LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'Comparative metabolomics analysis reveals high-altitude adaptations in a toad-headed viviparous lizard, Phrynocephalus vlangalii'.
Answer: Extreme environmental conditions at high altitude, such as hypobaric hypoxia, low temperature, and strong UV radiation, pose a great challenge to the survival of animals. Although the mechanisms of adaptation to high-altitude environments have attracted much attention for native plateau species, the underlying metabolic regulation remains unclear. Here, we used a multi-platform metabolomic analysis to compare metabolic profiles of liver between high- and low-altitude populations of toad-headed lizards, Phrynocephalus vlangalii, from the Qinghai-Tibet Plateau. A total of 191 differential metabolites were identified, consisting of 108 up-regulated and 83 down-regulated metabolites in high-altitude lizards as compared with values for low-altitude lizards. Pathway analysis revealed that the significantly different metabolites were associated with carbohydrate metabolism, amino acid metabolism, purine metabolism, and glycerolipid metabolism. Most intermediary metabolites of glycolysis and the tricarboxylic acid cycle were not significantly altered between the two altitudes, but most free fatty acids as well as β-hydroxybutyric acid were significantly lower in the high-altitude population. This may suggest that high-altitude lizards rely more on carbohydrates as their main energy fuel rather than lipids. Higher levels of phospholipids occurred in the liver of high-altitude populations, suggesting that membrane lipids may undergo adaptive remodeling in response to low-temperature stress at high altitude. In summary, this study demonstrates that metabolic profiles differ substantially between high- and low-altitude lizard populations, and that these differential metabolites and metabolic pathways can provide new insights to reveal mechanisms of adaptation to extreme environments at high altitude.
Question: Write a study description for the study titled 'Atractylodin targets ASAH3L to regulate galactose metabolism and thereby modulates the HIF-1 signaling pathway for the treatment of acute lung injury'.
Answer: Acute lung injury (ALI) is a lung disease characterized by an excessive inflammatory response and damage to lung epithelial cells. Atractylodin (ATL) is the main active component of Atractylodes lancea (Thunb.) DC., which has good anti-inflammatory activity and protects the integrity of the epithelial cell barrier. However, the efficacy of ATL in the treatment of ALI and its mechanism are unclear. We investigated the efficacy of ATL in treating ALI in vivo and in vitro, and explored its targets and mechanisms of action from metabolic and signaling pathways. The results showed that, in vivo, ATL significantly reduced the wet-dry ratio of lungs of rats with ALI, improved the pathological changes, reduced the aggregation and activation of neutrophils and macrophages in the lungs, and lowered the expression of the inflammatory factors, MCP-1, and MPO. The transcriptomics results suggested that ATL exerts its therapeutic effects by modulating the HIF-1 signaling pathway and metabolic processes. Metabolomics results showed that ATL mainly affected the processes of lactose degradation and galactose metabolism. Combined metabolomic and transcriptomic analyses showed that ASAH3L, a gene related to galactose metabolism, was regulated by ATL, and further experiments demonstrated that ATL reduced the expression of ASAH3L and ROS thereby inhibiting the activation of the HIF-1 signaling pathway. Overexpression of ASAH3L reversed the therapeutic effect of ATL in rats with ALI. In conclusion, ATL can reduce inflammation by inhibiting activating the HIF-1 signaling pathway and targeting ASAH3L to regulate galactose metabolism, thereby alleviating ALI.
Question: Write a study description for the study titled 'Bioaccumulation of therapeutic drugs by human gut bacteria: duloxetine accumulation at different concentrations (L.saccharolytica;E.coli assays)'.
Answer: Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. Interactions at this level have only recently started to being systematically mapped and the main underlying mechanism proposed is chemical transformation of drugs by microbes (biotransformation). Here, we investigated the depletion of 15 structurally diverse drugs by 25 representative gut bacterial strains. This revealed 70 bacteria-drug interactions, 29 of which had not been reported before.Over half of the new interactions can be ascribed to bioaccumulation, that is bacteria storing the drug without chemically modifying it, and in most cases without their growth being affected. As a case in point, we studied the molecular basis of bioaccumulation of the widely used antidepressant duloxetine by using click-chemistry, thermal proteome profiling and metabolomics. We find that duloxetine binds to several metabolic enzymes and changes metabolite secretion of the respective bacteria. When tested in a defined microbial community of accumulators and non-accumulators, duloxetine markedly altered the community composition through metabolic cross-feeding. We further validated our findings in an animal model, showing that bioaccumulating bacteria attenuate the behavioral response of Caenorhabditis elegans to duloxetine.Taken together, bioaccumulation by gut bacteria might be a common mechanism that alters drug availability and bacterial metabolism, with implications for microbiota composition, pharmacokinetics, side effects and drug responses, likely in an individual manner.Linked studies;UPLC-MS/MS assays of Bifidobacterium animalis subsp. lactis are reported in MTBLS1264.UPLC-MS/MS assays of Escherichia coli ED1a, Clostridium saccharolyticum, Escherichia coli IAI1, Streptococcus salivarius, Eubacterium rectale, Lactobacillus plantarum WCFS1 and Lactococcus lactis subsp. lactis Il1403 are reported in MTBLS1627.UPLC-MS/MS assay of Bacteroides uniformis and Clostridium saccharolyticum is reported in MTBLS1757.UPLC-MS/MS assay of Clostridium saccharolyticum, Escherichia coli ED1a, Escherichia coli IAI1, Lactobacillus plantarum WCFS1, Lactococcus lactis subsp. lactis Il1403 and Streptococcus salivarius is reported in MTBLS1791.UPLC-MS/MS assay of Eubacterium rectale and Streptococcus salivarius is reported in MTBLS1792.UPLC-MS/MS assay of Lacrimispora saccharolytica and standards is reported in MTBLS2885.
Question: Write a study description for the study titled 'Lipid Droplet Inhibitors for Disrupting Lipid Accumulation in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)'.
Answer: Excessive lipid droplet accumulation in hepatocytes drives the progression of metabolic dysfunction-associated steatotic liver disease (MASLD), often leading to inflammation and fibrosis. As obesity and metabolic syndrome rise, MASLD has become a global concern, spurring research into effective treatments. Here, we present the design of a Lipid droplet inhibitor (LDI), incorporating ultra-large mesoporous silica nanostructures along with PKCα C1A and Candida Rugosa lipase, aimed at directly degrading lipid droplets. Through its dual-functional design, this nanostructure captures diacylglycerol using PKCα C1A while hydrolyzing triacylglycerol into smaller molecular fragments via the lipase. Notably, the amphiphilic biomolecules in LDI facilitate the formation of a Pickering emulsion, ensuring stable localization at the lipid-water interface for efficient interaction with lipid droplets. LDI reduced lipid droplet formation and growth in HepG2 cells. In a high-fat diet-induced MASLD model, it alleviated liver pathology and, lowered injury scores by up to 84%. Furthermore, lipidomic analysis confirmed that LDI effectively modulated the hepatic lipid profile, suggesting its potential as a nanoplatform for counteracting lipid droplet accumulation.
Question: Write a study description for the study titled 'Assessment of plasma metabolomic biomarkers in various pediatric diseases'.
Answer: BACKGROUND: Metabolites that are direct read-outs of the functional status of cells, tissues, and organs can be more closely associated with phenotype compared to other omics profiles. Previous studies showed the analytical validity of metabolomic platforms and demonstrated a utility in interpreting the impact of genetic variants.METHODS: To explore the utility of metabolomics in the context of precision medicine, we used an untargeted ultrahigh performance liquid chromatography-tandem mass spectroscopy to characterize plasma samples collected from generally healthy individuals and a deeply phenotyped cohort with various pediatric diseases.RESULTS: A total of 1244 metabolites including 224 xenobiotic compounds were quantitatively measured for 169 individuals and thus revealed complex correlation structure within and between metabolic pathways. As proofs-of-concept, perturbations of phenylalanine and tyrosine metabolic pathways in a patient with phenylketonuria and carbohydrate metabolism in patients with diabetes mellitus were recapitulated as well as highlighting other biomarkers such as 1,5−anhydroglucitol for monitoring glycemic control. We discovered multiple metabolites that were significantly associated with different diseases using an exposome-wide association analysis framework. Amino acids showed significantly changed in patients with congenital heart diseases, and multiple lipid compounds were significant for Crohn’s disease. Notably, gut microbial products showed different concentrations with the use of antibiotics. Each xenobiotic compound showed a distinct correlation pattern with endogenous metabolites.CONCLUSIONS: Untargeted metabolomics could be a powerful precision medicine platform in itself or in combination with WES. The impact of exogenous exposures such as microbial products, drugs and environmental toxicants can be directly estimated by monitoring internal exposome, enabling the discovery of novel diagnosis and treatment biomarkers in diverse diseases. A repository of metabolomics data is required, which will enable the comparison between different platforms and concentrations of thousands of metabolites across individuals.
Question: Write a study description for the study titled 'Multi-omic profiles of human nonalcoholic fatty liver disease tissue highlight heterogenic phenotypes'.
Answer: Non-alcoholic fatty liver disease (NAFLD) is a consequence of sedentary life style and high fat diets with an estimated prevalence of about 30% in western countries. It is associated with insulin resistance, obesity, glucose intolerance and drug toxicity. Additionally, polymorphisms in, e.g. APOC3, PNPLA3, NCAN and PPP1R3B, correlate with NAFLD. Several studies have already investigated later stages of the disease. This study characterizes and stratifies distinct grades of the early steatosis stages of the disease with the aim of identifying mechanisms underlying the etiology of the disease. We analyzed liver biopsies and serum samples from patients with distinct grades of steatosis (also pre-disease states) employing transcriptomics, serum biomarkers, metabolomics, and proteomics. We unveiled distinct transcriptome, proteome and metabolome profiles in patients with high-grade and low-grade steatosis. In line with previously reported causes of steatosis and insulin resistance our observed expression differences in the levels of cytokines, in the IGF-axis, in fat metabolism and branched chain amino acids provide a comprehensive image of the deregulated biological system underlying the disease.
Question: Write a study description for the study titled 'Arginine depletion-induced autophagy and metabolic dysregulation are involved in the disease severity of hand, foot, and mouth disease'.
Answer: Amino acid metabolism provides significant insight into the development and prevention of many viral diseases. Therefore, the present study aimed to compare the amino acid profiles of hand, foot, and mouth disease (HFMD) patients with those of healthy individuals and to further reveal the molecular mechanisms of HFMD severity. Using UPLC-MS/MS, we determined the plasma amino acid expression profiles of pediatric patients with HFMD (mild, n=42; severe, n=43) and healthy controls (n=25). Brain tissues from CVA6-infected mice were examined using untargeted metabolomics. Several amino acids were significantly different between the three groups. Pathway analysis revealed that arginine, proline, and tryptophan metabolism are implicated in the pathogenesis of HFMD. A similar arginine depletion was observed in the brain tissues of CVA6-infected mice. Importantly, L-arginine supplementation improved the survival rate of CVA6-infected mice, inhibited virus multiplication, and reduced pathological autophagy associated with mTOR-autophagy pathway in the brain. Collectively, arginine, as the hub amino acid metabolite of the mammalian target of rapamycin (mTOR) signaling pathway affecting autophagy, plays an important role in the pathogenesis of severe HFMD. L-arginine supplementation may serve as a potential therapeutic option for critical patients with HFMD.
Question: Write a study description for the study titled 'Metabolic changes of genetically engineered grapes (Vitis vinifera L.) studied by 1H-NMR, metabolite heatmaps and iPLS'.
Answer: The Deficiens homologue 9-iaaM (DefH9-iaaM) gene is an ovule-specific auxin-synthesizing gene which is expressed specifically in placenta/ovules and promotes auxin-synthesis. It was introduced into the genome of two grape cultivars Thompson Seedless and Silcora (SIL) and both transgenic cultivars had an increased number of berries per bunch. This study investigates the down-stream metabolic changes of Silcora and Thompson seedless grape cultivars when genetically modified through the insertion of the DefH9-iaaM gene into their genome. The effect of the genetic modification upon the grape metabolome was evaluated by 1H-NMR and exploratory data analysis and chemometrics methods. Interval Partial Least Squares regression (iPLS) and metabolite heatmaps were employed for scrutinizing the changes in the transgenic metabolome as compared to the wild type metabolome. The result shows that the pleiotropic effects on the metabolome as a function of the gene modifications is relatively low, but that the insertion of transgene caused a decrement in the malic acid and proline and an increment in the p-coumaric acid concentration. The results further show that the concentration of malic acid was correlated with the number of inserted copies of transgene in Silcora cultivar, proving that the inserted genes, which catered for increased berry quality and production, are made on the expense of a greater decrement in malic acid concentration in the berries. NMR together with chemometrics is able to identify specific metabolites that were up- or down regulated in the genetically engineered plants, and thus able to highlight alterations in the down-stream metabolic pathways due to the up-stream genetic modifications.
Question: Write a study description for the study titled 'Plasma Lipid Profile Reveals Plasmalogens as Potential Biomarkers for Colon Cancer Screening'.
Answer: In this era of precision medicine, there is an increasingly urgent need for highly sensitive tests for detecting tumors such as colon cancer (CC), a silent disease where the first symptoms may take 10-15 yr to appear. Mass spectrometry-based lipidomics is an emerging tool for such clinical diagnosis. We used ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry operating in high energy collision spectral acquisition mode (MSE) mode (UPLC-QTOF-MSE) and gas chromatography (GC) to investigate differences between the plasmatic lipidic composition of CC patients and control (CTR) subjects. Key enzymes in lipidic metabolism were investigated using immuno-based detection assays. Our partial least squares discriminant analysis (PLS-DA) resulted in a suitable discrimination between CTR and CC plasma samples. 42 statistically significant discriminating lipids were putatively identified. Ether lipids showed a prominent presence and accordingly, a decrease in glyceronephosphate O-acyltransferase (GNPAT) enzyme activity was found. A receiver operating characteristic (ROC) curve built for three plasmalogens of phosphatidylserine (PS), named PS(P-36:1), PS(P-38:3) and PS(P-40:5), presented an area under the curve (AUC) of 0.998, and sensitivity and specificity of 100 and 85.7% respectively. These results show significant differences in CC patients' plasma lipid composition that may be useful in discriminating them from CTR individuals with a special role for plasmalogens.
Question: Write a study description for the study titled 'Untargeted LC-MS metabolomic studies of Asteraceae species to discover inhibitors of Leishmania major dihydroorotate dehydrogenase'.
Answer: INTRODUCTION: Interesting data about the family Asteraceae as a new source of Leishmania major dihydroorotate dehydrogenase (LmDHODH) inhibitors are presented. This key macromolecular target for parasites causing neglected diseases catalyzes the fourth reaction of the de novo pyrimidine biosynthetic pathway, which takes part in major cell functions, including DNA and RNA biosynthesis.OBJECTIVES: We aimed to (1) determine LmDHODH inhibitor candidates, revealing the type of chemistry underlying such bioactivity, and (2) predict the inhibitory potential of extracts from new untested plant species, classifying them as active or inactive based on their LC-MS based metabolic fingerprints.METHODS: Extracts from 150 species were screened for the inhibition of LmDHODH, and untargeted UHPLC-(ESI)-HRMS metabolomic studies were carried out in combination with in silico approaches.RESULTS: The IC50 values determined for a subset of 59 species ranged from 148 µg/mL to 9.4 mg/mL. Dereplication of the metabolic fingerprints allowed the identification of 48 metabolites. A reliable OPLS-DA model (R2 > 0.9, Q2 > 0.7, RMSECV < 0.3) indicated the inhibitor candidates; nine of these metabolites were identified using data from isolated chemical standards, one of which-4,5-di-O-E-caffeoylquinic acid (IC50 73 µM)-was capable of inhibiting LmDHODH. The predictive OPLS model was also effective, with 60% correct predictions for the test set.CONCLUSION: Our approach was validated for (1) the discovery of LmDHODH inhibitors or interesting starting points for the optimization of new leishmanicides from Asteraceae species and (2) the prediction of extracts from untested species, classifying them as active or inactive.
Question: Write a study description for the study titled 'Trace elements and lipidomic datasets of stranding samples in the blubber of Turpsios truncatus from the Yucatan Coast: Association with biological features'.
Answer: Trace elements are the result of natural and anthropogenic sources. Some of them are toxic causing alterations in the properties of membranes and produce lipid peroxidation. The dataset presented here is associated with the research article paper entitled “Trace element and lipidomic analysis of bottlenose dolphin blubber from the Yucatan coast: Lipid composition relationships”. In this article, we presented the trace element concentrations found in blubber and their comparison with other studies. Lipidomic characterization of bottlenose dolphin blubber and their association with trace elements and the differences related to biological characteristics. This data provides a correlation analysis between trace element concentrations and lipid species related to biological characteristics. We used Spearman correlation analysis to identify the association with body length and Wicolxon rank-sum test to determine differences in lipids related to stranding code, growth stage and stomach content. The data indicates that Cr, Cd and Zn concentrations were higher compared to other studies. Cr, Co, As and Cd were found in higher concentration in larger organisms. A decrease in some ceramides, sterols, glycerolipids and phosphatydilglyceros related to higher dolphins were found. Decomposition causes a decrease in phosphoethanolamines. Organisms with empty stomachs showed higher concentrations of phosphoethanolamines suggesting a preferential metabolism of energy-rich lipids over structural lipids. The information in these datasets may contribute to understanding the potential associations of trace element, lipid and their associations with biological characteristics.
Question: Write a study description for the study titled 'Phosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in C. elegans'.
Answer: Metabolic stress due to nutrient excess and lipid accumulation is at the root of many age-associated disorders and the identification of therapeutic targets that mimic the beneficial effects of calorie restriction has clinical importance. Here, using C. elegans as a model organism, we study the roles of a recently discovered enzyme at the heart of metabolism in mammalian cells, glycerol-3-phosphate phosphatase (G3PP) (gene name Pgp) that hydrolyzes glucose-derived glycerol-3-phosphate to glycerol. We identify three Pgp homologues in C. elegans (pgph) and demonstrate in vivo that their protein products have G3PP activity, essential for glycerol synthesis. We demonstrate that PGPH/G3PP regulates the adaptation to various stresses, in particular hyperosmolarity and glucotoxicity. Enhanced G3PP activity reduces fat accumulation, promotes healthy aging and acts as a calorie restriction mimetic at normal food intake without altering fertility. Thus, PGP/G3PP can be considered as a target for age-related metabolic disorders.
Question: Write a study description for the study titled 'Gut Microbial Genes and Metabolism for Methionine and Branched-Chain Amino Acids in Diabetic Nephropathy'.
Answer: Diabetic mellitus nephropathy (DMN) is a serious complication of diabetes and a major health concern. Although the pathophysiology of diabetes mellitus (DM) leading to DMN is uncertain, recent evidence suggests the involvement of the gut microbiome. This study aimed to determine the relationships among gut microbial species, genes and metabolites in DMN through an integrated clinical, taxonomic, genomic and metabolomic analysis. Whole metagenome shotgun sequencing and nuclear magnetic resonance metabolomic analysis were performed on stool samples from 15 patients with DMNs and 22 healthy controls. Six bacterial species were identified to be significantly elevated in the DMN patients after adjusting for age, sex, body mass index and estimated glomerular filtration rate (eGFR). Multivariate analysis found 216 microbial genes and 6 metabolites (valine, isoleucine, methionine, valerate and phenylacetate levels in the DMN group and higher acetate levels in the control group) that were differentially present between the DMN and control groups. Integrated analysis of all these parameters and clinical data, using the random forest model, showed that methionine and branched-chain amino acids (BCAAs) were among the most significant features, next to eGFR and proteinuria, in differentiating DMN from the control group. Metabolic pathway gene analysis of BCAA and methionine also revealed that many genes involved in the biosynthesis of these metabolites were elevated in the 6 species that were more abundant in the DMN group. The suggested correlation among taxonomic, genetic and metabolic features of the gut microbiome would expand our understanding of gut microbial involvement in the pathogenesis of DMN and may provide potential therapeutic targets of DMN.Linked cross omic data sets:Raw sequencing data associated with this study are available in the European Nucleotide Archive (ENA): accession number PRJEB57320.