PubMed

J Community Genet. 2023 Apr 24. doi: 10.1007/s12687-023-00642-2. Online ahead of print.ABSTRACTBirth defects, also known as congenital disorders, are a significant health issue impacting at least five million births annually worldwide. For policymakers to mount a relevant healthcare response to care for those affected, the burden of disease of these conditions must be quantified. Estimates of the contribution of birth defects to under-5 child mortality and morbidity are generated by several groups globally. These estimates often differ, causing confusion for policymakers. While some differences may be attributed to the data sources and methods used, much is due to a lack of clarity in the terminology used for the group of disorders classed as "congenital". This study aimed to gain insight into the diversity of terms and definitions for birth defects, including those used routinely by relevant international/national organisations and in the peer-reviewed literature. This two-part study included (1) scoping review of peer-reviewed literature to identify terms and definitions in use for birth defects and (2) review of key websites and grey literature to identify terms and definitions used. The results of this study indicate a wide variety of terms being used, often interchangeably and undefined, in peer-reviewed publications, on institutional websites and related literature. This suggests a lack of clarity related to terminology and sets the scene for further discussion, recommending that the community of practice working on birth defects comes to a consensus on standard terminology and definitions for global uptake and implementation. Such standardisation will facilitate a common understanding of the burden of these disorders globally, regionally and within countries so that action can be taken to support affected children and their families.PMID:37093545 | DOI:10.1007/s12687-023-00642-2

Psychol Med. 2023 Apr 24:1-10. doi: 10.1017/S0033291723001009. Online ahead of print.ABSTRACTBACKGROUND: Depression is associated with metabolic alterations including lipid dysregulation, whereby associations may vary across individual symptoms. Evaluating these associations using a network perspective yields a more complete insight than single outcome-single predictor models.METHODS: We used data from the Netherlands Study of Depression and Anxiety (N = 2498) and leveraged networks capturing associations between 30 depressive symptoms (Inventory of Depressive Symptomatology) and 46 metabolites. Analyses involved 4 steps: creating a network with Mixed Graphical Models; calculating centrality measures; bootstrapping for stability testing; validating central, stable associations by extra covariate-adjustment; and validation using another data wave collected 6 years later.RESULTS: The network yielded 28 symptom-metabolite associations. There were 15 highly-central variables (8 symptoms, 7 metabolites), and 3 stable links involving the symptoms Low energy (fatigue), and Hypersomnia. Specifically, fatigue showed consistent associations with higher mean diameter for VLDL particles and lower estimated degree of (fatty acid) unsaturation. These remained present after adjustment for lifestyle and health-related factors and using another data wave.CONCLUSIONS: The somatic symptoms Fatigue and Hypersomnia and cholesterol and fatty acid measures showed central, stable, and consistent relationships in our network. The present analyses showed how metabolic alterations are more consistently linked to specific symptom profiles.PMID:37092859 | DOI:10.1017/S0033291723001009

JCI Insight. 2023 Apr 24;8(8):e166956. doi: 10.1172/jci.insight.166956.ABSTRACTBACKGROUNDElevated circulating branched chain amino acids (BCAAs), measured at a single time point in middle life, are strongly associated with an increased risk of developing type 2 diabetes mellitus (DM). However, the longitudinal patterns of change in BCAAs through young adulthood and their association with DM in later life are unknown.METHODSWe serially measured BCAAs over 28 years in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective cohort of apparently healthy Black and White young adults at baseline. Trajectories of circulating BCAA concentrations from years 2-30 (for prevalent DM) or years 2-20 (for incident DM) were determined by latent class modeling.RESULTSAmong 3,081 apparently healthy young adults, trajectory analysis from years 2-30 revealed 3 distinct BCAA trajectory groups: low-stable (n = 1,427), moderate-stable (n = 1,384), and high-increasing (n = 270) groups. Male sex, higher body mass index, and higher atherogenic lipid fractions were more common in the moderate-stable and high-increasing groups. Higher risk of prevalent DM was associated with the moderate-stable (OR = 2.59, 95% CI: 1.90-3.55) and high-increasing (OR = 6.03, 95% CI: 3.86-9.43) BCAA trajectory groups in adjusted models. A separate trajectory group analysis from years 2-20 for incident DM after year 20 showed that moderate-stable and high-increasing trajectory groups were also significantly associated with higher risk of incident DM, after adjustment for clinical variables and glucose levels.CONCLUSIONBCAA levels track over a 28-year span in most young adults, but serial clinical metabolomic measurements identify subpopulations with rising levels associated with high risk of DM in later life.FUNDINGThis research was supported by the NIH, under grants R01 HL146844 (JTW) and T32 HL069771 (MRC). The CARDIA study is conducted and supported by the NIH National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham (HHSN268201800005I and HHSN268201800007I), Northwestern University (HHSN268201800003I), the University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN268201800004I).PMID:37092552 | DOI:10.1172/jci.insight.166956

Analyst. 2023 Apr 24. doi: 10.1039/d3an00353a. Online ahead of print.ABSTRACTGadolinium-based contrast agents (GBCAs) are massively employed in radiology to increase the diagnostic power of MRI. However, investigations aiming at detecting possible metabolic perturbations or adverse health effects due to gadolinium deposition are still lacking. In this work, aqueous organs extract and plasma samples were analyzed by GC-MS and 1H-NMR, respectively, to investigate the effects of multiple administrations of one linear (Omniscan) and one macrocyclic (ProHance) GBCA, on the main metabolic pathways in healthy mice. Multivariate analysis revealed that plasma metabolome was not differently perturbed by the two GBCAs, while, the multiorgan analysis displayed a clear separation of the Omniscan-treated from the control and the ProHance-treated groups. Interestingly, the most affected organs were the brain, cerebellum and liver. Thus, this work paves the way to both the safest use of the commercially available GBCAs and the development of new GBCAs characterized by lower general toxicity.PMID:37092509 | DOI:10.1039/d3an00353a

Chin Med. 2023 Apr 23;18(1):44. doi: 10.1186/s13020-023-00734-8.ABSTRACTBACKGROUND: Taohong Siwu Decoction (THSWD) is a prescription which included in the "List of Ancient Classic Prescriptions (First Batch)" issued by the National Administration of Traditional Chinese Medicine (TCM) and the National Medical Products Administration of the People's Republic of China. THSWD is effective and widely applied clinically for many diseases caused by blood deficiency and stasis syndrome in TCM, such as primary dysmenorrhea, menopausal syndrome, coronary heart disease, angina pectoris, and diabetes.METHODS: The TCM model of blood deficiency and blood stasis syndrome was prepared by ice water bath combined with cyclophosphamide, and the rats were randomly divided into control group, blood deficiency, and blood stasis model group, positive group, and THSWD treatment group. Pharmacodynamics measured the blood routine, blood coagulation, and other related indexes in rats. UHPLC-MS technology was used to analyze the changes in the fingerprints of metabolites in the plasma of rats with blood deficiency and blood stasis syndrome, and combined with mass spectrometry information and public database retrieval, to find potential biomarkers for screening metabolites. At the same time, 16S rDNA sequencing technology was used to identify intestinal flora, and statistical analysis was used to find differences in strain diversity between groups.RESULTS: THSWD administration can significantly improve the physical signs, blood routine, and hematopoietic factors caused by the blood deficiency and blood stasis syndrome model, and improve the symptoms of blood deficiency. The results of the general pharmacological studies showed THSWD groups improved changes in blood plasma viscosity and coagulation-related factors caused by modeling, and improved coagulation function significantly. The metabolomic analysis found that compared to the model group, THSWD exerted better effects on β-alanine, taurine, L-tyrosine, L-arginine, Eugenol, sodium deoxycholate, and deethylatrazine. Twenty-three potential differential metabolites showed intervention effects, mainly involved in eight metabolic pathways, including amino acid metabolism, taurine and hypotaurine metabolism, vitamin metabolism, and nucleotide metabolism. Gut microbiota data showed that, compared to the control group, the relative abundance and value of Firmicutes and Bacteroidota of the blood deficiency and blood stasis model group was significantly reduced, while the relative abundance of Actinobacteria, Spirochaetota, Proteobacteria, Campilobacterota, and other pathogenic bacteria was significantly increased. Following THSWD intervention, the abundance of beneficial bacteria increased, and the abundance of pathogenic bacteria decreased. Correlation analysis between the gut microbiota and differential metabolites showed that the two are closely related. THSWD affected the host blood system through mutual adjustment of these two factors, and improved blood deficiency and blood stasis syndrome in rats.CONCLUSION: The blood deficiency and blood stasis syndrome model of TCM disease caused by ice bath combined with cyclophosphamide lead to changes in the pharmacology, metabolomics, and gut microbiota. The intervention of THSWD can improve the symptoms caused by blood deficiency and blood stasis. The mechanism is mainly through the regulation of platelet function and amino acid metabolism.PMID:37088809 | DOI:10.1186/s13020-023-00734-8

Environ Toxicol. 2023 Apr 23. doi: 10.1002/tox.23808. Online ahead of print.ABSTRACTGlyphosate is a widely used herbicide that has deleterious effects on animal reproduction. However, details regarding the systematic mechanisms of glyphosate-induced reproductive toxicity are limited. This study aimed to investigate the toxic effects of glyphosate-based herbicide (GBH) on reproduction in mice exposed to 0 (control group), 50 (low-dose group), 250 (middle-dose group), and 500 (high-dose group) mg/kg/day GBH for 30 days. Toxicological parameters, metabolomics, and transcriptomics were performed to reveal GBH-induced reproductive toxicity. Our findings demonstrated that GBH exposure damaged mitochondrial pyknosis and the nuclear membrane of spermatogonia. GBH triggered a significant increase in sperm malformations in the high-dose group. Omics data showed that GBH impaired the Krebs cycle and respiratory chain, blocked pyruvate metabolism and glycolysis/gluconeogenesis, and influenced the pentose phosphate pathway and nucleotide synthesis and metabolism. Overall, the multi-omics results revealed systematic and comprehensive evidence of the adverse effects of GBH exposure, providing new insights into the reproductive toxicity of organophosphorus pesticides.PMID:37087751 | DOI:10.1002/tox.23808

Food Res Int. 2023 May;167:112733. doi: 10.1016/j.foodres.2023.112733. Epub 2023 Mar 21.ABSTRACTSpent coffee grounds (SCG) is a solid waste generated from coffee brewing. We recently developed a novel SCG hydrolysate-derived alcoholic beverage fermented with Lachancea thermotolerans Concerto and Lactiplantibacillus plantarum ML Prime. To further understand the potential health benefits of the fermented SCG hydrolysate alcoholic beverage, an untargeted metabolomics-based approach (UPLC-QTOF-MS/MS) was applied to detect and identify bioactive metabolites especially low molecular weight compounds. Our results showed that, compared to yeast monoculture-fermented SCG alcoholic beverages, yeast-lactic acid bacterial coculture enriched the beverage with a range of bioactive compounds especially aromatic and branched-chain amino acid derivatives (e.g., 4-hydroxyphenyl lactic acid, phenyl lactic acid, indole lactic acid, (S)-(-)-2-hydroxyisocaproic acid, and 4-hydroxyphenyl ethanol). Although some endogenous phenolic compounds were metabolized during fermentation, many phenolic metabolites (e.g., vinyl phenols, dihydrocaffeic acid, 3,4-dihydroxybenzoic acid, 4-hydroxycoumarin) were produced. Our study provided a theoretical basis for further valorization of SCG hydrolysates from the health benefits point of view and the findings may be extended to other fermented products.PMID:37087284 | DOI:10.1016/j.foodres.2023.112733

Food Res Int. 2023 May;167:112704. doi: 10.1016/j.foodres.2023.112704. Epub 2023 Mar 21.ABSTRACTCatharina sour, the first internationally recognized Brazilian beer, is characterized by fermentation with lactic acid bacteria (LAB), which may have probiotic potential, and the addition of fruit juice. This study aimed to evaluate the use of the starter Streptococcus thermophilus TH-4 (TH-4) and the probiotics Lacticaseibacillus paracasei F19 and 431, associated with Saccharomyces cerevisiae US-05, in the absence (control)/presence of passion fruit or peach juices. Evaluation proceeded during fermentation and storage by enumeration using pour-plate and qPCR; gene expressions of hop resistance; proteome by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS); and odor, flavor, and metabolome by Headspace Solid-Phase Microextraction (HS-SPME), coupled with the gas chromatography-mass spectrometry (GC-MS) analysis. We concluded that the strains studied are recommended for applications in sour beers, due to the presence of defense mechanisms like membrane adhesion and H + pump. Furthermore, HS-SPME/GC-MS indicated that the strains may contribute to the beer flavor and odor.PMID:37087270 | DOI:10.1016/j.foodres.2023.112704

Food Res Int. 2023 May;167:112667. doi: 10.1016/j.foodres.2023.112667. Epub 2023 Mar 13.ABSTRACTCorn silk is commonly consumed in teas, food ingredients, and herbal medicines. Several varieties of corn silk are grown in different habitats in China. However, as information regarding their phytochemistry and genetic diversity is limited, their medicinal potential has not been utilized thoroughly. Thus, we aimed to use a combination of DNA barcoding based on specific primer ITSC sequences and ultra-performance liquid chromatography coupled with linear trap quadrupole-Orbitrap mass spectrometry (UPLC-LTQ/Orbitrap MS) approach for identifying and evaluating corn silk. ITSC barcoding helped us to identify that 52 samples could be classified into 7 groups of corn silk varieties, but the widely used nrITS and psbA-trnH barcodes failed to identify these varieties. UPLC-LTQ/Orbitrap MS was used to study the components in alcohol extracts derived from different corn silk varieties, and the detected chemical components were analyzed via bioinformatics techniques. We proposed 199 components using untargeted UPLC-LTQ/Orbitrap MS-based metabolomics analysis and identified 67 components. PCA and OPLS-DA analysis revealed two distinct chemotypes by selecting 27 components that could act as difference indicators. KEGG analysis showed that the 199 components were enriched in 12 metabolic pathways. The results showed that corn silk is rich in many types of chemicals and DNA barcoding is better than UPLC-LTQ/Orbitrap MS in distinguishing the differences between different varieties of corn silk. Our findings provide new insights into the chemical and molecular characteristics of different varieties of corn silk, which play a crucial role in the utilization of corn silk resources.PMID:37087254 | DOI:10.1016/j.foodres.2023.112667

Food Res Int. 2023 May;167:112640. doi: 10.1016/j.foodres.2023.112640. Epub 2023 Feb 24.ABSTRACTStingless bees (Meliponini) represent over than 500 species, found in tropical and sub-tropical regions of the world. They produce geopropolis, a resinous natural product containing bioactive compounds, which is commonly used in folk medicine. In the current study, LC-HRMS and bioinformatic tools were used to carry out for the first time the lipidomic analysis of geopropolis from indigenous Brazilian stingless bees. As a result, 61 compounds of several lipid classes were identified with elevated degree of confidence. Then, we demonstrated that lipids in geopropolis are not restricted to waxes and fatty acids; but fatty amides and amines, phenolic lipids, resorcinols, retinoids, abietanoids, diterpenoids, pentacyclic triterpenoids, prostaglandins, retinoids, and steroids were found. In addition, multivariate analysis, based on the lipidomic profile of extracts, reinforces the assumption that the species of stingless bees, as well as the geographical origin are relevant factors to affect geopropolis composition once that the lipidic profile allowed the discrimination of geopropolis in groups related to the geographical origin, bee specie or bee genus. The lipidic profile also suggest a selective forage habits of T. angustula, which seems to collect resins from more specific vegetal sources regardless geographic origin, while other stingless bees, such as M. marginata and M. quadrifasciata, are less selective and may adapt to collect resins from a wider variety of plants.PMID:37087233 | DOI:10.1016/j.foodres.2023.112640

Food Res Int. 2023 May;167:112719. doi: 10.1016/j.foodres.2023.112719. Epub 2023 Mar 18.ABSTRACTThe aroma profile of industrial Sichuan paocai is formed and regulated by complex physiological and biochemical reactions and microbial metabolism, but little is known so far. In this study, we comprehensively analyzed the changes of metabolic profile and gene expression profile, mainly explored the formation pathways of two skeleton aroma-active compounds, 4-ethylphenol and 4-ethylguaiacol, and verified the pathways at multiple levels. The results showed that a total of 136 volatile metabolites and 560 non-volatile metabolites were identified in the whole fermentation process. The types and concentrations of metabolites in paocai were higher than those in brine, and gradually converged with fermentation. Differential analysis of metabolism and transcription levels were both enriched in three pathways: amino acid metabolism, phenylpropanoid metabolism and lipid metabolism. Among them, 4-ethylphenol and 4-ethylguaiacol, the products of the phenylpropanoid metabolism, were converted from p-coumaric acid and ferulic acid in plant cell walls, respectively. Under the action of decarboxylase produced by yeast (such as Debaryomyces Hansenii) and lactic acid bacteria (such as Lactobacillus versmoldensis), intermediate metabolites vinylphenols were produced, and the intermediate metabolites further produce the final products under the action of vinylphenol reductase. The key gene copy number, enzyme activity, and metabolite concentration in the pathways were detected to provide stronger evidence for the formation pathways. This study provided meaningful new insights for the development of aroma-producing enzymes and further guidance for the flavor improvement of industrial paocai.PMID:37087217 | DOI:10.1016/j.foodres.2023.112719

Life Sci Space Res (Amst). 2023 May;37:78-87. doi: 10.1016/j.lssr.2023.03.008. Epub 2023 Mar 30.ABSTRACTPURPOSE: Astronauts on missions beyond low Earth orbit will be exposed to galactic cosmic radiation, and there is concern about potential adverse cardiovascular effects. Most of the research to identify cardiovascular risk of space radiation has been performed in rodent models. To aid in the translation of research results to humans, the current study identified long-term effects of high-energy charged particle irradiation on cardiovascular function and structure in a larger non-rodent animal model.MATERIALS AND METHODS: At the age of 12 months, male New Zealand white rabbits were exposed to whole-body protons (250 MeV) or oxygen ions (16O, 600 MeV/n) at a dose of 0 or 0.5 Gy and were followed for 12 months after irradiation. Ultrasonography was used to measure in vivo cardiac function and blood flow parameters at 10- and 12-months post-irradiation. At 12 months after irradiation, blood cell counts and blood chemistry values were assessed, and cardiac tissue and aorta were collected for histological as well as molecular and biochemical analyses. Plasma was used for metabolomic analysis and to quantify common markers of cardiac injury.RESULTS: A small but significant decrease in the percentage of circulating lymphocytes and an increase in neutrophil percentage was seen 12 months after 0.5 Gy protons, while 16O exposure resulted in an increase in monocyte percentage. Markers of cardiac injury, cardiac troponin I (cTnI) and N-Terminal pro-B-type Natriuretic Peptide were modestly increased in the proton group, and cTnI was also increased after 16O. On the other hand, metabolomics on plasma at 12 months revealed no changes. Both types of irradiation demonstrated alterations in cardiac mitochondrial morphology and an increase in left ventricular protein levels of inflammatory cell marker CD68. However, changes in cardiac function were only mild.CONCLUSION: Low dose charged particle irradiation caused mild long-term changes in inflammatory markers, cardiac function, and structure in the rabbit heart, in line with previous studies in mouse and rat models.PMID:37087182 | DOI:10.1016/j.lssr.2023.03.008

Sci Total Environ. 2023 Apr 22:163648. doi: 10.1016/j.scitotenv.2023.163648. Online ahead of print.ABSTRACTCarbendazim (CBZ) and procymidone (PRO) are two widely used fungicides in agriculture. However, there are still gaps in knowledge regarding about the potential hazards of joint exposure to CBZ and PRO in animals. Here, 6-week-old ICR mice were exposed to CBZ, PRO and CBZ + PRO for 30 days, and metabolomics were performed to discover the mechanism by which the mixture enhanced the effects on lipid metabolism. Co-exposure to CBZ + PRO elevated the body weights, relative liver weights and relative epididymis fat weights, but not in the single exposure groups. Molecular docking analysis suggested that CBZ and PRO combined with peroxisome proliferator-activated receptor (PPARγ) at the same amino acid site as the agonist rosiglitazone. The RT-qPCR and WB results demonstrated that the levels of PPARγ were higher in the co-exposure group than in the single exposure groups. In addition, hundreds of differential metabolites were discovered by metabolomics and enriched in different pathways, such as pentose phosphate pathway and purine metabolism. A unique effect, a decrease in glucose-6-phosphate (G6P) that promoted more NADPH production, was observed in the CBZ + PRO group. These results demonstrated that exposure to CBZ + PRO caused more serious lipid metabolism disorder in the liver than exposure to a single fungicide, which could provide some new insight for the toxic effects after fungicides joint exposure.PMID:37094686 | DOI:10.1016/j.scitotenv.2023.163648

Curr Opin Chem Biol. 2023 Apr 22;74:102307. doi: 10.1016/j.cbpa.2023.102307. Online ahead of print.ABSTRACTHyperpolarized NMR is a promising approach to address the sensitivity limits of conventional NMR metabolomics approaches, which currently fails to detect minute metabolite concentrations in biological samples. This review describes how tremendous signal enhancement offered by dissolution-dynamic nuclear polarization and parahydrogen-based techniques can be fully exploited for molecular omics sciences. Recent developments, including the combination of hyperpolarization techniques with fast multi-dimensional NMR implementation and quantitative workflows are described, and a comprehensive comparison of existing hyperpolarization techniques is proposed. High-throughput, sensitivity, resolution and other relevant challenges that should be tackled for a general application of hyperpolarized NMR in metabolomics are discussed.PMID:37094508 | DOI:10.1016/j.cbpa.2023.102307

Physiol Plant. 2023 Apr 22:e13918. doi: 10.1111/ppl.13918. Online ahead of print.ABSTRACTDifferential rootstock tolerance to Fusarium sp. supports viticulture worldwide. However, how plants stand against the fungus still needs to be explored. We hypothesize it involves a differential metabolite modulation. Thus, we performed a gas chromatography coupled with mass spectrometry (GC-MS) analysis of Paulsen P1103 and BDMG573 rootstocks, co-cultured with F. oxysporum (FUS) for short, medium, and long time (0, 4, and 8 days after treatment - DAT). In shoots, Principal Component Analysis (PCA) showed a complete overlap between BDMG573 CNT and FUS at 0 DAT, and P1103 treatments showed a slight overlap at both 4 and 8 DAT. In roots, PCA exhibited overlapping between BDMG573 treatments at 0 DAT, while P1103 treatments showed overlapping at 0 and 4 DAT. Further, there is a complete overlapping between BDMG573 and P1103 FUS profiles at 8 DAT. In shoots, 1,3-dihydroxyacetone at 0 and 4 DAT and maltose at 4 and 8 DAT were biomarkers for BDMG573. .For P1103, glyceric acid, proline, and sorbitol stood out at 0, 4, and 8 DAT, respectively. In BDMG573 roots, the biomarkers were β-alanine at 0 DAT, cellobiose and sorbitol at both 4 and 8 DAT. While in P1103 roots, they were galactose at 0 and 4 DAT and 1,3-dihydroxyacetone at 8 DAT. Overall, there is increase in amino acids, glycolysis, and TCA components in tolerant Paulsen P1103 shoots. Thus, it provides a new perspective on the primary metabolism of grapevine rootstocks to F. oxysporum that may contribute to strategies for genotype tolerance and early disease identification. This article is protected by copyright. All rights reserved.PMID:37087574 | DOI:10.1111/ppl.13918

Physiol Plant. 2023 Apr 22:e13917. doi: 10.1111/ppl.13917. Online ahead of print.ABSTRACTMild stresses induce "acquired tolerance traits" (ATT) that provide tolerance when stress becomes severe.Here, we identifiedthe genetic variability in ATTs among a panel of rice germplasm accessions and demonstrated their relevance in protecting growth and productivity under water-limited conditions. Diverse approaches, including physiological screens, association mapping and metabolomics, were adopted and revealed 43 significant marker-trait associations. Non-targeted metabolomic profiling of contrasting genotypes revealed 26 "Tolerance-related-induced" primary and secondary metabolites in the tolerant genotypes (AC-39000 and AC-39020) compared to the susceptible one (BPT-5204) under water-limited condition. Metabolites that help maintain cellular functions, especially Calvin cycle processes, significantly accumulated more in tolerant genotypes, which resulted in superior photosynthetic capacity and hence water use efficiency.Upregulation of the Glutathione cycle intermediates explains the ROS homeostasis among the tolerant genotypes, maintening spikelet fertility and grain yield under stress. Bioinformatic dissection of a major effect Quantitative trait locus (QTL) on chromosome 8 revealed genes controlling metabolic pathways leading to the production of osmolites and antioxidants, such as GABA and faffinose.The study also led to the identification of specific trait donor genotypes that can be effectively used in translational crop improvement activities. This article is protected by copyright. All rights reserved.PMID:37087573 | DOI:10.1111/ppl.13917

Nat Commun. 2023 Apr 22;14(1):2329. doi: 10.1038/s41467-023-37470-4.ABSTRACTRhinoviruses and allergens, such as house dust mite are major agents responsible for asthma exacerbations. The influence of pre-existing airway inflammation on the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely unknown. We analyse mechanisms of response to viral infection in experimental in vivo rhinovirus infection in healthy controls and patients with asthma, and in in vitro experiments with house dust mite, rhinovirus and SARS-CoV-2 in human primary airway epithelium. Here, we show that rhinovirus infection in patients with asthma leads to an excessive RIG-I inflammasome activation, which diminishes its accessibility for type I/III interferon responses, leading to their early functional impairment, delayed resolution, prolonged viral clearance and unresolved inflammation in vitro and in vivo. Pre-exposure to house dust mite augments this phenomenon by inflammasome priming and auxiliary inhibition of early type I/III interferon responses. Prior infection with rhinovirus followed by SARS-CoV-2 infection augments RIG-I inflammasome activation and epithelial inflammation. Timely inhibition of the epithelial RIG-I inflammasome may lead to more efficient viral clearance and lower the burden of rhinovirus and SARS-CoV-2 infections.PMID:37087523 | DOI:10.1038/s41467-023-37470-4

Microbiome. 2023 Apr 22;11(1):87. doi: 10.1186/s40168-023-01535-9.ABSTRACTBACKGROUND: Dairy cows are susceptible to postpartum systemic oxidative stress (OS), which leads to significant production loss and metabolic disorders. The gut microbiota has been linked to host health and stress levels. However, to what extent the gut microbiota is associated with postpartum OS remains unknown. In this study, the contribution of the fecal microbiota to postpartum systemic OS and its underlying mechanisms were investigated by integrating 16S rRNA gene sequencing, metagenomics, and metabolomics in postpartum dairy cattle and by transplanting fecal microbiota from cattle to mice.RESULTS: A strong link was found between fecal microbial composition and postpartum OS, with an explainability of 43.1%. A total of 17 significantly differential bacterial genera and 19 species were identified between cows with high (HOS) and low OS (LOS). Among them, 9 genera and 16 species showed significant negative correlations with OS, and Marasmitruncus and Ruminococcus_sp._CAG:724 had the strongest correlations. The microbial functional analysis showed that the fecal microbial metabolism of glutamine, glutamate, glycine, and cysteine involved in glutathione synthesis was lower in HOS cows. Moreover, 58 significantly different metabolites were identified between HOS and LOS cows, and of these metabolites, 19 were produced from microbiota or cometabolism of microbiota and host. Furthermore, these microbial metabolites were enriched in the metabolism of glutamine, glutamate, glycine, and cysteine. The mice gavaged with HOS fecal microbiota had significantly higher OS and lower plasma glutathione peroxidase and glutathione content than those orally administered saline or LOS fecal microbiota.CONCLUSIONS: Integrated results suggest that the fecal microbiota is responsible for OS and that lower glutathione production plays a causative role in HOS. These findings provide novel insights into the mechanisms of postpartum OS and potential regulatory strategies to alleviate OS in dairy cows. Video Abstract.PMID:37087457 | DOI:10.1186/s40168-023-01535-9

Geroscience. 2023 Apr 22. doi: 10.1007/s11357-023-00796-4. Online ahead of print.ABSTRACTAltered mitochondrial function is tightly linked to lifespan regulation, but underlying mechanisms remain unclear. Here, we report the chronological and replicative lifespan variation across 167 yeast knock-out strains, each lacking a single nuclear-coded mitochondrial gene, including 144 genes with human homologs, many associated with diseases. We dissected the signatures of observed lifespan differences by analyzing profiles of each strain's proteome, lipidome, and metabolome under fermentative and respiratory culture conditions, which correspond to the metabolic states of replicative and chronologically aging cells, respectively. Examination of the relationships among extended longevity phenotypes, protein, and metabolite levels revealed that although many of these nuclear-encoded mitochondrial genes carry out different functions, their inhibition attenuates a common mechanism that controls cytosolic ribosomal protein abundance, actin dynamics, and proteasome function to regulate lifespan. The principles of lifespan control learned through this work may be applicable to the regulation of lifespan in more complex organisms, since many aspects of mitochondrial function are highly conserved among eukaryotes.PMID:37086368 | DOI:10.1007/s11357-023-00796-4

Mol Oncol. 2023 Apr 22. doi: 10.1002/1878-0261.13441. Online ahead of print.ABSTRACTThe androgen receptor (AR) is an established orchestrator of cell metabolism in prostate cancer (PCa), notably by inducing an oxidative mitochondrial program. Intriguingly, AR regulates cytoplasmic isocitrate dehydrogenase 1 (IDH1) but not its mitochondrial counterparts IDH2 and IDH3. Here, we aimed to understand the functional role of IDH1 in PCa. Mouse models, in vitro human PCa cell lines, and human patient-derived organoids (PDOs) were used to study the expression and activity of IDH enzymes in the normal prostate and PCa. Genetic and pharmacological inhibition of IDH1 was then combined with extracellular flux analysis and gas chromatography-mass spectrometry for metabolomic analyses and cancer cell proliferation in vitro and in vivo. In PCa cells, more than 90% of the total IDH activity is mediated through IDH1 rather than its mitochondrial counterparts. This profile seems to originate from the specialized prostate metabolic program, as observed using mouse prostate and PDOs. Pharmacological and genetic inhibition of IDH1 impaired mitochondrial respiration, suggesting that this cytoplasmic enzyme contributes to the mitochondrial tricarboxylic acid cycle (TCA) in PCa. Mass spectrometry-based metabolomics confirmed this hypothesis, showing that inhibition of IDH1 impairs carbon flux into the TCA cycle. Consequently, inhibition of IDH1 decreased PCa cell proliferation in vitro and in vivo. These results demonstrate that PCa cells have a hybrid cytoplasmic-mitochondrial TCA cycle that depends on IDH1. This metabolic enzyme represents a metabolic vulnerability of PCa cells and a potential new therapeutic target.PMID:37086156 | DOI:10.1002/1878-0261.13441