflows, and alternate approaches to communicate compound identification confidence also have been developed based on identification points schema. However, neither qualitative levels of identification confidence nor quantitative scoring systems address the degree of ambiguity in compound identifications in context of the chemical space being considered, are easily automated, or are transferable between analytical platforms. In this perspective, we propose that the metabolomics and related communities consider identification probability as an approach for automated and transferable assessment of compound identification and ambiguity in metabolomics and related studies. Identification probability is defined simply as 1/N, where N is the number of compounds in a reference library or chemical space that match to an experimentally measured molecule within user-defined measurement precision(s), for example mass measurement or retention time accuracy, etc. We demonstrate the utility of identification probability in an in silico analysis of multi-property reference libraries constructed from the Human Metabolome Database and computational property predictions, provide guidance to the community in transparent implementation of the concept, and invite the community to further evaluate this concept in parallel with their current preferred methods for assessing metabolite identification confidence.PMID:39131324 | PMC:PMC11312557 | DOI:10.1101/2024.07.30.605945

bioRxiv [Preprint]. 2024 Aug 7:2024.08.02.606356. doi: 10.1101/2024.08.02.606356.ABSTRACTNature's molecular diversity is not random but displays intricate organization stemming from biological necessity. Molecular networking connects metabolites with structural similarity, enabling molecular discoveries from mass spectrometry data using arbitrary similarity thresholds that can fracture natural metabolite families. We present molecular community networking (MCN), that optimizes connectivity for each metabolite, rescuing lost relationships and capturing otherwise 'hidden' metabolite connections. Using MCN, we demonstrate the discovery of novel dipeptide-conjugated bile acids.PMID:39131284 | PMC:PMC11312580 | DOI:10.1101/2024.08.02.606356

Gastro Hep Adv. 2022 Jul 19;1(6):993-1005. doi: 10.1016/j.gastha.2022.07.008. eCollection 2022.ABSTRACTBACKGROUND AND AIMS: Inflammatory bowel disease (IBD), inclusive of ulcerative colitis and Crohn's disease, are chronic inflammatory conditions that impact women of childbearing age. It has been previously shown that IBD is associated with altered metabolomic profiles, but whether metabolomic changes also affect pregnant patients with IBD is completely unknown.METHODS: This was a prospective cohort study comprised of 48 pregnant women with IBD who were followed throughout preconception and pregnancy. IBD disease activity was measured using biochemical markers C-reactive protein or fecal calprotectin using enzyme-linked immunosorbent assay and clinical disease activity using Harvey-Bradshaw Index or partial Mayo scores. Serum and urine samples were collected from preconception, trimester 1, and trimester 2 and analyzed using nuclear magnetic resonance spectroscopy combined with metabolomics set enrichment analysis.RESULTS: We identified a total of 24 urine metabolites and 17 serum metabolites which were altered by active disease across pregnancy. First trimester (T1) active disease-associated metabolites were enriched in "amino acid metabolism" and "fatty-acid β-oxidation." The leading urine metabolites at T1 were trimethyl-N-oxide (TMAO), succinic acid, and 3-hydroxy-2-methylbutyric acid, and leading serum metabolites were TMAO, glucose, and acetic acid. Multivariate modeling using serum TMAO, glucose, and acetic acid predicts T1 disease activity and correlated with mode of delivery and infant weights at delivery. Moreover, cross-time point modeling using metabolomes predicted future disease flare-up during pregnancy.CONCLUSION: These results suggest select host metabolites may be able to discriminate and predict disease activity and are correlated with pregnancy outcomes at delivery. This warrants further validation of metabolomics to monitor IBD in pregnancy.PMID:39131249 | PMC:PMC11308627 | DOI:10.1016/j.gastha.2022.07.008

J Inflamm Res. 2024 Aug 5;17:5235-5249. doi: 10.2147/JIR.S472812. eCollection 2024.ABSTRACTBACKGROUND: Ulcerative colitis (UC), a highly relapsing non-specific disease, is difficult to cure completely. The investigation aims to determine the protective effect and potential action mechanism of Xuanbi yuyang decoction (XBD) on UC.METHODS: The chemical composition of XBD was determined through non-targeted metabolomics analysis. Subsequently, experimental mice were orally given 3% DSS for 6 days, followed by XBD treatment (0.3 mL, 0.4 mL). In vitro, the human colon epithelial cells were co-treated with DSS and medicated serum. The therapeutic effects of XBD on UC were evaluated in vivo and vitro. The mechanisms of XBD against UC were determined by detecting hallmarks related to pyroptosis and Interleukin (IL)-17 pathways using Western blot and ELISA. The recombinant human interleukin 17A (rhIL17A) and was applied for further verifying the effect of XBD on IL-17 pathway in UC cells.RESULTS: XBD supplementation restored DSS-induced weight loss, colon shortening and tissue damage, and reduced DAI. Moreover, XBD enhanced viability, repaired the intestinal mucosal barrier of colitis, decreased pro-inflammatory cytokines levels, and inhibited pyroptosis. Additionally, DSS increased the expression of IL-17 pathway was and cytokines (IL-17A, IL-6), which were blocked by XBD treatment. The rhIL17A treatment attenuated protective effect against DSS-induced colitis and could also enhance pyroptosis.CONCLUSION: XBD has a favorable protective effect against DSS-induced colitis through restraining pyroptosis via inhibition of IL-17 signaling pathway activation, suggesting XBD may be a new and effective treatment therapy for UC.PMID:39131209 | PMC:PMC11313599 | DOI:10.2147/JIR.S472812

Nat Sci Sleep. 2024 Aug 5;16:1153-1168. doi: 10.2147/NSS.S470154. eCollection 2024.ABSTRACTPURPOSE: There are currently no ideal indicators for predicting the cardiovascular risk of obstructive sleep apnea (OSA). This study aimed to employ urinary metabolomics to detect early cardiovascular risk in patients with moderate-to-severe OSA.PATIENTS AND METHODS: Male participants who underwent polysomnography from November 2020 to May 2021 were screened. Clinical data, polysomnography data and urine samples were collected. Untargeted metabolomics analyses of urine were performed. Multivariate analyses and receiver operating characteristic (ROC) curve analyses were subsequently performed to identify potential biomarkers. Associations between metabolites and clinical indicators and cardiovascular risk were examined through linear regression analyses with interaction and mediation analyses.RESULTS: Thirty-six male participants were included in the study, comprising 22 males with moderate-to-severe OSA and 14 age-matched controls, with an average age of 39.6 ± 9.2 years. We identified 65 metabolites in the study, involving pathways including pyrimidine, androgen, estrogen, vitamin B6 and sulfate/sulfite metabolism. Among them, epinephrine sulfate was the most significantly altered metabolite. ROC analyses highlighted that epinephrine sulfate had the highest area under the curve (AUC=0.883) for detecting moderate-to-severe OSA. Epinephrine sulfate was statistically correlated with OSA severity, hypoxia-related indicators (apnea-hypopnea index: r=0.685; oxygen desaturation index: r=0.743, p<0.0001), arterial stiffness (arterial augmentation index: r=0.361, p=0.031) and long-term cardiovascular risk (Framingham cardiovascular risk: r=0.375, p=0.024). Linear regression analysis revealed that epinephrine sulfate was significantly associated with an increased in the Framingham risk (β = 0.004, 95% CI = 0.000-0.009, p = 0.049), with the effect partly mediated by systolic blood pressure (27.6%) and not moderated by other factors. Additionally, it also significantly associated with the increased in the arterial augmentation index (β = 0.019, 95% CI = 0.000-0.037, p = 0.046), with the effect fully mediated by blood pressure and not moderated by other indices statistically.CONCLUSION: There are significant metabolic pathway alterations in moderate-to-severe OSA patients. Urinary epinephrine sulfate markedly predicts early cardiovascular risk in OSA patients.PMID:39131167 | PMC:PMC11314438 | DOI:10.2147/NSS.S470154

JHEP Rep. 2024 Apr 27;6(8):101103. doi: 10.1016/j.jhepr.2024.101103. eCollection 2024 Aug.ABSTRACTBACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis of the bile ducts. PSC is a complex disease of largely unknown aetiology that is strongly associated with inflammatory bowel disease (IBD). Diagnosis, especially at an early stage, is difficult and to date there is no diagnostic biomarker. The present study aimed to assess the diagnostic potential of volatile organic compounds (VOCs) in exhaled breath to detect (early) PSC in an IBD population.METHODS: Breath samples were obtained from 16 patients with PSC alone, 47 with PSC and IBD, and 53 with IBD alone during outpatient clinic visits. Breath sampling was performed using the ReCIVA breath sampler and subsequently analysed by gas chromatography mass spectrometry. Random forest modelling was performed to find discriminatory VOCs and create a predictive model that was tested using an independent test set.RESULTS: The final model to discriminate patients with PSC, with or without IBD, from patients with IBD alone included twenty VOCs and achieved a sensitivity, specificity, and area under the receiver-operating curve on the test set of 77%, 83%, and 0.84 respectively. Three VOCs (isoprene, 2-octanone and undecane) together correlated significantly with the Amsterdam-Oxford score for PSC disease prognosis. A sensitivity analysis showed stable results across early-stage PSC, including in those with normal alkaline phosphatase levels, as well as further progressed PSC.CONCLUSION: The present study demonstrates that exhaled breath can distinguish PSC cases from IBD and has potential as a non-invasive clinical breath test for (early) PSC.IMPACT AND IMPLICATIONS: Primary sclerosing cholangitis is a complex chronic liver disease, which ultimately results in cirrhosis, liver failure, and death. Detection, especially in early disease stages, can be challenging, and therefore therapy typically starts when there is already some irreversible damage. The current study shows that metabolites in exhaled breath, so called volatile organic compounds, hold promise to non-invasively detect primary sclerosing cholangitis, including at early disease stages.PMID:39131082 | PMC:PMC11315128 | DOI:10.1016/j.jhepr.2024.101103

Food Chem X. 2024 Jul 16;23:101631. doi: 10.1016/j.fochx.2024.101631. eCollection 2024 Oct 30.ABSTRACTCitrus fruits possess a distinctive aroma and flavor, with Citrus aurantium Changshan-huyou (CACH) standing out due to their considerable edible and medicinal value. However, the volatile components (VOCs) in the CACH pericarp (CP) remain underexplored. In this study, gas chromatography-mass spectrometry (GC-MS) was utilized to qualitatively analyze VOCs in 27 CP samples across different growth stages. A total of 544 VOCs were identified, including 91 terpenoids. The types, quantities and distributions of VOCs were conducted. Detailed discussions on the major terpenoids in CP were also presented. A metabolomics approach combining multivariate statistical analysis with univariate analysis was employed for screening the differential metabolites. The study provides comprehensive insights into the VOCs in CP and citrus plants. Moreover, it delivers the first in-depth analysis of differential metabolites in CP throughout the entire CACH growth and development process, laying a foundation for ongoing research and development of the VOCs in CP.PMID:39130723 | PMC:PMC11315122 | DOI:10.1016/j.fochx.2024.101631

Food Sci Biotechnol. 2023 Dec 1;33(9):2169-2178. doi: 10.1007/s10068-023-01479-8. eCollection 2024 Jul.ABSTRACTPlasma metabolites offer insights into aging processes and aging-related biomarkers. Here, the dietary effects of various functional foods on older adult mice were evaluated using metabolomic techniques. Fifty-week-old mice were divided into four groups (n = 4 each) and fed either a normal diet (AC) or the diets from Triticum aestivum sprout (TA), Schisandra chinensis (SZ), or Pisum sativum sprout (PS) extracts. Additionally, a group of 8-week-old mice fed a normal diet (YC; n = 5) was included for the comparison. The PS group had a significantly lower free fatty acid content and higher ornithine, proline, citric acid, and oxalic acid contents than the AC group. The PS group also showed reduced oxidative stress and muscle damage, suggesting the higher anti-aging efficacy of P. sativum sprouts than the other diets. These findings suggest plasma metabolite profiling is an effective tool to assess the anti-aging effects of functional foods.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-023-01479-8.PMID:39130654 | PMC:PMC11315845 | DOI:10.1007/s10068-023-01479-8

Heliyon. 2024 Jul 10;10(14):e34396. doi: 10.1016/j.heliyon.2024.e34396. eCollection 2024 Jul 30.ABSTRACTXijiao Huojiu (Xijiao), an ancient Chinese rice wine (ACRW), is produced using traditional methods, which involve biological-ageing-like process and result in distinctive sensory profiles. However, its aroma composition is still unclear. In this study, the aroma characteristics of three samples with varying ageing times were examined. Xijiao_SCT, with a short cellar time, exhibited a strong fruity and floral aroma and a less grain-like aroma. Conversely, Xijiao_LCT, which had a long cellar time, had a deep cocoa- and caramel-like aroma. A total of 27 key odorants that greatly influenced the aroma characteristics of Xijiao were identified. Comparative studies were used to identify 12 key odorants that distinguish Xijiao from modern Chinese rice wine (MCRW) and grape wines (GW). Additionally, 13 dominant latent ageing markers differentiated Xijiao_SCT from Xijiao_LCT. Our results suggested that ACRW and MCRW have overlapping but distinct volatile metabolomic profiles, highlighting the characteristics of ACRW during ageing process.PMID:39130457 | PMC:PMC11315155 | DOI:10.1016/j.heliyon.2024.e34396

Crit Rev Clin Lab Sci. 2024 Aug 12:1-20. doi: 10.1080/10408363.2024.2387038. Online ahead of print.ABSTRACTThe study of metabolomics is revealing immense potential for diagnosis, therapy monitoring, and understanding of pathogenesis processes. Volatilomics is a subcategory of metabolomics interested in the detection of molecules that are small enough to be released in the gas phase. Volatile compounds produced by cellular processes are released into the blood and lymph, and can reach the external environment through different pathways, such as the blood-air interface in the lung that are detected in breath, or the blood-water interface in the kidney that leads to volatile compounds detected in urine. Besides breath and urine, additional sources of volatile compounds such as saliva, blood, feces, and skin are available. Volatilomics traces its roots back over fifty years to the pioneering investigations in the 1970s. Despite extensive research, the field remains in its infancy, hindered by a lack of standardization despite ample experimental evidence. The proliferation of analytical instrumentations, sample preparations and methods of volatilome sampling still make it difficult to compare results from different studies and to establish a common standard approach to volatilomics. This review aims to provide an overview of volatilomics' diagnostic potential, focusing on two key technical aspects: sampling and analysis. Sampling poses a challenge due to the susceptibility of human samples to contamination and confounding factors from various sources like the environment and lifestyle. The discussion then delves into targeted and untargeted approaches in volatilomics. Some case studies are presented to exemplify the results obtained so far. Finally, the review concludes with a discussion on the necessary steps to fully integrate volatilomics into clinical practice.PMID:39129534 | DOI:10.1080/10408363.2024.2387038

Foodborne Pathog Dis. 2024 Aug 12. doi: 10.1089/fpd.2024.0031. Online ahead of print.ABSTRACTEnterococcus spp. have been shown to have gastrointestinal tract protective functions; our recent results suggest that membrane vesicles (MVs) play an important role in the gastric protection of Enterococcus faecium (E. faecium). The specific function is determined by molecular compositions of MVs. To resolve biocargo components in E. faecium MVs (EfmMVs), MVs were isolated from E. faecium culture. Transcriptomics, label-free quantitative proteomics, and untargeted metabolomics were performed to obtain information about the complexity of ribonucleic acids (RNAs), proteins, and metabolites biocargo they carry, respectively. RNA-sequencing identified a total of 2122 transcripts. The top 20 transcripts accounted for 27.63% of total counts, which, including enzymes, participate in glycolysis, ribosomal proteins, DNA-directed RNA polymerases, protein-synthesizing relative enzymes, molecules associated with protein post-translational processing and transport, and peptidoglycan lyases. Label-free quantitative proteomics analysis identified a total of 711 proteins. The top 20 proteins accounted for 48.02% of all identified proteins, which including ribosomal proteins, enzymes participate in glycolysis, DNA-directed RNA polymerases, protein-synthesizing relative enzymes, peptidoglycan lyases, and autolysin. Untargeted metabolomics analysis identified a total of 519 metabolites. The top 20 metabolites accounted for 79.55% of all identified metabolites, which included amino acids, substrates, or products in the metabolism of amino acids, natural organic acids, products in the metabolism of organic acids, ketone compounds, and two other compounds. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that the identified biocargo components enriched in metabolism, genetic, and environmental information processing. Overall, we hope that the current exploration of multiple "-omics" analyses of this EfmMVs will provide useful information and further groundwork for future studies on E. faecium application.PMID:39129487 | DOI:10.1089/fpd.2024.0031

Commun Biol. 2024 Aug 11;7(1):975. doi: 10.1038/s42003-024-06675-8.ABSTRACTLymphatic vessels are essential for preventing the accumulation of harmful components within peripheral tissues, including the artery wall. Various endogenous mechanisms maintain adequate lymphatic function throughout life, with platelets being essential for preserving lymphatic vessel integrity. However, since lymph lacks platelets, their impact on the lymphatic system has long been viewed as restricted to areas where lymphatics intersect with blood vessels. Nevertheless, platelets can also exert long range effects through the release of extracellular vesicles (EVs) upon activation. We observed that platelet EVs (PEVs) are present in lymph, a compartment to which they could transfer regulatory effects of platelets. Here, we report that PEVs in lymph exhibit a distinct signature enabling them to interact with lymphatic endothelial cells (LECs). In vitro experiments show that the internalization of PEVs by LECs maintains their functional integrity. Treatment with PEVs improves lymphatic contraction capacity in atherosclerosis-prone mice. We suggest that boosting lymphatic pumping with exogenous PEVs offers a novel therapeutic approach for chronic inflammatory diseases characterized by defective lymphatics.PMID:39128945 | DOI:10.1038/s42003-024-06675-8

Eur J Pharmacol. 2024 Aug 9:176885. doi: 10.1016/j.ejphar.2024.176885. Online ahead of print.ABSTRACTThe distinct chemical structure of thiourea derivatives provides them with an advantage in selectively targeting cancer cells. In our previous study, we selected the most potent compounds, 2 and 8, with 3,4-dichloro- and 3-trifluoromethylphenyl substituents, respectively, across colorectal (SW480 and SW620), prostate (PC3), and leukemia (K-562) cancer cell lines, as well as non-tumor HaCaT cells. Our research has demonstrated their anticancer potential by targeting key molecular pathways involved in cancer progression, including caspase 3/7 activation, NF-κB (Nuclear Factor Kappa-light-chain-enhancer of activated B cells) activation decrease, VEGF (Vascular Endothelial Growth Factor) secretion, ROS (Reactive Oxygen Species) production, and metabolite profile alterations. Notably, these processes exhibited no significant alterations in HaCaT cells. The effectiveness of the studied compounds was also tested on spheroids (3D culture). Both derivatives 2 and 8 increased caspase activity, decreased ROS production and NF-κB activation, and suppressed the release of VEGF in cancer cells. Metabolomic analysis revealed intriguing shifts in cancer cell metabolic profiles, particularly in lipids and pyrimidines metabolism. Assessment of cell viability in 3D spheroids showed that SW620 cells exhibited better sensitivity to compound 2 than 8. In summary, structural modifications of the thiourea terminal components, particularly dihalogenophenyl derivative 2 and para-substituted analog 8, demonstrate their potential as anticancer agents while preserving safety for normal cells.PMID:39128803 | DOI:10.1016/j.ejphar.2024.176885

J Ethnopharmacol. 2024 Aug 9:118663. doi: 10.1016/j.jep.2024.118663. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Depression is a prevalent stress disorder, yet the underlying physiological mechanisms linking stress to appetite and weight loss remain elusive. While most antidepressants are associated with excessive weight and appetite gain, sertraline (SER) exhibits a lower risk of these side effects. Metacinnabar (β-HgS), the primary component of Tibetan medicine Zuotai, has been shown to enhance mice's resilience against external stress without causing excessive increases in weight or appetite. However, the precise physiological pathway through which β-HgS restores appetite and weight in stressed mice remains unclear.AIM OF THE STUDY: The objective of this study is to assess the efficacy of β-HgS in ameliorating weight loss and appetite suppression induced by pressure stimulation in mice, as well as elucidate its potential mechanisms of action.METHODS: The present study employed chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS) as experimental models to simulate environmental stress encountered in daily life. Subsequently, a series of experiments were conducted, including behavior tests, HE staining of rectal and hippocampal pathological sections, detection of depression-related biological indicators, analysis of intestinal flora diversity, as well as metabolomics analysis of hippocampal and intestinal contents.RESULT: Dysregulation of glycerophospholipid metabolism may represent the principal pathway underlying reduced appetite, body weight, neurotransmitter and appetite hormone levels, heightened inflammatory response, hippocampal and rectal tissue damage, as well as altered composition of intestinal microbiota in stressed mice. Following intervention with SER and β-HgS in stressed mice, the deleterious effects induced by stress can be ameliorated, in which the medium-dose β-HgS exhibited superior performance.CONCLUSION: The aforementioned research findings suggest that the stress-induced decrease in appetite and body weight in mice may be associated with dysregulation in glycerophospholipid metabolism connecting the gut-brain axis. β-HgS exhibits potential in ameliorating depressive-like symptoms in mice subjected to stress, while concurrently restoring their body weight and appetite without inducing excessive augmentation. Its therapeutic effect may also be attributed to its ability to modulate glycerophospholipid metabolism status and exert influence on the gut-brain axis.PMID:39128797 | DOI:10.1016/j.jep.2024.118663

J Biol Chem. 2024 Aug 9:107662. doi: 10.1016/j.jbc.2024.107662. Online ahead of print.ABSTRACTPropionic acid links the oxidation of branched-chain amino acids and odd-chain fatty acids to the TCA cycle. Gut microbes ferment complex fiber remnants, generating high concentrations of short chain fatty acids, acetate, propionate and butyrate, which are shared with the host as fuel sources. Analysis of vitamin B12-dependent propionate utilization in skin biopsy samples has been used to characterize and diagnose underlying inborn errors of cobalamin (or B12) metabolism. In these cells, the B12-dependent enzyme, methylmalonyl-CoA mutase (MMUT), plays a central role in funneling propionate to the TCA cycle intermediate, succinate. Our understanding of the fate of propionate in other cell types, specifically, the involvement of the β-oxidation-like and methylcitrate pathways, is limited. In this study, we have used [14C]-propionate tracing in combination with genetic ablation or inhibition of MMUT, to reveal the differential utilization of the B12-dependent and independent pathways for propionate metabolism in fibroblast versus colon cell lines. We demonstrate that itaconate can be used as a tool to investigate MMUT-dependent propionate metabolism in cultured cell lines. While MMUT gates the entry of propionate carbons into the TCA cycle in fibroblasts, colon-derived cell lines exhibit a quantitatively significant or exclusive reliance on the β-oxidation-like pathway. Lipidomics and metabolomics analyses reveal that propionate elicits pleiotropic changes, including an increase in odd-chain glycerophospholipids, and perturbations in the purine nucleotide cycle and arginine/nitric oxide metabolism. The metabolic rationale and the regulatory mechanisms underlying the differential reliance on propionate utilization pathways at a cellular, and possibly tissue level, warrant further elucidation.PMID:39128713 | DOI:10.1016/j.jbc.2024.107662

Brain Behav Immun. 2024 Aug 9:S0889-1591(24)00533-6. doi: 10.1016/j.bbi.2024.08.011. Online ahead of print.ABSTRACTRecent research has unveiled conflicting evidence regarding the link between aggression and the gut microbiome. Here, we compared behavior profiles of control, germ-free (GF) and antibiotic-treated mice, as well as re-colonized GF mice to understand the impact of gut microbiome on aggression using the resident-intruder paradigm. Our findings revealed a link between gut microbiome depletion and higher aggression, accompanied by notable changes in urine metabolite profiles and brain gene expression. Our study extends beyond classical murine models to humanized mice to reveal the clinical relevance of early-life antibiotic use on aggression. Fecal microbiome transplant from infants exposed to antibiotics in early life (and sampled one month later) into mice led to increased aggression compared to mice receiving transplants from unexposed infants. This study sheds light on the role of the gut microbiome in modulating aggression and highlights its potential avenues of action, offering insights for development of therapeutic strategies for aggression-related disorders.PMID:39128572 | DOI:10.1016/j.bbi.2024.08.011

Pathol Res Pract. 2024 Jul 30;262:155503. doi: 10.1016/j.prp.2024.155503. Online ahead of print.ABSTRACTGastric cancer (GC), a globally prevalent and lethal malignancy, continues to be a key research focus. However, due to its considerable heterogeneity and complex pathogenesis, the treatment and diagnosis of gastric cancer still face significant challenges. With the rapid development of spatial omics technology, which provides insights into the spatial information within tumor tissues, it has emerged as a significant tool in gastric cancer research. This technology affords new insights into the pathology and molecular biology of gastric cancer for scientists. This review discusses recent advances in spatial omics technology for gastric cancer research, highlighting its applications in the tumor microenvironment (TME), tumor heterogeneity, tumor genesis and development mechanisms, and the identification of potential biomarkers and therapeutic targets. Moreover, this article highlights spatial omics' potential in precision medicine and summarizes existing challenges and future directions. It anticipates spatial omics' continuing impact on gastric cancer research, aiming to improve diagnostic and therapeutic approaches for patients. With this review, we aim to offer a comprehensive overview to scientists and clinicians in gastric cancer research, motivating further exploration and utilization of spatial omics technology. Our goal is to improve patient outcomes, including survival rates and quality of life.PMID:39128411 | DOI:10.1016/j.prp.2024.155503

Food Chem. 2024 Aug 6;460(Pt 3):140771. doi: 10.1016/j.foodchem.2024.140771. Online ahead of print.ABSTRACTHeat stress in summer causes softening disorder in papaya but the molecular mechanism is not clear. In this study, papaya fruit stored at 35 °C showed a softening disorder termed rubbery texture. Analysis of the transcriptome and metabolome identified numerous differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) between the fruit stored at 25 °C and 35 °C. The DEGs and DAMs related to lignin biosynthesis were upregulated, while those related to ethylene biosynthesis, sucrose metabolism, and cell wall degradation were downregulated under heat stress. Co-expression network analysis highlighted the correlation between the DEGs and metabolites associated with lignin biosynthesis, ethylene biosynthesis, and cell wall degradation under heat stress. Finally, the correlation analysis identified the key factors regulating softening disorder under heat stress. The study's findings reveal that heat stress inhibited papaya cell wall degradation and ethylene production, delaying fruit ripening and softening and ultimately resulting in a rubbery texture.PMID:39128369 | DOI:10.1016/j.foodchem.2024.140771

Food Chem. 2024 Aug 8;460(Pt 3):140797. doi: 10.1016/j.foodchem.2024.140797. Online ahead of print.ABSTRACTThe spoilage of refrigerated pork involves nutrient depletion and the production of spoilage metabolites by spoilage bacteria, yet the microbe-metabolite interactions during this process remain unclear. This study employed 16S rRNA high-throughput sequencing and non-targeted metabolomics based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to reveal the core microbiota and metabolite profiles of pork during refrigeration. A total of 45 potential biomarkers were screened through random forest model analysis. Metabolic pathway analysis indicated that eleven pathways, including biogenic amine metabolism, pentose metabolism, purine metabolism, pyrimidine metabolism, phospholipid metabolism, and fatty acid degradation, were potential mechanisms of pork spoilage. Correlation analysis revealed nine metabolites-histamine, tyramine, tryptamine, D-gluconic acid, UDP-d-glucose, xanthine, glutamine, phosphatidylcholine, and hexadecanoic acid-as spoilage biomarkers, with Pseudomonas, Serratia, and Photobacterium playing significant roles. This study provides new insights into the changes in microbial and metabolic characteristics during the spoilage of refrigerated pork.PMID:39128367 | DOI:10.1016/j.foodchem.2024.140797

Biochem Biophys Res Commun. 2024 Aug 6;736:150461. doi: 10.1016/j.bbrc.2024.150461. Online ahead of print.ABSTRACTTo understand why Chlamydia trachomatis (Ct) (L2/434/Bu) favors hypoxia, we examined the dynamics of infected cells using a glycolysis-related PCR array and metabolomic analysis, along with the perturbation of nucleotide synthesis. Our findings revealed that, compared to normoxia, hypoxia with infection significantly and selectively upregulates the expression of genes related to glycolysis, glycogen degradation, and the pentose phosphate pathway. Furthermore, hypoxia induced a significant decrease in metabolite levels, particularly methionine-related metabolites, independent of infection, indicating efficient metabolism under hypoxia. Additionally, the perturbation of nucleotide synthesis with adenosine derivatives impaired Ct growth. Collectively, our results suggest that Ct favors a hypoxic environment with efficient metabolism, in which Ct readily activates glycolysis responsible for stable nucleotide synthesis as well as ATP supply.PMID:39128263 | DOI:10.1016/j.bbrc.2024.150461