PubMed

Clin Immunol. 2024 Jul 30:110333. doi: 10.1016/j.clim.2024.110333. Online ahead of print.ABSTRACTUnderstanding the molecular mechanisms underpinning diverse vaccination responses is critical for developing efficient vaccines. Molecular subtyping can offer insights into heterogeneous nature of responses and aid in vaccine design. We analyzed multi-omic data from 62 haemagglutinin seasonal influenza vaccine recipients (2019-2020), including transcriptomics, proteomics, glycomics, and metabolomics data collected pre-vaccination. We performed a subtyping analysis on the integrated data revealing five subtypes with distinct molecular signatures. These subtypes differed in the expression of pre-existing adaptive or innate immunity signatures, which were linked to significant variation in baseline immunoglobulin A (IgA) and hemagglutination inhibition (HAI) titer levels. It is worth noting that these differences persisted through day 28 post-vaccination, indicating the effect of initial immune state on vaccination response. These findings highlight the significance of interpersonal variation in baseline immune status as a crucial factor in determining the effectiveness of seasonal vaccines. Ultimately, incorporating molecular profiling could enable personalized vaccine optimization.PMID:39089348 | DOI:10.1016/j.clim.2024.110333

Comput Methods Programs Biomed. 2024 Jul 26;255:108346. doi: 10.1016/j.cmpb.2024.108346. Online ahead of print.ABSTRACTBACKGROUND & AIMS: We previously identified subsets of patients with metabolic (dysfunction)-associated steatotic liver disease (MASLD) with different metabolic phenotypes. Here, we aimed to refine this classification based on genetic algorithms implemented in a Python package. The use of these genetic algorithms can help scientists to solve problems which cannot be solved with other methods. We present this package and its capabilities with specific problems. The name, PyGenMet, comes from its main goal, solving problems in Python with Genetic Algorithms and Metabolomics data.METHODS: We collected serum from methionine adenosyltransferase 1a knockout (Mat1a-KO) mice, which have chronically low level of hepatic S-adenosylmethionine (SAMe) and the metabolomes of all samples were determined. We also analyzed serum metabolomes of 541 patients with biopsy proven MASLD (182 with simple steatosis and 359 with metabolic (dysfunction)-associated steatohepatitis or MASH) and compared them with the serum metabolomes of this specific MASLD mouse model using Genetic Algorithms in order to select patients with a specific phenotype.RESULTS: By applying genetic algorithms, we have found a subgroup of patients with a lipid profile similar to that observed in the mouse model. When analyzing the two groups of patients, we have seen that patients with a lipid profile reflecting the mouse model characteristics show significant differences in lipoproteins, especially in LDL-4, LDL-5, and LDL-6 associated with atherogenic risk.CONCLUSION: The results show that the application of genetic algorithms to subclassify patients with MASLD (or other metabolic disease) give consistent results and are a good approximation for the treatment of large volumes of data such as those from omics sciences and patient classification.PMID:39089186 | DOI:10.1016/j.cmpb.2024.108346

Food Chem. 2024 Jul 26;460(Pt 2):140612. doi: 10.1016/j.foodchem.2024.140612. Online ahead of print.ABSTRACTSorghum seeds can discolor during storage. Treatment of seeds with citric acid improves sensory quality and antioxidant activity. This study compared the differences in phenotypic and antioxidant activity between citric acid-treated and water-treated sorghum seeds. The study used transcriptomics and metabolomics approaches to investigate the regulatory mechanisms. The ∆a, ∆b and ∆l values of citric acid-treated sorghum seeds significantly increased after 6 months of storage. The SOD, POD and CAT enzyme activities of the citric acid-treated group were 1.94, 1.91 and 2.45 times higher than those of the control, respectively. The joint transcriptome and metabolome analysis showed that the citric acid-induced changes were mainly focused on the flavonoid biosynthetic pathway. Citric acid treatment up-regulated CHS, ANR, MYB and bHLH genes and promoted flavonoid accumulation. In conclusion, citric acid treatment promotes flavonoid accumulation, delays sorghum seed discoloration, and enhances antioxidant activity and storage life.PMID:39089034 | DOI:10.1016/j.foodchem.2024.140612

Food Chem. 2024 Jul 25;460(Pt 2):140564. doi: 10.1016/j.foodchem.2024.140564. Online ahead of print.ABSTRACTEucommia ulmoides, a plant native to China, is valued for its medicinal properties and has applications in food, health products, and traditional Chinese medicine. Processed Eucommiae Cortex (EC) has historically been a highly valued medicine. Ancient doctors had ample experience processing EC, especially with ginger juice, as documented in traditional Chinese medical texts. The combination of EC and ginger juice helps release and transform the active ingredients, strengthening the medicine's effectiveness and improving its taste and shelf life. However, the lack of quality control standards for Ginger-Eucommiae Cortex (G-EC), processed from EC and ginger, presents challenges for its industrial and clinical use. This study optimized G-EC processing using the CRITIC and Box-Behnken methods. Metabolomics showed 517 chemical changes between raw and processed G-EC, particularly an increase in coniferyl aldehyde (CFA). Explainable artificial intelligence techniques revealed the feasibility of using color to CFA content, providing insights into quality indicators.PMID:39089015 | DOI:10.1016/j.foodchem.2024.140564

Food Chem. 2024 Jul 25;460(Pt 2):140614. doi: 10.1016/j.foodchem.2024.140614. Online ahead of print.ABSTRACTMigraine as a common neurological disorder still lacks effective therapies. Tetramethylpyrazine (TMP) is the main bioactive component from Ligusticum chuanxiong hort., a traditional edible-medicinal herb. This study aimed to investigate the action of TMP on migraine by metabolomics with mass spectrometry imaging (MSI) analysis and molecular exploring, including random forest model analysis, KEGG enrichment analysis and metabolite-metabolite interaction network analysis. The results indicated that 26 key representative metabolic biomarkers were identified, especially γ-glu-cys, which were highly related to glutathione (GSH) metabolism. MSI found the abundance of eleven endogenous metabolites were modulated by TMP, particularly glucose, the most important energy metabolism molecule, and GSH were increased that maintains intracellular redox balance, which was consistent with activation of Nrf2 signals by TMP. These findings provide insights into the effectiveness of metabolomics integrated with MSI in explaining the metabolic mechanisms of TMP, and afford valuable information for healthy development of TMP in migraine.PMID:39089013 | DOI:10.1016/j.foodchem.2024.140614

Int Immunopharmacol. 2024 Jul 31;140:112813. doi: 10.1016/j.intimp.2024.112813. Online ahead of print.ABSTRACTPrior research has shown the effectiveness of dalbergin (DL), dalbergin nanoformulation (DLF), and dalbergin-loaded PLGA-galactose-modified nanoparticles (DLMF) in treating hepatocellular carcinoma (HCC) cells. The present investigation constructs upon our previous research and delves into the molecular mechanisms contributing to the anticancer effects of DLF and DLMF. This study examined the anti-cancer effects of DL, DLF, and DLMF by diethyl nitrosamine (DEN)-induced HCC model in albino Wistar rats. In addition, we performed biochemical, antioxidant, lipid profile tests, and histological studies of liver tissue. The anticancer efficacy of DLMF is equivalent to that of 5-fluorouracil, a commercially available therapy for HCC. Immunoblotting studies revealed a reduction in the expression of many apoptotic markers, such as p53, BAX, and Cyt-C, in HCC. Conversely, the expression of Bcl-2, TNF-α, NFκB, p-AKT, and STAT-3 was elevated. Nevertheless, the administration of DL, DLF, and DLMF effectively controlled the levels of these apoptotic markers, resulting in a considerable decrease in the expression of Bcl-2, TNF-α, NFκB, p-AKT, and STAT-3. Specifically, the activation of TNF-alpha and STAT-3 triggers the signalling pathways that include the Bcl-2 family of proteins, Cyt-C, caspase 3, and 9. This ultimately leads to apoptosis and the suppression of cell growth. Furthermore, metabolomic analysis using 1H NMR indicated that the metabolites of animals reverted to normal levels after the treatment.PMID:39088916 | DOI:10.1016/j.intimp.2024.112813

PLoS Pathog. 2024 Aug 1;20(8):e1012412. doi: 10.1371/journal.ppat.1012412. Online ahead of print.ABSTRACTInfections with the pathogenic free-living amoebae Naegleria fowleri can lead to life-threatening illnesses including catastrophic primary amoebic meningoencephalitis (PAM). Efficacious treatment options for these infections are lacking and the mortality rate remains >95% in the US. Glycolysis is very important for the infectious trophozoite lifecycle stage and inhibitors of glucose metabolism have been found to be toxic to the pathogen. Recently, human enolase 2 (ENO2) phosphonate inhibitors have been developed as lead agents to treat glioblastoma multiforme (GBM). These compounds, which cure GBM in a rodent model, are well-tolerated in mammals because enolase 1 (ENO1) is the predominant isoform used systemically. Here, we describe findings that demonstrate these agents are potent inhibitors of N. fowleri ENO (NfENO) and are lethal to amoebae. In particular, (1-hydroxy-2-oxopiperidin-3-yl) phosphonic acid (HEX) was a potent enzyme inhibitor (IC50 = 0.14 ± 0.04 μM) that was toxic to trophozoites (EC50 = 0.21 ± 0.02 μM) while the reported CC50 was >300 μM. Molecular docking simulation revealed that HEX binds strongly to the active site of NfENO with a binding affinity of -8.6 kcal/mol. Metabolomic studies of parasites treated with HEX revealed a 4.5 to 78-fold accumulation of glycolytic intermediates upstream of NfENO. Last, nasal instillation of HEX increased longevity of amoebae-infected rodents. Two days after infection, animals were treated for 10 days with 3 mg/kg HEX, followed by one week of observation. At the end of the one-week observation, eight of 12 HEX-treated animals remained alive (resulting in an indeterminable median survival time) while one of 12 vehicle-treated rodents remained, yielding a median survival time of 10.9 days. However, intranasal HEX delivery was not curative as brains of six of the eight survivors were positive for amoebae. These findings suggest that HEX requires further evaluation to develop as a lead for treatment of PAM.PMID:39088549 | DOI:10.1371/journal.ppat.1012412

PLoS One. 2024 Aug 1;19(8):e0308214. doi: 10.1371/journal.pone.0308214. eCollection 2024.ABSTRACTThe main objective of the study was to investigate the effects of prenatal exercise interventions on maternal body composition at 28 weeks gestation and 7-14 days after delivery. We also explored associations between physical activity (PA) per se and body composition. This study presents secondary outcomes of the FitMum randomized controlled trial, which included healthy inactive pregnant women at gestational age ≤ 15+0 weeks. They were randomized to structured supervised exercise training, motivational counselling on PA, or standard care. Maternal body composition was measured by doubly labeled water at 28 weeks gestation (n = 134) and by dual-energy X-ray absorptiometry scan 7-14 days after delivery (n = 117). PA, including moderate-to-vigorous-intensity PA (MVPA), active kilocalories, and steps, were measured continuously from inclusion to delivery by a wrist-worn activity tracker. One hundred fifty pregnant women were included with a median pre-pregnancy body mass index (BMI) of 24.1 (21.6-27.9) kg/m2. We found no differences between groups in fat mass, fat percentage or fat-free mass at 28 weeks gestation or 7-14 days after delivery. Visceral adipose tissue mass and bone mineral density measured 7-14 days after delivery did not differ between groups either. Linear regression analyses adjusted for pre-pregnancy BMI showed that a higher number of daily steps was associated with lower fat mass, fat percentage, and visceral adipose tissue mass at 28 weeks gestation and 7-14 days after delivery. Active kilocalories during pregnancy was positively associated with fat-free mass 7-14 days after delivery. Neither structured supervised exercise training nor motivational counselling on PA during pregnancy affected maternal body composition at 28 weeks gestation or 7-14 days after delivery compared to standard care. Interestingly, when adjusted for pre-pregnancy BMI, higher number of daily steps was associated with lower fat content during pregnancy and after delivery, whereas MVPA and active kilocalories were not. Trial registration: ClinicalTrials.gov; NCT03679130; 20/09/2018.PMID:39088510 | DOI:10.1371/journal.pone.0308214

Appl Biochem Biotechnol. 2024 Aug 1. doi: 10.1007/s12010-024-04998-0. Online ahead of print.ABSTRACTIn disease treatment, the utilisation of medicinal plants has witnessed a discernible rise, driven by concerns over the adverse effects associated with synthetic drugs available in the market. Analyses of the plant Christia vespertilionis (L.f.) Bakh. F., indigenous to Malaysia, has suggested its antidiabetic property linked to α-glucosidase inhibition, but metabolites responsible for antidiabetic are unexplored. The metabolomics approaches and molecular docking simulations were integrated to identify the putative α-glucosidase inhibitors and their enzyme interaction. In this study, the crude leaves extracted from this plant were extracted using solvents of varying polarity, followed by gas and liquid chromatography coupled with mass spectrometry metabolomics. The highest inhibition activity in a mixture of n-hexane and ethyl acetate (1:1, v/v)) was observed. Six putative metabolites corresponding to antidiabetic activity were identified: palmitic acid (2), linolenic acid (4), 7-tetradecenal (5), aloeemodin-8-monoglucoside (14), bruceine I (15), and sanjidin B (16). The mechanism of action of all the identified compounds is competitive, mainly involving hydrophobic and hydrogen bonding interactions with the protein residues. Compounds 14, 15, and 16 exhibited strong binding capabilities with both enzyme crystal structures compared to the positive control, quercetin. The metabolites extracted from C. vespertilionis leaves have demonstrated promising antidiabetic effects. These antidiabetic compounds can potentially commercialise new drug candidates in managing diabetes conditions.PMID:39088027 | DOI:10.1007/s12010-024-04998-0

J Environ Sci Health A Tox Hazard Subst Environ Eng. 2024 Aug 1:1-16. doi: 10.1080/10934529.2024.2384216. Online ahead of print.ABSTRACTArtemia is a brine shrimp genus adapted to extreme habitats like ranges salinity from 5-25 g/L and in temperatures from 9 to 35 °C. It is widely distributed and used as an environmental quality biomarker. Artemia franciscana and Artemia salina species are commonly used in ecotoxicological studies and genotoxicity assays due to their short life cycle, high fecundity rate, easy culture, and availability. Thus, considering the importance of these tests in ecotoxicological studies, the present study aimed to present Artemia genus as a biological model in genotoxicity research. To this end, we reviewed the literature, analyzing data published until July 2023 in the Web of Science, SCOPUS, Embase, and PubMed databases. After screening, we selected 34 studies in which the genotoxicity of Artemia for various substances. This review presents the variability of the experimental planning of assays and biomarkers in genotoxicity using Artemia genus as a biological model for ecotoxicological studies and show the possibility of monitoring biochemical alterations and genetic damage effects. Also highlight innovative technologies such as transcriptomic and metabolomic analysis, as well as studies over successive generations to identify changes in DNA and consequently in gene expression.PMID:39087887 | DOI:10.1080/10934529.2024.2384216

Am J Bot. 2024 Aug 1:e16383. doi: 10.1002/ajb2.16383. Online ahead of print.ABSTRACTPREMISE: In plants, whole-genome duplication (WGD) is a common mutation with profound evolutionary potential. Given the costs associated with a superfluous genome copy, polyploid establishment is enigmatic. However, in the right environment, immediate phenotypic changes following WGD can facilitate establishment. Metabolite abundances are the direct output of the cell's regulatory network and determine much of the impact of environmental and genetic change on the phenotype. While it is well known that an increase in the bulk amount of genetic material can increase cell size, the impact of gene dosage multiplication on the metabolome remains largely unknown.METHODS: We used untargeted metabolomics on four genetically distinct diploid-neoautotetraploid pairs of the greater duckweed, Spirodela polyrhiza, to investigate how WGD affects metabolite abundances per cell and per biomass.RESULTS: Autopolyploidy increased metabolite levels per cell, but the response of individual metabolites varied considerably. However, the impact on metabolite level per biomass was restricted because the increased cell size reduced the metabolite concentration per cell. Nevertheless, we detected both quantitative and qualitative effects of WGD on the metabolome. Many effects were strain-specific, but some were shared by all four strains.CONCLUSIONS: The nature and impact of metabolic changes after WGD depended strongly on the genotype. Dosage effects have the potential to alter the plant metabolome qualitatively and quantitatively, but were largely balanced out by the reduction in metabolite concentration due to an increase in cell size in this species.PMID:39087852 | DOI:10.1002/ajb2.16383

Ann Surg. 2024 Aug 1. doi: 10.1097/SLA.0000000000006463. Online ahead of print.ABSTRACTOBJECTIVE: To investigate the spermidine pathway capability to predict patients at risk for tumor recurrence following colorectal cancer (CRC) surgery.SUMMARY BACKGROUND DATA: Recurrence rates after CRC surgery remain about 20%, despite an optimal technique and adjuvant therapy when necessary. Identification of risk biomarkers of recurrence is an unmet need. The spermidine pathway is indispensable for cell proliferation and differentiation, and is suggested to accelerate tumor spread.METHODS: Prospective cohort study of patients undergoing CRC surgery from 2015 to 2018. Plasma samples were collected before surgery and on postoperative day 4, and the spermidine pathway was assessed through mass spectrometry. Oncological outcomes were registered.RESULTS: 146 patients were included and 24 (16.4%) developed tumor recurrence. Higher levels of preoperative spermidine pathway components (spermidine, spermine, spermidine synthase enzyme, and spermine/arginine balance) were positively associated with recurrence. Surgery promoted a decrease in these pathway elements. The greater the decline was, the lower the risk of recurrence. Preoperative spermidine over the cut-off 0.198 µM displayed a 4.69-fold higher risk of recurrence. The spermine synthase enzyme behaved in the opposite direction.CONCLUSIONS: The spermidine pathway is associated with tumor recurrence following CRC surgery and, after confirmation in larger cohorts, could be translated as a risk biomarker of recurrence into clinical practice.PMID:39087328 | DOI:10.1097/SLA.0000000000006463

Front Mol Med. 2022 Apr 27;2:844280. doi: 10.3389/fmmed.2022.844280. eCollection 2022.ABSTRACTBackground: Pregnancy triggers longitudinal metabolic alterations in women to allow precisely-programmed fetal growth. Comprehensive characterization of such a "metabolic clock" of pregnancy may provide a molecular reference in relation to studies of adverse pregnancy outcomes. However, a high-resolution temporal profile of metabolites along a healthy pregnancy remains to be defined. Methods: Two independent, normal pregnancy cohorts with high-density weekly urine sampling (discovery: 478 samples from 19 subjects at California; validation: 171 samples from 10 subjects at Alabama) were studied. Urine samples were profiled by liquid chromatography-mass spectrometry (LC-MS) for untargeted metabolomics, which was applied for gestational age dating and prediction of time to delivery. Results: 5,473 urinary metabolic features were identified. Partial least-squares discriminant analysis on features with robust signals (n = 1,716) revealed that the samples were distributed on the basis of the first two principal components according to their gestational age. Pathways of bile secretion, steroid hormone biosynthesis, pantohenate, and CoA biosynthesis, benzoate degradation, and phenylpropanoid biosynthesis were significantly regulated, which was collectively applied to discover and validate a predictive model that accurately captures the chronology of pregnancy. With six urine metabolites (acetylcholine, estriol-3-glucuronide, dehydroepiandrosterone sulfate, α-lactose, hydroxyexanoy-carnitine, and l-carnitine), models were constructed based on gradient-boosting decision trees to date gestational age in high accordance with ultrasound results, and to accurately predict time to delivery. Conclusion: Our study characterizes the weekly baseline profile of the human pregnancy metabolome, which provides a high-resolution molecular reference for future studies of adverse pregnancy outcomes.PMID:39086969 | PMC:PMC11285704 | DOI:10.3389/fmmed.2022.844280

Front Plant Sci. 2024 Jul 17;15:1367121. doi: 10.3389/fpls.2024.1367121. eCollection 2024.ABSTRACTINTRODUCTION: The research on plant leaf morphology is of great significance for understanding the development and evolution of plant organ morphology. As a relict plant, the G. biloba leaf morphology typically exhibits bifoliate and peltate forms. However, throughout its long evolutionary history, Ginkgo leaves have undergone diverse changes.METHODS: This study focuses on the distinct "trumpet" leaves and normal fan-shaped leaves of G. biloba for analysis of their phenotypes, photosynthetic activity, anatomical observations, as well as transcriptomic and metabolomic analyses.RESULTS: The results showed that trumpet-shaped G. biloba leaves have fewer cells, significant morphological differences between dorsal and abaxial epidermal cells, leading to a significantly lower net photosynthetic rate. Additionally, this study found that endogenous plant hormones such as GA, auxin, and JA as well as metabolites such as flavonoids and phenolic acids play roles in the formation of trumpet-shaped G. biloba leaves. Moreover, the experiments revealed the regulatory mechanisms of various key biological processes and gene expressions in the trumpet-shaped leaves of G. biloba.DISCUSSION: Differences in the dorsal and abdominal cells of G. biloba leaves can cause the leaf to curl, thus reducing the overall photosynthetic efficiency of the leaves. However, the morphology of plant leaves is determined during the primordia leaf stage. In the early stages of leaf development, the shoot apical meristem (SAM) determines the developmental morphology of dicotyledonous plant leaves. This process involves the activity of multiple gene families and small RNAs. The establishment of leaf morphology is complexly regulated by various endogenous hormones, including the effect of auxin on cell walls. Additionally, changes in intracellular ion concentrations, such as fluctuations in Ca2+ concentration, also affect cell wall rigidity, thereby influencing leaf growth morphology.PMID:39086912 | PMC:PMC11288918 | DOI:10.3389/fpls.2024.1367121

World J Gastroenterol. 2024 Jul 21;30(27):3290-3303. doi: 10.3748/wjg.v30.i27.3290.ABSTRACTBACKGROUND: The annual incidence of metabolic-associated fatty liver disease (MAFLD) in China has been increasing and is often overlooked owing to its insidious characteristics. Approximately 50% of the patients have a normal weight or are not obese. They are said to have lean-type MAFLD, and few studies of such patients are available. Because MAFLD is associated with abnormal lipid metabolism, lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis.AIM: To investigate the serum fatty-acid metabolic characteristics in lean-type MAFLD patients using targeted serum metabolomic technology.METHODS: Between January and June 2022, serum samples were collected from MAFLD patients and healthy individuals who were treated at Shanghai Putuo District Central Hospital for serum metabolomics analysis. Principal component analysis and orthogonal partial least squares-discriminant analysis models were developed, and univariate analysis was used to screen for biomarkers of lean-type MAFLD and analyze metabolic pathways. UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid (PA), oleic acid (OA), linoleic acid (LA), and arachidonic acid (AA) levels in lean-type MAFLD patients.RESULTS: Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.05). Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.01). The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals (P < 0.05) and the expression of triglycerides and fasting blood glucose were increased (P < 0.01). A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P < 0.05 and variable importance in projection > 1". The levels of PA, OA, LA, and AA were significantly increased compared with healthy individuals.CONCLUSION: The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly, yielding 65 identified biomarkers. PA, OA, LA, and AA exhibited the most significant changes, offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.PMID:39086751 | PMC:PMC11287418 | DOI:10.3748/wjg.v30.i27.3290

Front Microbiol. 2024 Jul 17;15:1427195. doi: 10.3389/fmicb.2024.1427195. eCollection 2024.ABSTRACTBACKGROUND: Cellular and molecular biology, combined with research on the human microbiome and metabolome, have provided new insights into the pathogenesis of systemic sclerosis (SSc). However, most studies on gut microbiota (GM) and metabolome in SSc are observational studies. The impact of confounding factors and reverse causation leads to different insights. To shed light on this matter, we utilized Mendelian randomization (MR) to determine the causal effect of GM/metabolites on SSc.METHODS: Based on summary-level data from genome-wide association studies, bidirectional Two-sample MR was conducted involving 196 GM, 1400 plasma metabolism, and 9,095 SSc. Inverse Variance Weighting (IVW) was mainly used for effect estimation.RESULTS: Forward MR analysis found that three GM and two plasma metabolites are causally related to SSc. IVW results showed Victivallaceae (family) (OR, 1.469; 95%CI, 1.099-1.963; p = 0.009) and LachnospiraceaeUCG004 (genus) (OR, 1.548; 95%CI, 1.020-2.349; p = 0.04) were risk factor of SSc. Conversely, Prevotella7 (genus) (OR, 0.759; 95%CI, 0.578-0.997; p = 0.048)was a protective factor of SSc. The results on plasma metabolites indicated that Pregnenediol disulfate (C21H34O8S2) levels (OR, 1.164; 95%CI, 1.006-1.347; p = 0.041)was a risk factor of SSc, while Sphingomyelin (d18:1/19:0, d19:1/18:0) levels (OR, 0.821; 95%CI, 0.677-0.996; p = 0.045)was a protective factor of SSc. Reverse MR analysis did not find causally relationship between SSc and the above GM/plasma metabolites.CONCLUSION: Our results revealed the causally effect between GM/plasma metabolites and SSc. These findings provided new insights into the mechanism of SSc. In particular, we demonstrated Prevotella7 was a protective factor of SSc despite its controversial role in SSc in previous researches.PMID:39086645 | PMC:PMC11288946 | DOI:10.3389/fmicb.2024.1427195

Front Cell Infect Microbiol. 2024 Jul 17;14:1404678. doi: 10.3389/fcimb.2024.1404678. eCollection 2024.ABSTRACTBACKGROUND: Aberrant activation of the classic renin-angiotensin system (RAS) and intestinal micro dysbiosis adversely affect insulin resistance (IR), dyslipidemia, and other metabolic syndrome markers. However, the action of angiotensin-converting enzyme 2 (ACE2) and gut health in systemic homeostasis vary, and their interaction is not completely understood.METHODS: We adopted a combinatory approach of metabolomics and fecal 16S rRNA analysis to investigate gut microbiota and metabolite in two different mouse models, ACE2 knockout (ACE2 KO) mice and the ACE2-overexpressing obese mice.RESULTS: 16S rRNA gene sequencing revealed that ACE2 influences microbial community composition and function, and ACE2 KO mice had increased Deferribacteres, Alcaligenaceae, Parasutterella, Catenibacterium, and Anaerotruncus, with decreased short-chain fatty acid (SCFA)-producing bacteria (Marvinbryantia and Alistipes). In contrast, ACE2-overexpressed mice exhibited increased anti-inflammatory probiotic (Oscillospiraceae, Marinifilaceae, and Bifidobacteriaceae) and SCFA-producing microbes (Rikenellaceae, Muribaculaceae, Ruminococcaceae, Odoribacter, and Alistipes) and decreased Firmicutes/Bacteroidetes, Lactobacillaceae, Erysipelotrichaceae, and Lachnospiraceae. Metabolome analysis indicated differential metabolites in ACE2 KO and ACE2-overexpression mice, especially the glucolipid metabolism-related compounds. Furthermore, correlation analysis between gut microbiota and metabolites showed a dynamic mutual influence affecting host health.CONCLUSION: Our study confirms for the first time a significant association between ACE2 status and gut microbiome and metabolome profiles, providing a novel mechanism for the positive effect of ACE2 on energy homeostasis.PMID:39086603 | PMC:PMC11288824 | DOI:10.3389/fcimb.2024.1404678

Environ Sci Technol. 2024 Jul 31. doi: 10.1021/acs.est.4c02929. Online ahead of print.ABSTRACTPrenatal and early life air pollution exposure has been linked with several adverse health outcomes. However, the mechanisms underlying these relationships are not yet fully understood. Therefore, this study utilizes fecal metabolomics to determine if pre- and postnatal exposure to ambient air pollutants (i.e., PM10, PM2.5, and NO2) is associated with the fecal metabolome in the first 2 years of life in a Latino cohort from Southern California. The aims of this analysis were to estimate associations between (1) prenatal air pollution exposure with fecal metabolic features at 1-month of age, (2) prior month postnatal air pollution exposure with fecal metabolites from 1-month to 2 years of age, and (3) how postnatal air pollution exposure impacts the change over time of fecal metabolites in the first 2 years of life. Prenatal exposure to air pollutants was associated with several Level-1 metabolites, including those involved in vitamin B6 and tyrosine metabolism. Prior month air pollution exposure in the postnatal period was associated with Level-1 metabolites involved in histidine metabolism. Lastly, we found that pre- and postnatal ambient air pollution exposure was associated with changes in metabolic features involved in metabolic pathways including amino acid metabolism, histidine metabolism, and fatty acid metabolism.PMID:39086199 | DOI:10.1021/acs.est.4c02929

Arch Pharm (Weinheim). 2024 Jul 31:e2400418. doi: 10.1002/ardp.202400418. Online ahead of print.ABSTRACTGreen seaweed (Ulva sp.) is frequently used as a food component and nutraceutical agent because of its high polysaccharide and natural fiber content in Asian countries. This study investigates both metabolomic profiling of Ulva sp. and the neuroprotective efficacy of its ethanol extract and its underlying mechanisms in a rotenone-induced rat model of neurodegeneration, mimicking Parkinson's disease (PD) in humans. Metabolomic profiling of Ulva sp. extract was done using liquid chromatography high resolution electrospray ionization mass spectrometry and led to the identification of 22 compounds belonging to different chemical classes.Catenin Beta Additionally, this study demonstrated the neuroprotective properties against rotenone-induced PD, which was achieved through the suppression of elevated levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 together with the inhibition of reactive oxygen species (ROS) generation, apoptosis, inflammatory mediators, and the phosphoinositide 3-kinases/serine/threonine protein kinase (PI3K/AKT) pathway. Using a protein-protein interaction network, AKT1, GAPDH, TNF-α, IL-6, caspase 3, signal transducer and activator of transcription 3, Catenin Beta 1, epidermal growth factor receptor, B-cell lymphoma -2, and HSP90AA1 were identified as the top 10 most significant genes. Finally, molecular docking results showed that compounds 1, 3, and 7 might possess a promising anti-parkinsonism effect by binding to active sites of selected hub genes. Therefore, it is hypothesized that the Ulva sp. extract has the potential to be further developed as a potential therapeutic agent for the treatment of PD.PMID:39086040 | DOI:10.1002/ardp.202400418

Pestic Biochem Physiol. 2024 Aug;203:106015. doi: 10.1016/j.pestbp.2024.106015. Epub 2024 Jul 3.ABSTRACTBeauveria bassiana is a popular and eco-friendly biopesticide. During its pathogen-pest interaction, both N-acetylglucosamine (GlcNAc) catabolism and anabolism are crucial for nutrient supply and cell-wall construction. The initiation of GlcNAc metabolism relies on the catalysis of GlcNAc kinase, which has been extensively studied in the human pathogen Candida albicans. However, the physiological function of GlcNAc kinase remains poorly understood in entomopathogenic fungi. In the present study, a GlcNAc kinase homolog was identified and designated as BbHxk1 in B. bassiana. Deletion of BbHxk1 resulted in viable but reduced vegetative growth on various carbon sources. ΔBbHxk1 mutants displayed severe defects in cell wall integrity, making them more susceptible to cell wall stress cues. Furthermore, the absence of BbHxk1 resulted in an increase in conidial yield and blastospore production, and a faster rate of germination and filamentation, potentially attributed to higher intracellular ATP levels. BbHxk1 deficiency led to a reduction in the activities of cuticle-degrading enzymes, which might contribute to the attenuated pathogenicity specifically through cuticle penetration rather than hemocoel infection towards Galleria mellonella larvae. Being different from C. albicans Hxk1, which facultatively acts as a catalyzing enzyme and transcriptional regulator, BbHxk1 primarily acts as a catalyzing enzyme and metabolic regulator. The altered metabolomic profiling correlated with the phenotypic defects in ΔBbHxk1 mutants, further implicating a potential metabolism-dependent mechanism of BbHxk1 in mediating physiologies of B. bassiana. These findings not only unveil a novel role for GlcNAc kinase in B. bassiana, but also provide a solid theoretical basis to guide metabolic reprogramming in order to maintain or even enhance the efficiency of fungi for practical applications.PMID:39084806 | DOI:10.1016/j.pestbp.2024.106015