PubMed

Gastroenterol Rep (Oxf). 2024 Dec 13;12:goae106. doi: 10.1093/gastro/goae106. eCollection 2024.ABSTRACTBACKGROUND: Early detection of colorectal cancer (CRC) is crucial to enhance the disease treatment and prognosis of patients. Colonoscopy remains the gold standard for CRC detection; however, it requires trained personnel with expensive tools. Currently, serum metabolites have been discovered to be used to discriminate patients with polyps and CRC. This study aimed to identify the most commonly detected predictive serum metabolites for polyps and CRC.METHODS: A systematic search of the Web of Science, PubMed, and Cochrane Library databases was conducted using PRISMA guidelines. Ten studies investigating serum metabolite biomarkers of CRC and polyps using different analytical platforms and study populations were included. QUADOMICS tool was used to analyse the quality of the included studies. All reported metabolites were then enriched into the pathways using MetaboAnalyst 5.0.RESULTS: We found that several potential signature metabolites overlapped between studies, including tyrosine, lysine, cystine, arabinose, and lactate for CRC and lactate and glutamate for polyps. The most affected pathways related to CRC were the urea cycle, glutathione metabolism, purine metabolism, glutamate metabolism, and ammonia recycling. In contrast, those affected in the polyps were the urea cycle, glutamate metabolism, glutathione metabolism, arginine and proline metabolism, and carnitine synthesis.CONCLUSIONS: This review has found commonly detected serum metabolites for polyps and CRC with huge potential to be used in clinical settings. However, the differences between altered pathways in polyps and CRC, other external factors, and their effects on the regulation level, sensitivity, and specificity of each identified metabolite remained unclear, which could benefit from a further extensive cohort study and well-defined analysis equipment.PMID:39678161 | PMC:PMC11646065 | DOI:10.1093/gastro/goae106

bioRxiv [Preprint]. 2024 Dec 2:2024.11.26.625478. doi: 10.1101/2024.11.26.625478.ABSTRACTNon-steroidal anti-inflammatory drugs (NSAIDs) are popular choices for the mitigation of pain and inflammation; however, they are accompanied by side effects in the gastrointestinal and cardiovascular systems. We compared the effects of naproxen, a traditional NSAID, and celecoxib, a cyclooxygenase -2 (Cox-2) inhibitor, in humans. Our findings showed a decrease in tryptophan and kynurenine levels in plasma of volunteers treated with naproxen. We further validated this result in mice. Additionally, we find that the depression of tryptophan was independent of both Cox-1 and Cox-2 inhibition, but rather was due to the displacement of bound tryptophan by naproxen. Supplementation of tryptophan in naproxen-treated mice rescued fecal blood loss and inflammatory gene expression driven by IL-1β in the heart.PMID:39677795 | PMC:PMC11642787 | DOI:10.1101/2024.11.26.625478

bioRxiv [Preprint]. 2024 Dec 3:2024.11.27.625762. doi: 10.1101/2024.11.27.625762.ABSTRACTPancreatic ductal adenocarcinoma has a unique tumor microbiome and the systemic depletion of bacteria or fungi using antibiotic/antifungal cocktails leads to a decrease in pancreatic tumor burden in mice. However, functional studies remain rare due to the limited availability of clinically relevant microbiota. Here, we describe in detail the isolation of bacteria and fungi from the small intestine and tumor of pancreatic cancer patients at the Rogel Cancer Center. We then further characterized the impact of a newly isolated Klebsiella oxytoca strain ( UMKO1 ) on the pancreatic tumor microenvironment using bacterial genome sequencing, untargeted and targeted metabolomics, as well as an ex vivo tumor transplant system. We found that UMKO1 possesses a gene for the long form of cytidine deaminase, which can inactivate the standard PDAC chemotherapeutic agent gemcitabine. In addition, we found that UMKO1 can produce several indoles when grown in tumor-like conditions, metabolites that can lead to an immune suppressive environment and interfere with therapy outcome. To test this in detail, we assessed changes in immune populations in pancreatic tumor explants upon exposure to the supernatant of UMKO1 and other isolated bacteria grown in tumor Interstitial fluid media (TIFM). We found that while none of the bacterial supernatants changed the abundance of CD8 T cells, granzyme B positive CD8 T cells were the lowest in tumor explants exposed to UMKO1 , and not other isolated Klebsiella species or the non-pathogenic laboratory strain E. coli K12 . In summary, the isolated collection of bacteria and fungi from this study are a valuable toolbox to study the impact of microbiota on pancreatic cancer.PMID:39677718 | PMC:PMC11642792 | DOI:10.1101/2024.11.27.625762

bioRxiv [Preprint]. 2024 Dec 5:2024.12.01.626207. doi: 10.1101/2024.12.01.626207.ABSTRACTIn previous work, we found that short sleep caused sensitivity to oxidative stress; here we set out to characterize the physiological state of a diverse group of chronically short-sleeping mutants during hyperoxia as an acute oxidative stress. Using RNA-sequencing analysis, we found that short-sleeping mutants had a normal transcriptional oxidative stress response relative to controls. In both short-sleeping mutants and controls, hyperoxia led to downregulation of glycolytic genes and upregulation of genes involved in fatty acid metabolism, reminiscent of metabolic shifts during sleep. We hypothesized that short-sleeping mutants may be sensitive to hyperoxia because of defects in metabolism. Consistent with this, short-sleeping mutants were sensitive to starvation. Using metabolomics, we identified a pattern of low levels of long chain fatty acids and lysophospholipids in short-sleeping mutants relative to controls during hyperoxia, suggesting a defect in lipid metabolism. Though short-sleeping mutants did not have common defects in many aspects of lipid metabolism (basal fat stores, usage kinetics during hyperoxia, respiration rates, and cuticular hydrocarbon profiles), they were all sensitive to dehydration, suggesting a general defect in cuticular hydrocarbons, which protect against dehydration. To test the bi-directionality of sleep and lipid metabolism, we tested flies with both diet-induced obesity and genetic obesity. Flies with diet-induced obesity had no sleep or oxidative stress phenotype; in contrast, the lipid metabolic mutant, brummer , slept significantly more than controls but was sensitive to oxidative stress. Previously, all short sleepers tested were sensitive and all long sleepers resistant to oxidative stress. brummer mutants, the first exceptions to this rule, lack a key enzyme required to mobilize fat stores, suggesting that a defect in accessing lipid stores can cause sensitivity to oxidative stress. Taken together, we found that short-sleeping mutants have many phenotypes in common: sensitivity to oxidative stress, starvation, dehydration, and defects in lipid metabolites. These results argue against a specific role for sleep as an antioxidant and suggest the possibility that lipid metabolic defects underlie the sensitivity to oxidative stress of short-sleeping mutants.PMID:39677628 | PMC:PMC11642809 | DOI:10.1101/2024.12.01.626207

medRxiv [Preprint]. 2024 Dec 8:2024.12.06.24318612. doi: 10.1101/2024.12.06.24318612.ABSTRACTThe lack of accurate, cost-effective, and clinically relevant biomarkers remains a major barrier to incorporating omic data into clinical practice. Previous studies have shown that DNA methylation algorithms have utility as surrogate measures for selected proteins and metabolites. We expand upon this work by creating DNAm surrogates, termed epigenetic biomarker proxies (EBPs), across clinical laboratories, the metabolome, and the proteome. After screening >2,500 biomarkers, we trained and tested 1,694 EBP models and assessed their incident relationship with 12 chronic diseases and mortality, followed up to 15 years. We observe broad clinical relevance: 1) there are 1,292 and 4,863 FDR significant incident and prevalent associations, respectively; 2) most of these associations are replicated when looking at the lab-based counterpart, and > 62% of the shared associations have higher odds and hazard ratios to disease outcomes than their respective observed measurements; 3) EBPs of current clinical biochemistries detect deviations from normal with high sensitivity and specificity. Longitudinal EBPs also demonstrate significant changes corresponding to the changes observed in lab-based counterparts. Using two cohorts and > 30,000 individuals, we found that EBPs validate across healthy and sick populations. While further study is needed, these findings highlight the potential of implementing EBPs in a simple, low-cost, high-yield framework that benefits clinical medicine.PMID:39677461 | PMC:PMC11643242 | DOI:10.1101/2024.12.06.24318612

World J Nucl Med. 2024 Jul 11;23(4):270-274. doi: 10.1055/s-0044-1788334. eCollection 2024 Dec.ABSTRACTIntroduction Equilibrium radionuclide angiography (ERNA) has long been assumed as the preferred method to assess cardiac volumes as well as left ventricular systolic and diastolic indices. ERNA was used to diagnose subtle changes in cardiac function during chemotherapy or early stages of heart failure. Gated myocardial perfusion SPECT (GMPS) was introduced as a more feasible and versatile alternative to ERNA, but the precision of GMPS to assess systolic and diastolic indices has not yet been fully reviewed. Method We studied the left ventricular systolic and diastolic functional indices measured by a 16-frame GMPS and compared the results with those of ERNA in 25 patients. All the images were analyzed visually, semi-quantitatively, and quantitatively using quantitative gated SPECT (QGS), quantitative blood pool SPECT (QBS), and planar gated blood pool (PGBP) software. The left ventricular functional indices calculated using QGS compared with those obtained using QBS and PGBP Result Our study found a significant correlation between the left ventricular ejection fraction (LVEF) calculated using the PGBP, QGS, and QBS methods. There was a significant correlation between the LV peak ejection rate (LVPER) calculated by the PGBP and QGS analyses, and there was no significant difference in the LVPER calculated with the QGS and QBS methods. This study also revealed a significant correlation between the LV peak filling rate (LVPFR) calculated by QBS and QGS, with no significant difference between them. We also found a significant correlation between LV end systolic volume (LVESV) calculated using QGS and QBS and between LV end diastolic volume (LVEDV) calculated using QGS and QBS software. This study also revealed a significant correlation between the LV mean filling rate over the first third of diastole (LVMFR/3) calculated using the QGS and QBS software. Conclusion Considering the significant correlation between LVEF, LVPER, LVPFR, LVESV, LVMFR/3, and LVEDV calculated using the QGS and QBS methods in our study, the 16-frame GMPS could be regarded as an acceptable substitute for ERNA in the investigation of systolic and diastolic indices.PMID:39677339 | PMC:PMC11637634 | DOI:10.1055/s-0044-1788334

J Inflamm Res. 2024 Dec 10;17:10849-10869. doi: 10.2147/JIR.S493892. eCollection 2024.ABSTRACTPURPOSE: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease influenced by environmental triggers, including the commensal microbiota. Recent research has highlighted distinctive features of the gut microbiota in RA patients. This study investigates the therapeutic potential of berberine (BBR), a gut microbiota modulator known for its significant anti-RA effects, and elucidates the underlying mechanisms.METHODS: Utilizing the collagen-induced arthritis (CIA) rat model, we comprehensively evaluated the anti-rheumatoid arthritis effects of BBR in vivo through various indices, such as paw edema, arthritis index, ankle diameter, inflammatory cytokine levels, pathological conditions, and micro-CT analysis. Employing network pharmacology, we identified potential targets involved in RA alleviation by BBR. To analyze comprehensive metabolic profiles and identify underlying metabolic pathways, we conducted a serum-based widely targeted metabolomics analysis utilizing LC-MS technology. An integrated network encompassing metabolomics and network pharmacology data was constructed using Cytoscape. The potential therapeutic targets and signaling pathways of BBR in the management of RA were predicted using network pharmacology. Key targets and pathways were further validated by molecular docking and immunofluorescent staining, which integrated findings from serum metabolomics and network pharmacology analysis. Additionally, we analyzed the gut microbiota composition in rats employing 16S rDNA sequencing and investigated the effects of BBR on the microbiota of CIA rats through bioinformatics and statistical methods.RESULTS: Our results showed that BBR demonstrated significant efficacy in alleviating RA symptoms in CIA rats, as evidenced by improvements in paw redness and swelling, attenuation of bone and cartilage damage, reduction in synovial hyperplasia, inflammatory cell infiltration, and suppression of proinflammatory cytokines IL-1β, IL-6, IL-17A, and TNF-α. KEGG analysis highlighted the PI3K/AKT signaling pathway as a key mediator of BBR's anti-RA effects. Metabolomics profiling via LC-MS revealed 22 potential biomarkers. Arginine and proline metabolism, cutin, suberine and wax biosynthesis, glycine, serine and threonine metabolism and taurine and hypotaurine metabolism are the most related pathways of BBR anti-RA. Molecular docking studies corroborated high affinities between BBR and key targets. Furthermore, 16S analysis demonstrated BBR's capacity to modulate gut bacteria composition, including an increase in the abundance of Lachnoclostridium, Akkermansia, Blautia, Romboutsia, and Faecalibacterium genera, alongside a decrease in Prevotella_9 abundance in genus level. Integrated analysis underscored a strong correlation between serum microbiota and fecal metabolites.CONCLUSION: Our findings elucidate the multifaceted mechanisms underlying BBR's therapeutic efficacy in RA, involving inhibition of the PI3K/AKT pathway, modulation of intestinal flora, and regulation of host metabolites. These insights provide novel perspectives on BBR's role in RA management.PMID:39677295 | PMC:PMC11645930 | DOI:10.2147/JIR.S493892

ACS Omega. 2024 Nov 27;9(49):48727-48737. doi: 10.1021/acsomega.4c08215. eCollection 2024 Dec 10.ABSTRACTThe preanalytical handling of plasma, how it is drawn, processed, and stored, influences its composition. Samples in biobanks often lack this information and, consequently, important information about their quality. Especially metabolite concentrations are affected by preanalytical handling, making conclusions from metabolomics studies particularly sensitive to misinterpretations. The perturbed metabolite profile, however, also offers an attractive choice for assessing the preanalytical history from the measured data. Here we show that it is possible using Orthogonal Projections to Latent Structures Discriminative Analysis to divide plasma NMR data into a multivariate "original sample space" suitable for further less biased metabolomics analysis and an orthogonal "preanalytical handling space" describing the changes occurring from preanalytical mishandling. Apart from confirming established preanalytical effects on metabolite levels, e.g., the consequent changes in glucose, lactate, ornithine, and pyruvate, the sample preparation protocol involved methanol precipitation which allowed the observation of reversible changes in short-chain fatty acid concentrations as a function of temperature.PMID:39676944 | PMC:PMC11635485 | DOI:10.1021/acsomega.4c08215

Front Immunol. 2024 Nov 29;15:1505966. doi: 10.3389/fimmu.2024.1505966. eCollection 2024.ABSTRACTBACKGROUND: Progress in immunotherapy for pancreatic ductal adenocarcinoma (PDAC) has been slow, yet the relationship between microorganisms and metabolites is crucial to PDAC development. This study compares the biliary microbiota and metabolomic profiles of PDAC patients with those of benign pancreatic disease patients to investigate PDAC pathogenesis and its relationship with immunotherapy.METHODS: A total of 27 patients were recruited, including 15 diagnosed with PDAC and 12 with benign pancreaticobiliary conditions, all of whom underwent surgical treatment. Intraoperative bile samples were collected and analyzed using 16S rRNA sequencing in conjunction with liquid chromatography-mass spectrometry (LC-MS). Multivariate statistical methods and correlation analyzes were employed to assess differences in microbial composition, structure, and function between malignant and benign pancreatic diseases. Additionally, a retrospective analysis was conducted on PDAC patients post-surgery regarding immunotherapy and its correlation with metabolic components.RESULTS: PDAC patients exhibited a significantly higher abundance of bile microbiota compared to controls, with notable differences in microbiota structure between the two groups (P < 0.05). At the genus level, Muribaculum was markedly enriched in the bile of PDAC patients and was strongly correlated with phosphatidic acid (PA) (10:0/a-17:0). Both of these components, along with the tumor marker CA199, formulated a predictor of PDAC. Furthermore, PA (10:0/a-17:0) demonstrated a strong correlation with PDAC immunotherapy outcomes (Rho: 0.758; P=0.011).CONCLUSION: These findings suggest that the biliary microbiota and associated metabolites play a crucial role in the development of PDAC and may serve as potential predictive biomarkers and therapeutic targets for disease management.PMID:39676871 | PMC:PMC11638228 | DOI:10.3389/fimmu.2024.1505966

Plant Cell Environ. 2024 Dec 16. doi: 10.1111/pce.15311. Online ahead of print.ABSTRACTPlants exude a wide variety of compounds into the rhizosphere, modulating soil functioning and diversity. The number of studies investigating exudation has exponentially increased over the past decades. Yet, the high inter-study variability of the results is slowing down our understanding of root-soil interactions. This variability is partly due to the absence of harmonized methodologies to collect and characterize exudation. Here, we discuss how various experimental aspects influence exudation profiles by performing a literature review, and we suggest best practices for different experimental setups. We discuss state-of-the-art of spatially resolved exudate collection, collection in controlled versus field conditions and plant growth setups ranging from hydroponics to soil. We highlight the importance of preparing experimental blanks, in situ versus ex situ exudate collection, various collection media and timing of collection, exudate storage and processing and analytical considerations. We summarize best practices for experimental setup and reporting of parameters in an easily accessible table format to facilitate discussion of best practices in the field. An increased standardization in the field together with the systematic studies suggested will improve our knowledge of how plant exudation shapes interactions with organisms in soil.PMID:39676732 | DOI:10.1111/pce.15311

Gut Microbes. 2024 Jan-Dec;16(1):2431648. doi: 10.1080/19490976.2024.2431648. Epub 2024 Dec 16.ABSTRACTMultiple emerging lines of evidence indicate that the microbiome contributes to aging and cognitive health. However, the roles of distinct microbial components, such as viruses (virome) and their interactions with bacteria (bacteriome), as well as their metabolic pathways (metabolome) in relation to aging and cognitive function, remain poorly understood. Here, we present proof-of-concept results from a pilot study using datasets (n = 176) from the Microbiome in Aging Gut and Brain (MiaGB) consortium, demonstrating that the human virome signature significantly differs across the aging continuum (60s vs. 70s vs. 80+ years of age) in older adults. We observed that the predominant virome signature was enriched with bacteriophages, which change considerably with aging continuum. Analyses of interactions between phages and the host bacteriome suggest that lytic or temperate relationships change distinctly across the aging continuum, as well as cognitive impairment. Interestingly, the phage-bacteriome-metabolome interactions develop unique patterns that are distinctly linked to aging and cognitive dysfunction in older adults. The phage-bacteriome interactions affect bacterial metabolic pathways, potentially impacting older adults' health, including the risk of cognitive decline and dementia. Further comprehension of these studies could provide opportunities to target the microbiome by developing phage therapies to improve aging and brain health in older adults.PMID:39676708 | DOI:10.1080/19490976.2024.2431648

Am J Med Genet A. 2024 Dec 16:e63971. doi: 10.1002/ajmg.a.63971. Online ahead of print.ABSTRACTMonozygotic (MZ) and dizygotic (DZ) twins are studied to understand genetic and environmental influences on complex traits, however the mechanisms behind twinning are not completely understood. (Epi)genomic studies identified SNPs associated with DZ twinning and DNA methylation sites with MZ twinning. To find molecular biomarkers of twinning, we compared transcriptomics and metabolomics data from MZ and DZ twins. We analyzed 42,663 RNA transcripts in 1453 MZ twins and 1294 DZ twins from the Netherlands Twin Register (NTR), followed by sex-stratified analyses. The top 5% transcripts with lowest p-values were analyzed for replication in 217 MZ and 158 DZ twins from the older Finnish Twin cohort (FTC). In the NTR, one transcript (PURG) was significantly differentially expressed between MZ and DZ twins; but this did not replicate in FTC. Pathway analyses highlighted the WNT-pathway, previously associated with MZ twinning, and the TGF-B and SMAD pathway, previously associated with DZ twinning. Meta-analysis of 169 serum metabolites in 2797 MZ and 2040 DZ twins from the NTR, FTC and FinnTwin12, showed no metabolomic differences. Overall, we did not find replicable transcript-level expression differences in blood between MZ and DZ twins, but highlighted the TGF-B/SMAD pathway as a potential transcriptional biomarker for DZ twinning.PMID:39676692 | DOI:10.1002/ajmg.a.63971

J Appl Toxicol. 2024 Dec 15. doi: 10.1002/jat.4743. Online ahead of print.ABSTRACTThe clinical application of cantharidin (CTD) is seriously limited due to its nephrotoxicity. Therefore, this study aims to investigate sensitive biomarkers for the evaluation and prediction of nephrotoxicity induced by CTD in rat. A total of 80 rats were randomly divided into four groups: control group and three doses of CTD groups. After 0, 1, 5, 15, and 28 days of intragastric administration, rat serum and urine were collected for biochemical indexes, then serum was used for metabolomic analyses, and rat kidney was collected for pathological and ultrastructural observation. The levels of serum crea (Scr), blood urea nitrogen (BUN), urea, urine crea (Ucrea), and urinary microalbumin (UmALB) were significantly increased after administration of different doses of CTD (p < 0.05). Additionally, histopathology and cell ultrastructure observation of kidney showed significant cell inflammatory infiltration and glomerular edema. Seven metabolic biomarkers including 6-hydroxymelatonin were significantly disturbed by CTD. The CatBoost Classifier prediction model was used to establish the CTD nephrotoxicity prediction model, and the prediction accuracy and precision were 0.645 and 0.640, respectively. Moreover, 6-hydroxymelatonin was found to be most useful biomarkers for evaluating the CTD nephrotoxicity. Finally, the seven metabolic biomarkers were found mainly involved in pyruvate metabolism, pantothenate and CoA biosynthesis.PMID:39676217 | DOI:10.1002/jat.4743

Metabolomics. 2024 Dec 15;21(1):9. doi: 10.1007/s11306-024-02199-8.ABSTRACTINTRODUCTION: Outside of case-control settings, ethnicity specific changes in the human metabolome are understudied especially in community dwelling, ageing men. Characterising serum for age and ethnicity specific features can enable tailored therapeutics research and improve our understanding of the interplay between age, ethnicity, and metabolism in global populations.OBJECTIVE: A metabolomics approach was adopted to profile serum metabolomes in middle-aged and elderly men of different ethnicities from the Northwest of England, UK.METHODS: Serum samples from 572 men of White European (WE), South Asian (SA), and African-Caribbean (AC) ethnicities, ranging between 40 and 86 years were analysed. A combination of liquid chromatography (LC) and gas chromatography (GC) coupled to high-resolution mass spectrometry (MS) was used to generate the metabolomic profiles. Partial Least Squares Discriminant Analysis (PLS-DA) based classification models were built and validated using resampling via bootstrap analysis and permutation testing. Features were putatively annotated using public Human Metabolome Database (HMDB) and Golm Metabolite Database (GMD). Variable Importance in Projection (VIP) scores were used to determine features of interest, after which pathway enrichment analysis was performed.RESULTS: Using profiles from our analysis we classify subjects by their ethnicity with an average correct classification rate (CCR) of 90.53% (LC-MS data) and 85.58% (GC-MS data). Similar classification by age (< 60 vs. ≥ 60 years) returned CCRs of 90.20% (LC-MS) and 71.13% (GC-MS). VIP scores driven feature selection revealed important compounds from putatively annotated lipids (subclasses including fatty acids and carboxylic acids, glycerophospholipids, steroids), organic acids, amino acid derivatives as key contributors to the classifications. Pathway enrichment analysis using these features revealed statistically significant perturbations in energy metabolism (TCA cycle), N-Glycan and unsaturated fatty acid biosynthesis linked pathways amongst others.CONCLUSION: We report metabolic differences measured in serum that can be attributed to ethnicity and age in healthy population. These results strongly emphasise the need to consider confounding effects of inherent metabolic variations driven by ethnicity of participants in population-based metabolic profiling studies. Interpretation of energy metabolism, N-Glycan and fatty acid biosynthesis should be carefully decoupled from the underlying differences in ethnicity of participants.PMID:39676138 | DOI:10.1007/s11306-024-02199-8

Metabolomics. 2024 Dec 15;21(1):7. doi: 10.1007/s11306-024-02202-2.ABSTRACTBACKGROUND: Soccer is the most recognized sports worldwide. It is a fertile ground for the use of metabolomics analyses, considering the multifactorial nature of soccer's physical demands on the body. Although scientific studies have tried using it to better understand the impacts of soccer into different contexts of the sport, no systematic review is available on metabolomics analyses in soccer athletes subjected to physical exertion interventions.AIM OF REVIEW: Retrieve scientific articles that conducted metabolomics analyses on soccer athletes subjected to physical exertion interventions.KEY SCIENTIFIC CONCEPTS OF REVIEW: Initially, 271 studies were screened, and 48 were retrieved for abstract analysis. Of these, 26 met the eligibility criteria, but 5 failed to meet inclusion criteria. The 21 studies included in this systematic review demonstrate that responses from physical training or acute exercise sessions, followed by the effects of soccer matches, have been the primary focus of researchers to date, highlighting alterations on metabolites from the energy metabolism, immunological pathway, purines, tryptophan/phenylalanine metabolism, as well as oxidative species and antioxidant capacity. Other studies suggest, albeit preliminarily, that organic metabolites have the potential to distinguish soccer players' performance and physical fitness, as well as provide valuable insights into diet, physical condition, training load, and recovery throughout the season. Despite metabolomics great potential to understand physiological alterations provoked by soccer as shown by the included studies, future studies should consider female athletes, explore the cause-and-effect relationship between metabolites and soccer performance more deeply, and examine the effects of different training periodizations on these markers.PMID:39676125 | DOI:10.1007/s11306-024-02202-2

Metabolomics. 2024 Dec 15;21(1):6. doi: 10.1007/s11306-024-02207-x.ABSTRACTBACKGROUND: Due to the high prevalence of myopia, there is a growing need for the identification of myopia intervention mechanisms and targets. Metabolomics has been gradually used to investigate changes in myopia tissue metabolites over the last few years, but the potential physiological and pathological roles of amino acids and their downstream metabolites discovered by metabolomics in myopia are not fully understood.AIM OF REVIEW: Aim to explore the possible relationship between amino acid metabolism and the occurrence and development of myopia, we collected a total of 21 experimental studies related to myopia metabolomics. Perform pathway analysis using MetaboAnalyst online software. We have identified over 20 amino acids that may be associated with the development of myopia. Among them, 19 types of amino acids are common amino acids. We discussed their possible mechanisms affecting myopia and proposed future prospects for treating myopia.KEY SCIENTIFIC CONCEPTS OF REVIEW: Our analysis results show that metabolomics research on myopia involves many important amino acids. We have collected literature and found that research on amino acid metabolism in myopia mainly focuses on downstream small molecule substances. Amino acids and their downstream metabolites affect the development of myopia by participating in important biochemical processes such as oxidative stress, glucose metabolism, and lipid metabolism. Enzymes, receptors, and cytokines that regulate amino acid metabolism may become potential targets for myopia treatment.PMID:39676079 | DOI:10.1007/s11306-024-02207-x

Metabolomics. 2024 Dec 15;21(1):8. doi: 10.1007/s11306-024-02206-y.ABSTRACTINTRODUCTION: Rapid detection and identification of pathogens and antimicrobial susceptibility is essential for guiding appropriate antimicrobial therapy and reducing morbidity and mortality associated with sepsis.OBJECTIVES: The metabolic response of clinical isolates of Klebsiella oxytoca exposed to different concentrations of ciprofloxacin (the second generation of quinolones antibiotics) were studied in order to investigate underlying mechanisms associated with antimicrobial resistance (AMR).METHODS: Metabolomics investigations were performed using Fourier-transform infrared (FT-IR) spectroscopy as a metabolic fingerprinting approach combined with gas chromatography-mass spectrometry (GC-MS) for metabolic profiling.RESULTS: Our findings demonstrated that metabolic fingerprints provided by FT-IR analysis allowed for the differentiation of susceptible and resistant isolates. GC-MS analysis validated these findings, while also providing a deeper understanding of the metabolic alterations caused by exposure to ciprofloxacin. GC-MS metabolic profiling detected 176 metabolic features in the cellular extracts cultivated on BHI broth, and of these, 137 could be identified to Metabolomics Standards Initiative Level 2. Data analysis showed that 40 metabolites (30 Level 2 and 10 unknown) were differentiated between susceptible and resistant isolates. The identified metabolites belonging to central carbon metabolism; arginine and proline metabolism; alanine, aspartate and glutamate metabolism; and pyruvate metabolism. Univariate receiver operating characteristic (ROC) curve analyses revealed that six of these metabolites (glycerol-3-phosphate, O-phosphoethanolamine, asparagine dehydrate, maleimide, tyrosine, and alanine) have a crucial role in distinguishing susceptible from resistant isolates (AUC > 0.84) and contributing to antimicrobial resistance in K. oxtytoca.CONCLUSION: Our study provides invaluable new insights into the mechanisms underlying development of antimicrobial resistance in K. oxytoca suggests potential therapeutic targets for prevention and identification of AMR in K. oxytoca infections.PMID:39676074 | DOI:10.1007/s11306-024-02206-y

J Biol Chem. 2024 Dec 13:108091. doi: 10.1016/j.jbc.2024.108091. Online ahead of print.ABSTRACTNeutrophils are a part of the innate immune system and produce reactive oxygen species (ROS) to extinguish pathogens. The major source of ROS in neutrophils is NADPH oxidase, which is fueled by NADPH generated via the pentose phosphate pathway; however, it is unclear how other accessory glucose metabolism pathways and mitochondrial activity influence the respiratory burst. We examined the temporal dynamics of the respiratory burst and delineated how metabolism changes over time after neutrophil activation. Bone marrow-derived neutrophils were stimulated with phorbol 12-myristate 13-acetate (PMA), and the respiratory burst was measured via extracellular flux analysis. Metabolomics experiments utilizing 13C6-glucose highlighted the activation of glycolysis as well as ancillary pathways of glucose metabolism in activated neutrophils. PMA stimulation acutely increased 13C enrichment into glycerol 3-phosphate (G3P) and citrate, whereas increases in 13C enrichment in the glycogen intermediate, UDP-hexose, and end products of the hexosamine and serine biosynthetic pathways occurred only during the late phase of the oxidative burst. Targeted inhibition of the G3P shuttle, glycogenolysis, serine biosynthesis, and mitochondrial respiration demonstrated that the G3P shuttle contributes to the general magnitude of ROS production; that glycogen contributes solely to the early respiratory burst; and that the serine biosynthetic pathway activity and Complex III-driven mitochondrial activity influence respiratory burst duration. Collectively, these results show that the neutrophil oxidative burst is highly dynamic, with coordinated changes in metabolism that control the initiation, magnitude, and duration of ROS production.PMID:39675714 | DOI:10.1016/j.jbc.2024.108091

Pharmacol Res. 2024 Dec 13:107550. doi: 10.1016/j.phrs.2024.107550. Online ahead of print.ABSTRACTObesity-related glomerulopathy (ORG) represents an escalating public health with no effective treatments currently available. Abnormal lipid metabolism and lipid droplet deposition in the kidneys are key contributors to ORG. Cyanidin-3-glucoside (C3G) has shown potential in regulating lipid metabolism and may offer reno-protective effects; however, its therapeutic efficacy and underlying mechanisms in ORG remain unclear. An ORG mouse model was established, followed by an 8-week C3G intervention. The mice were divided into three groups: normal control (CT) group, ORG group, and C3G treatment group. Fecal 16S rRNA sequencing, metabolomics of feces-serum-kidney, and kidney single-cell RNA sequencing (scRNA-seq) were performed to investigate the effects and mechanisms of C3G. Compared to CT mice, ORG mice exhibited elevated serum CHO, TG, Cys-C, UACR, urinary Kim-1, and NAG levels, along with glomerular hypertrophy and tubular injury. These biochemical and pathological indicators improved following C3G treatment. Fecal 16S analysis revealed reduced gut microbiota diversity in ORG mice compared to CT mice, while C3G intervention increased gut microbiota diversity. Metabolic profiling of feces, serum, and kidney indicated reprogramming of glycerophospholipid metabolism in ORG mice, ameliorated by C3G treatment. Further analysis demonstrated that abnormal glycerophospholipid metabolites correlated with blood lipids, urinary protein, urinary tubular injury markers, and gut microbiota, specifically Lachnospiraceae and Blautia. Additionally, scRNA-seq analysis identified activation of the PPARγ/CD36 pathway in proximal tubule cells (PTCs) of ORG mice. C3G improved abnormal glycerophospholipid metabolism and alleviated injury in PTCs by inhibiting the PPARγ/CD36 pathway. C3G reduces lipid droplet accumulation in the PTCs of ORG mice by modulating the gut microbiota and inhibiting the PPARγ/CD36 pathway. These findings offer new insights and therapeutic targets for ORG.PMID:39675540 | DOI:10.1016/j.phrs.2024.107550

Free Radic Biol Med. 2024 Dec 13:S0891-5849(24)01138-9. doi: 10.1016/j.freeradbiomed.2024.12.029. Online ahead of print.ABSTRACTBACKGROUND: Neuronal protection is a well-established method of acute ischemic stroke (AIS) treatment. The pharmacodynamic effect of Piceatannol-3'-O-β-D-glucopyranoside (Chinese name: Quzhazhigan, QZZG) on AIS has been reported, but the molecular mechanism of this effect remains unknown.PURPOSE: The purpose of this study is to elucidate the pharmacodynamic effects and mechanisms of QZZG in the treatment of AIS.METHODS: A combined network pharmacology and metabolomics approach was used to predict the key targets and pathways of QZZG in the treatment of AIS and to elucidate the mechanism of QZZG through experimental validation.RESULTS: In this study, QZZG improved histopathologic features and reduced infarct volume and neurologic deficit scores. Integrated network pharmacology and metabolomics revealed that QZZG may protect neurons by regulating glutamate and its receptors, and that glutamate is closely related to NMDAR1, NRF2, and Caspase-3. Pathway analysis results suggested that NMDAR-mediated Ca2+ inward flow is one of the critical pathways. In terms of neuroexcitotoxicity QZZG inhibited glutamate content, reduced Ca2+ inward flow, protected mitochondrial function, and reduced ROS, as well as being able to effectively inhibit the expression of NMDAR1, Caspase-3, Bax, and promote the expression of Bcl-2, NMDAR2A. In terms of ferroptosis QZZG promoted NRF2, HO-1, GPX4 and nuclear-NRF2, inhibited the expression of BACH1 and ACSL4, and suppressed Fe2+ accumulation and lipid peroxidation. Silencing of BACH1 resulted in elevated expression of NRF2 and decreased expression of ACSL4, which inhibited the sensitivity of neurons to ferroptosis. QZZG was able to further increase NRF2 expression under conditions of silencing BACH1. QZZG induced NRF2 and inhibited BACH1, ACSL4 was inhibited by ML385, and inhibition of NRF2 induced the expression of BACH1 and ACSL4, QZZG protects neurons in an NRF2-dependent manner.CONCLUSION: In summary, QZZG inhibited neuroexcitotoxicity and ferroptosis by regulating the NMDAR/NRF2/BACH1/ACSL4 pathway. The study provided a relatively novel perspective on the mechanism of traditional Chinese medicine (TCM) treatment of the disease.PMID:39675532 | DOI:10.1016/j.freeradbiomed.2024.12.029