LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'Intergenerational Association of Gut Microbiota and Metabolism with Perinatal Folate Metabolism and Neural Tube Defects (Feces metabolomics)'.
Answer: Maternal folic acid intake is crucial for the development of the offspring's nervous system, and folic acid metabolism disorders during pregnancy lead to neural tube defects (NTDs) in the fetus. Folic acid and vitamins biosynthesis is a major biochemical feature of gut microbiota. The complex and diverse microbial ecosystem residing within maternal host contributes critically to these intergenerational impacts. However, the mechanisms still require further investigation. In this study, we found that the low folate diets combined MTX-induced changed the structure/composition of the gut microbiota and substantially altered the fecal metabolic phenotype of pregnant mice, including central carbon metabolism in cancer and vitamin digestion & absorption. We demonstrated that the correlation betweent gut microbiota of pregnant mice and the brain metabolic profiles of NTDs fetal mice. According to our data, the Lactobacillales and Bifidobacteriales abundances in pregnant mice gut were positively correlated with the abundances of lipid metabolites in fetal mice brain. The abundances of Enterobacterales and Clostridiales were negatively correlated with those lipid metabolites. Interestingly, the abundance of Inosine, Uridine, L-Carnitine and Glycerophosphocholine were down-regulated synchronously in pregnant feces and NTDs fetal mice brain. This was probably the intergenerational microbial-metabolism biomarkers of NTDs. Our study provides evidence for how perinatal microecological factors shape fetal neural tube development.Feces metabolomics is reported in the current study MTBLS4893.Brain tissue metabolomics is reported in MTBLS4894.
Question: Write a study description for the study titled 'Primary Osteocyte Supernatants Metabolomic Profiling of Two Transgenic Mice with Connexin43 Dominant Negative Mutants'.
Answer: Osteocytes could release some small molecules (≤ 1 kDa) through gap junctions and hemichannels to extracellular environment, such as prostaglandin E2 (PGE2), nitric oxide (NO) and adenosine triphosphate (ATP), which play key roles in transferring signals between bone cells and other tissue cells. Connexin (Cx) 43 is the most abundant connexin in osteocytes. To further discover molecules released by osteocytes through Cx43 channels and better understand the regulatory function of Cx43 channels in osteocytes, we performed non-targeted global metabolomics analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) on conditioned medium collected from osteocytes isolated from two transgenic mouse models with Cx43 dominant negative mutants driven by a 10 kb-DMP1 promoter: R76W (gap junctions are blocked, whereas hemichannels are promoted) and Δ130-136 (both gap junctions and hemichannels are blocked). The results revealed that several new categories of molecules, such as “fatty acyls” and “carboxylic acids and derivatives”, could be released through osteocytic Cx43 channels. In addition, alteration of Cx43 channel function affected the release of metabolites related to inflammatory reaction and oxidative stress. Pathway analysis further showed that citric acid cycle was the most differential metabolic pathway regulated by Cx43 channels. In sum, these results isolated new potential metabolites released by osteocytes through Cx43 channels, and offered a novel perspective to understand the regulatory mechanisms of osteocytes on themselves and other cells as well.
Question: Write a study description for the study titled 'Urine metabolomics phenotyping and urinary biomarker exploratory in mild cognitive impairment and Alzheimer's disease.'.
Answer: INTRODUCTION Alzheimer's disease is a prevalent disease with a heavy global burden and is suggested to be a metabolic disease in the brain in recent years. The metabolome is considered to be the most promising phenotype which reflects changes in genetic, transcript, and protein profiles as well as environmental effects. Aiming to obtain a comprehensive understanding and convenient diagnosis of MCI and AD from another perspective, researchers are working on AD metabolomics. Urine is more convenient which could reflect the change of disease at an earlier stage. Thus, we conducted a cross-sectional study to investigate novel diagnostic panels.METHODS We first enrolled participants from China-Japan Friendship Hospital from April 2022 to November 2022, collected urine samples and conducted an LC-MS/MS analysis. In parallel, clinical data were collected and clinical examinations were performed. After statistical and bioinformatics analyzes, significant risk factors and differential urinary metabolites were determined. We attempt to investigate diagnostic panels based on machine learning including LASSO and SVM.RESULTS 57 AD patients, 43 MCI patients and 62 CN subjects were enrolled. A total of 2,140 metabolites were identified among which 125 significantly differed between the AD and CN groups, including 46 upregulated ones and 79 downregulated ones. In parallel, there were 93 significant differential metabolites between the MCI and CN groups, including 23 upregulated ones and 70 downregulated ones. AD diagnostic panel (30 metabolites+ age + APOE) achieved an AUC of 0.9575 in the test set while MCI diagnostic panel (45 metabolites+ age + APOE) achieved an AUC of 0.7333 in the test set. Atropine, S-Methyl-L-cysteine-S-oxide, D-Mannose 6-phosphate (M6P), Spiculisporic Acid, N-Acetyl-L-methionine, 13,14-dihydro-15-keto-tetranor Prostaglandin D2, Pyridoxal 5'-Phosphate (PLP) and 17(S)-HpDHA were considered valuable for both AD and MCI diagnosis and defined as hub metabolites. Besides, diagnostic metabolites were weakly correlated with cognitive functions.DISCUSSION In conclusion, the procedure is convenient, non-invasive, and useful for diagnosis, which could assist physicians in differentiating AD and MCI from CN. Atropine, M6P and PLP were evidence-based hub metabolites in AD.
Question: Write a study description for the study titled 'PatA mediates biofilm formation and drugs resistance through regulating the synthesis of glycolipids and lipids in mycobacterium PatA mediates a novel mycolic acid synthesis pathway and regulates biofilm formation in mycobacterium'.
Answer: Glycolipids and lipids are prominent components of bacterial cell wall that play critical roles not only in maintaining the biofilm formation but also in resistance to environmental stress. PatA is an essential membrane associated acyltransferase involved in the biosynthesis of phosphatidyl-myo-inositol mannosides (PIMs), which are the key glycolipid components in the cell wall of Mycobacterium tuberculosis. However, whether or not PatA regulates the lipids synthesis and affects drugs resistance and biofilm formation in mycobacterium is unclear, and the mechanisms involved remain to be explored. Here we show that PatA can directly regulate the synthesis of glycolipids and lipids to maintain the drugs resistance and biofilm formation in Mycobacterium smegmatis. Interestingly, the INH resistance of patA-deleted mutant is significantly enhanced although its biofilm formation is reduced. This is due to PatA negative regulation the synthesis of mycolic acids through a novel mycolic acid synthesis pathway other than the FAS pathway, which could efficiently counteract the inhibition of isoniazid on mycolic acids synthesis in mycobacterium. Furthermore, PatA is highly conserved including amino acid sequences and physiological functions in mycobacterium. Therefore, PatA regulates the synthesis of glycolipids and lipids to affect drugs resistance and biofilm formation in mycobacterium. Our findings provide a novel mycolic acids synthetic pathway and novel insights into the molecular mechanism of glycolipids and lipids metabolism regulation and their correlation with bacterial physiological phenotypes.
Question: Write a study description for the study titled 'A gut Eggerthella lenta–derived metabolite impairs neutrophil function to aggravate bacterial lung infection'.
Answer: The “gut-lung” axis is crucial for the chronic infection in bronchiectasis. However, the responsible microbe and the mechanism in the “gut-lung” axis of bronchiectasis are still in demand for precise elucidation. Here, we reported that Eggerthella lenta in the gut and taurine ursodeoxycholic acid (TUDCA) both in the gut and serum are enriched in patients with bronchiectasis and positively associated with bronchiectasis severity. Fecal microbiota transfer from bronchiectasis with high E. lenta aggravates pulmonary Pseudomonas aeruginosa infection in mice. Mechanistically, elevated E. lenta-derived TUDCA resulted in reduced phosphorylation of AMP-activated protein kinase (AMPK) and hampered ATP production. Ultimately, the neutrophils with impaired function dampened the elimination of P. aeruginosa in the lung and resulted in aggravated injury. These findings indicate that E. lenta and TUDCA aggravate chronic pulmonary infection, providing insights into microbe-mediated gut-lung crosstalk in bronchiectasis.
Question: Write a study description for the study titled 'EMT alterations in the solute carrier landscape uncover SLC22A10/A15 imposed vulnerabilities in pancreatic cancer'.
Answer: The involvement of membrane-bound solute carriers (SLCs) in neoplastic transdifferentiation processes is poorly defined. Here, we examined changes in the SLC landscape during epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. We show that two SLCs from the organic anion/cation transporter family, SLC22A10 and SLC22A15, favor EMT via interferon (IFN) α and γ signaling activation of receptor tyrosine kinase-like orphan receptor 1 (ROR1) expression. In addition, SLC22A10 and SLC22A15 allow tumor cell accumulation of glutathione to support EMT via the IFNα/γ-ROR1 axis. Moreover, a pan-SLC22A inhibitor lesinurad reduces EMT-induced metastasis and gemcitabine chemoresistance to prolong survival in mouse models of pancreatic cancer, thus identifying new vulnerabilities for human PDAC.
Question: Write a study description for the study titled 'A neurotoxic cellular stress response linked to dark microglia and toxic lipid secretion'.
Answer: Microglia, the brain’s primary resident immune cells, can assume various phenotypes with diverse functional outcomes on brain homeostasis. In Alzheimer’s disease (AD), where microglia are a leading causal cell type, the identity of microglia subsets that drive neurodegeneration remains unresolved. Here, we discover that a conserved stress signaling pathway, the integrated stress response (ISR), characterizes a subset of microglia with neurodegenerative outcomes. ISR is activated in AD-associated microglia subsets, including the ultrastructurally distinct “dark” microglia linked to pathological synapse loss. Activation of ISR in microglia is sufficient to induce early features of dark microglia. In AD models, microglial ISR exacerbates neurodegenerative pathologies, such as Tau and synapse loss, while inhibiting microglial ISR ameliorates them. Mechanistically, we present evidence that ISR in microglia promotes the secretion of toxic long-chain lipids that impair neuron homeostasis and survival in vitro. Accordingly, pharmacological inhibition of ISR and lipid synthesis ameliorates synapse loss in AD models. Our results demonstrate that activation of ISR within microglia represents a pathway contributing to neurodegeneration and suggest that this may be sustained, at least in part, by the secretion of toxic long-chain lipids from ISR-activated microglia.
Question: Write a study description for the study titled 'Polymicrobial detection and metabolomics in saliva of children with early childhood caries'.
Answer: Cariogenic microorganisms as well as salivary metabolic status in early childhood caries (ECC) have been reported to differ from that in adult caries. The main aim of this study was to identify specific microbial species and salivary metabolites in children with ECC using species-specific qPCR and untargeted metabolomic approach. Scardovia wiggsiae, Streptococcus mutans, Streptococcus sobrinus, Lactobacillus salivarius and Candida albicans were more prevalent in ECC group. Prevalence of ECC was higher in children with two targeted species present. Histidine metabolism and valine, leucine and isoleucine degradation were activated in ECC group, while glyoxylate and dicarboxylate metabolism, Purine and Pyrimidine metabolism were inhibited. Histidine and glutathione metabolism was activated with enrichment of targeted microorganism, while linoleic acid and biotin metabolism was inhibited. These findings suggest that detection / co-detection of targeted microorganisms can well describe caries status in children. Microbial and metabolite biomarkers can be used in caries control for children.
Question: Write a study description for the study titled 'Comparative Metabolomic Sampling of Upper and Lower Airways by Four Different Methods to Identify Biochemicals That May Support Bacterial Growth'.
Answer: Bacteria need nutrients from the host environment to survive, yet we know little about which biochemicals are present in the airways (the metabolome), which of these biochemicals are essential for bacterial growth and how they change with airway disease. The aims of this pilot study were to develop and compare methodologies for sampling the upper and lower airway metabolomes and to identify biochemicals present in the airways that could potentially support bacterial growth. Eight healthy human volunteers were sampled by four methods: two standard approaches - nasal lavage and induced sputum, and two using a novel platform, synthetic adsorptive matrix (SAM) strips-nasosorption and bronchosorption. Collected samples were analyzed by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS). Five hundred and eighty-one biochemicals were recovered from the airways belonging to a range of metabolomic super-pathways. We observed significant differences between the sampling approaches. Significantly more biochemicals were recovered when SAM strips were used, compared to standard sampling techniques. A range of biochemicals that could support bacterial growth were detected in the different samples. This work demonstrates for the first time that SAM strips are a highly effective method for sampling the airway metabolome. This work will assist further studies to understand how changes in the airway metabolome affect bacterial infection in patients with underlying airway disease.
Question: Write a study description for the study titled 'Coupling between high-resolution mass spectrometry and focalized data-analysis methods provides the identification of new putative glycosidic non-anthocyanic flavonoids in grape'.
Answer: INTRODUCTION: The biochemical diversity of flavonoids is based on glycosylation, methylation, acylation, and many other modifications of the flavonoid backbone. Liquid chromatography coupled to high-resolution mass spectrometry demonstrated to be a powerful approach to gain new insights into the flavonoid composition of many plant species, including grapes.OBJECTIVES: Among different metabolomic approaches, suspect screening analysis relies on the construction of a specific database and on ultra-high performance liquid chromatography/quadrupole time-of-flight (UHPLC/QTOF) analysis to find new compounds of oenological interest.METHODS: A homemade database containing mass data information retrieved from the literature specific for plant flavonoid derivatives (GrapeFlavMet) was constructed. Tandem mass spectrometry analysis of V. vinifera and hybrid grape extracts was performed, and MS/MS fragmentation allowed to assign the putative flavonoid chemical structure to various identification levels, as established by the Metabolomics Standard Initiative.RESULTS: By this approach, putative flavonoid derivatives with different glycosylation and acylation patterns were identified. They include three pentoside derivatives of tetrahydroxy-flavone, tetrahydroxy-flavanone and myricetin isomers, a putative dihydrorhamnetin hexoside derivative, three cinchonain isomers (phenylpropanoid-substituted flavan-3-ols with antidiabetic properties), and two syringetin isomer derivatives (acetyl- and p-coumaroyl-hexoside). Two acetyl-hexoside derivatives of dihydrorhamnetin and pentahydroxy-methoxy-flavanone, and three derivatives of tetrahydroxy-dimethoxy-flavanone (acetyl, p-coumaroyl, and caffeoyl-hexoside) were tentatively annotated.CONCLUSIONS: Most of the compounds were identified in grape for the first time, while two putative syringetin derivatives previously proposed in the literature were confirmed. These findings deepen the current knowledge on grape flavonoids, suggesting more connections at the biochemical level.
Question: Write a study description for the study titled 'OGFOD1 enables AML chemo- and nutrient stress resistance by regulating protein synthesis'.
Answer: Acute Myeloid Leukemia (AML) commonly relapses after initial chemotherapy response. We assessed metabolic adaptations in chemoresistant cells in vivo before overt relapse, identifying altered branched-chain amino acid (BCAA) levels in patient-derived xenografts (PDX) and immunophenotypically identified leukemia stem cells from AML patients. Notably, this was associated with increased BCAA transporter expression with low BCAA catabolism. Restricting of BCAAs further reduced chemoresistant AML cells but relapse still occurred. Among the persisting cells we found an unexpected increase in protein production. This was accompanied by elevated translation of 2-oxoglutarate-and-iron-dependent oxygenase 1 (OGFOD1), a known ribosomal dioxygenase that adjusts the fidelity of tRNA anticodon pairing with coding mRNA1–3 and upregulates protein synthesis in AML driving disease aggressiveness. Inhibiting OGFOD1 impaired translation processing, decreased protein synthesis and improved animal survival even with chemoresistant AML through regulation of protein synthesis. Leukemic cells can therefore persist despite the stress of chemotherapy and nutrient deprivation through adaptive control of translation while sparing normal hematopoiesis. Targeting OGFOD1 may offer a distinctive, translation modifying means of reducing the chemopersisting cells that drive relapse.
Question: Write a study description for the study titled 'A metabolomic study of adipose tissue in mice with a disruption of the circadian system'.
Answer: Adipose tissue functions in terms of energy homeostasis as a rheostat for blood triglyceride, regulating its concentration, in response to external stimuli. In addition it acts as a barometer to inform the central nervous system of energy levels which can vary dramatically between meals and according to energy demand. Here a metabolomic approach, combining both Mass Spectrometry and Nuclear Magnetic Resonance spectroscopy, was used to analyse both white and brown adipose tissue in mice with adipocyte-specific deletion of Arntl (also known as Bmal1), a gene encoding a core molecular clock component. The results are consistent with a peripheral circadian clock playing a central role in metabolic regulation of both brown and white adipose tissue in rodents and show that Arntl induced global changes in both tissues which were distinct for the two types. In particular, anterior subcutaneous white adipose tissue (ASWAT) tissue was effected by a reduction in the degree of unsaturation of fatty acids, while brown adipose tissue (BAT) changes were associated with a reduction in chain length. In addition the aqueous fraction of metabolites in BAT were profoundly affected by Arntl disruption, consistent with the dynamic role of this tissue in maintaining body temperature across the day/night cycle and an upregulation in fatty acid oxidation and citric acid cycle activity to generate heat during the day when rats are inactive (increases in 3-hydroxybutyrate and glutamate), and increased synthesis and storage of lipids during the night when rats feed more (increased concentrations of glycerol, choline and glycerophosphocholine).The data and protocols for UPLC-QTOF-MS assay are reported in current study MTBLS380. The data and protocols for NMR are reported in study MTBLS382.The data and protocols for GC-FID are reproted in study MTBLS390.
Question: Write a study description for the study titled 'Analysis of lipid nutrient differences in the milk of 13 species from a quantitative non-targeted lipidomics perspective'.
Answer: Lipid, an important organic component in milk, has health benefits for newborns. Profiles of milk lipid in multi-species from multi-level haven’t been accessible, therefore, we established a lipid subclass, lipid molecule, and fatty acid profile of 13 species to compare interspecific lipid differences. We used lipidomic to analysis the absolute content of lipid molecules based on UPLC-Orbitrap mass spectrometry system. The content of Zymosterol (ZyE) in all livestock was much higher than that in human milk. Meanwhile, the content of PI (18: 0_20: 5) and SM(d30:1) are only high in camels, which it might be used as potential biomarkers for the identification of camel milk. High content of ultra-long chain fatty acids (ULCFAs), as well as high content of DHA, ARA, EPA were found in pig milk. It is hoped that this comprehensive analysis of multi-species lipidomic can provide new macro insights into the development of the dairy industry.
Question: Write a study description for the study titled 'Pregnancy-Induced Metabolic Phenotype Variations in Maternal Plasma'.
Answer: Metabolic variations occur during normal pregnancy to provide the growing fetus with a supply of nutrients required for its development and to ensure the health of the woman during gestation. Mass spectrometry-based metabolomics was employed to study the metabolic phenotype variations in the maternal plasma that are induced by pregnancy in each of its three trimesters. Nontargeted metabolomics analysis showed that pregnancy significantly altered the profile of metabolites in maternal plasma. The levels of six metabolites were found to change significantly throughout pregnancy, with related metabolic pathway variations observed in biopterin metabolism, phospholipid metabolism, amino acid derivatives, and fatty acid oxidation. In particular, there was a pronounced elevation of dihydrobiopterin (BH2), a compound produced in the synthesis of dopa, dopamine, norepinephrine, and epinephrine, in the second trimester, whereas it was markedly decreased in the third trimester. The turnover of BH2 and tryptophan catabolites indicated that the fluctuations of neurotransmitters throughout pregnancy might reveal the metabolic adaption in the maternal body for the growth of the fetus. Furthermore, 11 lipid classes and 41 carnitine species were also determined and this showed variations in the presence of long-chain acylcarnitines and lysophospholipids in later pregnancy, suggesting changes of acylcarnitines and lysophospholipids to meet the energy demands in pregnant women.