PubMed

Am J Med Genet A. 2024 May 6:e63645. doi: 10.1002/ajmg.a.63645. Online ahead of print.ABSTRACTProline-5-carboxylate reductase 2, encoded by PYCR2 gene, is an enzyme that catalyzes the last step of proline synthesis from pyrroline-5-carboxylate synthetase to proline. PYCR2 gene defect causes hypomyelinating leukodystrophy 10. Up until now, to our knowledge around 38 patients with PYCR2 defect have been reported. Herein, we describe clinical, neuroradiological, biochemical findings, and metabolomic profiling of three new genetically related cases of PYCR2 defects from a large family. Cerebrospinal fluid (CSF) amino acid levels were measured and untargeted metabolomic profiling of plasma and CSF were conducted and evaluated together with the clinical findings in the patients. While plasma and CSF proline levels were found to be totally normal, untargeted metabolomic profiling revealed mild increases of glutamate, alpha-ketoglutarate, and l-glutamate semialdehyde and marked increases of inosine and xanthine. Our findings and all the previous reports suggest that proline auxotrophy is not the central disease mechanism. Untargeted metabolomics point to mild changes in proline pathway and also in purine/pyrimidine pathway.PMID:38709052 | DOI:10.1002/ajmg.a.63645

J Agric Food Chem. 2024 May 6. doi: 10.1021/acs.jafc.4c01517. Online ahead of print.ABSTRACTMoringa seeds are an excellent dietary source of phytochemicals (i.e., glucosinolates, GSLs; isothiocyanates, ITCs) with health-beneficial effects. Although numerous studies have been conducted on moringa seeds, the effect of germination on the regulation of GSLs remains scarcely explored. The present study investigated the dynamic changes of GSLs in moringa seeds during germination (at 25, 30, and 35 °C for 6 days in the dark) through an untargeted metabolomics approach and compared the antioxidant capacity of ungerminated and germinated moringa seeds. Our results showed that germination significantly increased the total GSL content from 150 (day 0) to 323 μmol/g (35 °C, day 6) on a dry weight (DW) basis, especially glucomoringin (GMG), the unique glucosinolate in moringa seeds, which was significantly upregulated from 61 (day 0) to 149 μmol/g DW (35 °C, day 4). The upregulation of GMG corresponded to the metabolism of tyrosine, which might be the initial precursor for the formation of GMG. In addition, germination enhanced the total ITC content from 85 (day 0) to 239 μmol SE/g DW (35 °C, day 6), indicating that germination may have also increased the activity of myrosinase. Furthermore, germination remarkably increased the total phenolic content (109-507 mg GAE/100 g DW) and antioxidant capacity of moringa seeds. Our findings suggest that moringa sprouts could be promoted as a novel food and/or ingredient rich in GMG.PMID:38708781 | DOI:10.1021/acs.jafc.4c01517

Nan Fang Yi Ke Da Xue Xue Bao. 2024 Apr 20;44(4):780-786. doi: 10.12122/j.issn.1673-4254.2024.04.21.ABSTRACTOBJECTIVE: To explore the impact of diabetes on collateral circulation (CC) development in patients with chronic total coronary occlusion (CTO) and the underlying regulatory mechanism.METHODS: This study was conducted among 87 patients with coronary heart disease (CHD), who had CTO in at least one vessel as confirmed by coronary angiography. Among them 42 patients were found to have a low CC level (Cohen-Rentrop grades 0-1) and 45 had a high CC level (grades 2-3). In the 39 patients with comorbid diabetes mellitus and 48 non-diabetic patients, insulin resistance (IR) levels were compared between the subgroups with different CC levels. The steady-state mode evaluation method was employed for calculating the homeostatic model assessment for insulin resistance index (HOMA-IR) using a mathematical model. During the interventional procedures, collateral and peripheral blood samples were collected from 22 patients for comparison of the metabolites using non-targeted metabolomics analysis.RESULTS: NT-proBNP levels and LVEF differed significantly between the patients with different CC levels (P<0.05). In non-diabetic patients, HOMA-IR was higher in low CC level group than in high CC level groups. Compared with the non-diabetic patients, the diabetic patients showed 63 upregulated and 48 downregulated metabolites in the collateral blood and 23 upregulated and 14 downregulated metabolites in the peripheral blood. The differential metabolites in the collateral blood were involved in aromatic compound degradation, fatty acid biosynthesis, and steroid degradation pathways; those in the peripheral blood were related with pentose phosphate metabolism, bacterial chemotaxis, hexanoyl-CoA degradation, glycerophospholipid metabolism, and lysine degradation pathways.CONCLUSION: The non-diabetic patients with a low level of CC had significant insulin resistance. The degradation pathways of aromatic compounds, fatty acid biosynthesis, and steroid degradation are closely correlated with the development of CC.PMID:38708513 | DOI:10.12122/j.issn.1673-4254.2024.04.21

Phytochem Anal. 2024 May 6. doi: 10.1002/pca.3373. Online ahead of print.ABSTRACTINTRODUCTION: The leaves of Annona muricata L., known as "soursop" or "sirsak" in Indonesia, are used traditionally for cancer treatment. However, the bioactive components remain largely unidentified.OBJECTIVE: This study used untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomics to identify potential cytotoxic compounds in A. muricata leaf extracts on MCF-7 breast cancer cells in vitro.METHODS: A. muricata leaves were macerated with water, 99% ethanol, and aqueous mixtures containing 30%, 50%, and 80% ethanol. Cytotoxic activity of the extracts against MCF-7 breast cancer cells was determined using the MTT assay. Ultra-high-performance liquid chromatography-Q-Orbitrap high-resolution mass spectroscopy (UHPLC-Q-Orbitrap-HRMS) was used to characterize the metabolite composition of each extract. The correlations between metabolite profile and cytotoxic activities were evaluated using orthogonal partial least square discriminant analysis (OPLS-DA). The binding of these bioactive compounds to the tumorigenic alpha-estrogen receptor (3ERT) was then evaluated by in silico docking simulations.RESULTS: Ninety-nine percent ethanol extracts demonstrated the greatest potency for reducing MCF-7 cell viability (IC50 = 22 μg/ml). We detected 35 metabolites in ethanol extracts, including alkaloids, flavonoids, and acetogenins. OPLS-DA predicted that annoreticuin, squadiolin C, and xylopine, and six unknown acetogenin metabolites, might reduce MCF-7 cell viability. In silico analysis predicted that annoreticuin, squadiolin C, and xylopine bind to 3ERT with an affinity comparable to doxorubicin.CONCLUSION: Untargeted metabolomics and in silico modeling identified cytotoxic compounds on MCF-7 cells and binding affinity to 3ERT in A. muricata leaf extracts. The findings need to be further verified to prove the screening results.PMID:38708435 | DOI:10.1002/pca.3373

Biochem Biophys Rep. 2024 Apr 26;38:101719. doi: 10.1016/j.bbrep.2024.101719. eCollection 2024 Jul.ABSTRACTEmpirical studies have indicated that excessive tea consumption may potentially decrease folate levels within the human body. The main active component in green tea, epigallocatechin gallate (EGCG), significantly reduces the concentration of 5-methyltetrahydrofolate (5-MTHF) in both solution and serum. However, our findings also demonstrate that the pro-degradation effect of EGCG on 5-MTHF can be reversed by L-ascorbic acid (AA). Subsequent investigations suggest that EGCG could potentially expedite the degradation of 5-MTHF by generating hydrogen peroxide. In summary, excessive tea intake may lead to reduced folate levels in the bloodstream, yet timely supplementation of AA could potentially safeguard folate from degradation.PMID:38708422 | PMC:PMC11066525 | DOI:10.1016/j.bbrep.2024.101719

Data Brief. 2024 Apr 16;54:110431. doi: 10.1016/j.dib.2024.110431. eCollection 2024 Jun.ABSTRACTCortex, medulla and papilla are three major human kidney anatomic structures and they harbour unique metabolic functions, but the underlying metabolomic profiles are largely unknown at spatial resolution. Here, we generated a spatially resolved metabolomics dataset on human kidney cortex, medulla and papilla tissues dissected from the same donor. Matrix-Assisted Laser Desorption/Ionization-Imaging Mass Spectrometry (MALDI-IMS) was used to detect metabolite species over mass-to-charge ratios of 50 -1500 for each section at a resolution of 10 × 10 µm2 pixel size. We present raw data matrix of each sample, feature annotations, raw AnnData merged from three samples and processed AnnData files after quality control, dimensional reduction and data integration, which contains a total of 170,459 spatially resolved metabolomes with 562 features detected. This dataset can be either visualized through an interactive browser or further analyzed to study metabolomic heterogeneity across regional human kidney anatomy.PMID:38708307 | PMC:PMC11067325 | DOI:10.1016/j.dib.2024.110431

Front Pharmacol. 2024 Apr 19;15:1349244. doi: 10.3389/fphar.2024.1349244. eCollection 2024.ABSTRACTIntroduction: Herbal formulations are renowned for their complex biological activities, acting on multiple targets and pathways, as evidenced by in vitro studies. However, the hypoglycemic effect and underlying mechanisms of Shenqi Compound (SQ), a traditional Chinese herbal formula, remain elusive. This study aimed to elucidate the hypoglycemic effects of SQ and explore its mechanisms of action, focusing on intestinal flora and metabolomics. Methods: A Type 2 diabetes mellitus (T2DM) rat model was established through a high-fat diet, followed by variable glucose and insulin injections to mimic the fluctuating glycemic conditions seen in diabetes. Results: An eight-week regimen of SQ significantly mitigated hyperglycemia, inflammation, and insulin resistance in these rats. Notably, SQ beneficially modulated the gut microbiota by increasing populations of beneficial bacteria, such as Lachnospiraceae_NK4A136_group and Akkermansia, while reducing and inhibiting harmful strains such as Ruminococcus and Phascolarctobacterium. Metabolomics analyses revealed that SQ intervention corrected disturbances in Testosterone enanthate and Glycerophospholipid metabolism. Discussion: Our findings highlight the hypoglycemic potential of SQ and its mechanisms via modulation of the gut microbiota and metabolic pathways, offering a theoretical foundation for the use of herbal medicine in diabetes management.PMID:38708085 | PMC:PMC11066276 | DOI:10.3389/fphar.2024.1349244

Front Immunol. 2024 Apr 18;15:1370771. doi: 10.3389/fimmu.2024.1370771. eCollection 2024.ABSTRACTINTRODUCTION: Anti-PD-1/PD-L1 inhibitors therapy has become a promising treatment for hepatocellular carcinoma (HCC), while the therapeutic efficacy varies significantly among effects for individual patients are significant difference. Unfortunately, specific predictive biomarkers indicating the degree of benefit for patients and thus guiding the selection of suitable candidates for immune therapy remain elusive.no specific predictive biomarkers are available indicating the degree of benefit for patients and thus screening the preferred population suitable for the immune therapy.METHODS: Ultra-high-pressure liquid chromatography-mass spectrometry (UHPLC-MS) considered is an important method for analyzing biological samples, since it has the advantages of high rapid, high sensitivity, and high specificity. Ultra-high-pressure liquid chromatography-mass spectrometry (UHPLC-MS) has emerged as a pivotal method for analyzing biological samples due to its inherent advantages of rapidity, sensitivity, and specificity. In this study, potential metabolite biomarkers that can predict the therapeutic effect of HCC patients receiving immune therapy were identified by UHPLC-MS.RESULTS: A partial least-squares discriminant analysis (PLS-DA) model was established using 14 glycerophospholipid metabolites mentioned above, and good prediction parameters (R2 = 0.823, Q2 = 0.615, prediction accuracy = 0.880 and p < 0.001) were obtained. The relative abundance of glycerophospholipid metabolite ions is closely related to the survival benefit of HCC patients who received immune therapy.DISCUSSION: This study reveals that glycerophospholipid metabolites play a crucial role in predicting the efficacy of immune therapy for HCC.PMID:38707906 | PMC:PMC11067499 | DOI:10.3389/fimmu.2024.1370771

ISME Commun. 2024 Mar 26;4(1):ycae041. doi: 10.1093/ismeco/ycae041. eCollection 2024 Jan.ABSTRACTIn response to climate change, the nature of endophytes and their applications in sustainable agriculture have attracted the attention of academics and agro-industries. This work focused on the endophytic halophiles of the endangered Taiwanese salt marsh plant, Bolboschoenus planiculmis, and evaluated the functions of these isolates through in planta salinity stress alleviation assay using Arabidopsis. The endophytic strain Priestia megaterium BP01R2, which can promote plant growth and salinity tolerance, was further characterized through multi-omics approaches. The transcriptomics results suggested that BP01R2 could function by tuning hormone signal transduction, energy-producing metabolism, multiple stress responses, etc. In addition, the cyclodipeptide cyclo(L-Ala-Gly), which was identified by metabolomics analysis, was confirmed to contribute to the alleviation of salinity stress in stressed plants via exogenous supplementation. In this study, we used multi-omics approaches to investigate the genomics, metabolomics, and tropisms of endophytes, as well as the transcriptomics of plants in response to the endophyte. The results revealed the potential molecular mechanisms underlying the occurrence of biostimulant-based plant-endophyte symbioses with possible application in sustainable agriculture.PMID:38707842 | PMC:PMC11070113 | DOI:10.1093/ismeco/ycae041

Kidney Int Rep. 2024 Mar 28;9(5):1163-1166. doi: 10.1016/j.ekir.2024.03.025. eCollection 2024 May.NO ABSTRACTPMID:38707828 | PMC:PMC11069007 | DOI:10.1016/j.ekir.2024.03.025

Kidney Int Rep. 2024 Feb 6;9(5):1458-1472. doi: 10.1016/j.ekir.2024.01.060. eCollection 2024 May.ABSTRACTINTRODUCTION: Sugarcane workers are exposed to potentially hazardous agrochemicals, including pesticides, heavy metals, and silica. Such occupational exposures present health risks and have been implicated in a high rate of kidney disease seen in these workers.METHODS: To investigate potential biomarkers and mechanisms that could explain chronic kidney disease (CKD) among this worker population, paired urine samples were collected from sugarcane cutters at the beginning and end of a harvest season in Guatemala. Workers were then separated into 2 groups, namely those with or without kidney function decline (KFD) across the harvest season. Urine samples from these 2 groups underwent elemental analysis and untargeted metabolomics.RESULTS: Urine profiles demonstrated increases in silicon, certain pesticides, and phosphorus levels in all workers, whereas heavy metals remained low. The KFD group had a reduction in estimated glomerular filtration rate (eGFR) across the harvest season; however, kidney injury marker 1 did not significantly change. Cross-harvest metabolomic analysis found trends of fatty acid accumulation, perturbed amino acid metabolism, presence of pesticides, and other known signs of impaired kidney function.CONCLUSION: Silica and certain pesticides were significantly elevated in the urine of sugarcane workers with or without KFD. Future work should determine whether long-term occupational exposure to silica and pesticides across multiple seasons contributes to CKD in these workers. Overall, these results confirmed that multiple exposures are occurring in sugarcane workers and may provide insight into early warning signs of kidney injury and may help explain the increased incidence of CKD among agricultural workers.PMID:38707825 | PMC:PMC11069010 | DOI:10.1016/j.ekir.2024.01.060

Food Chem X. 2024 Apr 25;22:101412. doi: 10.1016/j.fochx.2024.101412. eCollection 2024 Jun 30.ABSTRACTIdentifying the geographic origin of a wine is of great importance, as origin fakery is commonplace in the wine industry. This study analyzed the mineral elements, volatile components, and metabolites in wine using inductively coupled plasma-mass spectrometry, headspace solid phase microextraction gas chromatography-mass spectrometry, and ultra-high-performance liquid chromatography-quadrupole-exactive orbitrap mass spectrometry. The most critical variables (5 mineral elements, 13 volatile components, and 51 metabolites) for wine origin classification were selected via principal component analysis and orthogonal partial least squares discriminant analysis. Subsequently, three algorithms-K-nearest neighbors, support vector machine, and random forest -were used to model single and fused datasets for origin identification. These results indicated that fused datasets, based on feature variables (mineral elements, volatile components, and metabolites), achieved the best performance, with predictive rates of 100% for all three algorithms. This study demonstrates the effectiveness of a multi-source data fusion strategy for authenticity identification of Chinese wine.PMID:38707779 | PMC:PMC11067470 | DOI:10.1016/j.fochx.2024.101412

Contemp Clin Dent. 2024 Jan-Mar;15(1):3-9. doi: 10.4103/ccd.ccd_23_21. Epub 2024 Mar 23.ABSTRACTAIM: Urine as a biofluid has been rarely used as a diagnostic fluid in oral diseases. The article aims to systematically review the utility of human urinary carcinogen metabolites as an approach for obtaining important information about tobacco and cancer.MATERIALS AND METHODS: The following article reviews the use of urine and its metabolites as biomarkers in various lesions of the oral cavity including oral squamous cell carcinoma and as a screening method in evaluating tobacco and its components. A bibliographic comprehensive search was carried out in the main databases: PUBMED, SciELO, Google Scholar, VHL, and LILACS for articles that were published from 1985 to 2020. The inclusion criteria were "urinary metabolites," "oral cancer/HNSCC," "body fluids," "tobacco," and "metabolomics." A total of 55 articles were collected which included laboratory studies, systematic reviews, and literature of urinary metabolites in tobacco users.RESULTS: Most of the studies carried out show accurate results with high sensitivity of urinary metabolite biomarkers in individuals with tobacco-based habits and lesions caused by them.CONCLUSION: The review indicates that urinary metabolite analysis demonstrates its applicability for the diagnosis and prognosis of disease. Urine is a remarkable and useful biofluid for routine testing and provides an excellent resource for the discovery of novel biomarkers, with an advantage over tissue biopsy samples due to the ease and less invasive nature of collection.PMID:38707674 | PMC:PMC11068250 | DOI:10.4103/ccd.ccd_23_21

Open Respir Arch. 2024 Apr 5;6(2):100324. doi: 10.1016/j.opresp.2024.100324. eCollection 2024 Apr-Jun.ABSTRACTAsthma is a chronic inflammatory disease that affects about 5% of the world's population and generates high health and social costs. Proper management of the disease requires a correct diagnosis, based on objective measures of functional impairment, as well as symptom control and assessment of the future risk of exacerbations.It has been estimated that 18% of asthma patients in Western Europe have severe asthma and approximately 50% of them have poor control. The severity of asthma is established based on the minimum maintenance treatment needs to achieve control. Asthma clinical practice guidelines recommend classifying severe patients into allergic asthma (T2); eosinophilic asthma (T2) and non-T2 asthma in order to establish the most appropriate treatment.In recent decades, new biological therapies have been developed that can be applied according to the phenotype and endotype of asthma, allowing for selective and personalized treatment. These phenotypes and endotypes can change over time and therefore, the identification of biomarkers capable of predicting the severity, the course of the disease and the response to a given treatment seems essential. A large number of biomarkers have been studied in asthma, but so far only a few can be readily used in routine clinical practice. The application of omics technologies (epigenomics, genomics, transcriptomics, proteomics, metabolomics, lipidomics, etc.) for this purpose is still in the research phase.PMID:38707659 | PMC:PMC11067451 | DOI:10.1016/j.opresp.2024.100324

Heliyon. 2024 Apr 22;10(9):e29936. doi: 10.1016/j.heliyon.2024.e29936. eCollection 2024 May 15.ABSTRACTIntact (whole) cell MALDI TOF mass spectrometry is a commonly used tool in clinical microbiology for several decades. Recently it was introduced to analysis of eukaryotic cells, including cancer and stem cells. Besides targeted metabolomic and proteomic applications, the intact cell MALDI TOF mass spectrometry provides a sufficient sensitivity and specificity to discriminate cell types, isogenous cell lines or even the metabolic states. This makes the intact cell MALDI TOF mass spectrometry a promising tool for quality control in advanced cell cultures with a potential to reveal batch-to-batch variation, aberrant clones, or unwanted shifts in cell phenotype. However, cellular alterations induced by change in expression of a single gene has not been addressed by intact cell mass spectrometry yet. In this work we used a well-characterized human ovarian cancer cell line SKOV3 with silenced expression of a tumor suppressor candidate 3 gene (TUSC3). TUSC3 is involved in co-translational N-glycosylation of proteins with well-known global impact on cell phenotype. Altogether, this experimental design represents a highly suitable model for optimization of intact cell mass spectrometry and analysis of spectral data. Here we investigated five machine learning algorithms (k-nearest neighbors, decision tree, random forest, partial least squares discrimination, and artificial neural network) and optimized their performance either in pure populations or in two-component mixtures composed of cells with normal or silenced expression of TUSC3. All five algorithms reached accuracy over 90 % and were able to reveal even subtle changes in mass spectra corresponding to alterations of TUSC3 expression. In summary, we demonstrate that spectral fingerprints generated by intact cell MALDI-TOF mass spectrometry coupled to a machine learning classifier can reveal minute changes induced by alteration of a single gene, and therefore contribute to the portfolio of quality control applications in routine cell and tissue cultures.PMID:38707401 | PMC:PMC11066331 | DOI:10.1016/j.heliyon.2024.e29936

Front Nutr. 2024 Apr 19;11:1367589. doi: 10.3389/fnut.2024.1367589. eCollection 2024.ABSTRACTINTRODUCTION: Taurine has a prominent lipid-lowering effect on hyperlipidemia. However, a comprehensive analysis of the effects of taurine on endogenous metabolites in hyperlipidemia has not been documented. This study aimed to explore the impact of taurine on multiple metabolites associated with hyperlipidemia.METHODS: The hyperlipidemic mouse model was induced by high-fat diet (HFD). Taurine was administered via oral gavage at doses of 700 mg/kg/day for 14 weeks. Evaluation of body weight, serum lipid levels, and histopathology of the liver and adipose tissue was performed to confirm the lipid-lowering effect of taurine. Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS)-based metabonomics analyses of serum, urine, feces, and liver, coupled with multivariate data analysis, were conducted to assess changes in the endogenous metabolites.RESULTS AND DISCUSSION: Biochemical and histological examinations demonstrated that taurine administration prevented weight gain and dyslipidemia, and alleviated lipid deposition in the liver and adipose tissue in hyperlipidemic mice. A total of 76 differential metabolites were identified by UPLC-MS-based metabolomics approach, mainly involving BAs, GPs, SMs, DGs, TGs, PUFAs and amino acids. Taurine was found to partially prevent HFDinduced abnormalities in the aforementioned metabolites. Using KEGG database and MetaboAnalyst software, it was determined that taurine effectively alleviates metabolic abnormalities caused by HFD, including fatty acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, diacylglycerol metabolism, amino acid metabolism, bile acid and taurine metabolism, taurine and hypotaurine metabolism. Moreover, DGs, GPs and SMs, and taurine itself may serve as active metabolites in facilitating various anti-hyperlipidemia signal pathways associated with taurine. This study provides new evidence for taurine to prevent hyperlipidemia.PMID:38706565 | PMC:PMC11066166 | DOI:10.3389/fnut.2024.1367589

Cardiovasc Endocrinol Metab. 2024 May 2;13(2):e0303. doi: 10.1097/XCE.0000000000000303. eCollection 2024 Jun.ABSTRACTOBJECTIVES: Oxidative stress plays a pivotal role in the development of metabolic syndrome, including heart failure and insulin resistance. The N-terminal fragment of brain natriuretic peptide (NT-proBNP) has been associated with heightened oxidative stress in heart failure patients. Yet, its correlation with insulin resistance remains poorly understood. Our objective is to investigate the association between oxidative stress markers and NT-proBNP levels in insulin-resistant individuals.METHODS: In this cross-sectional study involving 393 participants from the Qatar Biobank, clinical and metabolic data were collected, and the association between NT-proBNP and 72 oxidative stress metabolites was compared between insulin-sensitive and insulin-resistant individuals.RESULTS: Our results showed significantly lower NT-proBNP levels in insulin-resistant individuals (median = 17 pg/ml; interquartile range = 10.3-29) when compared to their insulin-sensitive counterparts (median = 31 pg/ml; interquartile range = 19-57). Moreover, we revealed notable associations between NT-proBNP levels and antioxidant metabolic pathways, particularly those related to glutathione metabolism, in insulin-resistant, but not insulin-sensitive individuals.CONCLUSION: The significant decrease in NT-proBNP observed in individuals with insulin resistance may be attributed to a direct or indirect enhancement in glutathione production, which is regarded as a compensatory mechanism against oxidative stress. This study could advance our understanding of the interplay between oxidative stress during insulin resistance and cardiovascular risk, which could lead to novel therapeutic approaches for managing cardiovascular diseases. Further investigations are needed to assess the practical utility of these potential metabolites and understand the causal nature of their association with NT-proBNP in the etiology of insulin resistance.PMID:38706534 | PMC:PMC11068140 | DOI:10.1097/XCE.0000000000000303

Curr Protoc. 2024 May;4(5):e1043. doi: 10.1002/cpz1.1043.ABSTRACTTrypanosoma brucei (Tb) is the causative agent of human African trypanosomiasis (HAT), also known as sleeping sickness, which can be fatal if left untreated. An understanding of the parasite's cellular metabolism is vital for the discovery of new antitrypanosomal drugs and for disease eradication. Metabolomics can be used to analyze numerous metabolic pathways described as essential to Tb. brucei but has some limitations linked to the metabolites' physicochemical properties and the extraction process. To develop an optimized method for extracting and analyzing Tb. brucei metabolites, we tested the three most commonly used extraction methods, analyzed the extracts by hydrophilic interaction liquid chromatography high-resolution mass spectrometry (HILIC LC-HRMS), and further evaluated the results using quantitative criteria including the number, intensity, reproducibility, and variability of features, as well as qualitative criteria such as the specific coverage of relevant metabolites. Here, we present the resulting protocols for untargeted metabolomic analysis of Tb. brucei using (HILIC LC-HRMS). © 2024 Wiley Periodicals LLC. Basic Protocol 1: Culture of Trypanosoma brucei brucei parasites Basic Protocol 2: Preparation of samples for metabolomic analysis of Trypanosoma brucei brucei Basic Protocol 3: LC-HRMS-based metabolomic data analysis of Trypanosoma brucei brucei.PMID:38706422 | DOI:10.1002/cpz1.1043

Gut Microbes. 2024 Jan-Dec;16(1):2348441. doi: 10.1080/19490976.2024.2348441. Epub 2024 May 5.ABSTRACTColorectal cancer (CRC), a malignant tumor worldwide, is associated with gut microbiota. The influence of gut microbe-derived metabolites on CRC has attracted a lot of attention. However, the role of immunity mediated by commensal microbiota-derived metabolites in tumorigenesis of CRC is not intensively explored. Here we monitored the gut microbial dysbiosis in CRC mouse model (ApcMin/+ model) without dietary and pharmacological intervention, followed by characterized of metabolites enriched in CRC model mice. Profound changes of gut microbiome (bacteriome) were observed during intestinal disorders. Metabolomic profiling indicated that agmatine, derived from the gut bacteria i.e. Blautia, Odoribacter, Alistipes and Paraprevotella, could interact with Rnf128 to suppress the Rnf128-mediated ubiquitination of β-catenin to further upregulate the downstream targets of β-catenin including Cyclin D1, Lgr5, CD44 and C-myc, thus activating Wnt signaling. The activated Wnt signaling pathway promoted dysplasia of intestinal cells and inflammatory infiltration of lymphocytes via inducing the upregulation of pro-inflammatory cytokines (IL-6 and TNF-α) and downregulation of anti-inflammatory cytokine (IL-10), thereby contributing to colorectal carcinogenesis. Therefore, our study presented novel insights into the roles and mechanisms of gut microbiota in pathogenesis of CRC.PMID:38706224 | DOI:10.1080/19490976.2024.2348441

Clin Transl Med. 2024 May;14(5):e1679. doi: 10.1002/ctm2.1679.ABSTRACTMetabolic abnormalities represent one of the pathological features of chronic obstructive pulmonary disease (COPD). Glutamic pyruvate transaminase 2 (GPT2) is involved in glutamate metabolism and lipid synthesis pathways, whilst the exact roles of GPT2 in the occurrence and development of COPD remains uncertain. This study aims at investigating how GPT2 and the associated genes modulate smoking-induced airway epithelial metabolism and damage by reprogramming lipid synthesis. The circulating or human airway epithelial metabolomic and lipidomic profiles of COPD patients or cell-lines explored with smoking were assessed to elucidate the pivotal roles of GPT2 in reprogramming processes. We found that GPT2 regulate the reprogramming of lipid metabolisms caused by smoking, especially phosphatidylcholine (PC) and triacylglycerol (TAG), along with changes in the expression of lipid metabolism-associated genes. GPT2 modulated cell sensitivities and survival in response to smoking by enhancing mitochondrial functions and maintaining lipid and energy homeostasis. Our findings provide evidence for the involvement of GPT2 in the reprogramming of airway epithelial lipids following smoking, as well as the molecular mechanisms underlying GPT2-mediated regulation, which may offer an alternative of therapeutic strategies for chronic lung diseases.PMID:38706045 | DOI:10.1002/ctm2.1679