PubMed

Environ Int. 2024 May 22;188:108766. doi: 10.1016/j.envint.2024.108766. Online ahead of print.ABSTRACTEarly-life exposure to natural and synthetic chemicals can impact acute and chronic health conditions. Here, a suspect screening workflow anchored on high-resolution mass spectrometry was applied to elucidate xenobiotics in breast milk and matching stool samples collected from Nigerian mother-infant pairs (n = 11) at three time points. Potential correlations between xenobiotic exposure and the developing gut microbiome, as determined by 16S rRNA gene amplicon sequencing, were subsequently explored. Overall, 12,192 and 16,461 features were acquired in the breast milk and stool samples, respectively. Following quality control and suspect screening, 562 and 864 features remained, respectively, with 149 of these features present in both matrices. Taking advantage of 242 authentic reference standards measured for confirmatory purposes of food bio-actives and toxicants, 34 features in breast milk and 68 features in stool were identified and semi-quantified. Moreover, 51 and 78 features were annotated with spectral library matching, as well as 416 and 652 by in silico fragmentation tools in breast milk and stool, respectively. The analytical workflow proved its versatility to simultaneously determine a diverse panel of chemical classes including mycotoxins, endocrine-disrupting chemicals (EDCs), antibiotics, plasticizers, perfluorinated alkylated substances (PFAS), and pesticides, although it was originally optimized for polyphenols. Spearman rank correlation of the identified features revealed significant correlations between chemicals of the same classification such as polyphenols. One-way ANOVA and differential abundance analysis of the data obtained from stool samples revealed that molecules of plant-based origin elevated as complementary foods were introduced to the infants' diets. Annotated compounds in the stool, such as tricetin, positively correlated with the genus Blautia. Moreover, vulgaxanthin negatively correlated with Escherichia-Shigella. Despite the limited sample size, this exploratory study provides high-quality exposure data of matched biospecimens obtained from mother-infant pairs in sub-Saharan Africa and shows potential correlations between the chemical exposome and the gut microbiome.PMID:38801800 | DOI:10.1016/j.envint.2024.108766

Microb Biotechnol. 2024 May;17(5):e14476. doi: 10.1111/1751-7915.14476.ABSTRACTThis study aimed to investigate how parental genomes contribute to yeast hybrid metabolism using a metabolomic approach. Previous studies have explored central carbon and nitrogen metabolism in Saccharomyces species during wine fermentation, but this study analyses the metabolomes of Saccharomyces hybrids for the first time. We evaluated the oenological performance and intra- and extracellular metabolomes, and we compared the strains according to nutrient consumption and production of the main fermentative by-products. Surprisingly, no common pattern was observed for hybrid genome influence; each strain behaved differently during wine fermentation. However, this study suggests that the genome of the S. cerevisiae species may play a more relevant role in fermentative metabolism. Variations in biomass/nitrogen ratios were also noted, potentially linked to S. kudriavzevii and S. uvarum genome contributions. These results open up possibilities for further research using different "omics" approaches to comprehend better metabolic regulation in hybrid strains with genomes from different species.PMID:38801338 | DOI:10.1111/1751-7915.14476

JBRA Assist Reprod. 2024 May 23. doi: 10.5935/1518-0557.20240034. Online ahead of print.ABSTRACTFollowing the advancement of medically assisted reproduction (MAR) technology, and the rationale to extend the culture to the blastocyst stage, performing elective single embryo transfer (eSET), gamete quality and assessment have acquired large relevance in ART. Embryo quality is strictly correlated with gametes quality and culture conditions. Oocyte maturity assessment is therefore imperative for fertilization and embryo evolution. Mature oocytes at the metaphase II stage result in a higher fertilization rate compared to immature oocytes. Indeed, oocyte morphology evaluation represents an important and challenging task that may serve as a valuable prognostic tool for future embryo development and implantation potential. Different grading systems have been reported to assess human embryos, however, in many cases, it is still a major challenge to select the single embryo to transfer with the highest implantation potential. Further, eSET has conferred a challenge to embryologists, who must try to enhance embryo culture and selection to provide an adequate success rate, whilst reducing the overall number of embryos transferred. Above the standard morphological assessment, there are several invasive or non-invasive approaches for embryo selection such as preimplantation genetic testing, time-lapse technology, proteomics and metabolomics, as well as oxygen utilization and analysis of oxidative stress in culture medium. This short review is not designed to be a comprehensive review of all possible features that may influence oocyte quality. It does give, however, a brief overview and describes the prognostic value of the morphological characteristics of human oocytes on their developmental capacity following ART treatments.PMID:38801314 | DOI:10.5935/1518-0557.20240034

Physiol Plant. 2024 May-Jun;176(3):e14361. doi: 10.1111/ppl.14361.ABSTRACTNepenthes are carnivorous plants that colonize habitats poor in soil nutrients. To survive, Nepenthes develop pitchers capable of capturing and digesting attracted prey. Prey-derived nutrients are then absorbed to support plant growth and reproduction. So far, pitcher formation in Nepenthes is a poorly understood biological process. To shed light on the formation of Nepenthes pitchers, we grew dissected shoot apices of 3-month-old N. khasiana seedlings in Murashige and Skoog (MS) medium of varying strengths viz. full-strength MS (1 MS), quarter-strength MS (1/4 MS), and one-eighth strength MS (1/8 MS), including those lacking nitrogen (N), phosphorus (P), and potassium (K) and in the presence of N-1-naphthylphthalamic acid (NPA). We sequenced the transcriptome and performed gas chromatography-mass spectrometry to determine changes in gene expression patterns and primary metabolite accumulations in response to the varying nutrient conditions. Shoots grown in 1 MS or NPA-containing 1/4 MS and 1/8 MS failed to develop pitchers. Remarkably, pitcher formation is restored when N was removed from 1 MS. Transcriptomic response to nutrient-sufficient and nutrient-deficient conditions are associated with the enrichment of several defence-related genes, including two JA-mediated defence response genes, WRKY51 and WRKY11, respectively. Further, metabolomic response to the varying nutrient conditions identifies glutamic acid as a key metabolite, accumulating at lower and higher levels in shoots with and without pitchers, respectively. Together, our findings suggest that failure to form pitchers may be associated with the suppression of the JA-signalling pathway, whereas the induction of the JA-mediated defence response is linked to pitcher formation in N. khasiana.PMID:38801017 | DOI:10.1111/ppl.14361

Anim Nutr. 2024 Mar 30;17:283-296. doi: 10.1016/j.aninu.2024.03.009. eCollection 2024 Jun.ABSTRACTThis study was conducted to evaluate the effects of Monascus purpureus M-32 fermented soybean meal (MFSM) on growth, immunity, intestinal morphology, intestinal microbiota, and intestinal metabolome of Pacific white shrimp (Litopenaeus vannamei). Four groups of diets were formulated, including control group (30% fish meal and 30% soybean meal [SBM] included in the basal diet) and three experimental groups which MFSM replaced 20% (MFSM20), 40% (MFSM40), and 60% (MFSM60) of SBM in control group, respectively. Results showed that the soluble proteins larger than 49 kDa in MFSM were almost completely degraded. Meanwhile, the crude protein, acid-soluble protein, and amino acid in MFSM were increased. The results of shrimp culture experiment showed that the replacement of SBM with MFSM decreased FCR (P < 0.001) and content of malondialdehyde (P = 0.007) in the experimental groups, and increased weight gain rate (P = 0.006), specific growth rate (P = 0.002), survival rate (P = 0.005), intestinal villus height (P < 0.001), myenteric thickness (P = 0.002), the activities of superoxide dismutase (P = 0.002), and lysozyme (P = 0.006) in experimental groups, as well as increased content of calcium (Ca2+) and phosphorus (PO43-) in blood and muscle, and enhanced resistance to Vibrio parahaemolyticus infection. The gut microbiota of MFSM groups was significantly different from that of the control group, and the abundance of Actinobacteria and Verrucomicrobia increased significantly in the MFSM60 group, whereas Proteobacteria and Firmicutes decreased. Compared with the control group, there were significant changes in the levels of several intestinal metabolites in the MFSM60 group, including leukotriene C5, prostaglandin A1, taurochenodeoxycholic acid, carnosine, and itaconic acid. The fermentation of SBM by the strain M. purpureus M-32 has the potential to enhance the nutritional quality of SBM, promote the growth of L. vannamei, boost immune response, improve intestinal morphology and microbiota composition, as well as influence intestinal metabolites.PMID:38800738 | PMC:PMC11127234 | DOI:10.1016/j.aninu.2024.03.009

Anim Nutr. 2024 Mar 21;17:358-372. doi: 10.1016/j.aninu.2024.01.011. eCollection 2024 Jun.ABSTRACTThis study was to evaluate the effect of supplementing the diet of broilers with Neolamarckia cadamba leaf extract (NCLE) on meat quality by evaluating antioxidant parameters and the expression of genes in the p38 mitogen-activated protein kinase/nuclear factor-erythroid 2-related factor 2/antioxidant responsive element (p38 MAPK/Nrf2/ARE) signaling pathway, coupled with LC-MS-based metabolomic analysis. A total of 480 one-day-old male broilers were randomly allocated to four treatment groups-a control (CON) group, which was fed a basal diet, and three NCLE treatment groups, which were fed the basal diet supplemented with 100, 200, or 400 mg/kg NCLE (N1, N2, and N3 groups, respectively) for 42 d. Compared with the CON group, meat quality was improved in the N2 and N3 groups, as evidenced by the higher pH45min (P < 0.05) and lower shear force (P < 0.05) in breast muscle (BM) and lower drip loss at 48 h (P < 0.05) in leg muscle (LM). Moreover, BM antioxidant capacity was significantly enhanced in the N3 group, characterized by an increase in the total antioxidant capacity (T-AOC), the concentrations of glutathione peroxidase (GSH-Px) and catalase (CAT), and the relative mRNA expression of p38 MAPK, extracellular-signal regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), Nrf2, CAT, and GSH-Px (P < 0.05). Similarly, LM in the N3 group displayed higher T-AOC, increased GSH-Px and CAT concentrations, reduced malonaldehyde contents (P < 0.05), and upregulation of the relative mRNA levels of JNK, Nrf2, heme oxygenase, CAT, and superoxide dismutase (SOD) (P < 0.05). Metabolomics analysis revealed that D-arabinono-1,4-lactone and lyso-PAF C-16-d4 were negatively correlated with shear force and cooking loss (P < 0.05) and displayed increased abundance in BM of the N3 group. L-Serine levels were upregulated while D-fructose 1,6-diphosphate contents were downregulated in the three NCLE groups. Finally, the differential metabolites in both BM and LM were involved in amino acid metabolism pathways. Our results indicated that NCLE supplementation improved meat quality by enhancing antioxidant enzyme activities, promoting the expression of genes in the p38 MAPK/Nrf2/ARE signaling pathway, and regulating amino acid metabolism. The optimal NCLE concentration was found to be 400 mg/kg.PMID:38800732 | PMC:PMC11127102 | DOI:10.1016/j.aninu.2024.01.011

Front Endocrinol (Lausanne). 2024 May 10;15:1335855. doi: 10.3389/fendo.2024.1335855. eCollection 2024.ABSTRACTINTRODUCTION: Emerging data suggests liver disease may be initiated during development when there is high genome plasticity and the molecular pathways supporting liver function are being developed.METHODS: Here, we leveraged our Collaborative Cross mouse model of developmental vitamin D deficiency (DVD) to investigate the role of DVD in dysregulating the molecular mechanisms underlying liver disease. We defined the effects on the adult liver transcriptome and metabolome and examined the role of epigenetic dysregulation. Given that the parental origin of the genome (POG) influences response to DVD, we used our established POG model [POG1-(CC011xCC001)F1 and POG2-(CC001xCC011)F1] to identify interindividual differences.RESULTS: We found that DVD altered the adult liver transcriptome, primarily downregulating genes controlling liver development, response to injury/infection (detoxification & inflammation), cholesterol biosynthesis, and energy production. In concordance with these transcriptional changes, we found that DVD decreased liver cell membrane-associated lipids (including cholesterol) and pentose phosphate pathway metabolites. Each POG also exhibited distinct responses. POG1 exhibited almost 2X more differentially expressed genes (DEGs) with effects indicative of increased energy utilization. This included upregulation of lipid and amino acid metabolism genes and increased intermediate lipid and amino acid metabolites, increased energy cofactors, and decreased energy substrates. POG2 exhibited broader downregulation of cholesterol biosynthesis genes with a metabolomics profile indicative of decreased energy utilization. Although DVD primarily caused loss of liver DNA methylation for both POGs, only one epimutation was shared, and POG2 had 6.5X more differentially methylated genes. Differential methylation was detected at DEGs regulating developmental processes such as amino acid transport (POG1) and cell growth & differentiation (e.g., Wnt & cadherin signaling, POG2).CONCLUSIONS: These findings implicate a novel role for maternal vitamin D in programming essential offspring liver functions that are dysregulated in liver disease. Importantly, impairment of these processes was not rescued by vitamin D treatment at weaning, suggesting these effects require preventative measures. Substantial differences in POG response to DVD demonstrate that the parental genomic context of exposure determines offspring susceptibility.PMID:38800476 | PMC:PMC11116800 | DOI:10.3389/fendo.2024.1335855

Cell Stress. 2024 Apr 30;8:51-55. doi: 10.15698/cst2024.04.295. eCollection 2024.ABSTRACTIn a recent issue in Nature Cell Biology, Sung Min Son et al. unveil a novel layer in the regulation of the mTORC1/autophagy axis by EP300 which can undergo nucleocytoplasmic shuttling in response to alterations in nutrient availability. The study highlights that, in Hutchinson-Gilford progeria syndrome, overabundant cytoplasmic EP300 results in mTORC1 hyperactivation and impaired autophagy, potentially contributing to premature and accelerated aging.PMID:38800095 | PMC:PMC11118783 | DOI:10.15698/cst2024.04.295

F1000Res. 2024 Mar 8;13:169. doi: 10.12688/f1000research.141056.1. eCollection 2024.ABSTRACTBACKGROUND: The U.S. Federal Government has supported the generation of extensive amounts of nanomaterials and related nano Environmental Health and Safety (nanoEHS) data, there is a need to make these data available to stakeholders. With recent efforts, a need for improved interoperability, translation, and sustainability of Federal nanoEHS data in the United States has been realized. The NaKnowBase (NKB) is a relational database containing experimental results generated by the EPA Office of Research and Development (ORD) regarding the actions of engineered nanomaterials on environmental and biological systems. Through the interaction of the National Nanotechnology Initiative's Nanotechnology Environmental Health Implications (NEHI) Working Group, and the Database and Informatics Interest Group (DIIG), a U.S. Federal nanoEHS Consortium has been formed.METHODS: The primary goal of this consortium is to establish a "common language" for nanoEHS data that aligns with FAIR data standards. A second goal is to overcome nomenclature issues inherent to nanomaterials data, ultimately allowing data sharing and interoperability across the diverse U.S. Federal nanoEHS data compendium, but also in keeping a level of consistency that will allow interoperability with U.S. and European partners. The most recent version of the EPA NaKnowBase (NKB) has been implemented for semantic integration. Computational code has been developed to use each NKB record as input, modify and filter table data, and subsequently output each modified record to a Research Description Framework (RDF). To improve the accuracy and efficiency of this process the EPA has created the OntoSearcher tool. This tool partially automates the ontology mapping process, thereby reducing onerous manual curation.CONCLUSIONS: Here we describe the efforts of the US EPA in promoting FAIR data standards for Federal nanoEHS data through semantic integration, as well as in the development of NAMs (computational tools) to facilitate these improvements for nanoEHS data at the Federal partner level.PMID:38800073 | PMC:PMC11128042 | DOI:10.12688/f1000research.141056.1

J Pharm Anal. 2024 Apr;14(4):100980. doi: 10.1016/j.jpha.2024.100980. Epub 2024 May 10.ABSTRACT[This corrects the article DOI: 10.1016/j.jpha.2023.09.007.].PMID:38800053 | PMC:PMC11121172 | DOI:10.1016/j.jpha.2024.100980

Front Vet Sci. 2024 May 10;11:1396051. doi: 10.3389/fvets.2024.1396051. eCollection 2024.ABSTRACTMicroencapsulated essential oils (MEO)have been used as antibiotic alternatives that can be applied to alleviate diarrhea in weaning piglet. We examined a large group of weaned piglets and incorporated essential oil containing thymol (2%), carvacrol (5%) and cinnamaldehyde (3%) in the feed of weaned piglets on an intensive production farm. The piglets were divided into four groups; Control (no additions) and chlortetracycline (Chl), essential oil (EO) and microencapsulated essential oil (MEO) were fed ad libitum over a 28-day trial period. We found MEO significantly reduced the incidence of diarrhea in the piglets that was also accompanied by increased average daily weight gains from days 14-28 (p < 0.05). MEO enhanced the antioxidant capacity in the piglets and serum total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-px) levels were significantly increased (p < 0.05). MEO also significantly reduced expression of genes related to ileal inflammation (IL-6, TNF-α and TGF-β1) (p < 0.05) and significantly (p < 0.05) increased in sIgA antibody levels. MEO influenced the composition of the intestinal microbiome and reduced Bacteroidota (p < 0.05) and thus altered the Firmicutes/Bacteroidota ratio. However, none of the treatments produced significant changes in the most common tetracycline resistance genes (p > 0.05). Metagenomic analysis indicated that MEO impacted DNA expression, virulence factors, antioxidant activity and antimicrobial activity. Metabolomic analysis of the intestinal content also indicated that MEO impacted tyrosine metabolism and primary bile acid biosynthesis suggesting improved intestinal health and nutrient absorption. This study paves the way for further research into the development and optimization of MEO-based interventions aimed at improving piglet health and performance while also providing a reference for reducing reliance on antibiotics in animal agriculture.PMID:38799727 | PMC:PMC11117338 | DOI:10.3389/fvets.2024.1396051

iScience. 2024 May 8;27(6):109949. doi: 10.1016/j.isci.2024.109949. eCollection 2024 Jun 21.ABSTRACTAs the global aging population rises, finding effective interventions to improve aging health is crucial. Drug repurposing, utilizing existing drugs for new purposes, presents a promising strategy for rapid implementation. We explored naltrexone from the Library of Integrated Network-based Cellular Signatures (LINCS) based on several selection criteria. Low-dose naltrexone (LDN) has gained attention for treating various diseases, yet its impact on longevity remains underexplored. Our study on C. elegans demonstrated that a low dose, but not high dose, of naltrexone extended the healthspan and lifespan. This effect was mediated through SKN-1 (NRF2 in mammals) signaling, influencing innate immune gene expression and upregulating oxidative stress responses. With LDN's low side effects profile, our findings underscore its potential as a geroprotector, suggesting further exploration for promoting healthy aging in humans is warranted.PMID:38799567 | PMC:PMC11126937 | DOI:10.1016/j.isci.2024.109949

iScience. 2024 Apr 16;27(6):109737. doi: 10.1016/j.isci.2024.109737. eCollection 2024 Jun 21.ABSTRACTLong-chain acyl-CoA synthetase family 4 (ACSL4) metabolizes long-chain polyunsaturated fatty acids (PUFAs), enriching cell membranes with phospholipids susceptible to peroxidation and drive ferroptosis. The role of ACSL4 and ferroptosis upon endoplasmic-reticulum (ER)-stress-induced acute kidney injury (AKI) is unknown. We used lipidomic, molecular, and cellular biology approaches along with a mouse model of AKI induced by ER stress to investigate the role of ACSL4 regulation in membrane lipidome remodeling in the injured tubular epithelium. Tubular epithelial cells (TECs) activate ACSL4 in response to STAT3 signaling. In this context, TEC membrane lipidome is remodeled toward PUFA-enriched triglycerides instead of PUFA-bearing phospholipids. TECs expressing ACSL4 in this setting are not vulnerable to ferroptosis. Thus, ACSL4 activity in TECs is driven by STAT3 signaling, but ACSL4 alone is not enough to sensitize ferroptosis, highlighting the significance of the biological context associated with the study model.PMID:38799564 | PMC:PMC11126884 | DOI:10.1016/j.isci.2024.109737

Front Immunol. 2024 May 10;15:1376860. doi: 10.3389/fimmu.2024.1376860. eCollection 2024.ABSTRACTINTRODUCTION: Aeromonas hydrophila, a bacterium widely distributed in the natural environment, causes multiple diseases in various animals. Exploring the mechanism of the host defense against A. hydrophila can help develop efficient strategies against Aeromonas infection.METHODS: Herein, we investigated the temporal influence of A. hydrophila on the Chinese soft-shelled turtle, an economically important species, at the biochemical, transcriptomic, and metabolomic levels. Plasma parameters were detected with the test kits. Transcriptome and metabolome were respectively applied to screen the differentially expressed genes and metabolites.RESULTS: The contents or activities of these plasma parameters were significantly increased at 24 hpi and declined at 96 hpi, indicating that 24 and 96 hpi were two important time points during infection. Totals of 3121 and 274 differentially expressed genes (DEGs) from the transcriptome while 74 and 91 differentially abundant metabolites (DAMs) from the metabolome were detected at 24 and 96 hpi. The top DEGs at 24 hpi included Ccl2, Ccl3, Ccl4, Il1β, Il6, Il7, Il15, Tnf, and Tnfr1 while Zap70, Cd3g, Cd8a, Itk, Pik3r3, Cd247, Malt1, and Cd4 were the most abundant at 96 hpi. The predominant DAMs included O-phospho-L-serine, γ-Aminobutyric acid, orotate, L-tyrosine, and L-tryptophan at 24 hpi, as well as L-glutamic acid, L-arginine, glutathione, glutathione disulfide, and citric acid at 96 hpi.DISCUSSION: The combined analysis of DEGs and DAMs revealed that tryptophan metabolism, nicotinate and nicotinamide metabolism, as well as starch and sucrose metabolism, were the most important signaling pathways at the early infective stage while tyrosine metabolism, pyrimidine metabolism, as well as alanine, aspartate and glutamate metabolism were the most crucial pathways at the later stage. In general, our results indicated that the Chinese soft-shelled turtle displays stage-specific physiological responses to resist A. hydrophila infection.PMID:38799475 | PMC:PMC11116567 | DOI:10.3389/fimmu.2024.1376860

Front Immunol. 2024 May 10;15:1353903. doi: 10.3389/fimmu.2024.1353903. eCollection 2024.ABSTRACTINTRODUCTION: The global healthcare burden of COVID-19 pandemic has been unprecedented with a high mortality. Metabolomics, a powerful technique, has been increasingly utilized to study the host response to infections and to understand the progression of multi-system disorders such as COVID-19. Analysis of the host metabolites in response to SARS-CoV-2 infection can provide a snapshot of the endogenous metabolic landscape of the host and its role in shaping the interaction with SARS-CoV-2. Disease severity and consequently the clinical outcomes may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. Hence, the host metabolome can help predict potential clinical risks and outcomes.METHODS: In this prospective study, using a targeted metabolomics approach, we studied the metabolic signature in 154 COVID-19 patients (males=138, age range 48-69 yrs) and related it to disease severity and mortality. Blood plasma concentrations of metabolites were quantified through LC-MS using MxP Quant 500 kit, which has a coverage of 630 metabolites from 26 biochemical classes including distinct classes of lipids and small organic molecules. We then employed Kaplan-Meier survival analysis to investigate the correlation between various metabolic markers, disease severity and patient outcomes.RESULTS: A comparison of survival outcomes between individuals with high levels of various metabolites (amino acids, tryptophan, kynurenine, serotonin, creatine, SDMA, ADMA, 1-MH and carnitine palmitoyltransferase 1 and 2 enzymes) and those with low levels revealed statistically significant differences in survival outcomes. We further used four key metabolic markers (tryptophan, kynurenine, asymmetric dimethylarginine, and 1-Methylhistidine) to develop a COVID-19 mortality risk model through the application of multiple machine-learning methods.CONCLUSIONS: Metabolomics analysis revealed distinct metabolic signatures among different severity groups, reflecting discernible alterations in amino acid levels and perturbations in tryptophan metabolism. Notably, critical patients exhibited higher levels of short chain acylcarnitines, concomitant with higher concentrations of SDMA, ADMA, and 1-MH in severe cases and non-survivors. Conversely, levels of 3-methylhistidine were lower in this context.PMID:38799469 | PMC:PMC11127595 | DOI:10.3389/fimmu.2024.1353903

Front Immunol. 2024 May 10;15:1337208. doi: 10.3389/fimmu.2024.1337208. eCollection 2024.ABSTRACTOBJECTIVE: To describe the lipid metabolic profile of different patients with coronavirus disease 2019 (COVID-19) and contribute new evidence on the progression and severity prediction of COVID-19.METHODS: This case-control study was conducted in Peking University Third Hospital, China. The laboratory-confirmed COVID-19 patients aged ≥18 years old and diagnosed as pneumonia from December 2022 to January 2023 were included. Serum lipids were detected. The discrimination ability was calculated with the area under the curve (AUC). A random forest (RF) model was conducted to determine the significance of different lipids.RESULTS: Totally, 44 COVID-19 patients were enrolled with 16 mild and 28 severe patients. The top 5 super classes were triacylglycerols (TAG, 55.9%), phosphatidylethanolamines (PE, 10.9%), phosphatidylcholines (PC, 6.8%), diacylglycerols (DAG, 5.9%) and free fatty acids (FFA, 3.6%) among the 778 detected lipids from the serum of COVID-19 patients. Certain lipids, especially lysophosphatidylcholines (LPCs), turned to have significant correlations with certain immune/cytokine indexes. Reduced level of LPC 20:0 was observed in severe patients particularly in acute stage. The AUC of LPC 20:0 reached 0.940 in discriminating mild and severe patients and 0.807 in discriminating acute and recovery stages in the severe patients. The results of RF models also suggested the significance of LPCs in predicting the severity and progression of COVID-19.CONCLUSION: Lipids probably have the potential to differentiate and forecast the severity, progression, and clinical outcomes of COVID-19 patients, with implications for immune/inflammatory responses. LPC 20:0 might be a potential target in predicting the progression and outcome and the treatment of COVID-19.PMID:38799463 | PMC:PMC11116732 | DOI:10.3389/fimmu.2024.1337208

Front Immunol. 2024 May 10;15:1395018. doi: 10.3389/fimmu.2024.1395018. eCollection 2024.ABSTRACTBACKGROUND: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), continues to be a major public health problem worldwide. The human immunodeficiency virus (HIV) is another equally important life-threatening pathogen. HIV infection decreases CD4+ T cell levels markedly increasing Mtb co-infections. An appropriate animal model for HIV/Mtb co-infection that can recapitulate the diversity of the immune response in humans during co-infection would facilitate basic and translational research in HIV/Mtb infections. Herein, we describe a novel humanized mouse model.METHODS: The irradiated NSG-SGM3 mice were transplanted with human CD34+ hematopoietic stem cells, and the humanization was monitored by staining various immune cell markers for flow cytometry. They were challenged with HIV and/or Mtb, and the CD4+ T cell depletion and HIV viral load were monitored over time. Before necropsy, the live mice were subjected to pulmonary function test and CT scan, and after sacrifice, the lung and spleen homogenates were used to determine Mtb load (CFU) and cytokine/chemokine levels by multiplex assay, and lung sections were analyzed for histopathology. The mouse sera were subjected to metabolomics analysis.RESULTS: Our humanized NSG-SGM3 mice were able to engraft human CD34+ stem cells, which then differentiated into a full-lineage of human immune cell subsets. After co-infection with HIV and Mtb, these mice showed decrease in CD4+ T cell counts overtime and elevated HIV load in the sera, similar to the infection pattern of humans. Additionally, Mtb caused infections in both lungs and spleen, and induced granulomatous lesions in the lungs. Distinct metabolomic profiles were also observed in the tissues from different mouse groups after co-infections.CONCLUSION: The humanized NSG-SGM3 mice are able to recapitulate the pathogenic effects of HIV and Mtb infections and co-infection at the pathological, immunological and metabolism levels and are therefore a reproducible small animal model for studying HIV/Mtb co-infection.PMID:38799434 | PMC:PMC11116656 | DOI:10.3389/fimmu.2024.1395018

J Pharm Anal. 2024 May;14(5):100921. doi: 10.1016/j.jpha.2023.12.011. Epub 2023 Dec 16.ABSTRACTThe collision cross-sections (CCS) measurement using ion mobility spectrometry (IMS) in combination with mass spectrometry (MS) offers a great opportunity to increase confidence in metabolite identification. However, owing to the lack of sensitivity and resolution, IMS has an analytical challenge in studying the CCS values of very low-molecular-weight metabolites (VLMs ≤ 250 Da). Here, we describe an analytical method using ultrahigh-performance liquid chromatography (UPLC) coupled to a traveling wave ion mobility-quadrupole-time-of-flight mass spectrometer optimized for the measurement of VLMs in human urine samples. The experimental CCS values, along with mass spectral properties, were reported for the 174 metabolites. The experimental data included the mass-to-charge ratio (m/z), retention time (RT), tandem MS (MS/MS) spectra, and CCS values. Among the studied metabolites, 263 traveling wave ion mobility spectrometry (TWIMS)-derived CCS values (TWCCSN2) were reported for the first time, and more than 70% of these were CCS values of VLMs. The TWCCSN2 values were highly repeatable, with inter-day variations of <1% relative standard deviation (RSD). The developed method revealed excellent TWCCSN2 accuracy with a CCS difference (ΔCCS) within ±2% of the reported drift tube IMS (DTIMS) and TWIMS CCS values. The complexity of the urine matrix did not affect the precision of the method, as evidenced by ΔCCS within ±1.92%. According to the Metabolomics Standards Initiative, 55 urinary metabolites were identified with a confidence level of 1. Among these 55 metabolites, 53 (96%) were VLMs. The larger number of confirmed compounds found in this study was a result of the addition of TWCCSN2 values, which clearly increased metabolite identification confidence.PMID:38799238 | PMC:PMC11127212 | DOI:10.1016/j.jpha.2023.12.011

Front Pharmacol. 2024 May 10;15:1336369. doi: 10.3389/fphar.2024.1336369. eCollection 2024.ABSTRACTBACKGROUND: Polystyrene microplastics (PS-MPs) exhibit multi-target, multi-dimensional, chronic, and low toxicity to the cardiovascular system. They enter the bloodstream through the gastrointestinal tract and respiratory system, altering blood parameters and conditions, inducing thrombotic diseases, and damaging myocardial tissue through the promotion of oxidative stress and inflammatory responses in myocardial cells. However, many of the links and mechanisms remain unclear.METHODS: In this study, 48 wistar rats were randomly divided into four groups and exposed to different concentrations of PS-MPs: control group (0 mg/kg/d), low dose group (0.5 mg/kg/d), middle dose group (5 mg/kg/d) and high dose group (50 mg/kg/d), with 12 rats in each group. After 90 consecutive days of intragastric administration of PS-MPs, biochemical markers in myocardium, aorta and blood were detected, and HE staining was performed to observe the toxic effects of PS-mps on cardiovascular system. Furthermore, non-targeted metabolomics methods were used to analyze the effect of PS-MPs exposure on the metabolism of cardiovascular system in rats, and to explore its potential molecular mechanism.RESULTS: The results revealed no pathological changes in the heart and aorta following PS-MPs exposure. However, the myocardial enzyme levels in the high dose PS-MPs group of rats showed a significant increase. Moreover, exposure to polystyrene microplastics caused a disorder in lipid metabolism in rats, and led to an increase in indicators of inflammation and oxidative stress in myocardial and aortic tissues, but resulted in a decrease in the level of IL-6. Untargeted metabolomics results showed that metabolites with antioxidant and anti-inflammatory effects, including equol and 4-hydroxybenzoic acid, were significantly upregulated.CONCLUSION: These results suggest that long-term exposure to high concentrations of PS-MPs may lead to abnormal lipid metabolism and cardiovascular system damage. The mechanism may be related to oxidative stress and inflammatory response. Exogenous antioxidants and changes in own metabolites may have a protective effect on the injury. Therefore, understanding the toxicological mechanism of PS-MPs not only helps to elucidate its pathogenesis, but also provides new ideas for the treatment of chronic diseases.PMID:38799170 | PMC:PMC11127592 | DOI:10.3389/fphar.2024.1336369

Hortic Res. 2024 Mar 30;11(5):uhae089. doi: 10.1093/hr/uhae089. eCollection 2024 May.ABSTRACTRecent study has evidenced that traditional Chinese medicinal (TCM) plant-derived schaftoside shows promise as a potential drug candidate for COVID-19 treatment. However, the biosynthetic pathway of schaftoside in TCM plants remains unknown. In this study, the genome of the TCM herb Grona styracifolia (Osbeck) H.Ohashi & K.Ohashi (GSO), which is rich in schaftoside, was sequenced, and a high-quality assembly of GSO genome was obtained. Our findings revealed that GSO did not undergo recent whole genome duplication (WGD) but shared an ancestral papilionoid polyploidy event, leading to the gene expansion of chalcone synthase (CHS) and isoflavone 2'-hydroxylase (HIDH). Furthermore, GSO-specific tandem gene duplication resulted in the gene expansion of C-glucosyltransferase (CGT). Integrative analysis of the metabolome and transcriptome identified 13 CGTs and eight HIDHs involved in the biosynthetic pathway of schaftoside. Functional studies indicated that CGTs and HIDHs identified here are bona fide responsible for the biosynthesis of schaftoside in GSO, as confirmed through hairy root transgenic system and in vitro enzyme activity assay. Taken together, the ancestral papilionoid polyploidy event expanding CHSs and HIDHs, along with the GSO-specific tandem duplication of CGT, contributes, partially if not completely, to the robust biosynthesis of schaftoside in GSO. These findings provide insights into the genomic mechanisms underlying the abundant biosynthesis of schaftoside in GSO, highlighting the potential of GSO as a source of bioactive compounds for pharmaceutical development.PMID:38799125 | PMC:PMC11119794 | DOI:10.1093/hr/uhae089