PubMed

Environ Sci Technol. 2024 Nov 13. doi: 10.1021/acs.est.4c10434. Online ahead of print.ABSTRACTKnowledge of the biotransformation of tetrabromobisphenol A (TBBPA) and its related contaminants by human gut microbiota (GM) remains unexplored. Here, TBBPA and its four analogs were incubated with mixed GM strains, and nine rhamnosylated or debrominated transformation products (TPs) were discovered. Remarkably, rhamnosylation was identified as a common and unique microbial transformation pathway for these contaminants, and six of the seven rhamnosylated TPs were reported for the first time. Additionally, a kinetic transformation study also showed a rapid and strong bioaccumulation of TBBPA and TPs by Clostridium manihotivorum. Genomic analysis and phylogenetic studies identified C1.1_02053 as the gene encoding the C. manihotivorum working rhamnosyltransferase (CmRT), showing elevated gene expression with higher TBBPA exposure. Molecular docking identified five critical amino acid residues in CmRT that catalyze TBBPA rhamnosylation, and molecular dynamics simulations further confirmed the stability of the CmRT-TBBPA complex. Dynamic metabolomics analysis showed microbial growth-dependent disturbing effects in C. manihotivorum upon TBBPA exposure, and key metabolic pathways related to rhamnosyltransferase showed changes closely related to the transformation process. These findings provide insights into the unique transformation of environmental contaminants by the GM and highlight the disturbing effects of exogenous chemicals on the GM, as well as the potential impacts on overall human health.PMID:39536133 | DOI:10.1021/acs.est.4c10434

Proc Natl Acad Sci U S A. 2024 Nov 19;121(47):e2413837121. doi: 10.1073/pnas.2413837121. Epub 2024 Nov 13.ABSTRACTTyrosine phosphorylation of metabolic enzymes is an evolutionarily conserved posttranslational modification that facilitates rapid and reversible modulation of enzyme activity, localization, or function. Despite the high abundance of tyrosine phosphorylation events detected on metabolic enzymes in high-throughput mass spectrometry-based studies, functional characterization of tyrosine phosphorylation sites has been limited to a subset of enzymes. Since tyrosine phosphorylation is dysregulated across human diseases, including cancer, understanding the consequences of metabolic enzyme tyrosine phosphorylation events is critical for informing disease biology and therapeutic interventions. To globally identify metabolic enzyme tyrosine phosphorylation events and simultaneously assign functional significance to these sites, we performed parallel phosphoproteomics and polar metabolomics in nontumorigenic mammary epithelial cells (MCF10A) stimulated with epidermal growth factor (EGF) in the absence or presence of the EGF receptor inhibitor erlotinib. We performed an integrated analysis of the phosphoproteomic and metabolomic datasets to identify tyrosine phosphorylation sites on metabolic enzymes with functional consequences. We identified two previously characterized (pyruvate kinase muscle isozyme, phosphoglycerate mutase 1) and two uncharacterized (glutathione S-transferase Pi 1, glutamate dehydrogenase 1) tyrosine phosphorylation sites on metabolic enzymes with purported functions based on metabolomic analyses. We validated these hits using a doxycycline-inducible CRISPR interference system in MCF10A cells, in which target metabolic enzymes were depleted with simultaneous reexpression of wild-type, phosphomutant, or phosphomimetic isoforms. Together, these data provide a framework for identification, prioritization, and characterization of tyrosine phosphorylation sites on metabolic enzymes with functional significance.PMID:39536083 | DOI:10.1073/pnas.2413837121

PLoS One. 2024 Nov 13;19(11):e0312416. doi: 10.1371/journal.pone.0312416. eCollection 2024.ABSTRACTThe petroleum hydrocarbons in seawater have been worldwide concern contaminants. Biological method, with the advantages of low cost, minimal environmental impact, and no secondary pollution, is a promising method for petroleum hydrocarbon treatment. In this study, two strains, identified as Stenotrophomonas acidaminiphila and Ochrobactrum, were demonstrated to possess the ability to degrade petroleum hydrocarbons. The mixed culture composed of Stenotrophomonas acidaminiphila and Ochrobactrum at a 2:1 ratio was able to achieve 79.41% degradation of the total petroleum hydrocarbons after 5 days. Besides, the average removal efficiencies of C10-C30 components in petroleum hydrocarbons by Stenotrophomonas acidaminiphila, Ochrobactrum, and mixed culture were 62.98%, 59.14% and 73.30%, respectively. The possible degradation pathways of petroleum hydrocarbons had been speculated through gas chromatography-mass spectrometry (GC-MS) and differential gene expression metabolomics analyses. The toxicity of products from the biodegradation of petroleum hydrocarbons was greatly reduced.PMID:39535996 | DOI:10.1371/journal.pone.0312416

Gut Microbes. 2024 Jan-Dec;16(1):2424913. doi: 10.1080/19490976.2024.2424913. Epub 2024 Nov 13.ABSTRACTThe gut microbiota has been implicated in onset and progression of ulcerative colitis (UC). Here, we assess potential causal involvement of the microbiota and -associated fecal water (FW) metabolome in altering key functional parameters of the colonic epithelium. Fecal samples were collected from N = 51 healthy controls (HC), N = 36 patients with active UC (UC-A), and N = 41 subjects in remission N = 41 (UC-R). Using in vitro incubation experiments, the FW metabolome's impact on butyrate oxidation rates/gene expression and cell death (cytotoxicity) of HT-29 cells, cytokine production by PBMC, and barrier integrity of Caco2 monolayers was evaluated. The FW metabolome from patients and individuals hosting the Bacteroides 2 (Bact2) enterotype (69% of UC-A, 31% of UC-R, 3% of HC), characterized by lower levels of median- and short-chain fatty acids and furan compounds, left butyrate oxidation rates unaltered but affected associated gene expression profiles. UC patients/Bact2-carriers' FW lowered PBMC IL-8 production and increased IL-1β production. Patients' FW increased cytotoxicity, associated with sulfide compound levels. Bact2 carriers' FW, displaying higher levels of bile acids, lowered barrier function upon incubation of monolayers. The FW metabolome of patients and individuals hosting a dysbiotic microbiota could contribute to the disruption of functional processes of the colonic epithelium as observed in UC.PMID:39535140 | DOI:10.1080/19490976.2024.2424913

Int J Tryptophan Res. 2024 Nov 11;17:11786469241284423. doi: 10.1177/11786469241284423. eCollection 2024.ABSTRACTBACKGROUND: The kynurenine pathway (KP) is an important hub in neuroimmune crosstalk that is dysregulated in persons with multiple sclerosis (pwMS) and modulated by exercise in a modality-specific manner.OBJECTIVES: To compare changes in the KP metabolite profile of pwMS (1) following combined treatments including either high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) during a 3-week multimodal rehabilitation, (2) to evaluate exercise response in relation to baseline systemic inflammation, and (3) to investigate associations of kynurenines with physical capacity and clinical outcomes.METHODS: For this secondary analysis of a randomized controlled trial, serum concentrations of kynurenines at baseline and after 3 weeks were determined using targeted metabolomics (LC-MS/MS). Exercise-induced changes in the KP metabolite profile according to treatment and baseline systemic inflammation (neutrophil-to-lymphocyte ratio (NLR) <3.12 versus ⩾3.12) were investigated using covariance analyses.RESULTS: Regardless of treatment, concentrations of tryptophan and most kynurenines decreased over time. Quinolinic acid concentration increased (p < .001). Participants with low and high NLR revealed differential exercise-induced changes in concentrations of kynurenines and NLR. The systemic inflammation markers neopterin (p = .015) and NLR (p < .001) decreased in the whole group and in participants with high NLR, respectively.CONCLUSIONS: Combined treatments including HIIT or MICT do not differentially modulate the KP metabolite profile, with both reducing concentrations of most kynurenines. Baseline systemic inflammation may impact exercise-induced changes in the KP metabolite profile and anti-inflammatory effects of exercise in pwMS.TRIAL REGISTRATION: clinicaltrials.gov (identifier: NCT04356248).PMID:39534856 | PMC:PMC11555752 | DOI:10.1177/11786469241284423

MedComm (2020). 2024 Nov 11;5(11):e792. doi: 10.1002/mco2.792. eCollection 2024 Nov.ABSTRACTIdentification of therapeutic targets can directly elucidate the mechanism and effect of drug therapy, which is a central step in drug development. The disconnect between protein targets and phenotypes under complex mechanisms hampers comprehensive target understanding. Metabolomics, as a systems biology tool that captures phenotypic changes induced by exogenous compounds, has emerged as a valuable approach for target identification. A comprehensive overview was provided in this review to illustrate the principles and advantages of metabolomics, delving into the application of metabolomics in target identification. This review outlines various metabolomics-based methods, such as dose-response metabolomics, stable isotope-resolved metabolomics, and multiomics, which identify key enzymes and metabolic pathways affected by exogenous substances through dose-dependent metabolite-drug interactions. Emerging techniques, including single-cell metabolomics, artificial intelligence, and mass spectrometry imaging, are also explored for their potential to enhance target discovery. The review emphasizes metabolomics' critical role in advancing our understanding of disease mechanisms and accelerating targeted drug development, while acknowledging current challenges in the field.PMID:39534557 | PMC:PMC11555024 | DOI:10.1002/mco2.792

Front Cardiovasc Med. 2024 Oct 29;11:1433643. doi: 10.3389/fcvm.2024.1433643. eCollection 2024.ABSTRACTINTRODUCTION: Aspirin and indobufen are commonly used therapeutic drugs for the prevention of vascular restenosis (VR) after percutaneous transluminal angioplasty surgery. They both exhibited antiplatelet effects but molecular mechanisms underlying metabolic changes induced by them remain unclear.METHODS: In this study, we collected plasma samples from patients on aspirin medication (n = 5), patients on indobufen medication, patients with no medication after PTA, and healthy controls (CKs) (n = 5). Our investigation aimed to reveal the metabolic processes in patients during vascular restenosis and its amelioration through drug therapy using liquid chromatography-tandem mass spectrometry (LC-MS/MS).RESULTS: Our data showed significant alterations in amino acid and choline metabolism in patients without medication after PTA. Aspirin and indobufen were able to regulate these metabolic pathways to alleviate VR symptoms. We identified several characteristic amino acids, including pro-leu, L-citrulline, his-glu, and L-glutamate, as important biomarkers for VR assessment in patients without medication after PTA. A total of 17 and 4 metabolites involved in arginine and phenylalanine metabolism were specifically induced by aspirin and indobufen, respectively. Their expression levels were significantly regulated by aspirin or indobufen, nearly reaching normal levels.DISCUSSION: Taken together, our identification of metabolites involved in metabolic changes affected by aspirin and indobufen medication enhances the understanding of VR pathology after PTA. This may help identify early diagnostic biomarkers and therapeutic targets.PMID:39534497 | PMC:PMC11554490 | DOI:10.3389/fcvm.2024.1433643

Hortic Res. 2024 Aug 30;11(11):uhae243. doi: 10.1093/hr/uhae243. eCollection 2024 Nov.ABSTRACTRose (Rosa rugosa) petals are rich in diverse secondary metabolites, which have important physiological functions as well as great economic values. Currently, it remains unclear how saline and/or alkaline stress(es) influence the accumulation of secondary metabolites in rose. In this study, we analyzed the transcriptome and metabolite profiles of rose petals under aline-alkali stress and uncovered the induction mechanism underlying major metabolites. Dramatic changes were observed in the expression of 1363 genes and the abundances of 196 metabolites in petals in response to saline-alkali stress. These differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) are mainly associated with flavonoid and terpenoid metabolism and the reconstruction of cell walls. Of them, TERPENE SYNTHASE 31 (TPS31) overexpression in tobacco leaves driven by its own promoter resulted in significant alterations in the levels of diverse terpenoids, which were differentially influenced by saline-alkali stress. An integrated analysis of metabolomic and transcriptomic data revealed a high correlation between the abundances of flavonoids/terpenoids and the expression of the transcription factor MYB5. MYB5 may orchestrate the biosynthesis of sesquiterpenoids and proanthocyanidins through direct regulation of TPS31 and ANR expression under aline-alkali stress. Our finding facilitates improving the bioactive substance accumulation of rose petals by metabolic engineering.PMID:39534410 | PMC:PMC11554761 | DOI:10.1093/hr/uhae243

Front Endocrinol (Lausanne). 2024 Oct 29;15:1438405. doi: 10.3389/fendo.2024.1438405. eCollection 2024.ABSTRACTOBJECTIVE: This study integrates network pharmacology and metabolomics techniques to explore the potential regulatory mechanisms of Res on gouty arthritis (GA).METHODS: Network pharmacology was used to predict the mechanism of Res in regulating GA, and methods such as HE staining, ELISA, immunohistochemistry, Real-time PCR, Western blot, and molecular docking were used to verify the role of NF-κB, MAPK, and JAK/STAT inflammatory signaling pathways in the MSU-induced GA rat model. In addition, non-targeted metabolomics techniques were combined to further investigate the mechanism of Res in treating GA.RESULTS: The results of network pharmacology showed that Res may exert its therapeutic effects through the NF-κB signaling pathway. Animal experiments demonstrated that in the MSU-induced GA rat model, pathological damage, serum biochemical indicators, and levels of inflammatory factors were significantly increased, and the NF-κB signaling pathway was activated. The intervention of Res significantly reduced pathological damage, serum biochemical indicators, levels of inflammatory factors, and the activation of NF-κB, MAPK, and JAK/STAT signaling pathways in the model rats. Metabolomics results showed that Res could improve the metabolic trajectory deviations in serum and joint fluid of GA model rats. Through related metabolic pathway analysis, the most affected metabolic pathways were found to be Sphingolipid metabolism, Glycerophospholipid metabolism, Phenylalanine, tyrosine and tryptophan biosynthesis, Pantothenate and CoA, Citrate cycle (TCA cycle), and Arachidonic acid metabolism.CONCLUSION: Resveratrol can regulate the biosynthetic pathways of arachidonic acid, phenylalanine, tyrosine, and tryptophan, pantothenic acid and CoA biosynthesis pathways, TCA cycle, and other metabolic pathways, thereby regulating the NF-κB, MAPK, and JAK/STAT3 signaling pathways, and inhibiting the acute inflammatory response during GA attacks, showing characteristics of multi-pathway and multi-target action.PMID:39534253 | PMC:PMC11555470 | DOI:10.3389/fendo.2024.1438405

Psychiatry Clin Neurosci. 2024 Nov 12. doi: 10.1111/pcn.13761. Online ahead of print.ABSTRACTAIM: Methamphetamine use disorders (MUDs) cause widespread disruptions in metabolomic and immunologic processes, highlighting the need for new therapeutic approaches. The purpose of this study was to find molecular and neuroimaging biomarkers for methamphetamine addiction.METHODS: In this study, we recruited 231 patients with MUD at varying stages of withdrawal and 40 healthy controls to quantify the blood levels of 52 molecules using enzyme-linked immunosorbent assay.RESULTS: The overall molecular disruption caused by methamphetamine was inversely related to withdrawal time (P = 0.0008), with partial recovery observed after 1 year of follow-up (P = 2.20 × 10-5). Molecules related to stress, immune activation, oxidative products, and cardiac injury were significantly elevated in all MUD groups, while antioxidation enzymes were downregulated. Additionally, the blood level of brain-derived neurotrophic factor was significantly correlated with gray matter volumes in nine brain regions (fusiform gyrus, orbitofrontal cortex, temporal pole, caudate, cerebellum crus, and vermis, adjusted P < 0.05) among patients with MUD.CONCLUSION: These findings suggest that patients with MUD exhibit elevated levels of immune response, stress, and oxidative stress, which are associated with brain structural abnormalities.PMID:39533760 | DOI:10.1111/pcn.13761

EMBO J. 2024 Nov 12. doi: 10.1038/s44318-024-00301-3. Online ahead of print.ABSTRACTUbiquitin-conjugating enzymes (E2) play a crucial role in the attachment of ubiquitin to proteins. Together with ubiquitin ligases (E3), they catalyze the transfer of ubiquitin (Ub) onto lysines with high chemoselectivity. A subfamily of E2s, including yeast Ubc6 and human Ube2J2, also mediates noncanonical modification of serines, but the structural determinants for this chemical versatility remain unknown. Using a combination of X-ray crystallography, molecular dynamics (MD) simulations, and reconstitution approaches, we have uncovered a two-layered mechanism that underlies this unique reactivity. A rearrangement of the Ubc6/Ube2J2 active site enhances the reactivity of the E2-Ub thioester, facilitating attack by weaker nucleophiles. Moreover, a conserved histidine in Ubc6/Ube2J2 activates a substrate serine by general base catalysis. Binding of RING-type E3 ligases further increases the serine selectivity inherent to Ubc6/Ube2J2, via an allosteric mechanism that requires specific positioning of the ubiquitin tail at the E2 active site. Our results elucidate how subtle structural modifications to the highly conserved E2 fold yield distinct enzymatic activity.PMID:39533056 | DOI:10.1038/s44318-024-00301-3

Sci Rep. 2024 Nov 12;14(1):27729. doi: 10.1038/s41598-024-78727-2.ABSTRACTAnastrepha ludens (Mexican fruit-fly) is a highly polyphagous fruit fly species (Tephritidae) attacking wild and commercial fruit from Mexico to Panama. Here we report on a recent habitat and host range expansion as A. ludens lately started to attack apples (Malus domestica) in Mexico, a phenomenon likely influenced by global warming. We document natural infestations in apple-growing regions in the States of Nuevo León and Hidalgo, Mexico where A. ludens has started to attack the cultivars 'Golden Delicious', 'Rayada' and 'Criolla'. No infestations were found in the apple-growing region of Zacatlán, Puebla. To determine apple cultivar susceptibility to the attack of this emerging pest, we ran forced infestation assays in enclosed fruit-bearing branches in all three apple-growing regions and studied the metabolome of all fruit. A clear pattern emerged indicating that the cultivar 'Golden Delicious' was the most susceptible, with 'Criolla' exhibiting complete resistance in one location (Puebla). Although A. ludens can develop in this new host, development rates (egg-adult) and adult emergence were affected when compared with the performance in the natural host 'Marsh' grapefruit. Warmer temperatures and specific secondary metabolites of some apple cultivars are likely contributing to the territorial and host expansion of A. ludens.PMID:39533054 | DOI:10.1038/s41598-024-78727-2

Commun Biol. 2024 Nov 12;7(1):1496. doi: 10.1038/s42003-024-07145-x.ABSTRACTPolymicrobial co- and superinfections involving bacterial and fungal pathogens pose serious challenges for diagnosis and therapy, and are associated with elevated morbidity and mortality. However, the metabolic dynamics of bacterial-fungal interactions (BFI) and the resulting impact on disease outcome remain largely unknown. The fungus Aspergillus fumigatus and the bacterium Klebsiella pneumoniae are clinically important pathogens sharing common niches in the human body, especially in the lower respiratory tract. We have exploited an integrated multi-omics approach to unravel the complex and multifaceted processes implicated in the interspecies communication involving these pathogens in mixed biofilms. In this setting, A. fumigatus responds to the bacterial challenge by rewiring its metabolism, attenuating the translational machineries, and by connecting secondary with primary metabolism, while K. pneumoniae maintains its central metabolism and translation activity. The flexibility in the metabolism of A. fumigatus and the ability to quickly adapt to the changing microenvironment mediated by the bacteria highlight new possibilities for studying the impact of cross-communication between competing interaction partners. The data underscore the complexity governing the dynamics underlying BFI, such as pronounced metabolic changes mounted in A. fumigatus interacting with K. pneumoniae. Our findings identify candidate biomarkers potentially exploitable for improved clinical management of BFI.PMID:39533021 | DOI:10.1038/s42003-024-07145-x

Sci Rep. 2024 Nov 12;14(1):27637. doi: 10.1038/s41598-024-78992-1.ABSTRACTPatients with COVID-19 under invasive mechanical ventilation are at higher risk of developing ventilator-associated pneumonia (VAP), associated with increased healthcare costs, and unfavorable prognosis. The underlying mechanisms of this phenomenon have not been thoroughly dissected. Therefore, this study attempted to bridge this gap by performing a lung microbiota analysis and evaluating the host immune responses that could drive the development of VAP. In this prospective cohort study, mechanically ventilated patients with confirmed SARS-CoV-2 infection were enrolled. Nasal swabs (NS), endotracheal aspirates (ETA), and blood samples were collected initially within 12 h of intubation and again at 72 h post-intubation. Plasma samples underwent cytokine and metabolomic analyses, while NS and ETA samples were sequenced for lung microbiome examination. The cohort was categorized based on the development of VAP. Data analysis was conducted using RStudio version 4.3.1. In a study of 36 COVID-19 patients on mechanical ventilation, significant differences were found in the nasal and pulmonary microbiome, notably in Staphylococcus and Enterobacteriaceae, linked to VAP. Patients with VAP showed a higher SARS-CoV-2 viral load in respiratory samples, elevated neutralizing antibodies, and reduced inflammatory cytokines, including IFN-δ, IL-1β, IL-12p70, IL-18, IL-6, TNF-α, and CCL4. Metabolomic analysis revealed changes in 22 metabolites in non-VAP patients and 27 in VAP patients, highlighting D-Maltose-Lactose, Histidinyl-Glycine, and various phosphatidylcholines, indicating a metabolic predisposition to VAP. This study reveals a critical link between respiratory microbiome alterations and ventilator-associated pneumonia in COVID-19 patients with higher SARS-CoV-2 viral loads in respiratory samples, elevated neutralizing antibodies, and reduced inflammatory cytokines, including IFN-δ, IL-1β, IL-12p70, IL-18, IL-6, TNF-α, and CCL4. These findings provide novel insights into the underlying mechanisms of VAP, with potential implications for management and prevention.PMID:39532981 | DOI:10.1038/s41598-024-78992-1

Sci Rep. 2024 Nov 12;14(1):27712. doi: 10.1038/s41598-024-78447-7.ABSTRACTIn recent years, nutrition has become increasingly important in treating and managing gestational diabetes mellitus. The Health Belief Model (HBM) is a conceptual framework in health behavior research used in some medical research. The present study aimed to evaluate the effect of glycemic index training based on the HBM on metabolic indicators and pregnant women's health-related quality of life. In this open-label, parallel-controlled randomized trial, 90 pregnant women from primary health centers in Iran were recruited and randomly assigned to either the intervention group or the control group, using a block randomization method with a block size of six. The intervention group underwent 12 weeks of nutritional education on the glycemic index and load of foodstuff. The control group only received routine health care. Valid and reliable questionnaires included demographic and prenatal information, physical activity, three days of food records, quality of life (SF-12), and HBM constructs. Fasting blood samples were taken at baseline and end of the study, to assess fasting blood glucose (FBS), fasting insulin, hs-CRP, and lipids. Eighty-four pregnant women with an age mean of 30.12 ± 4.35 completed 12 weeks of intervention. At baseline, there were no significant differences between groups in the HBM subscales (P > 0.05). However, within the intervention group, there was an increase in perceived susceptibilities (mean change 1.45 ± 4.21; P = 0.03) and cue to action (mean change: 1.22 ± 3.38; P = 0.02). In the adjusted model, the General Health subscale of Quality of Life showed a significant increase in the comparison between groups (mean change 13.69 ± 29.83 vs. 0.00 ± 29.58; P = 0.04). Additionally, the adjusted model revealed a notable difference between the groups in serum hs-CRP level, (mean change -0.877 ± 3.47 vs. -0.067 ± 3.40; P = 0.01) and triglyceride level (mean change - 55.24 ± 111.21 vs. 40.92 ± 142.01; P = 0.001). However, in the adjusted model, the total cholesterol levels increased between groups (mean change 22.75 ± 66.17 vs. 30.12 ± 61.33; P = 0.01) at the end of the study. There was no significant difference in glycemic indices (P > 0.05). Participation in a nutrition education program might positively impact nutritional beliefs, behaviors, and some biochemical indicators among pregnant women. Future studies with larger sample sizes and longer follow-ups are warranted.Trial registration number: IRCTID: IRCT20190227042858N1. Registration date: 2019-07-18.PMID:39532953 | DOI:10.1038/s41598-024-78447-7

Sci Rep. 2024 Nov 12;14(1):27681. doi: 10.1038/s41598-024-78965-4.ABSTRACTWe investigated the long-term effects of prenatal nutrition on pre-slaughter Nelore bulls using integrative transcriptome and metabolome analyses of liver tissue. Three prenatal nutritional treatments were administered to 126 cows: NP (control, mineral supplementation only), PP (protein-energy supplementation in the third trimester), and FP (protein-energy supplementation throughout pregnancy). Liver samples from 22.5 ± 1-month-old bulls underwent RNA-Seq and targeted metabolomics. Weighted correlation network analysis (WGCNA) identified treatment-associated gene and metabolite co-expression modules, further analyzed using MetaboAnalyst 6.0 (metabolite over-representation analysis and transcriptome-metabolome integrative analysis) and Enrichr (gene over-representation analysis). We identified several significant gene and metabolite modules, as well as hub components associated with energy, protein and oxidative metabolism, regulatory mechanisms, epigenetics, and immune function. The NP transcriptome-metabolome analysis identified key pathways (aminoacyl t-RNA biosynthesis, gluconeogenesis, and PPAR signaling) and hub components (glutamic acid, SLC6A14). PP highlighted pathways (arginine and proline metabolism, TGF-beta signaling, glyoxylate and dicarboxylate metabolism) with arginine and ODC1 as hub components. This study highlights the significant impact of prenatal nutrition on the liver tissue of Nelore bulls, shedding light on critical metabolic pathways and hub components related to energy and protein metabolism, as well as immune system and epigenetics.PMID:39532951 | DOI:10.1038/s41598-024-78965-4

Sci Rep. 2024 Nov 12;14(1):27684. doi: 10.1038/s41598-024-75734-1.ABSTRACTEthyl pyruvate (EP) has emerged as a promising compound with potential therapeutic benefits attributed to its anti-inflammatory and antioxidant properties. This study aimed to understand the effects of EP on plasma metabolites and immune cells in horses, utilizing advanced liquid chromatography-mass spectrometry (LC-MS)-based metabolomics, quantitative polymerase chain reaction (qPCR), and blood chemistry analyses. Our comprehensive analysis detected 2,366 ions, and 126 metabolites were accurately identified. Remarkably, EP administration induced significant changes in 28 metabolites at 1 h and 11 metabolites at 8 h, highlighting its time-dependent impact on metabolic pathways such as phenylalanine and arginine biosynthesis. Moreover, EP significantly lowered the expression of inflammatory markers interleukin (IL)-6 and heme oxygenase (HO)-1, indicating its potential as an anti-inflammatory agent. Blood chemistry analysis revealed notable reductions in glucose and triglyceride levels. These findings demonstrate that EP is a substance with potential effects on pathways associated with inflammation, oxidative stress, and metabolic processes.PMID:39532936 | DOI:10.1038/s41598-024-75734-1

Biochem Genet. 2024 Nov 12. doi: 10.1007/s10528-024-10954-8. Online ahead of print.ABSTRACTChickpea is a major source of proteins and is considered the most economically vital food legume. Chickpea production is threatened by several abiotic and biotic factors worldwide. The main constraints limiting worldwide chickpea production are abiotic conditions such as drought, heat, salinity, and cold. It is clear that chickpea is treasured for its nutritive value, in particular its high protein content, and hence study of problems like drought, cold and salinity stresses are very important concerning chickpeas. In this regard, several physiological, biochemical, and molecular mechanisms are reviewed to confer tolerance to abiotic stress. The most crippling economic losses in agriculture occur due to these abiotic stressors, which affect plants in many ways. All these abiotic stresses affect the water relations of the plant, both at the cellular level as well as the whole-plant level, causing both specific and non-specific reactions, damage and adaptation reactions. These stresses share common features. Breeding programs use a huge collection of over 100,000 chickpea accessions as their foundation. Significant advancements in conventional breeding, including mutagenesis, gene/allele introgression, and germplasm introduction, have been made through this method. Abiotic tolerance and yield component selection are made easier by creating unique DNA markers for the genus Cicer, which has been made possible by developments in high-throughput sequencing and molecular biology. Transcriptomics, proteomics, and metabolomics have also made it possible to identify particular genes, proteins, and metabolites linked to chickpea tolerance to abiotic stress. Chickpea abiotic stress tolerance has been directly and potentially improved by biotechnological applications, which are covered by all 'Omics' approaches. It requires information on the abiotic stress response at the different molecular levels, which comprises gene expression analysis for metabolites or proteins and its impact on phenotype. Studies on chickpea genome-wide expression profiling have been conducted to determine important candidate genes and their regulatory networks for abiotic stress response. This study aimed to offer a detailed overview of the diverse 'Omics' approaches for resilience's to abiotic stresses on chickpea plants.PMID:39532827 | DOI:10.1007/s10528-024-10954-8

Int Microbiol. 2024 Nov 13. doi: 10.1007/s10123-024-00613-8. Online ahead of print.ABSTRACTSocial separation, or the absence of social support, can cause physical and psychological health issues. Social separation is crucial for the welfare of the Yangtze finless porpoise (YFP) in captivity because they face many challenges like frequent social separation, noise from visitors, and animal replacement, which can cause psychological and physiological stress. This research is aimed at assessing the potential negative impacts of social separation on the gut microbiome and metabolome of captive YFP, focusing on the potential imbalances caused by mother-calf separation. The study found that social separation did not alter the alpha and beta diversity of the gut microbes but increased the abundance of disease-associated taxa such as Romboutsia, Terrisporobacter, and Clostridium_sensu_stricto_13 in the MC (mother-calf) group while increasing Paeniclostridium and Clostridium_sensu_stricto_1 associated with host health in the MS (mother-separated) group. The fecal metabolome underwent significant changes during social separation, with stress-associated metabolites like kainic acid, phenethylamine glucuronide, and paxilline upregulated in the MC group and host health-associated metabolites like butyric acid, 6-hydroxyhexanoic acid, and fosinopril downregulated in the MS group. In addition, there was a strong association between the fecal microbiome and the metabolome of captive YFPs. The study enhances our comprehension of the detrimental effects of social separation, which result in disruptions in the gut microbiome and fecal metabolome. The study is aimed at introducing a new method for assessing the health and welfare of endangered mammals in captivity.PMID:39532805 | DOI:10.1007/s10123-024-00613-8

Alcohol Clin Exp Res (Hoboken). 2024 Nov 12. doi: 10.1111/acer.15476. Online ahead of print.ABSTRACTThis critical review summarizes the current state of omics-based biomarkers in the alcohol research field. We first provide definitions and background information on alcohol and alcohol use disorder (AUD), biomarkers, and "omic" technologies. We next summarize using (1) genetic information as risk/prognostic biomarkers for the onset of alcohol-related problems and the progression from regular drinking to problematic drinking (including AUD), (2) epigenetic information as diagnostic biomarkers for AUD and risk biomarkers for alcohol consumption, (3) transcriptomic information as diagnostic biomarkers for AUD, risk biomarkers for alcohol consumption, and (4) metabolomic information as diagnostic biomarkers for AUD, risk biomarkers for alcohol consumption, and predictive biomarkers for response to acamprosate in subjects with AUD. In the final section, the clinical implications of the findings are discussed, and recommendations are made for future research.PMID:39532676 | DOI:10.1111/acer.15476