PubMed

J Ethnopharmacol. 2024 Apr 25:118201. doi: 10.1016/j.jep.2024.118201. Online ahead of print.ABSTRACTBACKGROUND: Recent developments in metabolomics, transcriptomic and epigenetics open up new horizons regarding the pharmacological understanding of phytocannabinoids as neuromodulators in treating anxiety, depression, epilepsy, Alzheimer's, Parkinson's disease and autism.METHODS: The present review is an extensive search in public databases, such as Google Scholar, Scopus, the Web of Science, and PubMed, to collect all the literature about the neurobiological roles of cannabis extract, cannabidiol, 9-tetrahydrocannabinol specially focused on metabolomics, transcriptomic, epigenetic, mechanism of action, in different cell lines, induced animal models and clinical trials. We used bioinformatics, network pharmacology and enrichment analysis to understand the effect of phytocannabinoids in neuromodulation.RESULTS: Cannabidomics studies show wide variability of metabolites across different strains and varieties, which determine their medicinal and abusive usage, which is very important for its quality control and regulation. CB receptors interact with other compounds besides cannabidiol and Δ9-tetrahydrocannabinol, like cannabinol and Δ8-tetrahydrocannabinol. Phytocannabinoids interact with cannabinoid and non-cannabinoid receptors (GPCR, ion channels, and PPAR) to improve various neurodegenerative diseases. However, its abuse because of THC is also a problem found across different epigenetic and transcriptomic studies. Network enrichment analysis shows CNR1 expression in the brain and its interacting genes involve different pathways such as Rap1 signalling, dopaminergic synapse, and relaxin signalling. CBD protects against diseases like epilepsy, depression, and Parkinson's by modifying DNA and mitochondrial DNA in the hippocampus. Network pharmacology analysis of 8 phytocannabinoids revealed an interaction with 10 (out of 60) targets related to neurodegenerative diseases, with enrichment of ErbB and PI3K-Akt signalling pathways which helps in ameliorating neuro-inflammation in various neurodegenerative diseases. The effects of phytocannabinoids vary across sex, disease state, and age which suggests the importance of a personalized medicine approach for better success.CONCLUSIONS: Phytocannabinoids present a range of promising neuromodulatory effects. It holds promise if utilized in a strategic way towards personalized neuropsychiatric treatment. However, just like any drug irrational usage may lead to unforeseen negative effects. Exploring neuro-epigenetics and systems pharmacology of major and minor phytocannabinoid combinations can lead to success.PMID:38677573 | DOI:10.1016/j.jep.2024.118201

J Ethnopharmacol. 2024 Apr 25:118256. doi: 10.1016/j.jep.2024.118256. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: A herbal formula Tong-Xie-Yao-Fang (TXYF) is traditionally used to treat irritable bowel syndrome (IBS), modern pharmacological evidence supports that the formula efficacy is associated with altered gut microbiota. Yet, the mechanistic role of gut microbiota in the therapy of TXYF remains unclear. We previously clarified that gut microbiota-dysregulated bile acid (BA) metabolism contribute to the pathogenesis of IBS, deriving a hypothesis that microbiota-BA metabolic axis might be a potential target of TXYF.AIM OF THE STUDY: We aim to investigate a new gut microbiota-mediated mechanism underlying anti-IBS efficacy of TXYF.MATERIALS AND METHODS: We established an IBS rat model with a combination of stressors, compared the herbal efficacy in models undergone gut bacterial manipulations, also examined BA metabolism-related microbiota, metabolites, genes and proteins by 16S rRNA gene sequencing, targeted metabolomics, qPCR and multiplex immunofluorescence staining.RESULTS: We observed that TXYF attenuated visceral hyperalgesia and diarrhea in IBS rats but not in those underwent gut bacteria depletion. Transferring gut microbiota from TXYF-treated donors also decreased visceral sensitivity and slightly relief diarrhea-like behaviors in IBS recipient rats. Fecal 16S rRNA gene sequencing revealed that TXYF modulated microbial β-diversity and taxonomic structure of IBS rats, with a significant increase in relative abundance of bile salt hydrolase (BSH)-expressing Bacteroidaceae. qPCR and culturing data validated that TXYF had a promotive effect on the growth and BSH activity of Bacteroides species. TXYF-reshaped microbiota upregulated the expression of intestinal Fgf15, a feedback signal to control BA synthesis in the liver. As a result, the BA synthetic and excretory levels in IBS rats were decreased by TXYF, so as that colonic BA membrane receptor Tgr5 sensing and its mediated Calcitonin gene-related peptide (Cgrp)-positive neuronal response were attenuated.CONCLUSION: This study poses a new microbiota-driven therapeutic action for TXYF, highlighting the potential of developing new anti-IBS strategies from the herbal formula targeting BSH-expressing gut bacteria.PMID:38677571 | DOI:10.1016/j.jep.2024.118256

Am J Clin Nutr. 2024 Apr 25:S0002-9165(24)00444-1. doi: 10.1016/j.ajcnut.2024.04.022. Online ahead of print.ABSTRACTBACKGROUND: Dietary choices can affect human health through alterations in gut microbial metabolism, and gut microbial metabolites could serve as biomarkers for disease risk conferred by dietary intake. However, self-reported dietary intake may not reflect true intake.OBJECTIVE: We identified circulating metabolites, including gut microbiome-related metabolites, associated with adherence to a healthy diet in the ChooseWell 365 study. In this randomized clinical trial, the dietary choices of hospital employees were assessed over 24 months using not only 24-hour dietary recalls, but also electronic records of hospital cafeteria purchases.METHODS: Plasma metabolites were profiled from 470 participants. Two targeted metabolomics methods were developed and implemented to expand detection coverage for metabolites related to gut microbial activity. Linear regression models were used to associate metabolites with Healthy Purchasing Scores (HPS) derived from cafeteria purchases and Healthy Eating Index-2015 (HEI-15) scores derived from dietary recalls.RESULTS: Fourteen metabolites were concordantly associated with the HPS and HEI-15 scores in multivariable models adjusted for age, sex, and race, including the gut microbiome-related metabolites indole-3-propionic acid (HPS, β=0.16, 95% CI [0.07, 0.26], p=7.32x10-4; HEI-15, β=0.16, 95% CI [0.07, 0.25], p=6.79x10-4), hippuric acid (HPS, β=0.11, 95% CI [0.02, 0.21], p=1.97x10-2; HEI-15, β=0.10, 95% CI [0.01, 0.19], p=3.14x10-2), and indoxyl sulfate (HPS, β= -0.13, 95% CI [-0.23, -0.03], p=8.21x10-3; HEI-15, β= -0.12, 95% CI [-0.22, -0.03], p=8.50x10-3). These gut microbial metabolites were associated with the intake of specific food groups, such as whole fruits. These metabolites were also associated with clinical variables, including blood pressure, diabetes or prediabetes, and body mass index.CONCLUSIONS: In a secondary analysis of the ChooseWell 365 study, associations between circulating gut microbiome-related metabolites and a healthy diet were confirmed using both objective and subjective measures of consumption. Accurate identification of diet-associated metabolites may help guide dietary or microbiome-based interventions aimed at disease prevention.PMID:38677520 | DOI:10.1016/j.ajcnut.2024.04.022

Sci Total Environ. 2024 Apr 25:172795. doi: 10.1016/j.scitotenv.2024.172795. Online ahead of print.ABSTRACTThe ubiquitous presence of micro-and nanoplastics (MNPs) in the environment and everyday products has attracted attention due to their hazardous risks. However, the effects of MNPs on reproduction and the underlying mechanisms remain unclear. The present study investigated the impact of polystyrene (PS) nanoplastics of 80, 200 and 500 nm diameters on zebrafish reproduction at an environmentally relevant concentration of 0.5 mg/L. Exposure to PS delayed spermatogenesis and caused aberrant follicular growth, resulting in dysgenesis in F0 adults and impacting F1 embryo development. Notably, the reproductive toxicity exhibited size-dependency, with the 500 nm PS being the most detrimental. Combined analyses of transcriptomics and metabolomics in ovary tissue revealed that treatment with 500 nm PS affected the peroxisome proliferator-activated receptor (PPAR) signaling pathway, dysregulated lipid transport, binding and activity processes, and led to dysgenesis in zebrafish. Specifically, the ovulatory dysfunction induced by PS exposure resembled clinical manifestations of polycystic ovary syndrome (PCOS) and can be attributed to lipid metabolism disorder involving glycerophospholipid, sphingolipid, arachidonic acid, and alpha-linolenic acid. Collectively, our results provide new evidence revealing the molecular mechanisms of PS-induced reproductive toxicity, highlighting that MNPs may pose a risk to female reproductive health.PMID:38677429 | DOI:10.1016/j.scitotenv.2024.172795

Bioresour Technol. 2024 Apr 25:130732. doi: 10.1016/j.biortech.2024.130732. Online ahead of print.ABSTRACTAcetaminophen (APAP) is a frequently used, over-the-counter analgesic and antipyretic medication. Considering increase in global consumption, its ubiquity in environment with potential toxic impacts has become a cause of great concern. Hence, bioremediation of this emerging contaminant is of paramount significance. The present study incorporates a microcosm centric omics approach to gain in-depth insights into APAP degradation by Paracoccus sp. APAP_BH8. It can metabolize APAP (300 mg kg-1) within 16 days in soil microcosms. Genome analysis revealed potential genes capable of mediating degradation includes M20 aminoacylase family protein, guanidine deaminase, 4-hydroxybenzoate 3-monooxygenase, and 4-hydroxyphenylpyruvate dioxygenase. Whole proteome analysis showed differential expression of enzymes and bioinformatics provided evidence for stable binding of intermediates at the active site of considered enzymes. Metabolites identified were 4-aminophenol, hydroquinone, and 3-hydroxy-cis, cis-muconate. Therefore, Paracoccus sp. APAP_BH8 with versatile enzymatic and genetic attributes can be a promising candidate for formulating improved in situ APAP bioremediation strategies.PMID:38677386 | DOI:10.1016/j.biortech.2024.130732

Phytomedicine. 2024 Apr 6;129:155571. doi: 10.1016/j.phymed.2024.155571. Online ahead of print.ABSTRACTBACKGROUND: Repairing the intestinal mucosal barrier and reducing persistent inflammation is the key strategies for the treatment of ulcerative colitis (UC). Zhilining Formula (ZLN), composed of Andrographis herba (AH), Sophorae flavescentis radix (SFA), and Aucklandia radix (AR), is a well-tried formula for the clinical treatment of enteritis and dysentery in China, and its mechanism has not been clarified.PURPOSE: This study aims to investigate the effect of ZLN on UC and elucidate its underlying mechanism via metabolomics analysis and experimental verification.METHODS: The effect of ZLN on UC was evaluated in a 3.5 % dextran sulfate sodium (DSS)-induced mice model via the body weight, disease activity index (DAI), colon length, colonic histopathology, expression of inflammation factors, and intestinal barrier in mice. An UPLC-Q-TOF-MS/MS approach-based metabolomics analysis was performed to preliminary explore the mechanism of ZLN in colitis. Based on the results of metabolomics analysis, the expression of related protein or mRNA in AHR/NF-κBp65 axis was determined by qPCR and western blotting. Moreover, the potential interactions of active ingredients of ZLN with NF-κBp65 and AHR were investigated in vitro through using agonists and inhibitors of NF-κBp65 and AHR, respectively.RESULTS: ZLN alleviated body weight loss and colonic shortening in colitis mice, and down-regulated the DAI and histopathological score as well. ZLN also decreased the levels of inflammatory factors (MPO, IL-1β, TNF-α and IL-18), protected goblet cell function and intestinal barrier in DSS-induced mice. Metabolomics results revealed that 36 metabolites that were significantly altered in mice after induction with DSS, which involved in 16 metabolic pathways, including biosynthesis of unsaturated fatty acid, phenylalanine metabolism, arachidonic acid (AA) metabolism, tryptophan (Trp) metabolism, retinol metabolism, and sphingolipid metabolism, etc. ZLN restored 26 different metabolites (DEMs) of them to normal-like levels, indicating ZLN regulated the AA metabolism and Trp-metabolism in UC mice, which hinted its potential pharmacological mechanism related to AHR/NF-κBp65 axis. We further confirmed that ZLN could restrain the activation of NF-κBp65 signaling pathway and then inhibit the expression of its mediated inflammatory cytokines, such as IL-1β, TNF-α, COX-2 and IL17A. Moreover, ZLN increased nuclear translocation of AHR and IL22 expression, which is an important regulatory signal for intestinal mucosal barrier repaired. Finally, we elucidated in vitro that the active ingredients of ZLN exerted anti-colitis effects by activating AHR and simultaneously inhibiting NF-κBp65.CONCLUSION: ZLN relieved colitis by AHR/NF-κBp65 axis. This study highlighted the important role of AHR and NF-κBp65 in UC, and provided a theoretical basis for the application of ZLN.PMID:38677270 | DOI:10.1016/j.phymed.2024.155571

J Magn Reson. 2024 Apr 24;362:107689. doi: 10.1016/j.jmr.2024.107689. Online ahead of print.ABSTRACTβ-Lactamases (EC 3.5.2.6) confer resistance against β-lactam group-containing antibiotics in bacteria and higher eukaryotes, including humans. Pathogenic bacterial resistance against β-lactam antibiotics is a primary concern for potential therapeutic developments and drug targets. Here, we report putative β-lactamase activity, sulbactam binding (a β-lactam analogue) in the low μM affinity range, and site-specific interaction studies of a 14 kDa UV- and dark-inducible protein (abbreviated as UVI31+, a BolA homologue) from Chlamydomonas reinhartii. Intriguingly, the solution NMR structure of UVI31 + bears no resemblance to other known β-lactamases; however, the sulbactam binding is found at two sites rich in positively charged residues, mainly at the L2 loop regions and the N-terminus. Using NMR spectroscopy, ITC and MD simulations, we map the ligand binding sites in UVI31 + providing atomic-level insights into its β-lactamase activity. Current study is the first report on β-lactamase activity of UVI31+, a BolA analogue, from C. reinhartii. Furthermore, our mutation studies reveal that the active site serine-55 is crucial for β-lactamase activity.PMID:38677224 | DOI:10.1016/j.jmr.2024.107689

J Hazard Mater. 2024 Apr 25;471:134439. doi: 10.1016/j.jhazmat.2024.134439. Online ahead of print.ABSTRACTMicrocystins (MCs) have a significant influence on aquatic ecosystems, but little is known about their terrestrial fate and impact. Here, we investigated the fate of two MCs (MC-LR and MC-RR) in the soil-earthworm system, with consideration of their congener-specific impact on earthworm health, soil bacteria, and soil metabolome. Although MCs had little acute lethal effect on earthworms, they caused obvious growth inhibition and setae rupture. Relative to MC-RR, MC-LR exhibited higher bioaccumulation and the resulting dermal lesions and deformation of longitudinal muscles. While the incorporation of both MCs into soils stimulated pathogenic bacteria and depressed oxidative stress tolerant bacteria, the response among soil nitrification and glutathione metabolism differed between the two congeners. The dissipation kinetics of MCs obeyed the first-order model. Earthworms stimulated soil N-cycling enzyme activities, increased the abundance of MC-degrading bacteria, and promoted bacterial metabolic functions related to glutathione metabolism, xenobiotics biodegradation, and metabolism of amino acids that comprise MCs, which accelerated the dissipation of MC-LR and MC-RR by 227% and 82%, respectively. These results provide evidence of significant congener differences in the terrestrial fate and impact of MCs, which will enable a better understanding of their role in mediating soil functions and ecosystem services.PMID:38677123 | DOI:10.1016/j.jhazmat.2024.134439

Alzheimers Dement. 2024 Apr 27. doi: 10.1002/alz.13851. Online ahead of print.ABSTRACTINTRODUCTION: Increasing evidence suggests that metabolic impairments contribute to early Alzheimer's disease (AD) mechanisms and subsequent dementia. Signals in metabolic pathways conserved across species can facilitate translation.METHODS: We investigated differences in serum and brain metabolites between the early-onset 5XFAD and late-onset LOAD1 (APOE4.Trem2*R47H) mouse models of AD to C57BL/6J controls at 6 months of age.RESULTS: We identified sex differences for several classes of metabolites, such as glycerophospholipids, sphingolipids, and amino acids. Metabolic signatures were notably different between brain and serum in both mouse models. The 5XFAD mice exhibited stronger differences in brain metabolites, whereas LOAD1 mice showed more pronounced differences in serum.DISCUSSION: Several of our findings were consistent with results in humans, showing glycerophospholipids reduction in serum of apolipoprotein E (apoE) ε4 carriers and replicating the serum metabolic imprint of the APOE ε4 genotype. Our work thus represents a significant step toward translating metabolic dysregulation from model organisms to human AD.HIGHLIGHTS: This was a metabolomic assessment of two mouse models relevant to Alzheimer's disease. Mouse models exhibit broad sex-specific metabolic differences, similar to human study cohorts. The early-onset 5XFAD mouse model primarily alters brain metabolites while the late-onset LOAD1 model primarily changes serum metabolites. Apolipoprotein E (apoE) ε4 mice recapitulate glycerophospolipid signatures of human APOE ε4 carriers in both brain and serum.PMID:38676929 | DOI:10.1002/alz.13851

Pest Manag Sci. 2024 Apr 27. doi: 10.1002/ps.8153. Online ahead of print.ABSTRACTBACKGROUND: Rice sheath blight caused by Rhizoctonia solani is a severe threat to the yield and quality of rice. Due to the unscientific abuse of common fungicides causing resistance and environmental issues, the development of new fungicides is necessary. In this study, we used citral as the lead compound, designed and synthesized a series of novel citral amide derivatives, and evaluated their antifungal activity and mode of action against R. solani.RESULT: Bioassay results indicated that antifungal activities of most citral amide derivatives against R. solani were significantly improved compared to citral, with EC50 values ranging from 9.50-27.12 mg/L. Among them, compound d21 containing the N-(Pyridin-4-yl)carboxamide group exhibited in vitro and in vivo fungicidal activities, with curative effects at 500 mg/L as effectively as the commercial fungicide validamycin·bacillus. Furthermore, d21 prolonged lag phase of the growth curve of R. solani, reduced the amount of growth, and inhibited sclerotium germination and formation. Mechanistically, d21 deformed the mycelia, increased cell membrane permeability, and inhibited the activities of antioxidant and TCA-related enzymes. Metabolome analysis showed the abundance of some energy-related metabolites within R. solani increased, and simultaneously the antifungal substances secreted by itself reduced. Transcriptome analysis showed that most genes encoding ABC transporters and peroxisomes upregulated after the treatment of d21, and cell membrane destruction.CONCLUSION: This study indicates that novel citral amide derivatives possess antifungal activity against R. solani and are expected to develop an alternative option for chemical control of rice sheath blight. This article is protected by copyright. All rights reserved.PMID:38676622 | DOI:10.1002/ps.8153

Mol Nutr Food Res. 2024 Apr 27:e2300856. doi: 10.1002/mnfr.202300856. Online ahead of print.ABSTRACTSCOPE: Obesity and its metabolic comorbidities pose a major global challenge for public health. Glucoraphanin (GRN) is a natural bioactive compound enriched in broccoli that is known to have potential health benefits against various human chronic diseases.METHODS AND RESULTS: This study investigats the effects of broccoli GRN supplementation on body weight, metabolic parameters, gut microbiome and metabolome associated with obesity. The study is conducted on an obese-related C57BL/6J mouse model through the treatment of normal control diet, high-fat diet (HFD)and GRN-supplemented HFD (HFD-GRN) to determine the metabolic protection of GRN. The results shows that GRN treatment alleviates obesity-related traits leading to improved glucose metabolism in HFD-fed animals. Mechanically, the study noticed that GRN significantly shifts the gut microbial diversity and composition to an eubiosis status. GRN supplement also significantly alters plasma metabolite profiles. Further integrated analysis reveal a complex interaction between the gut microbes and host metabolism that may contribute to GRN-induced beneficial effects against HFD.CONCLUSION: These results indicate that beneficial effects of broccoli GRN on reversing HFD-induced adverse metabolic parameters may be attributed to its impacts on reprogramming microbial community and metabolites. Identification of the mechanistic functions of GRN further warrants it as a dietary candidate for obesity prevention.PMID:38676466 | DOI:10.1002/mnfr.202300856

Viruses. 2024 Apr 17;16(4):625. doi: 10.3390/v16040625.ABSTRACTA devastating bluetongue (BT) epidemic caused by bluetongue virus serotype 3 (BTV-3) has spread throughout most of the Netherlands within two months since the first infection was officially confirmed in the beginning of September 2023. The epidemic comes with unusually strong suffering of infected cattle through severe lameness, often resulting in mortality or euthanisation for welfare reasons. In total, tens of thousands of sheep have died or had to be euthanised. By October 2023, more than 2200 locations with ruminant livestock were officially identified to be infected with BTV-3, and additionally, ruminants from 1300 locations were showing BTV-associated clinical symptoms (but not laboratory-confirmed BT). Here, we report on the spatial spread and dynamics of this BT epidemic. More specifically, we characterized the distance-dependent intensity of the between-holding transmission by estimating the spatial transmission kernel and by comparing it to transmission kernels estimated earlier for BTV-8 transmission in Northwestern Europe in 2006 and 2007. The 2023 BTV-3 kernel parameters are in line with those of the transmission kernel estimated previously for the between-holding spread of BTV-8 in Europe in 2007. The 2023 BTV-3 transmission kernel has a long-distance spatial range (across tens of kilometres), evidencing that in addition to short-distance dispersal of infected midges, other transmission routes such as livestock transports probably played an important role.PMID:38675966 | DOI:10.3390/v16040625

Viruses. 2024 Apr 10;16(4):582. doi: 10.3390/v16040582.ABSTRACTIn people living with HIV (PLHIV), integrase strand transfer inhibitors (INSTIs) are part of the first-line combination antiretroviral therapy (cART), while non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are alternatives. Distinct cART regimens may variably influence the risk for non-AIDS comorbidities. We aimed to compare the metabolome and lipidome of INSTI and NNRTI-based regimens. The 2000HIV study includes asymptomatic PLHIV (n = 1646) on long-term cART, separated into a discovery cohort with 730 INSTI and 617 NNRTI users, and a validation cohort encompassing 209 INSTI and 90 NNRTI users. Baseline plasma samples from INSTI and NNRTI users were compared using mass spectrometry-based untargeted metabolomic (n = 500) analysis. Perturbed metabolic pathways were identified using MetaboAnalyst software. Subsequently, nuclear magnetic resonance spectroscopy was used for targeted lipoprotein and lipid (n = 141) analysis. Metabolome homogeneity was observed between the different types of INSTI and NNRTI. In contrast, higher and lower levels of 59 and 45 metabolites, respectively, were found in the INSTI group compared to NNRTI users, of which 77.9% (81/104) had consistent directionality in the validation cohort. Annotated metabolites belonged mainly to 'lipid and lipid-like molecules', 'organic acids and derivatives' and 'organoheterocyclic compounds'. In pathway analysis, perturbed 'vitamin B1 (thiamin) metabolism', 'de novo fatty acid biosynthesis', 'bile acid biosynthesis' and 'pentose phosphate pathway' were detected, among others. Lipoprotein and lipid levels in NNRTIs were heterogeneous and could not be compared as a group. INSTIs compared to individual NNRTI types showed that HDL cholesterol was lower in INSTIs compared to nevirapine but higher in INSTIs compared to doravirine. In addition, LDL size was lower in INSTIs and nevirapine compared to doravirine. NNRTIs show more heterogeneous cardiometabolic effects than INSTIs, which hampers the comparison between these two classes of drugs. Targeted lipoproteomic and lipid NMR spectroscopy showed that INSTI use was associated with a more unfavorable lipid profile compared to nevirapine, which was shifted to a more favorable profile for INSTI when substituting nevirapine for doravirine, with evidently higher fold changes. The cardiovascular disease risk profile seems more favorable in INSTIs compared to NNRTIs in untargeted metabolomic analysis using mass-spectrometry.PMID:38675924 | DOI:10.3390/v16040582

Viruses. 2024 Apr 9;16(4):580. doi: 10.3390/v16040580.ABSTRACTChildren with perinatally acquired human immunodeficiency virus (PHIV) are growing into adulthood with HIV and treatment-associated comorbidities, such as dyslipidemia and insulin resistance. HIV is identified as independent risk factor for cardiovascular disease (CVD). The hypothesis behind increased CVD risk associated with HIV includes vascular inflammation, dyslipidemia and combination antiretroviral therapy (cART) metabolomic toxicity. To investigate differences in lipid profiles and pathophysiological mechanisms of CVD risk in adolescents with PHIV, we compared the plasma lipidome of PHIV adolescents and HIV-negative controls. We additionally investigated the influence of current cART regimens and increased lipoprotein(a) (Lp(a)) levels on the plasma lipidome. We included 20 PHIV-infected adolescents and 20 HIV-negative controls matched for age, sex, ethnic origin and socio-economic status. Plasma lipidome was measured using Thermo Scientific Ultimate 3000 binary high-performance liquid chromatography (HPLC)-mass spectrometry. We evaluated the plasma lipidome in PHIV adolescents using different cART regimens (including those known to be associated with lipid alterations). The median age was 17.5 years (15.5-20.7) and 16.5 years (15.7-19.8) for PHIV adolescents and controls, respectively. Of PHIV adolescents, 45% used a non-nucleotide reverse transcriptase inhibitor (NNRTI)-based (25%) or protease inhibitor (PI)-based (20%) cART regimen. In this pilot study, we observed no significant differences between lipidomic profiles between PHIV adolescents and controls. We observed no differences in the plasma lipidome in participants with increased versus normal Lp(a) levels. Different cART regimens appear to influence chain length differences in the plasma lipidome of PHIV adolescents; however, the significance and causality of this observation remains undetermined. Further research on the influence of cART on lipid composition could further identify these alterations.PMID:38675922 | DOI:10.3390/v16040580

Molecules. 2024 Apr 19;29(8):1877. doi: 10.3390/molecules29081877.ABSTRACTThe allelopathic autotoxicity of ginsenosides is an important cause of continuous cropping obstacles in ginseng planting. There is no report on the potential molecular mechanism of the correlation between polarity of ginsenoside components and their allelopathic autotoxicity. This study applied a combination of metabolomics and transcriptomics analysis techniques, combined with apparent morphology, physiological indexes, and cell vitality detection of the ginseng hairy roots, through which the molecular mechanism of correlation between polarity and allelopathic autotoxicity of ginsenosides were comprehensively studied. The hairy roots of ginseng presented more severe cell apoptosis under the stress of low-polarity ginsenoside components (ZG70). ZG70 exerted allelopathic autotoxicity by regulating the key enzyme genes of cis-zeatin (cZ) synthesis pathway, indole-3-acetic acid (IAA) synthesis pathway, and jasmonates (JAs) signaling transduction pathway. The common pathway for high-polarity ginsenoside components (ZG50) and ZG70 to induce the development of allelopathic autotoxicity was through the expression of key enzymes in the gibberellin (GA) signal transduction pathway, thereby inhibiting the growth of ginseng hairy roots. cZ, indole-3-acetamid (IAM), gibberellin A1 (GA1), and jasmonoyl-L-isoleucine (JA-ILE) were the key response factors in this process. It could be concluded that the polarity of ginsenoside components were negatively correlated with their allelopathic autotoxicity.PMID:38675697 | DOI:10.3390/molecules29081877

Molecules. 2024 Apr 17;29(8):1827. doi: 10.3390/molecules29081827.ABSTRACTAntibiotic resistance in Gram-negative bacteria remains one of the most pressing challenges to global public health. Blocking the transportation of lipopolysaccharides (LPS), a crucial component of the outer membrane of Gram-negative bacteria, is considered a promising strategy for drug discovery. In the transportation process of LPS, two components of the LPS transport (Lpt) complex, LptA and LptC, are responsible for shuttling LPS across the periplasm to the outer membrane, highlighting their potential as targets for antibacterial drug development. In the current study, a protein-protein interaction (PPI) model of LptA and LptC was constructed, and a molecular screening strategy was employed to search a protein-protein interaction compound library. The screening results indicated that compound 18593 exhibits favorable binding free energy with LptA and LptC. In comparison with the molecular dynamics (MD) simulations on currently known inhibitors, compound 18593 shows more stable target binding ability at the same level. The current study suggests that compound 18593 may exhibit an inhibitory effect on the LPS transport process, making it a promising hit compound for further research.PMID:38675646 | DOI:10.3390/molecules29081827

Molecules. 2024 Apr 12;29(8):1747. doi: 10.3390/molecules29081747.ABSTRACTDrying is an inseparable part of industrial microalgae production. In this work, the impacts of eight different drying methods on the metabolome and lipidome of Arthrospira platensis were investigated. The studied drying methods were freeze drying (FD), sun drying (SD), air drying at 40 and 75 °C (AD' and AD″), infrared drying at 40 and 75 °C (IRD' and IRD″), and vacuum drying at 40 and 75 °C (VD' and VD″). Results gathered by reversed-phase liquid chromatography separation coupled with high-resolution tandem mass spectrometry with electrospray ionization (RP-LC-ESI-Orbitrap HRMS/MS) analysis allowed researchers to identify a total of 316 metabolites (including lipids) in aqueous and ethanolic extracts. The compounds identified in ethanolic extracts were mainly lipids, such as neutral and polar lipids, chlorophylls and carotenoids, while the compounds identified in the aqueous extracts were mainly amino acids and dipeptides. Among the identified compounds, products of enzymatic and chemical degradation, such as pyropheophytins, monoacylglycerols and lysophosphatidylcholines were also identified and their amounts depended on the drying method. The results showed that except for FD method, recognized as a control, the most protective method was AD'. Contrary to this, VD' and VD″, under the conditions used, promoted the most intense degradation of valuable metabolites.PMID:38675566 | DOI:10.3390/molecules29081747

Molecules. 2024 Apr 11;29(8):1733. doi: 10.3390/molecules29081733.ABSTRACTIn traditional Chinese medicine, Aurantii Fructus Immatures (AFIs) have been utilized for more than 2000 years. The proportions of different fruit parts are crucial for evaluating AFI quality in China. However, the basis for this statement's substance is unclear. Differences in quality are intimately correlated with a plant's metabolite composition. On the basis of a widely targeted metabolome, this study intended to investigate the metabolite composition and evaluate the antioxidant capacity of the peel and pulp of an AFI. Metabolites were identified and quantified by UHPLC-QqQ-MS. To assess their antioxidant ability, DPPH and ABTS assays were carried out. There were 1327 chemical compounds identified by UHPLC-QqQ-MS. After screening the differential metabolites using a multivariate statistical analysis, it was found that there were 695 significant differences in the metabolites between the peel and the pulp. Among them, it was discovered that the content of active ingredients in the peel group was higher than that in the pulp group. Furthermore, the aqueous extracts from the peel showed stronger antioxidant capacities than those from the pulp. The metabolites and antioxidant capacities were significantly different between the peel and the pulp. This study of different fruit parts might provide a guide for AFI quality assessments.PMID:38675553 | DOI:10.3390/molecules29081733

Molecules. 2024 Apr 10;29(8):1713. doi: 10.3390/molecules29081713.ABSTRACTTraditional Chinese medicine (TCM) possesses the potential of providing good curative effects with no side effects for the effective management of slow transit constipation (STC), an intestinal disease characterized by colonic dyskinesia. Mulberry leaves (Morus alba L.) and black sesame (Sesamum indicum L.), referred to as SH, are processed and conditioned as per standardized protocols. SH has applications as food and medicine. Accordingly, we investigated the therapeutic potential of SH in alleviating STC. The analysis of SH composition identified a total of 504 compounds. The intervention with SH significantly improved intestinal motility, reduced the time for the first black stool, increased antioxidant activity, and enhanced water content, thereby effectively alleviating colon damage caused by STC. Transcriptome analysis revealed the SH in the treatment of STC related to SOD1, MUC2, and AQP1. The analysis of 16S rRNA gene sequences indicated notable differences in the abundance of 10 bacteria between the SH and model. Metabolomic analysis further revealed that SH supplementation increased the levels of nine metabolites associated with STC. Integrative analysis revealed that SH modulated amino acid metabolism, balanced intestinal flora, and targeted key genes (i.e., SOD1, MUC2, AQP1) to exert its effects. SH also inhibited the AQP1 expression and promoted SOD1 and MUC2 expression.PMID:38675536 | DOI:10.3390/molecules29081713

Pharmaceuticals (Basel). 2024 Apr 15;17(4):502. doi: 10.3390/ph17040502.ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is usually associated with obesity. However, it is crucial to recognize that NAFLD can also occur in lean individuals, which is frequently overlooked. Without an approved pharmacological therapy for lean NAFLD, we aimed to investigate whether the Ganjianglingzhu (GJLZ) decoction, a representative traditional Chinese medicine (TCM), protects against lean NAFLD and explore the potential mechanism underlying these protective effects. The mouse model of lean NAFLD was established with a methionine-choline-deficient (MCD) diet in male C57BL/6 mice to be compared with the control group fed the methionine-choline-sufficient (MCS) diet. After four weeks, physiological saline, a low dose of GJLZ decoction (GL), or a high dose of GJLZ decoction (GH) was administered daily by gavage to the MCD group; the MCS group was given physiological saline by gavage. Untargeted metabolomics techniques were used to explore further the potential mechanism of the effects of GJLZ on lean NAFLD. Different doses of GJLZ decoction were able to ameliorate steatosis, inflammation, fibrosis, and oxidative stress in the liver; GL performed a better effect on lean NAFLD. In addition, 78 candidate differential metabolites were screened and identified. Combined with metabolite pathway enrichment analysis, GL was capable of regulating the glucose and lipid metabolite pathway in lean NAFLD and regulating the glycerophospholipid metabolism by altering the levels of sn-3-O-(geranylgeranyl)glycerol 1-phosphate and lysoPC(P-18:0/0:0). GJLZ may protect against the development of lean NAFLD by regulating glucose and lipid metabolism, inhibiting the levels of sn-3-O-(geranylgeranyl)glycerol 1-phosphate and lysoPC(P-18:0/0:0) in glycerophospholipid metabolism.PMID:38675462 | DOI:10.3390/ph17040502