LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'The Metabolostasis System Regulates the Aggregation and Toxicity of Essential Metabolites'.
Answer: Although metabolites are essential across all branches of life, it has been recently reported that they can form cytotoxic aggregates that resemble those formed by proteins in misfolding diseases. The phenomenon of metabolite aggregation suggests the existence of a metabolite homeostasis (metabolostasis) system capable of maintaining metabolites within a concentration range optimal for cellular function. To investigate this system, using Saccharomyces cerevisiae as a model organism, we identified the critical upper limits of metabolite consumption, beyond which metabolostasis is disrupted, leading to toxicity and growth inhibition. By enforcing a metabolite intake near the upper limits, we monitored the changes at the metabolome, transcriptome and proteome levels, enabling us to map the metabolostasis system. Among the most affected pathways, we identified oxidative phosphorylation and intracellular membrane trafficking, particularly within the vacuole, which emerges as a containment and detoxification hub for potentially toxic metabolites. Near the upper limits of metabolite consumption, we observed the formation of amyloid-like metabolite aggregates, suggesting that the cytotoxicity is, at least in part, related to the conformational state of the metabolites and, in turn, the physicochemical properties that determine their solubility. Our findings characterize metabolostasis as the cellular system that maintains metabolites within their safe concentration limits and prevents their aberrant accumulation into cytotoxic aggregates.
Question: Write a study description for the study titled 'Biological Effects of Amphiphilic Copolymer Nanoparticle-Encapsulated Multi-target Chemotherapeutic Drugs on MCF-7 Human Breast Cancer Cells'.
Answer: INTRODUCTION: Amphiphilic copolymer nanoparticle-encapsulated multi-target chemotherapeutic drugs have attracted considerable attention due to their favorable drug efficiency and potential application prospect. Studies have shown that an amphiphilic copolymer, methoxypoly(ethylene glycol)-poly(lactide-co-glycolide) modified with e-polylysine, and encapsulated with hydrophilic doxorubicin, hydrophobic paclitaxel and survivin siRNA profoundly improved the therapeutic effect both in vitro and in vivo.OBJECTIVES: To investigate how MCF-7 cells would response to the exposure of these nanoparticles over with time and assess the biological effects of these nanoparticles and their encapsulated drugs in a holistic manner.METHODS: MCF-7 cells were treated with PBS, nanocarrier and three encapsulated drugs, respectively. Metabolic alterations associated with nano-drugs exposure were investigated by performing untargeted NMR metabolomics with combination of targeted fatty acids analysis by GC-MS on cell extracts. Altered metabolic pathways were further validated by qRT-PCR approach.RESULTS: Copolymers showed great biocompatibility with cells as it induced transit metabolic disruptions without affecting cell survival rate. The rapid release of encapsulated doxorubicin resulted in inhibition of glycolysis and DNA synthesis, active proteolysis; these metabolic alternations were recovered after 10 h exposure. However, the combination use of multiple drugs consistently induced cell cycle arrest and apoptosis evidenced by reduction in glycolysis, active proteolysis, stimulated O-GlcNAcylation, reduced the PC:GPC ratio and fatty acids accumulation. Prolonged exposure to encapsulated-multiple-drugs also induced oxidative stress to cells.CONCLUSION: These findings provide important insight into the biological effects of nanoparticles and their encapsulated drugs while demonstrate that metabolomics is a powerful approach to evaluate the biological effects of nano-drugs.
Question: Write a study description for the study titled 'Metabolic Effects of a Chronic Dietary Exposure to a Low-Dose Pesticide Cocktail in Mice: Sexual Dimorphism and Role of the Constitutive Androstane Receptor (Untargeted urine, plasma and liver NMR assay)'.
Answer: "BACKGROUND: Epidemiological evidence suggests a link between pesticide exposure and the development of metabolic diseases. However, most experimental studies have evaluated the metabolic effects of pesticides using individual molecules, often at non-relevant doses or in combination with other risk factors such as high fat diets.OBJECTIVES: We aimed to evaluate, in mice, the metabolic consequences of chronic dietary exposure to a pesticide mixture at non-toxic doses, relevant to consumers’ risk assessment.METHODS: A mixture of six pesticides commonly used in France i.e. boscalid, captan, chlorpyrifos, thiofanate, thiacloprid, and ziram was incorporated in a standard chow diet, at doses exposing mice to the acceptable daily intake (ADI) of each pesticide. Wild-type (WT) and Constitutive Androstane Receptor knock-out (CAR-/-) C57Bl6/J male and female mice were exposed for 52 weeks. We assessed metabolic parameters (body-weight, food and water consumption, glucose tolerance, urinary metabolome) throughout the experiment. At the end of the experiment, we evaluated liver metabolism (histology, transcriptomics, metabolomics) and pesticide detoxification using LC/MS.RESULTS: In males, pesticide exposure increased body weight and adiposity and induced hepatic steatosis and glucose intolerance. Exposed females exhibited fasted hyperglycaemia, hepatic oxidative stress and perturbations of gut microbiota-related urinary metabolites. The Constitutive Androstane Receptor is involved in the sexually dimorphic response to pesticide exposure. CONCLUSIONS: We show for the first time the sexually dimorphic obesogen and diabetogen effects of a chronic dietary exposure to a realistic mixture of pesticides, which are partially mediated through CAR. This raises questions about the relevance of ADI for individual pesticides when present in a mixture.Untargeted urine, plasma and liver NMR assay protocols and data are reported in the current study MTBLS602.Untargeted urine UPLC-MS assay protocols and data associated to this study are reported in MTBLS596."
Question: Write a study description for the study titled 'Sequential multi-omics analysis identifies clinical phenotypes and predictive biomarkers for long COVID'.
Answer: The post-acute sequelae of COVID-19 (PASC), also known as long COVID, is often associated with debilitating symptoms and adverse multisystem consequences. We obtain plasma samples from 117 individuals during and 6 mth following their acute phase of infection to comprehensively profile and assess changes in cytokines, proteome, and metabolome. Network analysis reveals sustained inflammatory response, platelet degranulation, and cellular activation during convalescence accompanied by dysregulation in arginine biosynthesis, methionine metabolism, taurine metabolism, and tricarboxylic acid (TCA) cycle processes. Furthermore, we develop a prognostic model composed of 20 molecules involved in regulating T cell exhaustion and energy metabolism that can reliably predict adverse clinical outcomes following discharge from acute infection with 83% accuracy and an area under the curve (AUC) of 0.96. Our study reveals pertinent biological processes during convalescence that differ from acute infection, and it supports the development of specific therapies and biomarkers for patients suffering from long COVID.
Question: Write a study description for the study titled 'Assessing the impact of nitrogen supplementation in oats across multiple growth locations and years with targeted phenotyping and high-resolution metabolite profiling approaches'.
Answer: Oats (Avena sativa L.) are a healthy food, being high in dietary fibre (e.g. β-glucans), antioxidants, minerals, and vitamins. Understanding the effect of variety and crop management on nutritional quality is important. The response of four oat varieties to increased nitrogen levels was investigated across multiple locations and years with respect to yield, grain quality and metabolites (assessed via GC- and LC- MS). A novel high-resolution UHPLC-PDA-MS/MS method was developed, providing improved metabolite enrichment, resolution, and identification. The combined phenotyping approach revealed that, amino acid levels were increased by nitrogen supplementation, as were total protein and nitrogen containing lipid levels, whereas health-beneficial avenanthramides were decreased. Although nitrogen addition significantly increased grain yield and β-glucan content, supporting increasing the total nitrogen levels recommended within agricultural guidelines, oat varietal choice as well as negative impacts upon health beneficial secondary metabolites and the environmental burdens associated with nitrogen fertilisation, require further consideration.
Question: Write a study description for the study titled 'Dynamic utilization of low-molecular-weight organic substrates across a microbial growth rate gradient'.
Answer: AIM: Low-molecular-weight organic substances (LMWOSs) are at the nexus between micro-organisms, plant roots, detritus and the soil mineral matrix. The nominal oxidation state of carbon (NOSC) has been suggested as a potential parameter for modelling microbial uptake rates of LMWOSs and the efficiency of carbon incorporation into new biomass.METHODS AND RESULTS: In this study, we assessed the role of compound class and oxidation state on uptake kinetics and substrate-specific carbon use efficiency (SUE) during the growth of three model soil micro-organisms, a fungal isolate (Penicillium spinulosum) and two bacterial isolates (Paraburkholderia solitsugae, and Ralstonia pickettii). Isolates were chosen that spanned a growth rate gradient (0.046-0.316 h-1) in media containing 34 common LMWOSs at realistically low initial concentrations (25 μM each). Clustered, co-utilization of LMWOSs occurred for all three organisms. Potential trends (p < 0.05) for early utilization of more oxidized substrates were present for the two bacterial isolates (P. solitsugae and R. pickettii), but high variability (R2 < 0.15) and a small effect of NOSC indicate these relationships are not useful for prediction. The SUEs of selected substrates ranged from 0.16 to 0.99 and there was no observed relationship between NOSC and SUE.CONCLUSION: Our results do not provide compelling population-level support for NOSC as a predictive tool for either uptake kinetics or the efficiency of use of LMWOS in soil solution.SIGNIFICANCE AND IMPACT OF THE STUDY: Metabolic strategies of organisms are likely more important than chemical identity in determining LMWOS cycling in soils. Previous community-level observations may be biased towards fast-responding bacterial community members.
Question: Write a study description for the study titled 'Environmental Chemical Diethylhexyl Phthalate Alters Intestinal Microbiota Community Structure and Metabolite Profile in Mice'.
Answer: Exposure to environmental chemicals during windows of development is a potentially contributing factor in gut microbiota dysbiosis, and linked to chronic diseases and developmental disorders. We used a community-level model of microbiota metabolism to investigate the effects of diethylhexyl phthalate (DEHP), a ubiquitous plasticizer implicated in neurodevelopmental disorders, on the composition and metabolite outputs of gut microbiota in young mice. Administration of DEHP by oral gavage increased the abundance of Lachnoclostridum, while decreasing Akkermansia, Odoribacter, and Clostridium sensu stricto. Addition of DEHP to in vitro cultured cecal microbiota increased the abundance of Alistipes, Paenibacillus, and Lachnoclostridium. Untargeted metabolomics showed that DEHP broadly altered the metabolite profile in the culture. Notably, DEHP enhanced the production of p-cresol, while inhibiting butyrate synthesis. Metabolic model-guided correlation analysis indicated that the likely sources of p-cresol are Clostridium species. Our results suggest that DEHP can directly modify the microbiota to affect production of bacterial metabolites linked with neurodevelopmental disorders.
Question: Write a study description for the study titled 'Integrated metagenomic and metabolomic analyses of the effects of total flavonoids of Rhizoma Drynariae on reducing ovariectomized-induced osteoporosis by regulating gut microbiota and related metabolites.'.
Answer: TFRD has been widely used in China to treat osteoporosis (OP). However, the specific molecular mechanism of TFRD against OP has not been fully clarified. Our previous studies have also proved that TFRD could attenuate OP and the clinical equivalent dose of 67.5 mg/kg/d is the effective dose for TFRD treating OP. Therefore, this study used 67.5 mg/kg as the dosage of TFRD in combination with multi omics to investigate the mechanism of action of TFRD in the treatment of OP. The aim of this study was to further elucidate molecular mechanism of TFRD for treating OP based on metagenomic and metabolomic analyses. In this study, hematoxylin-eosin (H&E) staining, micro computed tomography (micro-CT) and bone mineral density (BMD) analysis were used to observe pharmacological effects of TFRD against ovariectomized (OVX)-induced OP. Subsequently, multiomics analysis including metagenomics, untargeted and short chain fatty acids (SCFAs) metabolomics were carried out to identify whether the anti-osteoporosis mechanism of TFRD correlated with gut microbiota and related metabolites. Our results indicate that TFRD could improve the microstructure and density of trabecular bone in OVX rats. 17 differential species, which mainly from Akkermansia, Bacteroides and Phascolarctobacterium genus, 14 related differential metabolites and acetic acid in SCFAs were significantly altered by OVX and reversed by TFRD. Furthermore, according to results of untargeted metabolomics analysis, it was found that several metabolic pathways such as phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis and so on might play an important role in TFRD against OP. In order to further study the relationship between gut microbiota and related metabolites, spearman correlation analysis was used, and showed that gut microbiota such as Akkermansia muciniphila might be closely related to several metabolites and metabolic pathways. These findings suggest that TFRD treatment could reduce the effects of OVX-induced OP by altering.
Question: Write a study description for the study titled 'Dynamic single-cell metabolomics reveals cell-cell interaction between tumor cells and macrophages'.
Answer: Single-cell metabolomics reveals cell heterogeneity and elucidates intracellular molecular mechanisms. However, general concentration measurement of metabolites can only provide a static delineation of metabolomics, lacking the metabolic activity information of biological pathways. Herein, we developed a universal system for dynamic metabolomics by stable isotope tracing at the single-cell level. This system comprises an organic mass cytometry-based single-cell metabolomic platform and an automated metabolite quantification and untargeted metabolic flux data processing platform, providing an integrated workflow for dynamic metabolomics of living single cells. As a proof-of-concept, a total of 40 labeled metabolites were tracked in single breast cancer cells, enabling the global profiling and correlation analysis of metabolic activities across various metabolic pathways, as well as flow analysis of interlaced metabolic networks. The significance of metabolic activity profiling was underscored by a 2-deoxyglucose inhibition model, demonstrating delicate metabolic alteration within single cells which cannot reflected by concentration analysis. Significantly, the system combined with a neural network model successfully enabled the metabolomic profiling of direct co-cultured tumor cells and macrophages. This revealed intricate cell-cell interaction mechanisms within the tumor microenvironment and firstly identified versatile polarization subtypes of tumor-associated macrophages based on their metabolic signatures. Importantly, these findings are in line with the renewed diversity atlas of macrophages from genome features obtained through single-cell RNA-sequencing. The developed system facilitates a comprehensive understanding and opens a new avenue of single-cell metabolomics from both static and dynamic perspectives.
Question: Write a study description for the study titled 'Metabolomic profiles in long day, before bolting, single leaf analysis, Arabidopsis thaliana'.
Answer: Metabolomic profiles in short or long day, before and after bolting, single leaf analysis, Arabidopsis thaliana
Question: Write a study description for the study titled 'Dysregulation of the 3β-Hydroxysteroid Dehydrogenase Type 2 Enzyme and Steroid Hormone Biosynthesis in Chronic Kidney Disease'.
Answer: Chronic kidney disease (CKD) presents a critical global health challenge, marked by the progressive decline of renal function. This study explores the role of the 3β-hydroxysteroid dehydrogenase type 2 enzyme (HSD3B2) and steroid hormone biosynthesis pathway in CKD pathogenesis and progression. Using an adenine-induced CKD mouse model, we conducted an untargeted metabolomic analysis of plasma samples to identify key metabolite alterations associated with CKD. Metabolic characteristics revealed significant metabolic shifts in CKD, with 61 metabolites increased and 65 metabolites decreased, highlighting the disruption in steroid hormone biosynthesis pathways influenced by HSD3B2. A detailed examination of seven key metabolites underscored the enzyme's central role. Further supported by Nephroseq and Human Protein Atlas data, HSD3B2 exhibited a strong correlation with kidney function. A drastic reduction in its expression in CKD-affected kidneys was confirmed through immunohistochemistry, Western blotting and qPCR analyses in both human and mouse tissues. Suppressed proliferation and increased apoptosis rate in HSD3B2 knocked down HK2 cells further demonstrated its significance in regulating renal pathophysiology. These findings underscore the potential of HSD3B2 as a clinical diagnostic and therapeutic target in CKD. While further studies are warranted to elucidate the mechanisms fully, our results provide valuable insights into the intricate interplay between steroid hormone biosynthesis and CKD, offering a promising avenue for precision medicine approaches and personalized treatment strategies.
Question: Write a study description for the study titled 'Osh2 mediates Candida resistance to miltefosine by regulating zymosterol transport'.
Answer: Miltefosine has been identified for its antifungal properties, yet the mechanisms underlying its action and the development of resistance remain unclear. In this study, we induced drug resistance in various Candida species through concentration gradient exposure, successfully obtaining a miltefosine-resistant strain of Candida glabrata. Whole-genome sequencing revealed a premature stop codon mutation in the OSH2 gene within the resistant strain. To further investigate the function of the Osh2, we deleted it in Candida albicans, observing a significant increase in miltefosine resistance in the knockout strain. RNA-seq and lipidomics analyses indicated that Osh2 influences the ergosterol biosynthetic pathway by regulating zymosterol transport, thereby mediating miltefosine resistance. Additionally, exogenous supplementation of zymosterol significantly enhanced the resistance of Candida to miltefosine. Further studies revealed that deletion of the ERG11 gene, a rate-limiting enzyme in the zymosterol synthesis pathway, rendered the strain highly sensitive to miltefosine, while deletion of the ERG6 gene, which catalyzes the conversion of zymosterol to fecosterol, led to miltefosine resistance. This study is the first to elucidate that the Osh2 gene mediates miltefosine resistance in Candida by regulating zymosterol transport and affecting the ergosterol biosynthetic pathway, providing new theoretical insights into the mechanism of action of miltefosine and strategies to overcome fungal resistance.
Question: Write a study description for the study titled 'Azithromycin promotes relapse by disrupting immune and metabolic networks after allogeneic stem cell transplantation'.
Answer: Administration of azithromycin after allogeneic hematopoietic stem cell transplantation for hematological malignancies has been associated with relapse in a randomized phase 3 controlled clinical trial. Studying 240 samples from patients randomized in this trial is a unique opportunity to better understand the mechanisms underlying relapse, the first cause of mortality after transplantation. We used multi-omics on patients' samples to decipher immune alterations associated with azithromycin intake and post-transplant relapsed malignancies. Azithromycin was associated with a network of altered energy metabolism pathways and immune subsets, including T cells biased toward immunomodulatory and exhausted profiles. In vitro, azithromycin exposure inhibited T cells cytotoxicity against tumor cells and impaired T cells metabolism through glycolysis inhibition, mitochondrial genes downregulation, and immunomodulatory genes upregulation, notably SOCS1. These results highlight that azithromycin directly affects immune cells that favor relapse, which raises caution about long-term use of azithromycin treatment in patients at high risk of malignancies.
Question: Write a study description for the study titled 'Altered Fecal Microbiome and Correlations of the Metabolome with Plasma Metabolites in Dairy Cows with Left Displaced Abomasum'.
Answer: Left displaced abomasum (LDA) in postpartum dairy cows contributes to significant economic losses. LDA is characterized by excessive lipolysis and insulin resistance. Although gut dysbiosis is implicated, little is known about the role of the gut microbiota in the abnormal metabolic processes of LDA. To investigate the functional links among microbiota, metabolites, and disease phenotypes in LDA, we performed liquid chromatography-tandem mass spectrometry of fecal samples from cows with LDA (n = 10) and healthy cows (n = 10) matched for parity and days in milk. Plasma marker profiling was synchronously analyzed. Compared with the healthy group, the LDA group showed increased alpha diversity and a shifted microbial community, accompanied by differences in the fecal metabolome and plasma amino acid pools. Based on integrated analysis with the plasma metabolome, eight genera and eight metabolites were associated with LDA. Akkermansia and Oscillospira abundances negatively correlated with 4-pyridoxic acid and tryptophan levels, and positively correlated with non-esterified fatty acid (NEFA) and β-hydroxybutyric acid (BHBA) in amino acid deficit, indicating pyridoxal metabolism-associated gut dysbiosis and lipolysis. The level of salicylic acid derived from microbiota catabolism was decreased in LDA, which negatively correlated with Prevotella, NEFA, and BHBA levels. Conversely, levels of lithocholic acid and taurolithocholic acid were increased in cows with LDA. Changes in branched-chain amino acids implicated novel host–microbial metabolic pathways involving lipolysis and insulin resistance in cows with LDA. Overall, these results suggest interplay between host and gut microbes contributing to LDA pathogenesis.