PubMed

Chemosphere. 2023 May 6:138864. doi: 10.1016/j.chemosphere.2023.138864. Online ahead of print.ABSTRACTHair has recently emerged as a biospecimen for characterizing the long-term chemical exposome in biomonitoring investigations spanning several months, as chemical compounds circulating in the bloodstream accumulate in hair. Although there has been interest in using human hair as a biospecimen for exposome studies, it has yet to be widely adopted compared to blood and urine. Here, we applied a high-resolution mass spectrometry (HRMS)-based suspect screening strategy to characterize the long-term chemical exposome in human hair. Hair samples were collected from 70 subjects and cut into 3 cm segments, which were then mixed to prepare pooled samples. The pooled hair samples underwent a sample preparation procedure, and the hair extracts were further analyzed using an HRMS-based suspect screening approach. An in-house chemical suspect list containing 1227 chemical entries from National Report on Human Exposure to Environmental Chemicals (Report) published by the U.S. CDC and the Exposome-Explorer 3.0 database developed by the WHO was subsequently used to screen and filter the suspect features against the HRMS dataset. Overall, we matched 587 suspect features in the HRMS dataset to 246 unique chemical formulas in the suspect list, and the structures of 167 chemicals were further identified through a fragmentation analysis. Among these, chemicals such as mono-2-ethylhexyl phthalate, methyl paraben, and 1-naphthol, which have been detected in the urine or blood for exposure assessment, were also identified in human hair. This suggests that hair reflects the accumulation of environmental compounds to which an individual is exposed. Exposure to exogenous chemicals may exert adverse effects on cognitive function, and we discovered 15 chemicals in human hair that may contribute to the pathogenesis of Alzheimer's disease. This finding suggests that human hair may be a promising biospecimen for monitoring long-term exposure to multiple environmental chemicals and perturbations in endogenous chemicals in biomonitoring investigations.PMID:37156292 | DOI:10.1016/j.chemosphere.2023.138864

J Gerontol A Biol Sci Med Sci. 2023 May 9:glad122. doi: 10.1093/gerona/glad122. Online ahead of print.ABSTRACTBiological mechanisms that lead to multimorbidity are mostly unknown, and metabolomic profiles are promising to explain different pathways in the aging process. The aim of this study was to assess the prospective association between plasma fatty acids and other lipids, and multimorbidity in older adults. Data were obtained from the Spanish Seniors-ENRICA 2 cohort, comprising non-institutionalized adults ≥65 years old. Blood samples were obtained at baseline and after a two-year follow-up period for a total of 1488 subjects. Morbidity was also collected at baseline and end of the follow-up from electronic health records. Multimorbidity was defined as a quantitative score, after weighting morbidities (from a list of 60 mutually exclusive chronic conditions) by their regression coefficients on physical functioning. Generalized estimating equation models were employed to assess the longitudinal association between fatty acids and other lipids, and multimorbidity, and stratified analyses by diet quality, measured with the Alternative Healthy Eating Index-2010, were also conducted. Among study participants, higher concentrations of omega-6 fatty acids [coef. per 1-SD increase (95% CI) = -0.76 (-1.23, -0.30)], phosphoglycerides [-1.26 (-1.77, -0.74)], total cholines [-1.48 (-1.99, -0.96)], phosphatidylcholines [-1.23 (-1.74, -0.71)], and sphingomyelins [-1.65 (-2.12, -1.18)], were associated with lower multimorbidity scores. The strongest associations were observed for those with a higher diet quality. Higher plasma concentrations of omega-6 fatty acids, phosphoglycerides, total cholines, phosphatidylcholines, and sphingomyelins were prospectively associated with lower multimorbidity in older adults, while diet quality could modulate the associations found. These lipids may serve as risk markers for multimorbidity.PMID:37156635 | DOI:10.1093/gerona/glad122

Food Chem. 2023 Feb 17;422:135716. doi: 10.1016/j.foodchem.2023.135716. Online ahead of print.ABSTRACTYunnan pickled tea is produced from fresh tea-leaves through fixation, rolling, anaerobic fermentation and sun-drying. In this study, widely targeted metabolomics using UHPLC-QQQ-MS/MS and HPLC analysis were carried out to elaborate its quality formation during the whole process. Results confirmed the contribution of preliminary treatments and anaerobic fermentation to the quality formation. A total of 568 differential metabolites (VIP > 1.0, P < 0.05, FC > 1.50 or < 0.67) were screened through OPLS-DA. (-)-Epigallocatechin and (-)-epicatechin significantly (P < 0.05) increased from the hydrolyzation of ester catechins, such as (-)-epigallocatechin gallate and (-)-epicatechin gallate in anaerobic fermentation. Additionally, the anaerobic fermentation promoted vast accumulations of seven essential amino acids, four phenolic acids, three flavones and flavone glycosides, pelargonidin and pelargonidin glycosides, flavonoids and flavonoid glycosides (i.e. kaempferol, quercetin, taxifolin, apigenin, myricetin, luteolin and their glycosides) through relevant N-methylation, O-methylation, hydrolyzation, glycosylation and oxidation.PMID:37156017 | DOI:10.1016/j.foodchem.2023.135716

Anal Chem. 2023 May 8. doi: 10.1021/acs.analchem.3c01109. Online ahead of print.ABSTRACTMetabolic footprinting as a convenient and non-invasive cell metabolomics strategy relies on monitoring the whole extracellular metabolic process. It covers nutrient consumption and metabolite secretion of in vitro cell culture, which is hindered by low universality owing to pre-treatment of the cell medium and special equipment. Here, we report the design and a variety of applicability, for quantifying extracellular metabolism, of fluorescently labeled single-stranded DNA (ssDNA)-AuNP encoders, whose multi-modal signal response is triggered by extracellular metabolites. We constructed metabolic response profiling of cells by detecting extracellular metabolites in different tumor cells and drug-induced extracellular metabolites. We further assessed the extracellular metabolism differences using a machine learning algorithm. This metabolic response profiling based on the DNA-AuNP encoder strategy is a powerful complement to metabolic footprinting, which significantly applies potential non-invasive identification of tumor cell heterogeneity.PMID:37155931 | DOI:10.1021/acs.analchem.3c01109

Anal Chem. 2023 May 8. doi: 10.1021/acs.analchem.3c00804. Online ahead of print.ABSTRACTTargeted metabolomics has been broadly used for metabolite measurement due to its good quantitative linearity and simple metabolite annotation workflow. However, metabolite interference, the phenomenon where one metabolite generates a peak in another metabolite's MRM setting (Q1/Q3) with a close retention time (RT), may lead to inaccurate metabolite annotation and quantification. Besides isomeric metabolites having the same precursor and product ions that may interfere with each other, we found other metabolite interferences as the result of inadequate mass resolution of triple-quadruple mass spectrometry and in-source fragmentation of metabolite ions. Characterizing the targeted metabolomics data using 334 metabolite standards revealed that about 75% of the metabolites generated measurable signals in at least one other metabolite's MRM setting. Different chromatography techniques can resolve 65-85% of these interfering signals among standards. Metabolite interference analysis combined with the manual inspection of cell lysate and serum data suggested that about 10% out of ∼180 annotated metabolites were mis-annotated or mis-quantified. These results highlight that a thorough investigation of metabolite interference is necessary for accurate metabolite measurement in targeted metabolomics.PMID:37155916 | DOI:10.1021/acs.analchem.3c00804

Proc Natl Acad Sci U S A. 2023 May 16;120(20):e2220334120. doi: 10.1073/pnas.2220334120. Epub 2023 May 8.ABSTRACTEsophageal squamous cell carcinoma (ESCC) is a deadly disease with few prevention or treatment options. ESCC development in humans and rodents is associated with Zn deficiency (ZD), inflammation, and overexpression of oncogenic microRNAs: miR-31 and miR-21. In a ZD-promoted ESCC rat model with upregulation of these miRs, systemic antimiR-31 suppresses the miR-31-EGLN3/STK40-NF-κB-controlled inflammatory pathway and ESCC. In this model, systemic delivery of Zn-regulated antimiR-31, followed by antimiR-21, restored expression of tumor-suppressor proteins targeted by these specific miRs: STK40/EGLN3 (miR-31), PDCD4 (miR-21), suppressing inflammation, promoting apoptosis, and inhibiting ESCC development. Moreover, ESCC-bearing Zn-deficient (ZD) rats receiving Zn medication showed a 47% decrease in ESCC incidence vs. Zn-untreated controls. Zn treatment eliminated ESCCs by affecting a spectrum of biological processes that included downregulation of expression of the two miRs and miR-31-controlled inflammatory pathway, stimulation of miR-21-PDCD4 axis apoptosis, and reversal of the ESCC metabolome: with decrease in putrescine, increase in glucose, accompanied by downregulation of metabolite enzymes ODC and HK2. Thus, Zn treatment or miR-31/21 silencing are effective therapeutic strategies for ESCC in this rodent model and should be examined in the human counterpart exhibiting the same biological processes.PMID:37155893 | DOI:10.1073/pnas.2220334120

Proc Natl Acad Sci U S A. 2023 May 16;120(20):e2219953120. doi: 10.1073/pnas.2219953120. Epub 2023 May 8.ABSTRACTThe Golgi is a membrane-bound organelle that is essential for protein and lipid biosynthesis. It represents a central trafficking hub that sorts proteins and lipids to various destinations or for secretion from the cell. The Golgi has emerged as a docking platform for cellular signaling pathways including LRRK2 kinase whose deregulation leads to Parkinson disease. Golgi dysfunction is associated with a broad spectrum of diseases including cancer, neurodegeneration, and cardiovascular diseases. To allow the study of the Golgi at high resolution, we report a rapid Golgi immunoprecipitation technique (Golgi-IP) to isolate intact Golgi mini-stacks for subsequent analysis of their content. By fusing the Golgi-resident protein TMEM115 to three tandem HA epitopes (GolgiTAG), we purified the Golgi using Golgi-IP with minimal contamination from other compartments. We then established an analysis pipeline using liquid chromatography coupled with mass spectrometry to characterize the human Golgi proteome, metabolome, and lipidome. Subcellular proteomics confirmed known Golgi proteins and identified proteins not previously associated with the Golgi. Metabolite profiling established the human Golgi metabolome and revealed the enrichment of uridine-diphosphate (UDP) sugars and their derivatives, which is consistent with their roles in protein and lipid glycosylation. Furthermore, targeted metabolomics validated SLC35A2 as the subcellular transporter for UDP-hexose. Finally, lipidomics analysis showed that phospholipids including phosphatidylcholine, phosphatidylinositol, and phosphatidylserine are the most abundant Golgi lipids and that glycosphingolipids are enriched in this compartment. Altogether, our work establishes a comprehensive molecular map of the human Golgi and provides a powerful method to study the Golgi with high precision in health and disease.PMID:37155866 | DOI:10.1073/pnas.2219953120

Proc Natl Acad Sci U S A. 2023 May 16;120(20):e2214942120. doi: 10.1073/pnas.2214942120. Epub 2023 May 8.ABSTRACTAberrant accumulation of succinate has been detected in many cancers. However, the cellular function and regulation of succinate in cancer progression is not completely understood. Using stable isotope-resolved metabolomics analysis, we showed that the epithelial mesenchymal transition (EMT) was associated with profound changes in metabolites, including elevation of cytoplasmic succinate levels. The treatment with cell-permeable succinate induced mesenchymal phenotypes in mammary epithelial cells and enhanced cancer cell stemness. Chromatin immunoprecipitation and sequence analysis showed that elevated cytoplasmic succinate levels were sufficient to reduce global 5-hydroxymethylcytosinene (5hmC) accumulation and induce transcriptional repression of EMT-related genes. We showed that expression of procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) was associated with elevation of cytoplasmic succinate during the EMT process. Silencing of PLOD2 expression in breast cancer cells reduced succinate levels and inhibited cancer cell mesenchymal phenotypes and stemness, which was accompanied by elevated 5hmC levels in chromatin. Importantly, exogenous succinate rescued cancer cell stemness and 5hmC levels in PLOD2-silenced cells, suggesting that PLOD2 promotes cancer progression at least partially through succinate. These results reveal the previously unidentified function of succinate in enhancing cancer cell plasticity and stemness.PMID:37155842 | DOI:10.1073/pnas.2214942120

Metabolomics. 2023 May 8;19(5):50. doi: 10.1007/s11306-023-02012-y.ABSTRACTINTRODUCTION: Gestational hypertension (GH) is defined as the presence of systolic blood pressure (BP) ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg, measured at least 4 h apart after 20 weeks of gestation. Early identification of women at high-risk of developing GH could contribute significantly towards improved maternal and fetal outcomes.OBJECTIVES: To determine early metabolic biomarkers in women with GH as compared with normotensive women.METHODS: Serum samples were collected from subjects during three stages of their pregnancy: 8-12 weeks, 18-20 weeks and after 28 weeks (< 36 weeks) of gestation and studied using nuclear magnetic resonance (NMR) metabolomics approach. Multivariate and univariate analyses were performed to determine the significantly altered metabolites in GH women.RESULTS: A total of 10 metabolites, including isoleucine, glutamine, lysine, proline, histidine, phenylalanine, alanine, carnitine, N-acetyl glycoprotein and lactic acid were observed to be significantly downregulated during all pregnancy stages in women with GH as compared with controls. Furthermore, expression of 5 metabolites in the first trimester i.e., phenylalanine [area under the curve (AUC) = 0.745], histidine [AUC = 0.729], proline [AUC = 0.722], lactic acid [AUC = 0.722], and carnitine [AUC = 0.714] exhibited highest potential in discriminating GH from normotensive women.CONCLUSION: The present study is the first of its kind to identify significantly altered metabolites that have the potential to discriminate between women at risk of developing GH and normotensive women across three trimesters of pregnancy. This opens up the possibility of exploring these metabolites as potential early predictive markers of GH.PMID:37154845 | DOI:10.1007/s11306-023-02012-y

Mol Nutr Food Res. 2023 May 8:e2300056. doi: 10.1002/mnfr.202300056. Online ahead of print.ABSTRACTSCOPE: The aging biomarkers are alternatives and none of them could act as a strong predictor of frailty during the progression of aging. Several studies revealed the relationship between metabolites and frailty or gut microbiota and frailty. However, the connection between metabolites and gut microbiota in non-robust older adults hasn't been discussed yet. Our study aims to combine the findings of serum metabolites and gut microbiota in non-robust subjects as a possible diagnostic biomarker.METHODS AND RESULTS: Frailty-related assessments were conducted to ensure the discrimination of non-robustness. The serum and fecal were collected for serum metabolomics and gut microbiota analysis. Robust and non-robust subjects showed very different gut microbial compositions. Among the gut microbial differences, Escherichia/Shigella and its higher taxonomic ranks were found to have the most discriminative abundance among compared groups. More importantly, the abundance of Escherichia/Shigella was found to be positively correlated (p<0.05) with the level of discriminant metabolites, such as serum oxoglutarate, glutamic acid, and 1-methyladenosine.CONCLUSION: These results indicate that the obvious interrelation between gut microbiota and serum metabolites in non-robust older adults. Besides, our findings suggested that Escherichia/Shigella could be a potential biomarker candidate for robustness sub-phenotypic identification. This article is protected by copyright. All rights reserved.PMID:37154673 | DOI:10.1002/mnfr.202300056

Alcohol Alcohol. 2023 May 8:agad034. doi: 10.1093/alcalc/agad034. Online ahead of print.ABSTRACTAIM: Differentiating alcoholic hepatitis (AH) from acute decompensation of alcoholic cirrhosis (DC) is challenging, as the presentation and biochemistry are similar. We aimed to identify potential metabolomic biomarkers to differentiate between AH and DC, and to predict short-term mortality.METHODS: We included consecutive biopsy proven AH and DC patients, which were managed according to current guidelines and followed up until the end of the study. Untargeted metabolomics was assessed in all patients at baseline. Specific analyses were successively performed to identify potential biomarkers, which were further semi-quantitatively analysed against relevant clinical endpoints.RESULTS: Thirty-four patients with AH and 37 with DC were included. UHPLC-MS analysis identified 83 molecules potentially differentiating between AH and DC. C16-Sphinganine-1P (S1P) was the most increased, whereas Prostaglandin E2 (PGE2) was the most decreased. The PGE2/S1P ratio < 1.03 excellently discriminates between AH and DC: AUC 0.965 (p < 0.001), Se 90%, Sp 100%, PPV 0.91, NPV 1, and diagnostic accuracy 95%. This ratio is not influenced by the presence of infection (AUC 0.967 vs. 0.962), correlates with the Lille score at 7 days (r = -0.60; P = 0.022) and tends to be lower in corticosteroid non-responders as compared with patients who responded [0.85(±0.02) vs. 0.89(±0.05), P = 0.069]. Additionally, decreased ursodeoxycholic acid levels are correlated with MELD and Maddrey scores and predict mortality with a 77.27% accuracy (NPV = 100%).CONCLUSION: This study suggests the PGE2 (decreased)/S1P (increased) ratio as a biomarker to differentiate AH from DC. The study also finds that low levels of ursodeoxycholic acid could predict increased mortality in AH.PMID:37154612 | DOI:10.1093/alcalc/agad034

Oral Dis. 2023 May 8. doi: 10.1111/odi.14594. Online ahead of print.ABSTRACTOBJECTIVES: The transforming growth factor-Beta (TGF-ß) pathway may be involved in the radioresistance of head and neck squamous cell carcinoma (HNSCC). This study analyzed TGF-ß receptor 1 (TGFBR1) expression in HNSCC patients and evaluated the antineoplastic and radiosensitizing effects of vactosertib, a novel TGFBR1 inhibitor, in vitro.MATERIALS AND METHODS: TGFBR1 expression was examined in HNSCC patients at the mRNA level in silico and the protein level by immunohistochemistry, including surgical specimens of primary tumors, matched lymph node metastasis, and recurrent disease. Furthermore, a novel small molecule TGFBR1 inhibitor was evaluated in HNSCC cell lines. Finally, an indirect coculture model using patient-derived cancer-associated fibroblasts was applied to mimic the tumor microenvironment.RESULTS: Patients with high TGFBR1 mRNA levels showed significantly worse overall survival in silico (OS, p = 0.024). At the protein level, an association between TGFBR1+ tumor and OS was observed for the subgroup with TGFBR1-stroma (p = 0.001). Those results prevailed in multivariable analysis. Inhibition of TGFBR1 showed antineoplastic effects in vitro. In combination with radiation, vactosertib showed synergistic effects.CONCLUSION: Our results indicate a high risk of death in tumorTGFBR1+ |stromaTGFBR1- expressing patients. In vitro data suggest a potential radiosensitizing effect of TGFBR1 inhibition by vactosertib.PMID:37154295 | DOI:10.1111/odi.14594

J Agric Food Chem. 2023 May 8. doi: 10.1021/acs.jafc.2c08372. Online ahead of print.ABSTRACTIn China, the endemic species Garcinia yunnanensis and native Garcinia xanthochymus are known as edible and medicinal plants. However, a systematic metabolomic and bioactivity evaluation of different plant parts from both species is lacking. In this study, comprehensive investigations of 11 plant parts of G. yunnanensis and 10 of G. xanthochymus employing UPLC-ESI-QTOF-MSE-based metabolomic analysis in conjunction with three bioactivity assays were undertaken. A customized chemotaxonomic-based in-house library containing 6456 compounds was constructed and coupled to the Progenesis QI informatic platform for metabolite annotations. From these two species, a total of 235 constituents were characterized using multiple criteria. Differences in metabolite profiles between the plant parts within each species were uncovered using multivariate analysis. Based on orthogonal partial least-squares discriminant analysis (OPLS-DA), 23 markers were identified as highly differential metabolites from G. xanthochymus and 20 from G. yunnanensis. Comparative assessment of the biological assays revealed the activity variations among different plant parts. The seeds of both species and G. yunnanensis latex exhibited excellent cytotoxic and antibacterial activities, while G. xanthochymus roots and G. yunnanensis arils showed strong anti-inflammatory effects. S-plot analysis identified 26 potential biomarkers for the observed activities, including the known cytotoxic agent cycloxanthochymol and the anti-inflammatory compound garcimultiflorone B, which likely explains some of the potent observed bioactivity.PMID:37154236 | DOI:10.1021/acs.jafc.2c08372

Theranostics. 2023 Apr 1;13(7):2088-2113. doi: 10.7150/thno.81488. eCollection 2023.ABSTRACTTuberculosis is an airborne disease caused by Mycobacterium tuberculosis (Mtb) and can manifest both pulmonary and extrapulmonary disease, including ocular tuberculosis (OTB). Accurate diagnosis and swift optimal treatment initiation for OTB is faced by many challenges combined with the lack of standardized treatment regimens this results in uncertain OTB outcomes. The purpose of this study is to summarize existing diagnostic approaches and recently discovered biomarkers that may contribute to establishing OTB diagnosis, choice of anti-tubercular therapy (ATT) regimen, and treatment monitoring. The keywords ocular tuberculosis, tuberculosis, Mycobacterium, biomarkers, molecular diagnosis, multi-omics, proteomics, genomics, transcriptomics, metabolomics, T-lymphocytes profiling were searched on PubMed and MEDLINE databases. Articles and books published with at least one of the keywords were included and screened for relevance. There was no time limit for study inclusion. More emphasis was placed on recent publications that contributed new information about the pathogenesis, diagnosis, or treatment of OTB. We excluded abstracts and articles that were not written in the English language. References cited within the identified articles were used to further supplement the search. We found 10 studies evaluating the sensitivity and specificity of interferon-gamma release assay (IGRA), and 6 studies evaluating that of tuberculin skin test (TST) in OTB patients. IGRA (Sp = 71-100%, Se = 36-100%) achieves overall better sensitivity and specificity than TST (Sp = 51.1-85.7%; Se = 70.9-98.5%). For nuclear acid amplification tests (NAAT), we found 7 studies on uniplex polymerase chain reaction (PCR) with different Mtb targets, 7 studies on DNA-based multiplex PCR, 1 study on mRNA-based multiplex PCR, 4 studies on loop-mediated isothermal amplification (LAMP) assay with different Mtb targets, 3 studies on GeneXpert assay, 1 study on GeneXpert Ultra assay and 1 study for MTBDRplus assay for OTB. Specificity is overall improved but sensitivity is highly variable for NAATs (excluding uniplex PCR, Sp = 50-100%; Se = 10.5-98%) as compared to IGRA. We also found 3 transcriptomic studies, 6 proteomic studies, 2 studies on stimulation assays, 1 study on intraocular protein analysis and 1 study on T-lymphocyte profiling in OTB patients. All except 1 study evaluated novel, previously undiscovered biomarkers. Only 1 study has been externally validated by a large independent cohort. Future theranostic marker discovery by a multi-omics approach is essential to deepen pathophysiological understanding of OTB. Combined these might result in swift, optimal and personalized treatment regimens to modulate the heterogeneous mechanisms of OTB. Eventually, these studies could improve the current cumbersome diagnosis and management of OTB.PMID:37153734 | PMC:PMC10157737 | DOI:10.7150/thno.81488

Front Neurol. 2023 Apr 20;14:1036453. doi: 10.3389/fneur.2023.1036453. eCollection 2023.ABSTRACTBACKGROUND: Qihuang needle therapy is a newly developed acupuncture therapy to treat tic disorders in clinical practice. However, the mechanism to reduce tic severity remains unknown. Changes in intestinal flora and circulation metabolites are perhaps the potential pathogenesis of tic disorders. As a result, we present a protocol for a controlled clinical trial using multi-omics analysis to probe the mechanism of the Qihuang needle in managing tic disorders.METHODS: This is a matched-pairs design, controlled, clinical trial for patients with tic disorders. Participants will be allocated to either an experimental group or a healthy control group. The main acupoints are Baihui (GV20), Yintang (EX-HN3), and Jueyinshu (BL14). The experimental group will receive Qihuang needle therapy for a month, while the control group will receive no interventions.EXPECTED OUTCOMES: The change in the severity of the tic disorder is set as the main outcome. Secondary outcomes include gastrointestinal severity index and recurrence rate, which will be calculated after a 12-week follow-up. Gut microbiota, measured by 16S rRNA gene sequencing; serum metabolomics, assessed via LC/MS; and serum zonulin, assessed by enzyme-linked immunosorbent assay (ELISA), will be used as biological specimen analysis outcomes. The present study will investigate the possible interactions between intestinal flora and serum metabolites and the improvement of clinical profiles, which may elucidate the mechanism of Qihuang needle therapy for tic disorders.TRIAL REGISTRATION: This trial is registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/). Registration number: ChiCTR2200057723, Date: 2022-04-14.PMID:37153669 | PMC:PMC10157291 | DOI:10.3389/fneur.2023.1036453

Therap Adv Gastroenterol. 2023 May 2;16:17562848231168199. doi: 10.1177/17562848231168199. eCollection 2023.ABSTRACTBACKGROUND: Therapeutic targets for ulcerative colitis (UC) and prediction models of antitumor necrosis factor (TNF) therapy outcomes have not been fully reported.OBJECTIVE: Investigate the characteristic metabolite and lipid profiles of fecal samples of UC patients before and after adalimumab treatment and develop a prediction model of clinical remission following adalimumab treatment.DESIGN: Prospective, observational, multicenter study was conducted on moderate-to-severe UC patients (n = 116).METHODS: Fecal samples were collected from UC patients at 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n = 37). Clinical remission was assessed using the Mayo score. Metabolomic and lipidomic analyses were performed using gas chromatography mass spectrometry and nano electrospray ionization mass spectrometry, respectively. Orthogonal partial least squares discriminant analysis was performed to establish a remission prediction model.RESULTS: Fecal metabolites in UC patients markedly differed from those in HC at baseline and were changed similarly to those in HC during treatment; however, lipid profiles did not show these patterns. After treatment, the fecal characteristics of remitters (RM) were closer to those of HC than to those of non-remitters (NRM). At 8 and 56 weeks, amino acid levels in RM were lower than those in NRM and similar to those in HC. After 56 weeks, levels of 3-hydroxybutyrate, lysine, and phenethylamine decreased, and dodecanoate level increased in RM similarly to those in HC. The prediction model of long-term remission in male patients based on lipid biomarkers showed a higher performance than clinical markers.CONCLUSION: Fecal metabolites in UC patients markedly differ from those in HC, and the levels in RM are changed similarly to those in HC after anti-TNF therapy. Moreover, 3-hydroxybutyrate, lysine, phenethylamine, and dodecanoate are suggested as potential therapeutic targets for UC. A prediction model of long-term remission based on lipid biomarkers may help implement personalized treatment.PMID:37153496 | PMC:PMC10161336 | DOI:10.1177/17562848231168199

Front Med (Lausanne). 2023 Apr 20;10:1153360. doi: 10.3389/fmed.2023.1153360. eCollection 2023.ABSTRACTBACKGROUND: ErXian decoction is a Chinese herbal compound that can prevent and control the course of osteoarthritis (OA) and osteoporosis (OP). OP and OA are two age-related diseases that often coexist in elderly individuals, and both are associated with dysregulation of the gut microbiome. In the initial study, Palmatine (PAL) was obtained by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and network pharmacological screening techniques, followed by 16S rRNA sequencing and serum metabolomics of intestinal contents, to explore the mechanism of PAL in the treatment of OA and OP.METHODS: The rats selected for this study were randomly divided into three groups: a sham group, an OA-OP group and a PAL group. The sham group was intragastrically administered normal saline solution, and the PLA group was treated with PAL for 56 days. Through microcomputed tomography (micro-CT), ELISA, 16S rRNA gene sequencing and non-targeted metabonomics research, we explored the potential mechanism of intestinal microbiota and serum metabolites in PAL treatment of OA-OP rats.RESULTS: Palmatine significantly repair bone microarchitecture of rat femur in OA-OP rats and improved cartilage damage. The analysis of intestinal microflora showed that PAL could also improve the intestinal microflora disorder of OA-OP rats. For example, the abundance of Firmicutes, Bacteroidota, Actinobacteria, Lactobacillus, unclassified_f_Lachnospiraceae, norank_f_Muribaculaceae, Lactobacillaceae, Lachnospiraceae and Muribaculaceae increased after PAL intervention. In addition, the results of metabolomics data analysis showed that PAL also change the metabolic status of OA-OP rats. After PAL intervention, metabolites such as 5-methoxytryptophol, 2-methoxy acetaminophen sulfate, beta-tyrosine, indole-3-carboxylic acid-O-sulfate and cyclodopa glucoside increased. Association analysis of metabolomics and gut microbiota (GM) showed that the communication of multiple flora and different metabolites played an important role in OP and OA.CONCLUSION: Palmatine can improve cartilage degeneration and bone loss in OA-OP rats. The evidence we provided supports the idea that PAL improves OA-OP by altering GM and serum metabolites. In addition, the application of GM and serum metabolomics correlation analysis provides a new strategy for uncovering the mechanism of herbal treatment for bone diseases.PMID:37153081 | PMC:PMC10159182 | DOI:10.3389/fmed.2023.1153360

Front Endocrinol (Lausanne). 2023 Apr 20;14:1084858. doi: 10.3389/fendo.2023.1084858. eCollection 2023.ABSTRACTHypertensive cerebral microbleeds (HCMB) may be the early stage of hypertensive intracerebral hemorrhage (HICH), which is a serious threat to health due to its high mortality and disability rates. The early clinical symptoms of HCMB may not be significant. Moreover, it is difficult to achieve early diagnosis and intervention for targeted prevention of HICH. Although hypertension (HTN) is a predisposition for HCMB, it remains unclear whether there is any difference between hypertensive patients with or without HCMB. Therefore, we carried out liquid chromatography-mass spectrometry (LC-MS) to analyze early biomarkers for HCMB in mice with hypertension and to lay the foundation for early prevention of HICH in hypertensive patients. In total, 18 C57 male mice were randomly divided into the HCMB (n = 6), HTN (n = 6), and control groups (CON, n = 6). Hematoxylin-eosin and diaminobenzidine staining were used to assess the reliability of the model. The metabolite expression level and sample category stability were tested using the displacement test of orthogonal partial least squares discriminant analysis (OPLS-DA). Significant differences in metabolites were screened out using variable importance in the projection (VIP > 1), which were determined using the OPLS-DA model and the P-value of the t-test (P < 0.05) combined with the nonparametric rank-sum test. With an area under the curve (AUC) > 0.85 and a P-value of 0.05, the receiver operating characteristic curve (ROC) was used to further screen the distinct metabolites of HCMB. Compared with the HTN and CON groups, the HCMB group had significantly higher blood pressure and lower average body weight (P < 0.05). Through untargeted LC-MS analysis, 93 distinct metabolites were identified in the HCMB (P < 0.05, VIP > 1) group. Among these potential biomarkers, six significantly decreased and eight significantly increased differential metabolites were found. Meanwhile, we found that the HCMB group had statistically distinct arginine and purine metabolism pathways (P < 0.05), and citrulline may be the most significant possible biomarker of HCMB (AUC > 0.85, P < 0.05). All of these potential biomarkers may serve as early biomarkers for HICH in hypertension.PMID:37152968 | PMC:PMC10159181 | DOI:10.3389/fendo.2023.1084858

Front Endocrinol (Lausanne). 2023 Apr 19;14:1120988. doi: 10.3389/fendo.2023.1120988. eCollection 2023.ABSTRACTINTRODUCTION: Several metabolite classes have been identified in human endometrium, including lipids, nucleotides, amino acids, organic acids, and sugars. The first studies suggest the importance of metabolites in endometrial functions, as imbalance in uterine metabolites has been associated with low implantation rate and endometriosis. Nevertheless, most of studies have put emphasis on specific metabolite classes, and we lack the knowledge of the whole metabolome composition in human uterus. Further, a healthy dietary pattern has been shown to potentially protect against different endometrial dysfunctions and is a potential modulator of metabolomic composition and, consequently, the intrauterine microenvironment. The Mediterranean Diet (MD), characterized by a high intake of fruits, vegetables, cereals, nuts, legumes, fish, and olive oil, and a low consumption of meat, dairy products, and processed foods, has been associated with a wide range of benefits for health. Indeed, the MD pattern has displayed a beneficial role in endometriosis management and fertility; however, the relationship between the MD and the endometrial metabolome is still unknown. In our study, we set out to analyze receptive-phase endometrial metabolome profiles among women with infertility and their associations with MD.METHODS: The study included women with male factor infertility (n=8), unexplained infertility (n=10), recurrent implantation failure (n=14), and endometriosis (n=13). The endometrial metabolome was analyzed with ultrahigh-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS). The MD adherence of the participants was assessed using the 14-point MEDAS questionnaire of adherence to the MD.RESULTS: We provide the whole metabolome profile of the endometrium, where 925 different metabolites were identified. Among these metabolites, lipids comprised the largest part, where polyunsaturated fatty acids (PUFAs) prevailed. Women with endometriosis and recurrent implantation failure were found to have lower levels of PUFAs compared to women with male factor and unexplained infertility (i.e., no clear endometrial alterations), identifying a metabolome profile associated with infertility diagnoses where altered endometrial functions are suspected. Moreover, MD adherence seemed to be associated with the endometrial metabolomic profile in a manner dependent on the health status of the uterus.CONCLUSION: The study findings provide insight into the molecular background of female infertility and lead to identification of potential molecular biomarkers and possibilities for modulating the endometrial microenvironment and, thereby, endometrial functions involved in embryo implantation and infertility.PMID:37152925 | PMC:PMC10155813 | DOI:10.3389/fendo.2023.1120988

Front Mol Biosci. 2023 Apr 21;10:1169449. doi: 10.3389/fmolb.2023.1169449. eCollection 2023.NO ABSTRACTPMID:37152901 | PMC:PMC10160367 | DOI:10.3389/fmolb.2023.1169449