PubMed

Discov Oncol. 2024 Dec 18;15(1):779. doi: 10.1007/s12672-024-01662-1.ABSTRACTThe progressive globalization of sedentary lifestyles and diets rich in lipids and processed foods has caused two major public health hazards-diabetes and obesity. The strong interlink between obesity and type 2 diabetes mellitus and their combined burden encompass them into a single term 'Diabesity'. They have also been tagged as the drivers for the onset of cancer. The clinical association between diabetes, obesity, and several types of human cancer demands an assessment of vital junctions correlating the three. This review focuses on revisiting the molecular axis linking diabetes and obesity to cancer through pathways that get imbalanced owing to metabolic upheaval. We also attempt to describe the functional disruptions of DNA repair mechanisms due to overwhelming oxidative DNA damage caused by diabesity. Genomic instability, a known cancer hallmark results when DNA repair does not work optimally, and as will be inferred from this review the obtruded metabolic homeostasis in diabetes and obesity creates a favorable microenvironment supporting metabolic reprogramming and enabling malignancies. Altered molecular and hormonal landscapes in these two morbidities provide a novel connection between metabolomics and oncogenesis. Understanding various aspects of the tumorigenic process in diabesity-induced cancers might help in the discovery of new biomarkers and prompt targeted therapeutic interventions.PMID:39692821 | DOI:10.1007/s12672-024-01662-1

Aging Cell. 2024 Dec 18:e14442. doi: 10.1111/acel.14442. Online ahead of print.ABSTRACTCalorie restriction (CR) and physical exercise (EX) are well-established interventions known to extend health span and lifespan in animal models. However, their impact on human biological aging remains unclear. With recent advances in omics technologies and biological age (BioAge) metrics, it is now possible to assess the impact of these lifestyle interventions without the need for long-term follow-up. This study compared BioAge biomarkers in 41 middle-aged and older adult long-term CR practitioners, 41 age- and sex-matched endurance athletes (EX), and 35 sedentary controls consuming Western diets (WD), through PhenoAge: a composite score derived from nine blood-biomarkers. Additionally, a subset of participants (12 CR, 11 EX, and 12 WD) underwent multi-omic profiling, including DNA methylation and RNAseq of colon mucosa, blood metabolomics, and stool metagenomics. A group of six young WD subjects (yWD) served as a reference for BioAge calculation using Mahalanobis distance across six omic layers. The results demonstrated consistently lower BioAge biomarkers in both CR and EX groups compared to WD controls across all layers. CR participants exhibited lower BioAge in gut microbiome and blood-derived omics, while EX participants had lower BioAge in colon mucosa-derived epigenetic and transcriptomic markers, suggesting potential tissue-specific effects. Multi-omic pathway enrichment analyses suggested both shared and intervention-specific mechanisms, including oxidative stress and basal transcription as common pathways, with ether lipid metabolism uniquely enriched in CR. Despite limitations due to sample size, these findings contribute to the broader understanding of the potential anti-aging effects of CR and EX, offering promising directions for further research.PMID:39692728 | DOI:10.1111/acel.14442

Microb Biotechnol. 2024 Dec;17(12):e70058. doi: 10.1111/1751-7915.70058.ABSTRACTActinomycetota are unrivalled producers of bioactive natural products, with strains living in association with macroalgae representing a prolific-yet largely unexplored-source of specialised chemicals. In this work, we have investigated the bioactive potential of Actinomycetota from macroalgae through culture-dependent and -independent approaches. A bioprospecting pipeline was applied to a collection of 380 actinobacterial strains, recovered from two macroalgae species collected in the Portuguese northern shore-Codium tomentosum and Chondrus crispus-in order to explore their ability to produce antibacterial, antifungal, anticancer and lipid-reducing compounds. Around 43% of the crude extracts showed activity in at least one of the screenings performed: 111 presented antimicrobial activity at 1 mg/mL, 83 significantly decreased cancer cells viability at 15 μg/mL and 5 reduced lipid content in zebrafish > 60% at 15 ug/mL. Dereplication of active extracts unveiled the presence of compounds that could explain most of the recorded results, but also unknown molecules in the metabolome of several strains, highlighting the opportunity for discovery. The bioactive potential of the actinobacterial community from the same macroalgae specimens, which served as the source for the aforementioned Actinomycetota collection, was also explored through metagenomics analysis, allowing to obtain a broader picture of its functional diversity and novelty. A total of 133 biosynthetic gene clusters recovered from metagenomic contigs and metagenome assembled genomes (MAGs). These were grouped into 91 gene cluster families, 83 of which shared less than 30% of similarity to database entries. Our findings provided by culture-dependent and -independent approaches underscore the potential held by actinomycetes from macroalgae as reservoirs for novel bioactive natural products.PMID:39692706 | DOI:10.1111/1751-7915.70058

mSystems. 2024 Dec 18:e0124424. doi: 10.1128/msystems.01244-24. Online ahead of print.ABSTRACTMetabolic state-reprogramming approach was extended from Gram-negative bacteria to Gram-positive bacterium methicillin-resistant Staphylococcus aureus (MRSA) for identifying desired reprogramming metabolites to synergize existing antibiotic killing to MRSA. Metabolomics comparison between MRSA and methicillin-sensitive Staphylococcus aureus showed a depressed metabolic state in MRSA. Valine was identified as the most depressed metabolite/biomarker, and valine, leucine and isoleucine biosynthesis as the most enriched metabolic pathway. Thus, valine was used as a reprogramming metabolite to potentiate existing antibiotic killing to MRSA. Among the tested antibiotics, valine synergized cefoperazone-sulbactam (SCF) to produce the greatest killing effect. The combined effect of SCF and valine was demonstrated in clinical MRSA isolates and in mouse systemic and thigh infection models. Underlying mechanisms were attributed to valine-induced the activation of the pyruvate cycle/the TCA cycle and fatty acid biosynthesis. The activated pyruvate cycle/the TCA cycle elevated proton motive force by NADH and the activated fatty acid biosynthesis promoted membrane permeability by lauric acid. Both together increased cefoperazone uptake, which outpaces efflux action and thereby intracellular drug is elevated to effectively kill MRSA. These results provide the combination of valine and SCF to produce a new drug candidate effective against MRSA.IMPORTANCE: Methicillin-resistant Staphylococcus aureus (MRSA) is possibly the most infamous example of antibiotic resistance and new antibiotics are urgently needed to control it. The present study used metabolic state-reprogramming approach to identify an ideal biomarker as an antibiotic adjuvant for reversing the metabolic state of MRSA. The most repressed valine was identified as the adjuvant. Exogenous valine most effectively potentiated cefoperazone-sulbactam (SCF) to kill MRSA in vitro and in vivo. Viability of 18 clinical MRSA isolates was reduced by the top 276.64-fold in the presence of valine and SCF. In mouse models, lower bacterial load in liver, spleen, kidney, thigh, and higher survival were determined in the SCF + valine than valine or SCF alone. Valine promoted MRSA to increase SCF uptake that overcomes the efflux and enzymatic hydrolysis. It also extended the PAE of SCF. These occur because valine activates the pyruvate cycle to elevate proton motive force by NADH and increases membrane permeability by lauric acid. Therefore, the combination of valine and SCF is a new drug candidate effective against MRSA.PMID:39692510 | DOI:10.1128/msystems.01244-24

Antimicrob Agents Chemother. 2024 Dec 18:e0127224. doi: 10.1128/aac.01272-24. Online ahead of print.ABSTRACTHand, foot, and mouth disease (HFMD) is a serious pediatric infectious disease that causes immeasurable physical and mental health burdens. Currently, there is a lack of information on the mechanisms of HFMD severity and early diagnosis. We performed metabolomic profiling of sera from 84 Enterovirus A71 (EV-A71) infections and 45 control individuals. Targeted metabolomics assays were employed to further validate some of the differential metabolic molecules. We identified significant molecular changes in the sera of HFMD patients compared to healthy controls (HCs). A total of 54, 60, 35, and 62 differential metabolites were screened between mild cases and HCs, severe cases and HCs, severe cases and mild cases, and among the three groups, respectively. These differential metabolites implicated dysregulation of the tricarboxylic acid cycle, alanine, aspartate, and glutamate metabolism, and valine, leucine, and isoleucine biosynthesis. The diagnostic panel based on some overlapped differential metabolites could effectively discriminate severe cases from mild cases with an AUC of 0.912 (95% CI: 0.85-0.97) using the logistic regression model. Next, we found the elevation of serum sphingosine 1-phosphate (S1P) level in EV-A71 infection mice, which was similar to clinical observation. Importantly, after blocking the release of S1P by MK571, the clinical symptoms and survival of mice were significantly improved, involving the reduction of leukocyte infiltration in infected brain tissues. Collectively, our data provided a landscape view of metabolic alterations in EV-A71 infected children and revealed regulating S1P metabolism was an exploitable therapeutic target against EV-A71 infection.PMID:39692504 | DOI:10.1128/aac.01272-24

Mol Carcinog. 2024 Dec 18. doi: 10.1002/mc.23869. Online ahead of print.ABSTRACTHepatocellular carcinoma (HCC) is viewed as a metabolism associated disease, and bile acid metabolism is reported to occupy a significant role in the progression of HCC. However, little is known about the association between gut microbes and bile acid metabolism in HCC. Our study was designed to clarify the role of bile acid metabolism and microbiome in the progression of HCC. We investigated the relationship between bile acid metabolism and prognosis and immune cells by mining GSE14520. We studied the microbial profiles and metabolic alterations between the low bile acid group and high bile acid group using 16S rRNA sequencing and metabolomics. HCC patients in the high bile acid metabolism group showed better survival outcome compared with those in the low bile acid metabolism. Immune analysis displayed the close correlation between low bile acid metabolism and infiltration of CD4 + T cells, and the close relationship between high bile acid metabolism and infiltration of CD8 + T cells, macrophage cells in HCC. 16S rRNA sequencing results demonstrated that Blautia, Ruminococcus_gnavus_group, Erysipelotrichaceae_UCG-003 were mostly enriched in the low bile acid group. Metabolomics of the 109 fecal samples showed that the most enriched metabolites in the low total bile acid group were dihydrocytochalasin B, cucurbic acid and 27-Norcholestanehexol. Finally, KEGG enrichment analysis identified secondary bile acid biosynthesis and endocrine resistance as the most significant metabolic pathways. High bile acid metabolism was associated with more infiltration of CD8 + T cells, macrophage cells, and better prognosis in HCC. Levels of bile acid were significantly associated with altered gut microbes and metabolites in HCC. Further research related to gut microbes and bile acid metabolism may provide a novel insight into the pathogenesis and therapeutic strategy of HCC.PMID:39692258 | DOI:10.1002/mc.23869

Allergy. 2024 Dec 18. doi: 10.1111/all.16434. Online ahead of print.ABSTRACTRATIONALE: Biologics are becoming increasingly important in the management of severe asthma. However, little is known about the systemic immunometabolic consequences of Th2 response blockage.OBJECTIVES: To provide a better immunometabolic understanding of the effects of mepolizumab and omalizumab treatments by identifying potential biomarkers for monitoring.METHODS: In this exploratory longitudinal study severe asthmatic patients were followed for 18 months after initiating mepolizumab (n = 36) or Omalizumab (n = 20) treatment. Serum samples were collected before, 6, and 18 months after treatment. Targeted omic approaches were performed to analyze inflammatory metabolites (n = 35) and proteins (n = 45). Multiomic integration was performed individually for each treatment applying supervised analysis Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) framework. Then, potential biomarkers were confirmed using multivariate ROC analyses and correlated with clinical variables along treatment.MEASUREMENTS AND MAIN RESULTS: Mepolizumab and omalizumab were both effective (improved clinical variables) and showed different and specific metabolic and protein profiles in severe asthmatic patients during treatment. Multiomic integration and multivariate ROC analyses identified specific biomarkers, such as arachidonic acid, palmitoleic acid, oleic acid, propionylcarnitine, bilirubin, CCL11, and TNFSF10, which can explain the differences observed with Mepolizumab treatment over 18 months and significantly correlate with clinical improvement. However, no significant biomolecules and no discriminative multivariate ROC curves were found for Omalizumab treatment.CONCLUSIONS: Our results provide a comprehensive insight into the differential effects of mepolizumab and omalizumab on the immunometabolic kinetics of the inflammatory response in severe asthma. We identified a set of biomolecules with potential for monitoring mepolizumab treatment which could be useful for personalized medicine.PMID:39692160 | DOI:10.1111/all.16434

J Sci Food Agric. 2024 Dec 18. doi: 10.1002/jsfa.14073. Online ahead of print.ABSTRACTBACKGROUND: The gut microbiome plays a critical role in human health and disease. Different dietary backgrounds play an important role in the uniqueness and diversity of the gut microbiota in different individuals, which promotes heterogeneity in disease phenotypes and treatment responses. Here, we explored how diet affects the composition and function of the native gut microbiome of model mice, based on the shotgun metagenomic and metabolomic, by analyzing the gut microbiome of C57B/6J mice in different dietary backgrounds.RESULTS: The gut microbiomes of mice receiving different diets consistently exhibit distinct compositions across bacterial species, strains, fungi and phages. This implies that native microbial communities cannot 'homogenize' rapidly becaise of priority effects and unchanging diets. Notably, hotspot bacteria such as Limosilactobacillus reuteri, Parabacteroides distasonis and Akkermansia muciniphila were significantly different among the groups. These species harbor diverse adaptive mutations, reflecting genomic evolutionary diversity. The functional profiles of the gut microbiota also exhibit selective differences, involving the capacity for carbohydrate, branched-chain amino acid and fatty acid synthesis, as well as virulence factors, carbohydrate-active enzymes and antibiotic resistance. Furthermore, the differences in the gut microbiota also propagate to the host's serum, where structural and specific metabolite differences were observed. Metabolites that directly impact host health, such as d-glucosamine 6-phosphate and testolic acid, also show significant differences between the different dietary groups.CONCLUSION: Our findings underscore the profound influence of different dietary the composition and functionality of the gut microbiome, offering valuable insights into optimizing health outcomes through personalized nutritional interventions. © 2024 Society of Chemical Industry.PMID:39692041 | DOI:10.1002/jsfa.14073

Front Immunol. 2024 Dec 3;15:1493377. doi: 10.3389/fimmu.2024.1493377. eCollection 2024.ABSTRACTINTRODUCTION: Early detection of oral squamous cell carcinoma (OSCC) is critical for improving clinical outcomes. Precision diagnostics integrating metabolomics and machine learning offer promising non-invasive solutions for identifying tumor-derived biomarkers.METHODS: We analyzed a multicenter public dataset comprising 61 OSCC patients and 61 healthy controls. Plasma metabolomics data were processed to extract 29 numerical and 47 ratio features. The Extra Trees (ET) algorithm was applied for feature selection, and the TabPFN model was used for classification and prediction.RESULTS: The model achieved an area under the curve (AUC) of 93% and an overall accuracy of 76.6% when using top-ranked individual biomarkers. Key metabolic features significantly differentiated OSCC patients from healthy controls, providing a detailed metabolic fingerprint of the disease.DISCUSSION: Our findings demonstrate the utility of integrating omics data with advanced machine learning techniques to develop accurate, non-invasive diagnostic tools for OSCC. The study highlights actionable metabolic signatures that have potential applications in personalized therapeutics and early intervention strategies.PMID:39691710 | PMC:PMC11649677 | DOI:10.3389/fimmu.2024.1493377

Ther Adv Med Oncol. 2024 Dec 16;16:17588359241307814. doi: 10.1177/17588359241307814. eCollection 2024.ABSTRACTBACKGROUND: Despite advances in the treatment of metastatic castration-resistant prostate cancer (mCRPC), primary and secondary resistance to current therapies remains. Elevated circulating sphingolipids are associated with poor outcomes in patients with mCRPC, including therapeutic resistance and shorter overall survival. PCPro is a clinically accessible, regulatory compliant plasma lipid biomarker of poor prognosis in mCRPC, which incorporates prognostic sphingolipids. We hypothesize that reversal of the PCPro signature in men with mCRPC by sphingolipid-lowering agents will improve their clinical outcomes. However, the first step is to determine whether this poor prognostic lipid signature can be modulated. A potential sphingolipid-lowering agent is the PCSK9-inhibitor evolocumab, which is used in the management of hypercholesterolemia.OBJECTIVES: Our primary objective is to assess whether treatment with evolocumab during standard anticancer therapy can safely modify the PCPro signature in men with mCRPC.DESIGN: This is a multicenter, open label phase II trial.METHODS: Men with mCRPC commencing docetaxel, cabazitaxel, abiraterone, enzalutamide, olaparib, or lutetium-177 PSMA for disease progression will be screened for the presence of PCPro. Those who are PCPro positive will receive a 12-week course of evolocumab concurrent with their standard therapy. Dosage is as per cardiovascular guidelines (420 mg subcutaneously every 4 weeks). PCPro will be repeated after 12 weeks. The primary endpoint is reversal of PCPro. The secondary endpoint is the safety of combination therapy with exploratory endpoints characterizing changes in comprehensive lipid profiles pre- and post-treatment.DISCUSSION: This study will evaluate whether evolocumab can safely modify the PCPro signature in men with mCRPC, providing essential data to the development of precision metabolic therapy in the management of prostate cancer.TRIAL REGISTRATION: This study is approved by the Human Research Ethics Committee (X22-0072 and 2022/ETH00427). It is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622001003763).PMID:39691585 | PMC:PMC11650517 | DOI:10.1177/17588359241307814

EJHaem. 2024 Oct 25;5(6):1243-1251. doi: 10.1002/jha2.1041. eCollection 2024 Dec.ABSTRACTINTRODUCTION: Acute myeloid leukemia (AML) remains one of the deadliest hematopoietic malignancies. A better understanding of the molecular biology governing AML may lead to improved risk stratification and facilitate the development of novel therapies. Proteins are responsible for much of the biology of cells. Several studies have examined the global proteome in bulk mononuclear cells (MNCs) from AML specimens, which are comprised a heterogenous population of cells at various stages of differentiation.METHODS: Given the potential impact of the nonleukemic cells on protein expression profiles, we applied an integrative proteogenomic approach utilizing next-generation sequencing and mass spectrometry-based proteomics to identify novel protein biomarkers in unsorted MNCs and viable leukemic blasts (VLBs) isolated from blood and bone marrow specimens obtained at the time of AML diagnosis.RESULTS: We identified significant differences in protein expression between VLBs and MNCs. Subsequent studies (N = 27) focused on proteomic profiling of VLBs that identified novel candidate biomarkers associated with mutational genotypes and clinical outcome, some of which were recapitulated in an independent cohort of patients. Using mass spectrometry, we also detected mutated protein products, some of which were predicted via in silico analyses to be potential neoantigens amenable to adoptive immunotherapy. As previously described, analyses comparing transcript and protein expression showed an overall modest correlation between mRNA and protein dataset, but enriching for genes associated with mutations significantly improved the protein-RNA correlation.CONCLUSION: Together, the results provide insight into the biology of VLBs and demonstrate the gains derived from examining the proteome in addition to genome and transcriptome.PMID:39691254 | PMC:PMC11647701 | DOI:10.1002/jha2.1041

Physiol Plant. 2024 Nov-Dec;176(6):e70005. doi: 10.1111/ppl.70005.ABSTRACTTransgenic Ocimum sanctum plants were engineered to produce vanillin by overexpressing the VpVAN gene using Agrobacterium-mediated transformation. Positive transformants developed shoots within 4-5 weeks and were transferred to a root induction medium and four independent transformants with no observed adverse effects were kept for anlysis. Quantitative RT-PCR indicated significantly higher VpVAN expression in transgenic lines AG_3 and AG_1, impacting the phenylpropanoid pathway and phenolic compound accumulation. Molecular docking studies indicated ferulic acid's higher binding affinity to vanillin synthase than eugenol. LC-MS/MS analysis revealed a marked increase in vanillin production in transgenic lines compared to wild type, with AG_3 exhibiting the highest vanillin content (1.98 ± 0.0047 mg/g extract) and AG_1 following (1.49 ± 0.0047 mg/g extract). AG_3 also showed elevated levels of benzoic acid, 4-hydroxy benzyl alcohol, and ferulic acid. This study highlights the potential of metabolic engineering in O. sanctum for enhanced vanillin production, suggesting pathways for large-scale production of natural vanillin and other valuable compounds in transgenic plants.PMID:39691076 | DOI:10.1111/ppl.70005

Mol Nutr Food Res. 2024 Dec 17:e202400726. doi: 10.1002/mnfr.202400726. Online ahead of print.ABSTRACTInflammatory bowel disease (IBD) is a chronic condition characterized by gut inflammation causing persistent diarrhea and abdominal pain. Despite the nutritional benefits of wolfberry honey (from Lycium barbarum L.), its potential to alleviate IBD remains underexplored. This study evaluated the protective effects of wolfberry honey and its extract (wolfberry honey extract [WHE]) against dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) using in vivo and in vitro models. Mice pretreated with wolfberry honey showed significant symptom improvement in DSS-induced UC, linked to reduced expression of proinflammatory markers (Il-1β, Il-6, Tnf-α, and Mcp-1) and increased antioxidant genes (Nrf2, Sod2). Increased Occludin levels indicated improved intestinal barrier function. In vitro, WHE protected DSS-treated Caco-2 cells by lowering reactive oxygen species (ROS), stabilizing mitochondrial membrane potential, and inhibiting TLR4/NF-κB signaling. It enhanced the expression of antioxidant genes and tight junction proteins (ZO-1, Occludin, and Claudin-1). Metabolomic analysis revealed that WHE modulated glycerophospholipid metabolism, increasing phosphatidylcholine and choline levels and decreasing lysophosphatidylcholine levels. These results highlight the potential of wolfberry honey and its extract as nutraceuticals for managing UC through their effects on inflammation, oxidative stress, and intestinal barrier function. Further research is warranted to elucidate their mechanisms of action and assess their long-term therapeutic benefits in IBD management.PMID:39690893 | DOI:10.1002/mnfr.202400726

J Agric Food Chem. 2024 Dec 17. doi: 10.1021/acs.jafc.4c11116. Online ahead of print.ABSTRACTPassion fruit is one of the most famous fruit crops in tropical and subtropical regions due to its high edible, medicinal, and ornamental value. Flavonoids, a class of plant secondary metabolites, have important health-related roles. In this study, a total of 151 flavonoid metabolites were identified, of which 25 key metabolites may be the main contributors to the purple phenotype. Using RNA sequencing, 11,180 differentially expressed genes (DEGs) were identified. Among these, 48 flavonoid biosynthesis genes (PAL, 4CL, C4H, CHS, CHI, F3H, DFR, ANS, and UFGT) and 123 transcription factors were identified. Furthermore, 12 distinct modules were identified through weighted gene coexpression network analysis, of which the brown module displays a robust positive correlation with numerous flavonoid metabolites. Overexpression of PeMYB114 significantly promoted flavonoids accumulation in tobacco leaves. Our study provided a key candidate gene for molecular breeding to improve color traits in passion fruit.PMID:39690798 | DOI:10.1021/acs.jafc.4c11116

J Am Chem Soc. 2024 Dec 17. doi: 10.1021/jacs.4c12607. Online ahead of print.ABSTRACTNMR is a central tool in the field of metabolomics, thanks to its ability to provide valuable structural and quantitative information with high precision. Most NMR-based metabolomics studies rely on 1D 1H detection, which is heavily limited by strong peak overlap. 13C NMR benefits from a wider spectral dispersion and narrower signal line width but is barely used in metabolomics due to its low sensitivity. Dissolution dynamic nuclear polarization (d-DNP) offers an opportunity to improve 13C NMR sensitivity by several orders of magnitude. Here, we show that this emerging hyperpolarized metabolomics approach can provide meaningful information about clinical samples. Achieving sub-mM limits of detection with 13C at natural abundance in urine samples was made possible by a meticulous design of the experimental workflow. The analysis of human urine samples from patients with different stages of chronic kidney disease (CKD) was performed using 13C d-DNP NMR and benchmarked to conventional 1H NMR metabolomics at a high magnetic field to explore the complementarity between the two methods. Multivariate analysis of the d-DNP 13C NMR dataset provided a statistical model able to distinguish patients with CKD from control patients. Moreover, 13C d-DNP NMR spectra highlighted several biomarkers known to be biologically relevant. Some of them were in agreement with those obtained with conventional 1H NMR, and the results also highlighted the complementarity of biomarker coverage between hyperpolarized and conventional NMR metabolomics. In particular, 13C hyperpolarized NMR allowed the annotation of two biomarkers that could not be detected by 1H NMR because of peak overlap (i.e., guanine and guanidoacetate).PMID:39690120 | DOI:10.1021/jacs.4c12607

Nutr Metab Cardiovasc Dis. 2024 Nov 9:103789. doi: 10.1016/j.numecd.2024.103789. Online ahead of print.ABSTRACTAIMS: Atherosclerosis is a life-threatening disease that develops when a plaque builds up inside an artery and progresses silently. Identifying the early pathological changes and the biomarkers of atherosclerosis deserves attention. We aimed to systematically study and integrate the various metabolites of atherosclerosis in the level of disease to provide more evidences to support early prevention and treatment of atherosclerosis.DATA SYNTHESIS: The protocol was registered with PROPSERO (CRD42023441845). We searched 14,985 records via EMBASE, PubMed, Web of Science, WanFang data, VIP data, and CNKI databases. The collected metabolites were for qualitative and quantitative meta-analysis. The I2 statistic estimated heterogeneity, with over 50 % considered to adopt the random-effects model. A total of 49 articles were included in the meta-analysis. We finally integrated 83 and 16 metabolites presented more than two times in inclusion studies, respectively in blood (plasma and serum) and urine. Among them, the level of citric acid (SMD = -10.35 [95%CI -15.03, -5.67], p < 0.001), lactic acid (SMD = 6.32 [95%CI 0.12, 12.52], p < 0.001) and TMAO (SMD = 1.40 [95%CI 0.27, 2.53], p < 0.001) had significant differences between atherosclerosis and controls. And we observed blood stasis syndrome of atherosclerosis patients present arterial ischemia and energy disorder obviously.CONCLUSIONS: The study provides an in-depth understanding of the roles of metabolites on atherosclerosis progression and prediction primarily in Chinese population, which contributing to development of prevention and therapeutic potential in the future.PMID:39690044 | DOI:10.1016/j.numecd.2024.103789

Comp Biochem Physiol C Toxicol Pharmacol. 2024 Dec 15:110111. doi: 10.1016/j.cbpc.2024.110111. Online ahead of print.ABSTRACTThe toxic effects of long-term exposure to low doses of chlorpyrifos (CPF) on Eriocheir sinensis were evaluated using acute toxicity tests, transcriptome analyses, and metabolome profiling. Four groups (three replicates per group, 60 crabs)-control (no CPF exposure), high exposure (0.12 mg/L CPF), medium exposure (0.036 mg/L), and low exposure (0.012 mg/L)-were subjected to CPF for 21 days. Tissue damage, antioxidant enzyme activity, transcriptional changes, and metabolic alterations in E. sinensis were analyzed. The results demonstrated that CPF disrupted the regulatory networks of transcription and metabolism in crabs under the experimental concentration conditions, with the severity of effects increasing as the duration of exposure lengthened despite the crabs' efforts to activate key defense mechanisms, such as upregulation of cholinesterase 1-like gene expression, to counteract organophosphorus toxicity and adapt to CPF presence in their environment. Even at low concentrations (0.012 mg/L), neurobehavioral development and the antioxidant kinase system in crabs were impaired, leading to hepatopancreatic tissue lesions that negatively affect their growth and survival rates. Additionally, E. sinensis accumulates significant levels of CPF, which may pose food safety concerns when humans consume them. Therefore, ensuring the rational use of CPF requires maintaining appropriate water concentrations to minimize direct harm to aquatic organisms and indirect impacts on food safety associated with this pesticide.PMID:39689750 | DOI:10.1016/j.cbpc.2024.110111

J Hazard Mater. 2024 Dec 14;485:136886. doi: 10.1016/j.jhazmat.2024.136886. Online ahead of print.ABSTRACTTetrabromobisphenol A (TBBPA) poses significant ecological risks owing to its toxicity; however, its specific effects on toxin-producing cyanobacteria in aquatic environments remain poorly understood. This study systematically investigated the effects of TBBPA at concentrations ranging from 100 ng/L to 100 mg/L on Microcystis aeruginosa (M. aeruginosa) by examining growth, photosynthesis, toxin production, antioxidant responses, and molecular-level changes. The results indicated that low levels of TBBPA (0.1-1000 μg/L) induced stimulatory effects on the growth and microcystin-leucine-arginine (MC-LR) production of M. aeruginosa. Metabolomic analysis revealed that low levels of TBBPA significantly upregulated metabolites associated with energy metabolism, xenobiotic biodegradation, oxidative stress responses, and protein biosynthesis in M. aeruginosa, potentially contributing to the observed hormetic effect. Conversely, higher doses (40-100 mg/L) inhibited growth and significantly increased MC-LR release by compromising cellular structural integrity. Proteomic analysis revealed that toxic levels of TBBPA significantly affected the expression of proteins associated with energy harvesting and utilization. Specifically, TBBPA disrupted electron flow in oxidative phosphorylation and the photosynthetic system (PS) by targeting PSI, PSII, and Complex I, impairing energy acquisition and causing oxidative damage, ultimately leading to algal cell death. Additionally, proteins involved in the biosynthesis and metabolism of cysteine, methionine, phenylalanine, tyrosine, and tryptophan were upregulated, potentially enhancing M. aeruginosa resistance to TBBPA-induced stress. This study offers insights into the effects of TBBPA on M. aeruginosa and its potential risks to aquatic ecosystems.PMID:39689566 | DOI:10.1016/j.jhazmat.2024.136886

Anal Bioanal Chem. 2024 Dec 18. doi: 10.1007/s00216-024-05688-w. Online ahead of print.ABSTRACTFolate, serving as a crucial micronutrient, plays an important role in promoting human growth and supporting transformations to a variety of metabolic pathways including one-carbon, pyrimidine, purine, and homocysteine metabolism. The 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme is pivotal in the folate metabolic pathway. Polymorphism in the MTHFR gene, especially C677T, was associated with decreased enzyme activity and disturbance of folate metabolism, which is linked to various diseases including birth defects in newborns and neural tube abnormalities. However, the detailed metabolic disturbance induced by MTHFR C677T polymorphism is still elusive. In this study, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the precise quantification of 93 metabolites from six important metabolic pathways related to folate metabolism. The method characteristics demonstrated high accuracy and precision, with r2 values ranging from 0.981 to 1.000 for all metabolites. Then the impact of the MTHFR C677T polymorphism on folate metabolism was further investigated, revealing a significant reduction in the level of 5-methyltetrahydrofolate and abnormal levels of metabolites associated with DNA synthesis pathways in individuals carrying the mutation. These data highlight the pivotal role of folic acid supplementation for individuals with the MTHFR C677T polymorphism to mitigate health risks and show the value of precision measurement of folate-related metabolites.PMID:39690314 | DOI:10.1007/s00216-024-05688-w

World J Microbiol Biotechnol. 2024 Dec 18;41(1):11. doi: 10.1007/s11274-024-04224-3.ABSTRACTPeriodontal disease is characterized by bacterial toxins within the oral biofilm surrounding the teeth, leading to gingivitis and the gradual dissolution of the alveolar bone, which supports the teeth. Notably, symptoms in the early stages of the disease are often absent. Similarly, dental caries occurs when oral bacteria metabolize dietary sugars, producing acids that dissolve tooth enamel and dentin. These bacteria are commonly present in the oral cavity of most individuals. Metabolomics, a relatively recent addition to the "omics" research landscape, involves the comprehensive analysis of metabolites in vivo to elucidate pathological mechanisms and accelerate drug discovery. Meanwhile, the term "microbiome" refers to the collection of microorganisms within a specific environmental niche or their collective genomes. The human microbiome plays a critical role in health and disease, influencing a wide array of physiological and pathological processes. Recent advances in microbiome research have identified numerous bacteria implicated in dental caries and periodontal disease. Additionally, studies have uncovered various pathogenic factors associated with these microorganisms. This review focuses on recent findings in metabolomics and the microbiome, specifically targeting oral bacteria linked to dental caries and periodontal disease. We acknowledge the limitation of relying exclusively on the MEDLINE database via PubMed, while excluding other sources such as gray literature, conference proceedings, and clinical practice guidelines.PMID:39690257 | DOI:10.1007/s11274-024-04224-3