PubMed

Imeta. 2023 Nov 6;2(4):e149. doi: 10.1002/imt2.149. eCollection 2023 Nov.ABSTRACT[This corrects the article DOI: 10.1002/imt2.10.].PMID:38868231 | PMC:PMC10989943 | DOI:10.1002/imt2.149

Imeta. 2023 Nov 6;2(4):e151. doi: 10.1002/imt2.151. eCollection 2023 Nov.ABSTRACT[This corrects the article DOI: 10.1002/imt2.17.].PMID:38868225 | PMC:PMC10989940 | DOI:10.1002/imt2.151

Imeta. 2023 Sep 25;2(4):e136. doi: 10.1002/imt2.136. eCollection 2023 Nov.ABSTRACTInflammatory bowel diseases (IBDs) are chronic inflammatory diseases of the gastrointestinal tract that have become a global health burden. Studies have revealed that Latilactobacillus sakei can effectively alleviate various immune diseases, including colitis, rheumatoid arthritis, and metabolic disorders. Here, we obtained 72 strains of L. sakei from 120 fermentation and fecal samples across China. In total, 16 strains from different sources were initially screened in an in vitro Caco-2 model induced by dextran sulfate sodium. Subsequently, six strains (four exhibiting effectiveness and two exhibiting ineffectiveness) were selected for further validation in an in vivo colitis mouse model. The results demonstrated that L. sakei strains exhibited varying degrees of amelioration of the colitis disease process. Notably, L. sakei CCFM1267, the most effective strain, significantly restored colon length and tight-junction protein expression, and reduced the levels of cytokines and associated inflammatory enzymes. Moreover, L. sakei CCFM1267 upregulated the abundance of Enterorhabdus, Alloprevotella, and Roseburia, leading to increased levels of acetic acid and propionic acid. Conversely, the other four strains (L. sakei QJSSZ1L4, QJSSZ4L10, QGZZYRHMT1L6, and QGZZYRHMT2L6) only exhibited a partial remission effect, while L. sakei QJSNT1L10 displayed minimal impact. Therefore, L. sakei CCFM1267 and QJSNT1L10 were selected for further exploration of the mechanisms underlying their differential mitigating effects. Comparative genomics analysis revealed significant variations between the two strains, particularly in genes associated with carbohydrate-active enzymes, such as the glycoside hydrolase family, which potentially contribute to the diverse profiles of short-chain fatty acids in vivo. Additionally, metabolome analysis demonstrated that acetylcholine and indole-3-acetic acid were the main differentiating metabolites of the two strains. Therefore, the strains of L. sakei exhibited varying degrees of effectiveness in alleviating IBD-related symptoms, and the possible reasons for these variations were attributed to discrepancies in the carbohydrate-active enzymes and metabolites among the strains.PMID:38868211 | PMC:PMC10989848 | DOI:10.1002/imt2.136

Heliyon. 2024 May 25;10(11):e31917. doi: 10.1016/j.heliyon.2024.e31917. eCollection 2024 Jun 15.ABSTRACTBACKGROUND AND AIMS: The mechanisms occur in children with obesity after lifestyle intervention remain poorly explained. Here, we investigated the serum proteomes and metabolomes of children with obesity who had undergone 30 days of weight loss intervention.METHODS AND RESULTS: Serum samples and clinical parameters were collected before and after lifestyle alteration interventions. Proteomic and metabolomic profiling was used to identify the differentially expressed proteins and differentially abundant metabolites in response to weight loss intervention. Lifestyle alteration interventions significantly decreased BMI, waist circumference, hip circumference and body fat, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL) and high non-HDL cholesterol, but not TG and high-density lipoprotein cholesterol (HDL), in children with obesity. By comparing the multiomics data, we identified 43 proteins and 165 metabolites that were significantly differentially expressed in children with obesity before and after lifestyle alteration interventions. Using integrated -omics analysis, we obtained 7 KEGG pathways that were organically integrated based on the correlations between differentially expressed proteins (DEPs) and metabolites (DMs). Further interaction analysis identified 7 proteins as candidate DEPs and 9 metabolites as candidate DMs. Interestingly, we found that some of these candidate DEPs and candidate DMs were significantly correlated with clinical parameters.CONCLUSION: Our results provide valuable proteome and metabolome data resources for better understanding weight loss-associated responses in children with obesity. In addition, we analyzed the number of significantly differentially expressed proteins and metabolites, shed new light on weight loss pathogenesis in children with obesity, and added potential therapeutic agents for obese children.PMID:38867950 | PMC:PMC11167357 | DOI:10.1016/j.heliyon.2024.e31917

Imeta. 2023 Jul 16;2(3):e128. doi: 10.1002/imt2.128. eCollection 2023 Aug.ABSTRACTBile salt hydrolases (BSHs) are enzymes that are essential for the enterohepatic metabolism of bile acids (BAs). BSHs catalyze the production of unconjugated BAs and regulate the homeostasis of BA pool. This study identified Lactobacillus as a crucial BSH-encoding genus, and 16 main species were obtained using metagenomic data from publicly available human gut microbiome databases. Then, the 16 species of lactobacilli were classified into four typical categories by BSH phylotypes, including five species encoding BSH-T0, six species encoding BSH-T2, four species encoding BSH-T3, and Ligilactobacillus salivarius encoding both BSH-T0 and BSH-T3. The lactobacilli with the highest in vitro deconjugation activities against seven conjugated BAs were the BSH-T3-encoding strains. Furthermore, in vivo studies in mice administered four representative lactobacilli strains encoding different BSH phylotypes showed that treatment with BSH-T3-encoding Limosilactobacillus reuteri altered the structure of the gut microbiome and metabolome and significantly increased the levels of unconjugated BAs and total BA excretion. Our findings facilitated the taxonomic identification of crucial BSH-encoding lactobacilli in human gut microbiota and shed light on their contributions toward modulation of the enterohepatic circulation of BAs, which will contribute to future therapeutic applications of BSH-encoding probiotics to improve human health.PMID:38867937 | PMC:PMC10989828 | DOI:10.1002/imt2.128

Imeta. 2022 Oct 13;1(4):e58. doi: 10.1002/imt2.58. eCollection 2022 Dec.ABSTRACTThe human gastrointestinal (GI) tract harbors diverse microbes, and the family Lachnospiraceae is one of the most abundant and widely occurring bacterial groups in the human GI tract. Beneficial and adverse effects of the Lachnospiraceae on host health were reported, but the diversities at species/strain levels as well as their metabolites of Lachnospiraceae have been, so far, not well documented. In the present study, we report on the collection of 77 human-originated Lachnospiraceae species (please refer hLchsp, https://hgmb.nmdc.cn/subject/lachnospiraceae) and the in vitro metabolite profiles of 110 Lachnospiraceae strains (https://hgmb.nmdc.cn/subject/lachnospiraceae/metabolites). The Lachnospiraceae strains in hLchsp produced 242 metabolites of 17 categories. The larger categories were alcohols (89), ketones (35), pyrazines (29), short (C2-C5), and long (C > 5) chain acids (31), phenols (14), aldehydes (14), and other 30 compounds. Among them, 22 metabolites were aromatic compounds. The well-known beneficial gut microbial metabolite, butyric acid, was generally produced by many Lachnospiraceae strains, and Agathobacter rectalis strain Lach-101 and Coprococcus comes strain NSJ-173 were the top 2 butyric acid producers, as 331.5 and 310.9 mg/L of butyric acids were produced in vitro, respectively. Further analysis of the publicly available cohort-based volatile-metabolomic data sets of human feces revealed that over 30% of the prevailing volatile metabolites were covered by Lachnospiraceae metabolites identified in this study. This study provides Lachnospiraceae strain resources together with their metabolic profiles for future studies on host-microbe interactions and developments of novel probiotics or biotherapies.PMID:38867908 | PMC:PMC10989990 | DOI:10.1002/imt2.58

Imeta. 2022 Nov 15;1(4):e63. doi: 10.1002/imt2.63. eCollection 2022 Dec.ABSTRACTFor the first time, updated molecular techniques were used to validate and elucidate the effect of the Panchagavya. Metagenomics was used to decipher the bacterial microbiome structure, which showed promising results for their existence and abundance in the Panchagavya.PMID:38867902 | PMC:PMC10989784 | DOI:10.1002/imt2.63

Imeta. 2022 Mar 21;1(1):e10. doi: 10.1002/imt2.10. eCollection 2022 Mar.ABSTRACTThe interactions between the gut microbiome and metabolome play an important role in human health and diseases. Current studies mainly apply statistical correlation analysis between the gut microbiome and all the identified metabolites to explore their relationship. However, it remains challenging to identify the specific metabolic functions of microbes without in vitro culture experiments for validation. Discriminating the microbial metabolites from others (e.g., host, food, or environment) and exploring their metabolic functions and correlations with microbiome specifically may improve the efficiency and accuracy of biomarker discovery. So far, there have been no such bioinformatics tools available. Herein, we developed MetOrigin, an interactive web server that discriminates metabolites originating from the microbiome, performs the origin-based metabolic pathway enrichment analysis, and integrates the statistical correlations and biological relationships in the database using Sankey network visualization. MetOrigin not only enables the quick identification of microbial metabolites and their metabolic functions but also facilitates the discovery of specific bacterial species that are closely associated with metabolites statistically and biologically. MetOrigin is freely available at http://metorigin.met-bioinformatics.cn/.PMID:38867728 | PMC:PMC10989983 | DOI:10.1002/imt2.10

Imeta. 2022 Mar 10;1(1):e7. doi: 10.1002/imt2.7. eCollection 2022 Mar.ABSTRACTMass cadmium (Cd) poisoning is a serious health problem in many parts of the world. We propose that dietary intervention can be a practical solution to this problem. This study aimed to identify effective dietary products from traditional Chinese herbs that can detoxify Cd. Five candidate herbal foods with detoxifying potential were selected and subjected to mouse toxicological tests. The chemical composition and dose-response effects of licorice on mouse hepatocytes were determined. Licorice was selected for further tests to examine its effects on growth, tissue Cd accumulation, and gut and liver fitness of mice. The expression of hepatic metallothionein (Mt) genes was quantified in vitro in hepatocytes and in vivo in liver tissues of mice. The results showed that licorice dietary intervention was effective in reducing blood Cd by >50% within 1 month. Cd was also substantially reduced in the heart and lung tissues, but increased 2.1-fold in the liver. The liver of Cd poisoned mice improved with licorice intervention. Licorice treatment significantly induced Cd accumulation and expression of the Mt1 gene in hepatic cells both in vitro and in vivo. Licorice intake substantially altered gut microbial structure and enriched Parabacteroides distasonis. Omics results showed that licorice improved gut metabolism, particularly the metabolic pathways for glycyrrhizin, bile acids, and amino acids. Dietary licorice effectively reduced mouse blood Cd and had a profound impact on liver and gut fitness. We conclude that herbal licorice can be used as a dietary intervention for mass Cd poisoning.PMID:38867726 | PMC:PMC10989944 | DOI:10.1002/imt2.7

Biomed Chromatogr. 2024 Jun 12:e5922. doi: 10.1002/bmc.5922. Online ahead of print.ABSTRACTThis study aims to explore the pharmacological substance basis of Qi Ge Decoction (QG) in antihyperlipidemia through a combination of metabolomics and serum pharmacochemistry. We used ultra-performance liquid chromatography quadrupole-time-of-flight/MS (UPLC Q-TOF/MS) to analyze and identify the chemical constituents of QG in vitro and in blood chemical components. The metabolomics technology was used to analyze serum biomarkers of QG in preventing and treating hyperlipidemia. We constructed a mathematical model of the relationship between constituents absorbed into the blood and endogenous biomarkers and explored the potential therapeutic application of QG for the prevention and treatment of hyperlipidemia. Compared with the model group, the levels of total cholesterol and triglyceride in the QG group were significantly decreased (P < 0.01). A total of 12 chemical components absorbed into the blood were identified, and 48 biomarkers of the hyperlipidemia model were obtained from serum metabolomic analysis, of which 15 metabolites were backregulated after QG intervention. Puerarin, hesperetin, puerarin xyloside, calycosin, and monohydroxy-tetramethoxyflavone had a high correlation with the biomarkers regulated by QG. This study elucidated the material basis of QG in the intervention of hyperlipidemia, thereby facilitating future research aimed at further revealing the pharmacodynamic material basis of QG's antihyperlipidemic effects.PMID:38867488 | DOI:10.1002/bmc.5922

Cardiovasc Diabetol. 2024 Jun 12;23(1):199. doi: 10.1186/s12933-024-02288-x.ABSTRACTBACKGROUND: Metformin and sodium-glucose-cotransporter-2 inhibitors (SGLT2i) are cornerstone therapies for managing hyperglycemia in diabetes. However, their detailed impacts on metabolic processes, particularly within the citric acid (TCA) cycle and its anaplerotic pathways, remain unclear. This study investigates the tissue-specific metabolic effects of metformin, both as a monotherapy and in combination with SGLT2i, on the TCA cycle and associated anaplerotic reactions in both mice and humans.METHODS: Metformin-specific metabolic changes were initially identified by comparing metformin-treated diabetic mice (MET) with vehicle-treated db/db mice (VG). These findings were then assessed in two human cohorts (KORA and QBB) and a longitudinal KORA study of metformin-naïve patients with Type 2 Diabetes (T2D). We also compared MET with db/db mice on combination therapy (SGLT2i + MET). Metabolic profiling analyzed 716 metabolites from plasma, liver, and kidney tissues post-treatment, using linear regression and Bonferroni correction for statistical analysis, complemented by pathway analyses to explore the pathophysiological implications.RESULTS: Metformin monotherapy significantly upregulated TCA cycle intermediates such as malate, fumarate, and α-ketoglutarate (α-KG) in plasma, and anaplerotic substrates including hepatic glutamate and renal 2-hydroxyglutarate (2-HG) in diabetic mice. Downregulated hepatic taurine was also observed. The addition of SGLT2i, however, reversed these effects, such as downregulating circulating malate and α-KG, and hepatic glutamate and renal 2-HG, but upregulated hepatic taurine. In human T2D patients on metformin therapy, significant systemic alterations in metabolites were observed, including increased malate but decreased citrulline. The bidirectional modulation of TCA cycle intermediates in mice influenced key anaplerotic pathways linked to glutaminolysis, tumorigenesis, immune regulation, and antioxidative responses.CONCLUSION: This study elucidates the specific metabolic consequences of metformin and SGLT2i on the TCA cycle, reflecting potential impacts on the immune system. Metformin shows promise for its anti-inflammatory properties, while the addition of SGLT2i may provide liver protection in conditions like metabolic dysfunction-associated steatotic liver disease (MASLD). These observations underscore the importance of personalized treatment strategies.PMID:38867314 | DOI:10.1186/s12933-024-02288-x

Nihon Koshu Eisei Zasshi. 2024 Jun 13. doi: 10.11236/jph.23-110. Online ahead of print.ABSTRACTObjectives Although self-reported questionnaires are widely used to collect information on medication use in epidemiological studies, their validity for studies involving older adults has not been sufficiently assessed. This study evaluated the validity of self-reported medication use using questionnaires in comparison with drug notebooks.Methods The study enrolled 370 older community dwellers who participated in an aging sub-study survey of the Tsuruoka Metabolomics Cohort Study between April 2019 and March 2021. Medication use was assessed by comparing self-reported questionnaire data with drug notebook records. We analyzed medications used for hypertension, dyslipidemia, myocardial infarction, angina, diabetes, rheumatism, osteoporosis/metabolic bone disease, constipation, anxiety/depression, dementia, asthma, allergy, thrombosis, and thyroid disease. Moreover, gastrointestinal (GI) medications, steroids, and antipyretic analgesics were assessed, and data on injectable medications for osteoporosis/metabolic bone disease was collected. Using drug notebook records, we identified regular medication users by assessing whether they had received oral medication prescriptions covering over 28 days and took the medication within the 90 days preceding the day of their survey. To define medication categories, we used Anatomical Therapeutic Chemical (ATC) classification codes. Sensitivity, specificity, and kappa statistics were calculated for each medication using drug notebooks as standards. Those who did not bring their drug notebooks on the day of the survey were defined as non-medication users.Results The mean age (standard deviation) of the 370 participants (146 men and 224 women) was 73.3 (4.0) years. The sensitivity and specificity for each medication were as follows: hypertension (0.97, 0.97), dyslipidemia (0.93, 0.98), myocardial infarction (0.24, 0.99), diabetes (0.94, 1.00), rheumatism (1.00, 1.00), osteoporosis/metabolic bone disease (0.82, 0.99), constipation (0.71, 0.98), GI conditions (0.63, 0.97), anxiety/depression (0.36, 1.00), dementia (0.67, 1.00), asthma (0.67, 0.98), allergy (0.57, 0.99), thrombosis (0.88, 0.98), steroids (0.80, 0.99), thyroid disease (1.00, 1.00) and antipyretic analgesics (0.75, 0.96).Conclusions Although sensitivity and specificity differed by medication categories, the results of our population-based cohort study suggested that self-reported questionnaires on medication use among older adults are valid, especially for medications with high sensitivity (≥ 0.8).PMID:38866534 | DOI:10.11236/jph.23-110

Environ Pollut. 2024 Jun 10:124357. doi: 10.1016/j.envpol.2024.124357. Online ahead of print.ABSTRACTAntimony (Sb) is known for its severe and extensive toxicity, and earthworms are considered important indicator organisms in soil ecosystems. Therefore, the present study investigated the mechanism of toxicity of the Sb at different concentrations (50, 200 mg/kg) on earthworms using biochemical indicators, pathological sections, as well as metabolomics and transcriptomics analyses. The results showed that as the exposure concentration increased, both the antioxidant system of earthworms, extent of intestinal damage, and their metabolomic characteristics were significantly enhanced. In the 50 and 200 mg/kg Sb treatment group, 30 and 177 significant differentially changed metabolites (DCMs) were identified, respectively, with the most DCMs being down- and up-regulated, respectively. Metabolomics analysis showed that the contents of dl-tryptophan, glutamic acid, glycine, isoleucine, l-methionine, involved in the protein digestion and absorption as well as aminoacyl-tRNA biosynthesis were significantly up-regulated under the 200 mg/kg treatment. At the transcriptional level, Sb mainly affected the immune system, nervous system, amino acid metabolism, endocrine system, and carbohydrate metabolism in earthworms. The integration of transcriptomic and metabolomic data indicated that high doses of Sb regulated the metabolites and genes related to the oxidative phosphorylation pathway in earthworms. Overall, these results revealed global responses beyond the scope of conventional toxicity endpoints and facilitated a more in-depth and comprehensive assessment of the toxic effects of Sb.PMID:38866316 | DOI:10.1016/j.envpol.2024.124357

Chem Biol Interact. 2024 Jun 10:111107. doi: 10.1016/j.cbi.2024.111107. Online ahead of print.ABSTRACTBenzene is the main environmental pollutant and risk factor of childhood leukemia and chronic benzene poisoning. Benzene exposure leads to hematopoietic stem and progenitor cell (HSPC) dysfunction and abnormal blood cell counts. However, the key regulatory targets and mechanisms of benzene hematotoxicity are unclear. In this study, we constructed a benzene-induced hematopoietic damage mouse model to explore the underlying mechanisms. We identified that Insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) was significantly reduced in benzene-exposed mice. Moreover, targeting IGF2BP1 effectively mitigated damages to hematopoietic function and hematopoietic molecule expression caused by benzene in mice. On the mechanics, by metabolomics and transcriptomics, we discovered that branched-chain amino acid (BCAA) metabolism and fatty acid oxidation were key metabolic pathways, and Branched-chain amino acid transaminase 1 (BCAT1) and Carnitine palmitoyltransferase 1a (CPT1A) were critical metabolic enzymes involved in IGF2BP1-mediated hematopoietic injury process. The expression of the above molecules in the benzene exposure population was also examined and consistent with animal experiments. In conclusion, targeting IGF2BP1 alleviated hematopoietic injury caused by benzene exposure, possibly due to the reprogramming of BCAA metabolism and fatty acid oxidation via BCAT1 and CPT1A metabolic enzymes. IGF2BP1 is a potential regulatory and therapeutic target for benzene hematotoxicity.PMID:38866309 | DOI:10.1016/j.cbi.2024.111107

Int J Biol Macromol. 2024 Jun 10:133059. doi: 10.1016/j.ijbiomac.2024.133059. Online ahead of print.ABSTRACTKratom, Mitragyna speciosa, is one of the most popular herbs in the West and Southeast Asia. A number of previous works have focused on bioactive alkaloids in this plant; however, non-alkaloids have never been investigated for their biological activities. Antiviral and virucidal assays of a methanol leaf extract of Kratom, M. speciosa, revealed that a crude extract displayed virucidal activity against the SARS-CoV-2. Activity-guided isolation of a methanol leaf extract of Kratom led to the identification of B-type procyanidin condensed tannins of (-)-epicatechin as virucidal compounds against SARS-CoV-2. The fraction containing condensed tannins exhibited virucidal activity with an EC50 value of 8.38 μg/mL and a selectivity index (SI) value >23.86. LC-MS/MS analysis and MALDI-TOF MS identified the structure of the virucidal compounds in Kratom as B-type procyanidin condensed tannins, while gel permeation chromatograph (GPC) revealed weight average molecular weight of 238,946 Da for high molecular-weight condensed tannins. In addition to alkaloids, (-)-epicatechin was found as a major component in the leaves of M. speciosa, but it did not have virucidal activity. Macromolecules of (-)-epicatechin, i.e., procyanidin condensed tannins, showed potent virucidal activity against SARS-CoV-2, suggesting that the high molecular weights of these polyphenols are important for virucidal activity.PMID:38866269 | DOI:10.1016/j.ijbiomac.2024.133059

Toxicon. 2024 Jun 10:107799. doi: 10.1016/j.toxicon.2024.107799. Online ahead of print.ABSTRACTThis case report investigated the outbreak of aflatoxicosis in a dairy herd in Pakistan, which resulted in 30 abortions of 40 confirmed (75%) pregnant cows for 35 days and in 18.8% depression of farm average milk production for the entire herd. The analysis of the concentrate feed of the total mixed ration (TMR), using enzyme-linked immunosorbent assay (ELISA) procedures from two different local laboratories, indicated concentrations of 60 μg/kg dry matter (DM) of aflatoxin B1 (AFB1) and 100 μg/kg DM of total aflatoxins (AFs: sum of B1, B2, G1 and G2). Subsequently, a confirmatory analysis with a more sensitive and validated multi-metabolite liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was performed. This analysis detected a concentration of total AFs in the TMR of 166 μg/kg DM ± 3.5 (AFB1:134, AFB2:17.4 and AFM1:14.9 μg/kg DM). The concentrate feed (55% of the TMR DM) was confirmed as a source of contamination, presenting a concentration >29 times higher than the EU-maximum limit value (5.68 μg/kg DM). Additionally, the multi-mycotoxin analysis evidenced the co-occurrence of 81 other toxic and potentially toxic fungal metabolites in the fed TMR. After replacing the contaminated concentrate feed with feedstuffs of the same formulation but from a new charge of ingredients, the abortion episodes ceased, and milk production increased significantly. In conclusion, the data of this case report suggest that AFs may be associated with pregnancy losses in dairy cattle and milk production depression. From the public health perspective, the data also indicate the need for a more careful examination of dairy animal feed in Pakistan. Since the high concentration of AFB1 detected in feed and considering the literature-reported transfer rates (1- 6%) of this toxin to AFM1 (carcinogen) in milk, the milk produced during the outbreak period is expected to be contaminated with AFM1, which raises public health concerns.PMID:38866254 | DOI:10.1016/j.toxicon.2024.107799

J Steroid Biochem Mol Biol. 2024 Jun 10:106561. doi: 10.1016/j.jsbmb.2024.106561. Online ahead of print.ABSTRACTThe role of mitochondria in steroidogenesis is well established. However, the specific effects of mitochondrial dysfunction on androgen synthesis are not fully understood. In this study, we investigate the effects of various mitochondrial and metabolic inhibitors in H295R adrenal cells and perform a comprehensive analysis of steroid and metabolite profiling. We report that mitochondrial complex I inhibition by rotenone shifts cells toward anaerobic metabolism with a concomitant hyperandrogenic phenotype characterized by rapid stimulation of dehydroepiandrosterone (DHEA, 2h) and slower accumulation of androstenedione and testosterone (24h). Screening of metabolic inhibitors confirmed DHEA stimulation, which included mitochondrial complex III and mitochondrial pyruvate carrier inhibition. Metabolomic studies revealed truncated tricarboxylic acid cycle with an inverse correlation between citric acid and DHEA production as a common metabolic marker of hyperandrogenic inhibitors. The current study sheds light on a direct interplay between energy metabolism and androgen biosynthesis that could be further explored to identify novel molecular targets for efficient treatment of androgen excess disorders.PMID:38866189 | DOI:10.1016/j.jsbmb.2024.106561

J Pharm Biomed Anal. 2024 Jun 10;248:116302. doi: 10.1016/j.jpba.2024.116302. Online ahead of print.ABSTRACTData quality and control parameters are becoming more important in metabolomics. For peak picking, open-source or commercial solutions are used. Other publications consider different software solutions or data acquisition types for peak picking, a combination, including proposed and new quality parameters for the process of peak picking, does not exist. This study tries to examine the performance of three different software in terms of reproducibility and quality of their output while also considering new quality parameters to gain a better understanding of resulting feature lists in metabolomics data. We saw best recovery of spiked analytes in MS-DIAL. Reproducibility over multiple projects was good among all software. The total number of features found was consistent for DDA and full scan acquisition in MS-DIAL but full scan data leading to considerably more features in MZmine and Progenesis Qi. Feature linearity proved to be a good quality parameter. Features in MS-DIAL and MZmine, showed good linearity while Progenesis Qi produced large variation, especially in full scan data. Peak width proved to be a very powerful filtering criteria revealing many features in MZmine and Progenesis Qi to be of questionable peak width. Additionally, full scan data appears to produce a disproportionally higher number of short features. This parameter is not yet available in MS-DIAL. Finally, the manual classification of true positive features proved MS-DIAL to perform significantly better in DDA data (62 % true positive) than the two other software in either mode. We showed that currently popular solutions MS-DIAL and MZmine perform well in targeted analysis of spiked analytes as well as in classic untargeted analysis. The commercially available solution Progenesis Qi does not hold any advantage over the two in terms of quality parameters, of which we proposed peak width as a new parameter and showed that already proposed parameters such as feature linearity in samples of increasing concentration are advisable to use.PMID:38865927 | DOI:10.1016/j.jpba.2024.116302

BMC Genomics. 2024 Jun 12;25(1):594. doi: 10.1186/s12864-024-10456-2.ABSTRACTBACKGROUND: Reverse transcription quantitative PCR (RT-qPCR) with intercalating dyes is one of the main techniques to assess gene expression levels used in basic and applied research as well as in diagnostics. However, primer design for RT-qPCR can be complex due to the high demands on primer quality. Primers are best placed on exon junctions, should avoid polymorphic regions, be specific to the target transcripts and also prevent genomic amplification accurately, among others. Current software tools manage to meet all the necessary criteria only insufficiently. Here, we present ExonSurfer, a novel, user-friendly web-tool for qPCR primer design.RESULTS: ExonSurfer combines the different steps of the primer design process, encompassing target selection, specificity and self-complementarity assessment, and the avoidance of issues arising from polymorphisms. Amplification of potentially contaminating genomic DNA is avoided by designing primers on exon-exon junctions, moreover, a genomic alignment is performed to filter the primers accordingly and inform the user of any predicted interaction. In order to test the whole performance of the application, we designed primer pairs for 26 targets and checked both primer efficiency, amplicon melting temperature and length and confirmed the targeted amplicon by Sanger sequencing. Most of the tested primers accurately and selectively amplified the corresponding targets.CONCLUSION: ExonSurfer offers a comprehensive end-to-end primer design, guaranteeing transcript-specific amplification. The user interface is intuitive, providing essential specificity and amplicon details. The tool can also be used by command line and the source code is available. Overall, we expect ExonSurfer to facilitate RT-qPCR set-up for researchers in many fields.PMID:38867172 | DOI:10.1186/s12864-024-10456-2

Sci Rep. 2024 Jun 12;14(1):13513. doi: 10.1038/s41598-024-63893-0.ABSTRACTFecal calprotectin is an established marker of gut inflammation in inflammatory bowel disease (IBD). Elevated levels of fecal calprotectin as well as gut microbial dysbiosis have also been observed in other clinical conditions. However, systemic and multi-omics alterations linked to elevated fecal calprotectin in older individuals remain unclear. This study comprehensively investigated the relationship between fecal calprotectin levels, gut microbiome composition, serum inflammation and targeted metabolomics markers, and relevant lifestyle and medical data in a large sample of older individuals (n = 735; mean age ± SD: 68.7 ± 6.3) from the TREND cohort study. Low (0-50 μg/g; n = 602), moderate (> 50-100 μg/g; n = 64) and high (> 100 μg/g; n = 62) fecal calprotectin groups were stratified. Several pro-inflammatory gut microbial genera were significantly increased and short-chain fatty acid producing genera were decreased in high vs. low calprotectin groups. In serum, IL-17C, CCL19 and the toxic metabolite indoxyl sulfate were increased in high vs. low fecal calprotectin groups. These changes were partially mediated by the gut microbiota. Moreover, the high fecal calprotectin group showed increased BMI and a higher disease prevalence of heart attack and obesity. Our findings contribute to the understanding of fecal calprotectin as a marker of gut dysbiosis and its broader systemic and clinical implications in older individuals.PMID:38866914 | DOI:10.1038/s41598-024-63893-0