LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'ECM deposition is driven by caveolin1-dependent regulation of exosomal biogenesis and cargo sorting'.
Answer: The composition and physical properties of the extracellular matrix (ECM) critically influence tumor progression, but the molecular mechanisms underlying ECM layering are poorly understood. Tumor-stroma interaction is critically dependent on cell-cell communication mediated by exosomes, small vesicles generated within multivesicular bodies (MVBs). Here, we show that caveolin-1 (Cav1) is a central modulator of both exosome biogenesis and exosomal protein cargo sorting through the regulation of cholesterol content at the endosomal compartment/MVBs. Quantitative proteomics profiling revealed that Cav1 is required for exosomal sorting of ECM protein cargo subsets including tenascin-C (TnC), and for fibroblast-derived exosomes to efficiently depose ECM and promote tumor cell invasiveness. Cav1-driven exosomal ECM deposition not only promotes local stromal remodeling, but also the generation of distant ECM-enriched stromal niches. These results support a model by which Cav1 is a central regulatory hub for tumor-stroma interactions through a novel exosome-dependent ECM deposition mechanism.Linked studies: MTBLS1977
Question: Write a study description for the study titled 'Bluebell saponins: Application of metabolomics and molecular networking'.
Answer: Bulb, leaf, scape and flower samples of British bluebells (Hyacinthoides non-scripta) were collected regularly for one growth period. Methanolic extracts of freeze-dried and ground samples showed antitrypanosomal activity, giving more than 50% inhibition, for 20 out of 41 samples. High-resolution mass spectrometry was used in the dereplication of the methanolic extracts of the different plant parts. The results revealed differences in the chemical profile with bulb samples being distinctly different from all aerial parts. High molecular weight metabolites were more abundant in the flowers, shoots and leaves compared to smaller molecular weight ones in the bulbs. The anti-trypanosomal activity of the extracts was linked to the accumulation of high molecular weight compounds, which were matched with saponin glycosides, while triterpenoids and steroids occurred in the inactive extracts. Dereplication studies were employed to identify the significant metabolites via chemotaxonomic filters and considering their previously reported bioactivities.
Question: Write a study description for the study titled 'Multiomics of synaptic junctions reveals altered lipid metabolism and signaling following environmental enrichment'.
Answer: Membrane lipids and their metabolism have key functions in neurotransmission. Here we provide a quantitative lipid inventory of mouse and rat synaptic junctions. To this end, we developed a multiomics extraction and analysis workflow to probe the interplay of proteins and lipids in synaptic signal transduction from the same sample. Based on this workflow, we generate hypotheses about novel mechanisms underlying complex changes in synaptic connectivity elicited by environmental stimuli. As a proof of principle, this approach reveals that in mice exposed to an enriched environment, reduced endocannabinoid synthesis and signaling is linked to increased surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in a subset of Cannabinoid-receptor 1 positive synapses. This mechanism regulates synaptic strength in an input-specific manner. Thus, we establish a compartment-specific multiomics workflow that is suitable to extract information from complex lipid and protein networks involved in synaptic function and plasticity.
Question: Write a study description for the study titled 'Molecular networking coupled to high-resolution mass spectrometry fragmentation reveals a multitude of urinary antihypertensive drug metabolites'.
Answer: Mass spectrometry is the current technique of choice in studying drug metabolism. High-resolution mass spectrometry (HR-MS) in combination with fragment analysis (MS/MS) has the potential to contribute to rapid advances in this field. However, the data emerging from such fragmentation spectra pose challenges to downstream analysis, given their complexity and size. Here we apply a molecular networking approach to seek drugs and their metabolites, in fragmentation spectra from urine derived from a cohort of 26 patients on antihypertensive therapy. In total, 165 separate drug metabolites were found and structurally annotated (17 by spectral matching and 122 by classification based on a clustered fragmentation pattern). The clusters could be traced to 13 drugs including the known antihypertensives verapamil, losartan and amlopidine. The molecular networking approach also generated networks of endogenous metabolites, including carnitine derivatives, and conjugates containing glutamine, glutamate and trigonelline. The approach offers unprecedented capability in the untargeted identification of drugs and their metabolites at the population level and has great potential to contribute to understanding stratified responses to drugs where differences in drug metabolism may determine treatment outcome. Keywords: Antihypertensive drugs, Drug metabolism, Fragmentation, High-resolution mass spectrometry, Metabolomics, Urine.
Question: Write a study description for the study titled 'Dietary restriction of cysteine and methionine sensitizes gliomas to ferroptosis and induces alterations in energetic metabolism'.
Answer: Ferroptosis is mediated by lipid peroxidation of phospholipids containing polyunsaturated fatty acyl moieties. Glutathione, the key cellular antioxidant capable of inhibiting lipid peroxidation via the activity of the enzyme glutathione peroxidase 4 (GPX-4), is generated directly from the sulfur-containing amino acid cysteine, and indirectly from methionine via the transsulfuration pathway. Herein we show that cysteine and methionine deprivation (CMD) can synergize with the GPX4 inhibitor RSL3 to increase ferroptotic cell death and lipid peroxidation in both murine and human glioma cell lines and in ex vivo organotypic slice cultures. We also show that a cysteine-depleted, methionine-restricted diet can improve therapeutic response to RSL3 and prolong survival in a syngeneic orthotopic murine glioma model. Finally, this CMD diet leads to profound in vivo metabolomic, proteomic and lipidomic alterations, highlighting the potential for improving the efficacy of ferroptotic therapies in glioma treatment with a non-invasive dietary modification.
Question: Write a study description for the study titled 'High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program'.
Answer: Systemic metabolic alterations associated with increased consumption of saturated fat and obesity are linked with increased risk of prostate cancer progression and mortality, but the molecular underpinnings of this association are poorly understood. Here, we demonstrate in a murine prostate cancer model, that high-fat diet (HFD) enhances the MYC transcriptional program through metabolic alterations that favour histone H4K20 hypomethylation at the promoter regions of MYC regulated genes, leading to increased cellular proliferation and tumour burden. Saturated fat intake (SFI) is also associated with an enhanced MYC transcriptional signature in prostate cancer patients. The SFI-induced MYC signature independently predicts prostate cancer progression and death. Finally, switching from a high-fat to a low-fat diet, attenuates the MYC transcriptional program in mice. Our findings suggest that in primary prostate cancer, dietary SFI contributes to tumour progression by mimicking MYC over expression, setting the stage for therapeutic approaches involving changes to the diet.
Question: Write a study description for the study titled 'Metabolic abnormalities of the cortico-striato-thalamo-cortical circuit of rats with tic disorder'.
Answer: Tic disorder (TD) is a developmental neuropsychiatric disorder that primarily occurs during childhood and impacts the quality of life and psychosocial function of patients. The pathogenesis of TD involves the dysregulation of the cortico-striato-thalamo-cortical (CSTC) circuit and metabolic abnormalities may serve an important role. The aim of the present study was to detect and analyze the metabolic abnormalities in the CSTC circuit in TD, providing a reference value for the study of its pathogenesis. A total of 10 male Wistar rats were randomly divided into the control (CK) group (n=5) and the TD group (n=5). Each rat received a daily intraperitoneal injection of 0.9% saline or 3,3'-iminodipropionitrile for 7 consecutive days. Tissues were collected from the striatum and cortex, and ultra-performance liquid chromatography-tandem mass spectrometry was used to measure metabolite concentrations in the brain tissue samples. Significant differences in the metabolites and metabolic pathways of the CK and TD groups were observed. In the striatum, 13 differentially present metabolites were observed between the CK group and TD group, while 21 differentially present metabolites were identified in the cortex. In the CSTC circuit, the common significantly differentially present metabolites were progesterone, corticosterone, deoxycorticosterone, 11-dehydrocorticosterone, chenodeoxycholic acid and hyodeoxycholic acid. The common differentially present metabolic pathways were ‘steroid hormone biosynthesis’ and ‘aldosterone synthesis and secretion’. Notably, the abnormality of the ‘tryptophan metabolism’ pathway was only present in the cortex. These results indicated that there were metabolic abnormalities in the CSTC circuit in TD. The most significantly differentially present metabolite was progesterone. ‘Steroid hormone biosynthesis’ and ‘aldosterone synthesis and secretion’ were the significantly altered metabolic pathways in TD.
Question: Write a study description for the study titled 'A multiplatform metabolomic approach to characterize fecal signatures of stressful postnatal events in chicks: a pilot study'.
Answer: Negative experiences in early life can induce long-lasting effects on the welfare, health, and performance of farm animals. A delayed placement of chicks in breeding houses has negative effects on their performance, and results in fecal-specific odours detectable by rats. Based on this observation, the volatile organic compounds (VOCs) and metabolites from the feces of 12-day-old chickens were screened for early markers of response to stressful events using gas-chromatography and liquid-chromatography coupled with mass spectrometry (GC-MS, LC-HRMS). The low reproducibility of solid-phase micro-extraction of the VOCs followed by GC-MS was not suitable for marker discovery, in contrast to liquid extraction of metabolites from freeze-dried feces followed by GC-MS or LC-HRMS analysis. Therefore, the fecal metabolome from 12-day-old chicks having experienced a normal or delayed placement were recorded by GC-MS and LC-HRMS in two genotypes from two experiments. From both experiments, 25 and 35 metabolites, respectively explaining 81% and 45% of the difference between delayed and control chickens, were identified by orthogonal partial least-squares discriminant analysis from LC-HRMS and GC-MS profiling. The sets of molecules identified will be useful to better understand the chicks’ response to stressful events over time and will contribute to define stress or welfare biomarkers. [Only the data from the GC-MS and LC-HRMS fecal metabolomes are deposed on Metabolights] This study was supported financially by a “crédits incitatifs” grant from the department of Animal Physiology and Livestock Systems (PHASE) at INRA and by a grant from the Integrated Management of Animal Health metaprogram of INRA for the “GISA-WHELP” project (www.gisa.inra.fr/en).
Question: Write a study description for the study titled 'LipidCreator workbench to probe the lipidomic landscape - Collision Energy Optimization and Fragment Intensity Prediction for Lipid Mediators, Thermo QExactive HF'.
Answer: Here we present LipidCreator, a software that fully supports targeted lipidomics assay development. LipidCreator offers a comprehensive framework to compute MS/MS fragment masses for over 60 lipid classes. LipidCreator provides all functionalities needed to define fragments, manage stable isotope labeling, optimize collision energy and generate in silico spectral libraries. We validate LipidCreator assays computationally and analytically and prove that it is capable to generate large targeted experiments to analyze blood and to dissect lipid-signaling pathways such as in human platelets.In MTBLS1333, 58 lipid mediator standards were used to study the lipid fragmentation, build optimal collision energy models, create in-silico spectral libraries and spike-in as internal standards. They were purchased from Cayman Chemical (Ann Arbor, Michigan, USA). Lipid fragment masses of mediators were validated with the Metlin database (https://metlin.scripps.edu/).Studies linked to this manuscript include;MTBLS1333; LipidCreator: Collision Energy Optimization and Fragment Intensity Prediction for Lipid Mediators - Thermo QExactive HFMTBLS1334; LipidCreator: Collision Energy Optimization and Fragment Intensity Prediction for Lipid Mediators - Agilent QTofMTBLS1369; LipidCreator: Platelet isolation and stimulation - Targeted Phospho- and Glycerolipid ProfilingMTBLS1375; LipidCreator: Targeted lipidomics analysis of Human Plasma samples and comparison with NIST SRM 1950 standardMTBLS1376; LipidCreator: Targeted lipidomics analysis of S. cerevisiae to determine true and false identificationMTBLS1381; LipidCreator: Platelet isolation and stimulation - Targeted Lipid Mediator ProfilingMTBLS1382; LipidCreator: Platelet isolation and stimulation - DIA Lipid Mediator Validation
Question: Write a study description for the study titled 'Bioaccumulation of therapeutic drugs by human gut bacteria: secreted metabolite analysis for resting cells (B.uniformis;C.saccharolyticum 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 assay of Lacrimispora saccharolytica and Escherichia coli IAI1 is reported in MTBLS1319.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 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 'Untargeted metabolomics as a hypothesis-generation tool in plant protection product discovery: Highlighting the potential of trehalose and glycerol metabolism of fungal conidiospores as novel targets'.
Answer: INTRODUCTION: The production of high quality and safe food represents a main priority for the agri-food sector in the effort to sustain the exponentially growing human population. Nonetheless, there are major challenges that require the discovery of new, alternative, and improved plant protection products (PPPs). Focusing on fungal plant pathogens, the dissection of mechanisms that are essential for their survival provides insights that could be exploited towards the achievement of the aforementioned aim. In this context, the germination of fungal spores, which are essential structures for their dispersal, survival, and pathogenesis, represents a target of high potential for PPPs. To the best of our knowledge, no PPPs that target the germination of fungal spores currently exist.OBJECTIVES: Within this context, we have mined for changes in the metabolite profiles of the model fungus Aspergillus nidulans FGSC A4 conidiospores during germination, in an effort to discover key metabolites and reactions that could potentially become targets of PPPs.METHODS: Untargeted GC/EI-TOF/MS metabolomics and multivariate analyses were employed to monitor time-resolved changes in the metabolomes of germinating A. nidulans conidiospores.RESULTS: Analyses revealed that trehalose hydrolysis plays a pivotal role in conidiospore germination and highlighted the osmoregulating role of the sugar alcohols, glycerol, and mannitol.CONCLUSION: The ineffectiveness to introduce active ingredients that exhibit new mode(s)-of-action as fungicides, dictates the urge for the discovery of PPPs, which could be exploited to combat major plant protection issues. Based on the crucial role of trehalose hydrolysis in conidiospore dormancy breakage, and the subsequent involvement of glycerol in their germination, it is plausible to suggest their biosynthesis pathways as potential novel targets for the next-generation antifungal PPPs. Our study confirmed the applicability of untargeted metabolomics as a hypothesis-generation tool in PPPs' research and discovery.
Question: Write a study description for the study titled 'Multi-omic Landscape of Airway Microbe-Host Interactions in Chronic Obstructive Pulmonary Disease'.
Answer: The mechanistic role of the airway microbiome in chronic obstructive pulmonary disease (COPD) remains largely unexplored. We present a landscape of airway microbe-host interactions in COPD by an in-depth profiling of sputum metagenome, metabolome, host transcriptome and proteome from 99 COPD patients and 36 healthy individuals. Multi-omic data were integrated using a sequential mediation analysis, to assess in silico associations of the microbiome with neutrophilic or eosinophilic inflammation, two primary COPD inflammatory endotypes, mediated through microbial metabolic interaction with host gene expression. Mechanistic links of microbiome-metabolite-host interaction were identified leveraging microbial genetic information and established metabolite-human gene pairs. The strongest link for neutrophil-predominant COPD was altered tryptophan metabolism driven by airway lactobacilli resulting in reduced indole-3-acetic acid (IAA), which was in turn linked to perturbed host IL-22 signaling and epithelial cell apoptosis pathways. In vivo and in vitro studies showed that airway microbiome-derived IAA mitigates neutrophilic inflammation, apoptosis, emphysema, and lung function decline, via IL-22-mediated macrophage-epithelial cell crosstalk. Intranasal inoculation of two airway lactobacilli restored IAA and recapitulated its protective effects in mice. These findings provide the rationale for therapeutically targeting microbe-host interaction in COPD.Linked studies:UPLC-MS/MS assays of original cohort human samples are reported in this study.UPLC-MS/MS assays of more recent cohort human samples are reported in MTBLS5423.UPLC-MS/MS assays of more recent murine samples are reported in MTBLS6894.
Question: Write a study description for the study titled 'Analysis of flavor formation and metabolite changes during production of buffalo milk Double-Layer Steamed Milk Custard'.
Answer: Metabolomics analysis showed that concentration of free amino acids and short-chain fatty acid lipids were increased in DLSMC, and they were more easily digested and absorbed. Key metabolic pathways, including alanine, aspartate, and glutamate metabolism, starch and sucrose metabolism, and glycerophospholipid metabolism, appear to be involved in forming essential flavors. Our research revealed that the manipulation of thermal processing and the oxidation of fatty acids in buffalo milk are crucial factors influencing the flavor profile of DLSMC.
Question: Write a study description for the study titled 'Bacillus subtilis inhibits African swine fever virus infection in vivo and in vitro based on its metabolites arctiin and genistein interfering with the function of viral topoisomerase II'.
Answer: African swine fever virus (ASFV) is an infectious disease with a mortality rate of nearly 100% in pigs; however, no safe commercial vaccines or antiviral drugs are currently available, which seriously threatens the global pig industry. Therefore, effective biologicals against ASFV are urgently needed. Here, we screened 138 Bacillus subtilis strains, four of which evidently inhibited ASFV replication in vitro. Pigs fed with biologics of different types from the four B. subtilis strains showed reduced pathological changes and viral loads in tissues, with a survival rate of up to 100%. The antiviral activity of B. subtilis was attributed to small-molecule metabolites, rather than to secretory proteins. A total of 169 small molecules were obtained from the metabolites of B. subtilis using LC-MS/MS, arctiin and genistein, which showed the highest inhibition efficiency, suppressing ASFV proliferation at the mid-stage of infection. These molecules acted as competitive inhibitors by complexing the ATP-binding domain of viral topoisomerase II, as demonstrated using molecular docking, biolayer interferometry binding and a competitive decatenation assay, thereby disrupting the catalytic activity of the enzyme and inhibiting ASFV replication. Furthermore, pigs administered arctiin and genistein orally showed decreased mortality and tissue damage. Collectively, these results suggest that the four B. subtilis strains screened may be preventative biologicals against ASFV infection. Our findings pave the way for ASFV prevention and control strategies in the pig industry to curb the economic losses caused by the disease.IMPORTANCE: African swine fever virus (ASFV) is a highly fatal swine disease that severely affects the pig industry. Although ASFV has been prevalent for more than 100 years, effective vaccines or antiviral strategies are still lacking. In this study, we identified four Bacillus subtilis strains that inhibited ASFV proliferation in vitro. Pigs fed with liquid biologicals or powders derived from four B. subtilis strains mixed with pellet feed showed reduced morbidity and mortality when challenged with ASFV. Further analysis showed that the antiviral activity of B. subtilis was based on its metabolites arctiin and genistein interfering with the function of viral topoisomerase II. Our findings offer a promising new strategy for the prevention and control of ASFV that may significantly alleviate the economic losses in the pig industry.