LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'Maternal lipid mobilization is essential for embryonic development in a key malaria vector'.
Answer: Lipid metabolism is an essential component in reproductive physiology. While lipid mobilization has been implicated in the growth of Plasmodium falciparum malaria parasites in their Anopheles vectors, the role of this process in the reproductive biology of these mosquitoes remains elusive. Here, we show that impairing lipolysis in Anopheles gambiae, the major malaria vectors, leads to embryonic lethality. Embryos derived from females in which we silenced the triglyceride lipase AgTL2 or the lipid storage droplet AgLSD1 develop normally during early embryogenesis but fail to hatch. These embryos show severely impaired metabolism and appear to have compromised neuronal functions. Embryonic lethality is efficiently recapitulated by exposing adult females to broad-spectrum lipase inhibitors prior to blood feeding, unveiling lipolysis as a novel target for inducing mosquito sterility. Our findings provide mechanistic insights into the importance of maternal lipid mobilization in embryonic health that could potentially inform studies on human reproduction.
Question: Write a study description for the study titled 'Norbergenin prevents LPS-induced inflammatory responses in macrophages through inhibiting NFkB, MAPK and STAT3 activation and blocking metabolic reprogramming'.
Answer: Inflammation is thought to be a key cause of many chronic diseases and cancer. However, current therapeutic agents to control inflammation have limited long-term use potential due to various side-effects. This study aimed to examine norbergenin, a constituent of traditional anti-inflammatory recipes, on LPS-induced proinflammatory signaling in macrophages and elucidate the underlying mechanisms by integrative metabolomics and proteomics platforms. We found that LPS-induced production of NO, IL1β, TNFα, IL6 and iNOS in macrophages was alleviated by norbergenin via suppressed activation of TLR2 mediated NFkB, MAPKs and STAT3 signaling pathways. In addition, norbergenin was capable of overcoming LPS-triggered metabolic reprogramming in macrophages and restrained the facilitated glycolysis, promoted the reduced OXPHOS, and restored the aberrant metabolites within the TCA cycle. This is linked to its modulation of metabolic enzymes to support its anti-inflammatory activity. Thus, our results uncover that norbergenin regulates inflammatory signaling cascades and metabolic reprogramming in LPS stimulated macrophages to exert its anti-inflammatory potential.
Question: Write a study description for the study titled 'Stable isotope resolved analysis of HUVEC Cells under normaxia and hypoxia'.
Answer: In order to analyze HUVECs under normoxia and hypoxia, cells were initially deprived of excess nutrients and hormones by maintaining them overnight in a restricted medium with only 2% fetal bovine serum, and incubated for 40 hours in the presence of the tracer [1,2-13C2]-glucose until sample collection. 13C propagation from labelled glucose to glycogen, RNA ribose, lactate and glutamate was measured. The resulting isotopologue distributions are provided for three biological replicates per metabolite. In order to correct the natural abundance effect and also the effect of possible interferences among different compounds, isotopologue distributions in biological samples without labelled glucose are provided for RNA ribose, lactate and glutamate. Also, isotopologue distributions for commercial glucose are provided, using commercial glucose as a reference compound to correct the natural abundance effect in samples for glycogen (glucose) analysis. Finally, additional results are provided with measured glucose uptake, glutamine uptake, glutamate secretion, lactate secretion and net re-utilization of glycogen.
Question: Write a study description for the study titled 'Metabotyping Patients' Journeys Reveals Early Predisposition to Lung Injury after Cardiac Surgery'.
Answer: Cardiovascular disease is the leading cause of death worldwide and patients with severe symptoms undergo cardiac surgery. Even after uncomplicated surgeries, some patients experience postoperative complications such as lung injury. We hypothesized that the procedure elicits metabolic activity that can be related to the disease progression, which is commonly observed two-three days postoperatively. More than 700 blood samples were collected from 50 patients at nine time points pre-, intra-, and postoperatively. Dramatic metabolite shifts were observed during and immediately after the intervention. Prolonged surgical stress was linked to an augmented anaerobic environment. Time series analysis showed shifts in purine-, nicotinic acid-, tyrosine-, hyaluronic acid-, ketone-, fatty acid, and lipid metabolism. A characteristic ‘metabolic biosignature’ was identified correlating with the risk of developing postoperative complications two days before the first clinical signs of lung injury. Hence, this study demonstrates the link between intra- and postoperative time-dependent metabolite changes and later postoperative outcome. In addition, the results indicate that metabotyping patients’ journeys early, during or just after the end of surgery, may have potential impact in hospitals for the early diagnosis of postoperative lung injury, and for the monitoring of therapeutics targeting disease progression.
Question: Write a study description for the study titled 'Serum Predose Metabolic Profiling For Prediction Of Rosuvastatin Pharmacokinetic Parameters In Healthy Volunteers'.
Answer: Rosuvastatin is a quite known lipid-lowering agent generally used for hypercholesterolemia treatment and coronary artery diseases prevention. There is substantial inter-individual variability in the absorption of statins usually caused by genetic polymorphisms leading to variation in the corresponding pharmacokinetic parameters, which may affect drug therapy safety and efficacy. Therefore, the investigation of metabolic markers associated with rosuvastatin inter-individual variability is exceedingly relevant for drug therapy optimization and minimizing side effects. This work describes the application of pharmacometabolomics strategies using liquid chromatography coupled to mass spectrometry to investigate endogenous plasma metabolites capable of predicting pharmacokinetic parameters in predose samples. First, a targeted method for the determination of plasma concentration levels of rosuvastatin was validated and applied to obtain the pharmacokinetic parameters from the 40 enrolled individuals, then predose samples were analyzed using the metabolomics approach to search for associations between endogenous metabolites and the corresponding pharmacokinetic parameters. Data processing using machine learning revealed some candidates including sterols and bile acids, carboxylated metabolites as well as lipids suggesting the approach herein described as promising for personalized drug therapy.
Question: Write a study description for the study titled 'A homeostatic switch causing glycerol-3-phosphate and phosphoethanolamine accumulation triggers senescence by rewiring lipid metabolism'.
Answer: Cellular senescence affects many physiological and pathological processes and is characterized by durable cell cycle arrest, an inflammatory secretory phenotype and metabolic reprogramming. Here, by using dynamic transcriptome and metabolome profiling in human fibroblasts with different subtypes of senescence, we show that a homeostatic switch which results in glycerol-3-phosphate (G3P) and phosphoethanolamine (PEtn) accumulation links lipid metabolism to the senescence gene expression program. Mechanistically, p53-dependent glycerol kinase (GK) activation and post-translational inactivation of Phosphate Cytidylyltransferase 2-Ethanolamine (PCYT2) regulate this metabolic switch, which promotes triglyceride accumulation in lipid droplets and induces the senescence gene expression program. Conversely, G3P phosphatase (G3PP) and Ethanolamine-Phosphate Phospho-Lyase (ETNPPL)-based scavenging of G3P and PEtn acts in a senomorphic way by reducing G3P and PEtn accumulation. Collectively, our study ties G3P and PEtn accumulation to controlling lipid droplet biogenesis and phospholipid flux in senescent cells, providing a potential therapeutic avenue for targeting senescence and related pathophysiology.
Question: Write a study description for the study titled 'Toxicometabolomics of the new psychoactive substances α-PBP and α-PEP studied in HepaRG cell incubates by means of untargeted metabolomics revealed unexpected amino acid adducts'.
Answer: Toxicometabolomics, essentially applying metabolomics to toxicology of endogenous compounds such as drugs of abuse or new psychoactive substances (NPS), can be investigated by using different in vitro models and dedicated metabolomics techniques to enhance the number of relevant findings. The present study aimed to study the toxicometabolomics of the two NPS α-pyrrolidinobutiophenone (1-phenyl-2-(pyrrolidin-1-yl)butan-1-one, α-PBP) and α-pyrrolidinoheptaphenone (1-phenyl-2-(pyrrolidin-1-yl)heptan-1-one, α-PEP, PV8) in HepaRG cell line incubates. Evaluation was performed using reversed-phase and normal-phase liquid chromatography coupled with high-resolution mass spectrometry in positive and negative ionization mode, respectively, to analyze cells and cell media. Statistical evaluation was performed using one-way ANOVA, principal component discriminant function analysis, as well as hierarchical clustering. In general, the analysis of cells did not mainly reveal any features, but the parent compounds of the drugs of abuse. For α-PBP an increase in N-methylnicotinamide was found, which may indicate hepatotoxic potential of the substance. After analysis of cell media, significant features led to the identification of several metabolites of both compounds. Amino acid adducts with glycine and alanine were found, and these have not been described in any study before and are likely to appear in vivo. Additionally, significant changes in the metabolism of cholesterol were revealed after incubation with α-PEP. In summary, the application of metabolomics techniques after HepaRG cells exposure to NPS did not lead to an increased number of identified drug metabolites compared to previously published studies, but gave a wider perspective on the physiological effect of the investigated compounds on human liver cells.
Question: Write a study description for the study titled 'Collagen induced arthritis in dba/1j mice associates with oxylipin changes in plasma'.
Answer: Oxylipins play important roles in various biological processes and are considered as mediators of inflammation for a wide range of diseases such as rheumatoid arthritis (RA). The purpose of this research was to study differences in oxylipin levels between a widely used collagen-induced arthritis (CIA) mice model and healthy control (Ctrl) mice. DBA/1J male mice (age: 6-7 weeks) were selected and randomly divided into two groups, viz. a CIA- and a Ctrl group. The CIA mice were injected intraperitoneal (i.p.) with the joint cartilage component collagen type II (CII) and an adjuvant injection of lipopolysaccharide (LPS). Oxylipin metabolites were extracted from plasma for each individual sample using solid phase extraction (SPE) and were detected with high performance liquid chromatography/tandem mass spectrometry (HPLC-ESI-MS/MS), using dynamic multiple reaction monitoring (dMRM). Both univariate and multivariate statistical analysis was applied. The results in univariate student's t-test revealed 10 significantly up- or down-regulated oxylipins in CIA mice, which were supplemented by another 6 additional oxylipins, contributing to group clustering upon multivariate analysis. The dysregulation of these oxylipins revealed the presence of ROS-generated oxylipins and an increase of inflammation in CIA mice. The results also suggested that the Collagen-induced arthritis might associate with dysregulation of apoptosis, possibly inhibited by activated NF- κ B because of insufficient PPAR-γ ligands.
Question: Write a study description for the study titled 'Identification of pre-diagnostic lipid sets associated with liver cancer risk using untargeted lipidomics and chemical set analysis – a nested case-control study within the ATBC cohort'.
Answer: In pre-disposed individuals, a reprogramming of the hepatic lipid metabolism may support liver cancer initiation. We conducted a high-resolution mass spectrometry based untargeted lipidomics analysis of pre-diagnostic serum samples from a nested case-control study (219 liver cancer cases and 219 controls) within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Out of 462 annotated lipids, 158 (34.2%) were associated with liver cancer risk in a conditional logistic regression analysis at a false discovery rate (FDR) < 0.05. A chemical set enrichment analysis (ChemRICH) and co-regulatory set analysis suggested that 22/28 lipid classes and 47/83 correlation modules were significantly associated with liver cancer risk (FDR < 0.05). Strong positive associations were observed for monounsaturated fatty acids (MUFA), triacylglycerols (TAGs), and phosphatidylcholines (PCs) having MUFA acyl chains. Negative associations were observed for sphingolipids (ceramides and sphingomyelins), lysophosphatidylcholines, cholesterol esters and polyunsaturated fatty acids (PUFA) containing TAGs and PCs. Stearoyl-CoA desaturase enzyme 1 (SCD1), a rate limiting enzyme in fatty acid metabolism and ceramidases seems to be critical in this reprogramming. In conclusion, our study reports pre-diagnostic lipid changes that provide novel insights into hepatic lipid metabolism reprogramming may contribute to a pro-cell growth and anti-apoptotic tissue environment and, in turn, support liver cancer initiation.
Question: Write a study description for the study titled 'Exploring the Fecal Metabolome in Infants With Cow's Milk Allergy: The Distinct Impacts of Cow's Milk Protein Tolerance Acquisition and of Synbiotic Supplementation.'.
Answer: SCOPE: Cow's milk allergy (CMA) is one of the most prevalent food allergies in early childhood, often treated via elimination diets including standard amino acid-based formula or amino acid-based formula supplemented with synbiotics (AAF or AAF-S). This work aimed to assess the effect of cow's milk (CM) tolerance acquisition and synbiotic (inulin, oligofructose, Bifidobacterium breve M-16 V) supplementation on the fecal metabolome in infants with IgE-mediated CMA.METHODS AND RESULTS: The CMA-allergic infants received AAF or AAF-S for a year during which fecal samples were collected. The samples were subjected to metabolomics analyses covering gut microbial metabolites including SCFAs, tryptophan metabolites and bile acids (BAs). Longitudinal data analysis suggested amino acids, BAs and branched SCFAs alterations in infants who outgrew CMA during the intervention. Synbiotic supplementation significantly modified the fecal metabolome after 6 months of intervention, including altered purine, BA and unsaturated fatty acid levels, and increased metabolites of infant-type Bifidobacterium species: indolelactic acid and 4-hydroxyphenyllactic acid.CONCLUSION: This study offers no clear conclusion on the impact of CM-tolerance acquisition on the fecal metabolome. However, our results show that 6 months of synbiotic supplementation successfully altered fecal metabolome and suggest induced bifidobacteria activity, which subsequently declined after 12 months of intervention.
Question: Write a study description for the study titled 'SOX2 Drives Esophageal Squamous Carcinoma by Reprogramming Lipid Metabolism and Histone Acetylation Landscape'.
Answer: SOX2 is not only a pioneer transcription factor with critical roles in stem cell function and cell reprogramming but also a potent oncogene for a multitude of squamous cancers. How SOX2 exerts a potent oncogenic activity in squamous lineage is largely unknown. Here we uncovered SOX2 a potent role in promoting global histone acetylation and super-enhancer formation in esophageal squamous cancer cells. Metabolic analysis revealed a role of SOX2 in suppressing fatty acid synthesis. SOX2 promotes global histone acetylation by two distinct mechanisms: stimulating the expression of a panel of histone acetyltransferases and repressing the expression of ACSL5, which down-regulates fatty acid synthesis and thus channels acetyl-CoA toward histone acetylation. Notably, we found that SOX2 enhanced histone acetylation is required for the formation of most squamous lineage-specific super-enhancers. Our findings provide new explanation for why SOX2 is a powerful cell fate reprogrammer and potent oncogene for squamous lineage cancers.
Question: Write a study description for the study titled 'Mitochondrial KMT9 methylates DLAT to control pyruvate dehydrogenase activity and prostate cancer growth'.
Answer: Prostate cancer (PCa) growth depends on de novo lipogenesis controlled by the mitochondrial pyruvate dehydrogenase complex (PDC). In this study, we identified lysine methyltransferase (KMT)9 as a novel regulator of PDC activity. KMT9 is localized in mitochondria of PCa cells, but not in mitochondria of other tumor cell types. Mitochondrial KMT9 regulates PDC activity by monomethylation of its subunit dihydrolipoamide transacetylase (DLAT) at lysine 596. Depletion of KMT9 compromises PDC activity, de novo lipogenesis, and PCa cell proliferation, both in vitro and in a PCa mouse model. Finally, in human patients, levels of mitochondrial KMT9 and DLAT K596me1 correlate with Gleason grade. Together, we present a novel mechanism of PDC regulation and the first example of a histone methyltransferase with nuclear and mitochondrial functions. The exceptional dependency of PCa cells on mitochondrial KMT9 allows to develop novel therapeutic strategies to selectively fight PCa.
Question: Write a study description for the study titled '3D DESI mass spectrometry imaging of 52 serial sections from a human colorectal adenocarcinoma'.
Answer: Fifty-two serial sections from a single human adenocarcinama are made available in this dataset. Four neighbouring sections were placed on a single slide and analysed together. The tissue sections were analysed by desorption electrospray ionisation mass spectrometry imaging (DESI-MSI) according to the procedure outlined in the associated publications. The data files are made available in centroid- and profile-mode imzML format. Additionally, H&E-stained optical images are included.
Question: Write a study description for the study titled 'Metabolic Changes of Maternal Uterine Fluid, Uterus, and Plasma during the Peri-implantation Period of Early Pregnancy in Mice'.
Answer: Embryo implantation is a complex process which involves biochemical and physiological interactions between an implantation-competent blastocyst and a receptive uterus. However, the exact biochemical changes of uterine fluid, uterus, and plasma during peri-implantation remain unclear. This study aims to characterize the biochemical and metabolic changes that occur during the peri-implantation period of early pregnancy, using mice as an animal model. Gas chromatography-mass spectrometry was used to analyze the metabolite profiles of the uterus, uterine fluid, and maternal plasma at pre-implantation and implantation. The multivariate analyses, ANOVA and Tukey's HSD test, were applied to detect significant changes in metabolites and metabolic pathways. The metabolic networks were reconstructed in silico based on the identified metabolites and KEGG metabolic framework. Between pre-implantation day 1 and day 4, dramatic metabolic changes were observed in the uterine fluid that could be important for blastocyst development and protection against the harsh uterine environment. Palmitoleic acid, fumaric acid, and glutaric acid changed levels at day 4 in the uterus, suggesting that they may be associated with endometrial receptivity. Both the uterus and maternal plasma showed profound changes in cellular metabolism at the early implantation period, including upregulation of branched-chain amino acids and intermediates of one-carbon metabolism, an upregulation of glyoxylate and dicarboxylate metabolism, and downregulation of aerobic respiration; all of which could be involved in the regulation of the maternal-fetal interface, alternative nutrient utilization, and energy preservation for implantation as well as later placentation and fetal development to ensure successful embryo implantation.
Question: Write a study description for the study titled 'CYP51A1-mediated alkaliptosis resistance is a targetable vulnerability in pancreatic cancer'.
Answer: Alkaliptosis, a pH-dependent form of regulated cell death characterized by impaired lysosomal function and lethal alkalinization, holds promise as a target for cancer therapy. Here, we utilize mass spectrometry-based drug target, transcriptomic screens, and lipid metabolomics to explore the metabolic mechanisms underlying alkaliptosis. We reveal CYP51A1, a gene involved in cholesterol synthesis, as a key suppressor of alkaliptosis in pancreatic cancer cells. Inducing alkaliptosis leads to a decrease in endoplasmic reticulum cholesterol levels, subsequently activating SREBF2, a transcription factor responsible for controlling the expression of genes involved in cholesterol biosynthesis. Specifically, SREBF2-driven upregulation of CYP51A1 prevents cholesterol accumulation within lysosomes, leading to TMEM175-dependent lysosomal proton efflux, ultimately resulting in the inhibition of alkaliptosis.PDAC-SW1990 cell line analysis is reported in the current study MTBLS9288.PDAC-PANC1 cell line analysis is reported in MTBLS9283.
Question: Write a study description for the study titled 'Lactobacillus acidophilus potentiates oncolytic virotherapy through modulating gut microbiota homeostasis in hepatocellular carcinoma'.
Answer: Oncolytic viruses (OVs) hold promise for cancer treatment. However, the antitumor efficacy is limited. Microbiota plays a pivotal role in cancer treatment and its impact on oncolytic virotherapy is unknown. Here, we show that VSVΔ51 has higher antitumor efficacy for hepatocellular carcinoma in the absence of microbiota in female mouse models. VSVΔ51 infection causes microbiota dysbiosis, increasing most of the gut bacteria abundance, while decreasing the commensal Lactobacillus. VSVΔ51 reduced intestinal expression of SLC20A1 that binds to Lactobacillus acidophilus (L. acidophilus) CdpA cell wall protein through IL6-JAK-STAT3 signaling, thereby attenuating attachment and colonization of L. acidophilus. L. acidophilus supplementation confers sensitivity to VSVΔ51 through restoring gut barrier integrity and microbiota homeostasis destroyed by VSVΔ51. In this work, we show that targeting microbiota homostasis holds substantial potential in improving therapeutic outcomes of oncolytic virotherapy