LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'A serum nuclear magnetic resonance-based metabolomic signature of antiphospholipid syndrome'.
Answer: Antiphospholipid syndrome (APS) is a rheumatic inflammatory chronic autoimmune disease inducing hypercoagulable state associated with vascular thrombosis and pregnancy loss in women. Cardiac, cerebral and vascular strokes in these patients are responsible for reduction in life expectancy. Timely diagnosis and accurate monitoring of disease are decisive to improve the accuracy of therapy. In the present work, we present a NMR-based metabolomic study of blood sera of APS patients. Our data show that individuals suffering APS have a characteristic metabolomic profile with abnormalities associated to the metabolism of methyl group donors, ketone bodies and amino acids. We have identified for the first time the metabolomic fingerprint characterizing APS disease having potential application to improve APS timely diagnosis and appropriate therapeutic approaches.
Question: Write a study description for the study titled 'UPLC-MS-Based Serum Metabolic Profiling Reveals Potential Biomarkers for Predicting Propofol Responsiveness in Females'.
Answer: Although previous studies have shown that certain factors interfere with the sensitivity of propofol, the mechanisms for interindividual variability in response to propofol remain unclear. This study aimed to screen the metabolites to predict patients' sensitivity to propofol and to identify metabolic pathways to explore possible mechanisms associated with propofol resistance. Sera from 40 female patients undergoing elective hysteroscopic surgery in a prospective cohort propofol study were obtained before the administration of propofol. The patients' responsiveness to propofol was differentiated based on propofol effect-site concentration. Serum samples from two sets, a discovery set (n = 24) and an independent validation set (n = 16), were analyzed using ultraperformance liquid chromatography coupled with mass spectrometry based untargeted metabolomics. In the discovery set, 494 differential metabolites were screened out, and then 391 potential candidate biomarkers with the area under receiver operating characteristic curve >0.80 were selected. Pathway analysis showed that the pathway of glycerophospholipid metabolism was the most influential pathway. In the independent validation set, six potential biomarkers enabled the discrimination of poor responders from good and intermediate responders, which might be applied to predict propofol sensitivity.
Question: Write a study description for the study titled 'Searching for metabolic changes in urine headspace composition as an effect of strenuous walking'.
Answer: The present investigation uses proton transfer reaction mass spectrometry (PTR-MS) combined with multivariate and univariate statistical analyses to study potential biomarkers for altered metabolism in urine due to strenuous walking. Urine samples, in concurrence with breath and blood samples, were taken from 51 participants (23 controls, 11 type-1 diabetes, 17 type-2 diabetes) during the Dutch endurance walking event, the International Four Days Marches. Multivariate analysis allowed for discrimination of before and after exercise for all three groups (control, type-1 and type-2 diabetes) and on three out of 4 days. The analysis highlighted 12 molecular ions contributing to this discrimination. Of these, acetic acid in urine is identified as a significant marker for exercise effects induced by walking; an increase is observed as an effect of walking. Analysis of acetone concentration with univariate tools resulted in different information when compared to breath as a function of exercise, revealing an interesting effect of time over the 4 days. In breath, acetone provides an immediate snapshot of metabolism, whereas urinary acetone will result from longer term diffusion processes, providing a time averaged view of metabolism. The potential to use PTR-MS measurements of urine to monitor exercise effects is exhibited, and may be utilized to monitor subjects in mass participation exercise events.
Question: Write a study description for the study titled 'Old mitochondria regulate niche renewal via stem cell metabolism'.
Answer: Cellular metabolism is emerging as a potent regulator of cell fate, raising the possibility that the recently discovered metabolic heterogeneity between newly synthesized and chronologically old organelles may impact stem cell fate in mammalian tissues. The small intestine is maintained by actively cycling intestinal stem cells (ISCs) that give rise to metabolically distinct progeny, including their Paneth cell niche. Here, we find that asymmetric cell division generates a subset of ISCs enriched for old mitochondria (ISCmito-O). Although ISCmito-O lack characteristics of reserve stem cells, they form organoids niche-independently, owing to their ability to recreate the Paneth cell niche. Mechanistically, mitochondria in ISCmito-O generate more alpha-ketoglutarate (aKG), driving ten-eleven translocation (Tet) methylcytosine dioxygenase-mediated epigenetic changes that are associated with differentiation towards the Paneth cell fate. aKG supplementation in vivo promotes Paneth cell turnover leading to niche renewal, which promotes recovery from chemotherapy-induced damage in aged animals. Our results reveal a subpopulation of intestinal stem cells whose old mitochondria metabolically regulate cell fate, and provide proof-of-principle for metabolically promoted replacement of specific aged cell types in vivo.
Question: Write a study description for the study titled 'Veterinary trypanocidal benzoxaboroles are peptidase-activated prodrugs (T. congolense assay)'.
Answer: Livestock diseases caused by Trypanosoma congolense, T. vivax and T. brucei, collectively known as nagana, are responsible for billions of dollars in lost food production annually. There is an urgent need for novel therapeutics. Encouragingly, promising antitrypanosomal benzoxaboroles are under veterinary development. Here, we show that the most efficacious subclass of these compounds are prodrugs activated by trypanosome serine carboxypeptidases (CBPs). Drug-resistance to a development candidate, AN11736, emerged readily in T. brucei, due to partial deletion within the locus containing three tandem copies of the CBP genes. T. congolense parasites, which possess a larger array of related CBPs, also developed resistance to AN11736 through deletion within the locus. A genome-scale screen in T. brucei confirmed CBP loss-of-function as the primary mechanism of resistance and CRISPR-Cas9 editing proved that partial deletion within the locus was sufficient to confer resistance. CBP re-expression in either T. brucei or T. congolense AN11736-resistant lines restored drug-susceptibility. CBPs act by cleaving the benzoxaborole AN11736 to a carboxylic acid derivative, revealing a prodrug activation mechanism. Loss of CBP activity results in massive reduction in net uptake of AN11736, indicating that entry is facilitated by the concentration gradient created by prodrug metabolism.T. congolense assay is reported in the current study MTBLS1309.T. brucei assay is reported in MTBLS1474.Linked cross omic data sets:Genome data associated with this study are available in the European Nucleotide Archive (ENA): accession number PRJEB34627.
Question: Write a study description for the study titled 'DESI mass spectrometry imaging of murine tissues'.
Answer: DESI-MS imaging results of a murine colorectal tumour tissue, a murine jejunum tissue and a Helicobacter pylori-infected murine stomach tissue are available. Data were all obtained under negative ion mode. Corresponding H&E staining results can be found in the associated publication
Question: Write a study description for the study titled 'Decipher aging related skin microbiome and metabolites crosstalk from a chronologically matched cohort'.
Answer: Aging has shown close link to shifts in the skin microbiome in population cohort study. However, how variations in microbial communities relate to divergent skin aging within individuals of the same chronological ages remains unclear. In this study, we performed phenotypic, metabolomic and metagenomic analyses on 103 women aged 39-41 to investigate how skin microbiota mediate metabolic pathways influencing divergent skin aging. The younger group (based on AI-predicted age and skin elasticity) exhibited fewer wrinkles and higher microbial diversity with more potential probiotics. Meanwhile, the older group displayed increased antibiotic resistance genes in microbiota, exacerbating skin aging vulnerability. Using skin metabolomics and genome-scale metabolic models (GEM), our study revealed that S. maltophilia, enriched in younger individuals, utilizes the glutathione cycle for antioxidant defense and protein thiol maintenance. In Vitro experiments and transcriptome analysis further demonstrated that S. maltophilia upregulates key genes, including GCLM, PGD, SOD2 and NQO1, to enhance GSH synthesis and alleviate oxidative stress-induced skin aging. Additionally, S. maltophilia was significantly correlated with WCSC, and GEM analysis further uncovered its potential anti-aging functions in betaine, lysolecithin and porphyrin metabolism. Moreover, we found that A. guillouiae modulates melanin precursor DA and 3-MT, suggesting a potential therapeutic strategy to mitigate pigmentation during skin aging. Together, our findings illustrate the dynamic regulation between skin microbiota and the host in skin aging, independent of chronological age. This study offers new insights for designing targeted anti-aging interventions.
Question: Write a study description for the study titled 'Amino Acid Metabolism is Significantly Altered at the Time of Admission in Hospital for Severe COVID-19 Patients: Findings from Longitudinal Targeted Metabolomics Analysis'.
Answer: The heterogeneity in severity and outcome of COVID-19 cases points out the urgent need for early molecular characterization of patients followed by risk-stratified care. The main objective of this study was to evaluate the fluctuations of serum metabolomic profiles of COVID-19 patients with severe illness during the different disease stages in a longitudinal manner. We demonstrate a distinct metabolomic signature in serum samples of 32 hospitalized patients at the acute phase compared to the recovery period, suggesting the tryptophan (tryptophan, kynurenine and 3-hydroxy-DL-kynurenine) and arginine (citrulline and ornithine) metabolism as contributing pathways in the immune response to SARS-CoV-2 with a potential link to the clinical severity of the disease. In addition, we suggest that glutamine deprivation may further result in inhibited M2 macrophage polarization as a complementary process, and highlight the contribution of phenylalanine and tyrosine in the molecular mechanisms underlying the severe course of the infection. In conclusion, our results provide several functional metabolic markers for disease progression and severe outcome with potential clinical application.
Question: Write a study description for the study titled 'Characterization of the heat-stable proteome during seed germination in Arabidopsis with special focus on LEA proteins'.
Answer: During seed germination, desiccation tolerance is lost in the radicle with progressing radicle protrusion and seedling establishment. This process is accompanied by comprehensive changes of the metabolome and proteome. Germination of Arabidopsis seeds was investigated over 72 h with special focus on the heat-stable proteome including late embryogenesis abundant (LEA) proteins together with changes of primary metabolites. Six metabolites in dry seeds known to be important for seed longevity decreased during germination and seedling establishment, while all other metabolites increased simultaneously with activation of growth and development. Thermo-stable proteins were associated with a multitude of biological processes. In the heat-stable proteome a relatively similar proportion of fully ordered and fully intrinsically disordered proteins (IDP) was discovered. Highly disordered proteins were found to be associated with functional categories development, protein, RNA and stress. As expected, the majority of LEA proteins decreased during germination and seedling establishment. However, four germination-specific dehydrins were identified, not present in dry seeds. A network analysis of proteins, metabolites and amino acids generated during the course of germination revealed a highly connected LEA protein network.
Question: Write a study description for the study titled 'Aftpo3 and Afdur3, the Aspergillus fumigatus Plasma Membrane Transporters of Polyamines, Regulate Polyamine Homeostasis and Itraconazole Susceptibility'.
Answer: Aspergillus fumigatus is a notorious opportunistic pathogen that causes Invasive Aspergillosis (IA) infections with high mortality in immunosuppressed individuals. Long-term antifungal drug azole abuse in clinical treatment and agriculture renders it ineffectual or drug resistant. Drug resistance can relate to the cellular metabolites and corresponding gene transcription. In this study, through untargeted metabolomics and transcriptomics following itraconazole (ITC) treatment we identified two plasma membrane-localized polyamine transporters Aftpo3 and Afdur3, which were important for polyamine homeostasis and ITC susceptibility in A. fumigatus. In the absence of Aftpo3 or Afdur3, the levels of cytoplasm polyamines had a moderate increase, accompanied by resistance to ITC. In comparison, overexpression of Aftpo3 or Afdur3 induced drastic increase of polyamines, which were linked with the sensitivity to ITC. Accordingly, our study demonstrated that concentration-dependence of polyamines affected susceptibility of A. fumigatus to ITC, by scavenging reactive oxygen species (ROS) at a moderate concentration or generating ROS at a high concentration rather than drug transport.
Question: Write a study description for the study titled 'Serine Metabolism Tunes Immune Responses To Promote Oreochromis niloticus Survival upon Edwardsiella tarda Infection'.
Answer: Overactive immune response is a critical factor triggering host death upon bacterial infection. However, the mechanism behind the regulation of excessive immune responses is still largely unknown, and the corresponding control and preventive measures are also to be explored. In this study, we find that the Nile tilapia, Oreochromis niloticus, died from Edwardsiella tarda infection had higher level of immune responses than those survived. Such immune responses are strongly associated with the metabolism that was altered at 6 h post-infection. By GC-MS-based metabolome profiling, we identify glycine, serine and threonine metabolism as the top three of the most impacted pathways, which were not properly activated in the fish died out of infection. Serine is one of the crucial biomarkers. Exogenous serine can promote O. niloticus survival both as prophylactic and therapeutic upon E. tarda infection. Our further analysis revealed that exogenous serine flux into the glycine, serine and threonine metabolism, and more importantly, to the glutathione metabolism via glycine. The increased glutathione synthesis could downregulate reactive oxygen species. Therefore, these data together suggest that metabolic modulation of immune responses could be a potential preventive strategy to control overactive immune responses.
Question: Write a study description for the study titled 'Low chorionic villous succinate accumulation associates with recurrent spontaneous abortion risk'.
Answer: Dysregulated extravillous trophoblast invasion and proliferation are known to increase the risk of recurrent spontaneous abortion (RSA); however, the underlying mechanism remains unclear. Herein, in our retrospective observational case-control study we show that villous samples from RSA patients, compared to healthy controls, display reduced succinate dehydrogenase complex iron sulfur subunit (SDHB) DNA methylation, elevated SDHB expression, and reduced succinate levels, indicating that low succinate levels correlate with RSA. Moreover, we find high succinate levels in early pregnant women are correlated with successful embryo implantation. SDHB promoter methylation recruited MBD1 and excluded c-Fos, inactivating SDHB expression and causing intracellular succinate accumulation which mimicked hypoxia in extravillous trophoblasts cell lines JEG3 and HTR8 via the PHD2-VHL-HIF-1α pathway; however, low succinate levels reversed this effect and increased the risk of abortion in mouse model. This study reveals that abnormal metabolite levels inhibit extravillous trophoblast function and highlights an approach for RSA intervention.
Question: Write a study description for the study titled 'Transcriptional Shift and Metabolic Adaptations during Leishmania Quiescence Using Stationary Phase and Drug Pressure as Models'.
Answer: Microorganisms can adopt a quiescent physiological condition which acts as a survival strategy under unfavourable conditions. Quiescent cells are characterized by slow or non-proliferation and deep down-regulation of processes related to biosynthesis. Although quiescence has been described mostly in bacteria, this survival skill is widespread, including in eukaryotic microorganisms. In Leishmania, a digenetic parasitic protozoan that causes a major infectious disease, quiescence has been demonstrated, but molecular and metabolic features enabling its maintenance are unknown. Here we quantified the transcriptome and metabolome of Leishmania promastigotes and amastigotes where quiescence was induced in vitro either through drug pressure or by stationary phase. Quiescent cells have a global and coordinated reduction in overall transcription, with levels dropping to as low as 0.4% of those in proliferating cells. However, a subset of transcripts did not follow this trend and were relatively upregulated in quiescent populations, including those encoding membrane components such as amastins and GP63 or processes such as autophagy. The metabolome followed a similar trend of overall downregulation albeit to a lesser magnitude than the transcriptome. Noteworthy, among the commonly upregulated metabolites were those involved in carbon sources as an alternative to glucose. This first integrated two omics layers affords novel insights into cell regulation and shows commonly modulated features across stimuli and stages.
Question: Write a study description for the study titled 'AMPK activation induces RALDH+ tolerogenic dendritic cells by rewiring glucose and lipid metabolism.'.
Answer: Dendritic cell (DC) activation and function are underpinned by profound changes in cellular metabolism. Several studies indicate that the ability of DCs to promote tolerance is dependent on catabolic metabolism. Yet the contribution of AMP-activated kinase (AMPK), a central energy sensor promoting catabolism, to DC tolerogenicity remains unknown. Here, we show that AMPK activation renders human monocyte-derived DCs tolerogenic as evidenced by an enhanced ability to drive differentiation of regulatory T cells, a process dependent on increased RALDH activity. This is accompanied by several metabolic changes, including increased breakdown of glycerophospholipids, enhanced mitochondrial fission-dependent fatty acid oxidation, and upregulated glucose catabolism. This metabolic rewiring is functionally important as we found interference with these metabolic processes to reduce to various degrees AMPK-induced RALDH activity as well as the tolerogenic capacity of moDCs. Altogether, our findings reveal a key role for AMPK signaling in shaping DC tolerogenicity and suggest AMPK as a target to direct DC-driven tolerogenic responses in therapeutic settings.
Question: Write a study description for the study titled 'Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma (Mouse NAD targeted time-course)'.
Answer: NAMPT plays a major role in NAD biosynthesis in many cancers and is an attractive potential cancer target. However, factors dictating therapeutic efficacy of NAMPT inhibitors (NAMPTi) are unclear. We report that neuroendocrine phenotypes predict lung and prostate carcinoma vulnerability to NAMPTi, and that NAMPTi therapy against those cancers is enhanced by dietary modification. Neuroendocrine differentiation of tumor cells was associated with down-regulation of genes relevant to QPRT-dependent de novo NAD synthesis, promoting NAMPTi susceptibility in vitro. We also found that circulating nicotinic acid riboside (NAR), a non-canonical niacin absent in culture media, antagonizes NAMPTi efficacy as it fuels NAMPT-independent but NMRK1-dependent NAD synthesis in tumors. In mouse transplantation models, depleting blood NAR by nutritional or genetic manipulations was synthetic lethal to tumors when combined with NAMPTi. Our findings provide a rationale for simultaneous targeting of NAR metabolism and NAMPT therapeutically in neuroendocrine carcinoma.Mouse NAD targeted time-course is reported in the current study MTBLS7253.Cell NAMPTi treatment is reported in MTBLS7251.Mouse NAMPT targeted therapy is reported in MTBLS7252.
Question: Write a study description for the study titled 'Efficacy of Zhuyu Pill Intervention in a Cholestasis Rat Model: Mutual Effects on Fecal Metabolism and Microbial Diversity'.
Answer: Cholestasis is a clinical condition resulting from the impairment of bile flow. Currently, patients with cholestasis still face several barriers in seeking diagnosis and treatment. Zhuyu Pill (ZYP) is an ancient classic formula of the Coptis-Evodia herb couples (CEHC), and has been used for cholestasis treatment in the clinic, however, its underlying biological mechanism in cholestasis remain to be clarified. In this study, a cholestasis rat model, induced by α-naphthyl-isothiocyanate (ANIT, 50mg/kg) and treated with ZYP (0.6g/kg or 1.2g/kg), was adopted. Serum biochemical indices and histopathological evaluation was performed, in addition to metabolomics analyses of fecal and 16S rDNA sequencing of the gut microbiota. We evaluated the anticholestatic activity of ZYP and investigated the mechanism underlying its correlation with gut microbiota and fecal metabolite regulation. The relationships between biochemical indices, fecal metabolites, and gut microbiota were analyzed. The results showed that both high and low doses of ZYP can effectively improve the blood biochemical parameters of cholestasis rats, and the intervention effect of high dose ZYP is superior to that that of lower dose. Based on a metabolomics test of fecal samples, significantly altered metabolites in the ANIT and ZYP treatment group were identified. In total, 734 metabolites were differentially expressed, and whose biological functions were mainly associated with amino acid metabolism, steroid hormone biosynthesis, and bile secretion. In addition, sequencing of the 16S rDNA unit in fecal samples revealed that the ZYP could improve the gut microbiota dysbiosis that ANIT had induced. Therefore, we conclude that ANIT altering of blood biochemical and metabolic profiles and gut microbiota can be effectively alleviated using ZYP treatment, this study contributes “TCM wisdom” to clinical diagnosis and treatment of cholestasis.