Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 1 hour 20 min ago

metabolomics; +20 new citations

7 hours 21 min ago
20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/08/15PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +33 new citations

Fri, 14/08/2020 - 21:03
33 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/08/14PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +33 new citations

Fri, 14/08/2020 - 14:57
33 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/08/14PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +20 new citations

Thu, 13/08/2020 - 14:47
20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/08/13PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +17 new citations

Wed, 12/08/2020 - 14:30
17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/08/12PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +33 new citations

Tue, 11/08/2020 - 14:10
33 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/08/11PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Metabolomics signature of the seminal plasma in men with severe oligoasthenospermia.

Mon, 10/08/2020 - 14:02
Related Articles Metabolomics signature of the seminal plasma in men with severe oligoasthenospermia. Andrology. 2020 Aug 08;: Authors: Boguenet M, Bocca C, Bouet PE, Serri O, Chupin S, Tessier L, Blanchet O, El Hachem H, Chao de la Barca JM, Reynier P, MayPanloup P Abstract BACKGROUND: Male factor is incriminated in approximately 50% of cases of infertility. The metabolomics approach has recently been used in the assessment of sperm quality and male fertility. MATERIALS AND METHODS: We analyzed the metabolomics signatures of the seminal plasma in 20 men with severe oligoasthenospermia (prewash total motile sperm count <5.106 ) (SOA) and compared it to 20 men with normal semen parameters, with a standardized approach of targeted and quantitative metabolomics using high-performance liquid chromatography, coupled with tandem mass spectrometry, and the Biocrates Absolute IDQ p180 kit. RESULTS: Among the 188 metabolites analyzed, 110 were accurately measured in the seminal plasma. A robust model discriminating the two populations (Q2(cum) = 55.2%) was obtained by OPLS-DA (orthogonal partial least-squares discriminant analysis), based on the drop in concentrations of 37 metabolites with a VIP (variable important for projection) greater than 1. Overall, in men with SOA, there was a significant decrease in: 17 phosphatidylcholines and four sphingomyelins; acylcarnitines, with free L-carnitine being the most discriminating metabolite; polyunsaturated fatty acids; six amino acids (glutamate, aspartate, methionine, tryptophan, proline and alanine); and four biogenic amines (spermine, spermidine, serotonin, alpha-aminoadipate). DISCUSSION: Our signature includes several metabolic changes with different impacts on the sperm quality: a change in phospholipids composition and the saturation of their fatty acids that is potentially linked to the deterioration of sperm membranes; a carnitine deficiency that can negatively impact the energy production via fatty acids oxidation and oxidative phosphorylation; and a decreased level of amino acids and biogenic amines that can lead to dysregulated metabolic and signaling pathways. CONCLUSION: We provide a global overview of the metabolic defects contributing to the structural and functional alteration of spermatozoa in severe oligoasthenospermia. These findings offer new insights into the pathophysiology of male factor infertility that could help to develop future specific treatments. PMID: 32770844 [PubMed - as supplied by publisher]

Air Pollution and Adverse Pregnancy and Birth Outcomes: Mediation Analysis Using Metabolomic Profiles.

Mon, 10/08/2020 - 14:02
Related Articles Air Pollution and Adverse Pregnancy and Birth Outcomes: Mediation Analysis Using Metabolomic Profiles. Curr Environ Health Rep. 2020 Aug 08;: Authors: Inoue K, Yan Q, Arah OA, Paul K, Walker DI, Jones DP, Ritz B Abstract PURPOSE OF REVIEW: Review how to use metabolomic profiling in causal mediation analysis to assess epidemiological evidence for air pollution impacts on birth outcomes. RECENT FINDINGS: Maternal exposures to air pollutants have been associated with pregnancy complications and adverse pregnancy and birth outcomes. Causal mediation analysis enables us to estimate direct and indirect effects on outcomes (i.e., effect decomposition), elucidating causal mechanisms or effect pathways. Maternal metabolites and metabolic pathways are perturbed by air pollution exposures may lead to adverse pregnancy and birth outcomes, thus they can be considered mediators in the causal pathways. Metabolomic markers have been used to explain the biological mechanisms linking air pollution and respiratory function, and of arsenic exposure and birth weight. However, mediation analysis of metabolomic markers has not been used to assess air pollution effects on adverse birth outcomes. In this article, we describe the assumptions and applications of mediation analysis using metabolomic markers that elucidate the potential mechanisms of the effects of air pollution on adverse pregnancy and birth outcomes. The hypothesis of mediation along specified pathways can be assessed within the structural causal modeling framework. For causal inferences, several assumptions that go beyond the data-including no uncontrolled confounding-need to be made to justify the effect decomposition. Nevertheless, studies that integrate metabolomic information in causal mediation analysis may greatly improve our understanding of the effects of ambient air pollution on adverse pregnancy and birth outcomes as they allow us to suggest and test hypotheses about underlying biological mechanisms in studies of pregnant women. PMID: 32770318 [PubMed - as supplied by publisher]

Integrated omics analysis reveals the alteration of gut microbe-metabolites in obese adults.

Mon, 10/08/2020 - 14:02
Related Articles Integrated omics analysis reveals the alteration of gut microbe-metabolites in obese adults. Brief Bioinform. 2020 Aug 07;: Authors: Li R, Huang X, Liang X, Su M, Lai KP, Chen J Abstract Obesity, a risk to health, is a global problem in modern society. The prevalence of obesity was approximately 13% among world's adult population. Recently, several reports suggested that the interference of gut microbiota composition and function is associated with metabolic disorders, including obesity. Gut microbiota produce a board range of metabolites involved in energy and glucose homeostasis, leading to the alteration in host metabolism. However, systematic evaluation of the relationship between gut microbiota, gut metabolite and host metabolite profiles in obese adults is still lacking. In this study, we used comparative metagenomics and metabolomics analysis to determine the gut microbiota and gut-host metabolite profiles in six normal and obese adults of Chinese origin, respectively. Following the functional and pathway analysis, we aimed to understand the possible impact of gut microbiota on the host metabolites via the change in gut metabolites. The result showed that the change in gut microbiota may result in the modulation of gut metabolites contributing to glycolysis, tricarboxylic acid cycle and homolactic fermentation. Furthermore, integrated metabolomic analysis demonstrated a possible positive correlation of dysregulated metabolites in the gut and host, including l-phenylalanine, l-tyrosine, uric acid, kynurenic acid, cholesterol sulfate and glucosamine, which were reported to contribute to metabolic disorders such as obesity and diabetes. The findings of this study provide the possible association between gut microbiota-metabolites and host metabolism in obese adults. The identified metabolite changes could serve as biomarkers for the evaluation of obesity and metabolic disorders. PMID: 32770198 [PubMed - as supplied by publisher]

COVID-19 salivary signature: diagnostic and research opportunities.

Mon, 10/08/2020 - 14:02
Related Articles COVID-19 salivary signature: diagnostic and research opportunities. J Clin Pathol. 2020 Aug 07;: Authors: Sapkota D, Søland TM, Galtung HK, Sand LP, Giannecchini S, To KKW, Mendes-Correa MC, Giglio D, Hasséus B, Braz-Silva PH Abstract The COVID-19 (caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) epidemic started in Wuhan (Hubei Province, China) in mid-December 2019 and quickly spread across the world as a pandemic. As a key to tracing the disease and to implement strategies aimed at breaking the chain of disease transmission, extensive testing for SARS-CoV-2 was suggested. Although nasopharyngeal/oropharyngeal swabs are the most commonly used biological samples for SARS-CoV-2 diagnosis, they have a number of limitations related to sample collection and healthcare personnel safety. In this context, saliva is emerging as a promising alternative to nasopharyngeal/oropharyngeal swabs for COVID-19 diagnosis and monitoring. Saliva collection, being a non-invasive approach with possibility for self-collection, circumvents to a great extent the limitations associated with the use of nasopharyngeal/oropharyngeal swabs. In addition, various salivary biomarkers including the salivary metabolomics offer a high promise to be useful for better understanding of COVID-19 and possibly in the identification of patients with various degrees of severity, including asymptomatic carriers. This review summarises the clinical and scientific basis for the potential use of saliva for COVID-19 diagnosis and disease monitoring. Additionally, we discuss saliva-based biomarkers and their potential clinical and research applications related to COVID-19. PMID: 32769214 [PubMed - as supplied by publisher]

Optimization and validation of a chiral CE-LIF method for quantitation of aspartate, glutamate and serine in murine osteocytic and osteoblastic cells.

Mon, 10/08/2020 - 14:02
Related Articles Optimization and validation of a chiral CE-LIF method for quantitation of aspartate, glutamate and serine in murine osteocytic and osteoblastic cells. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Jul 03;1152:122259 Authors: Lorenzo MP, Valiente L, Buendia I, R Gortázar A, Garcia A Abstract Asp, Glu, and D-Ser are chiral amino acids and neurotransmitters binding to the N-methyl-D-aspartate receptor (NMDA) and they participate in glutamate signalization. D-amino acids are increasingly being recognized as important signaling molecules and variations in their levels are considered a marker of different pathologies, however, there is still a lack of knowledge about the role of most of D-amino acids in living organisms such as bone cells. A method for determination of concentrations of L/D-Asp, L/D-Glu and L/D-Ser in two types of bone cell lines: murine osteocytes (MLOY4) and osteoblasts (MC3T3-E1) is presented. It is based on capillary electrophoresis coupled to laser-induced fluorescence detection in normal polarity with 4-fluoro-7-nitro-2,1,3-benzoxadiazole as derivatizing agent suitable for an Argon ion laser source. The electrolyte consists of 137.5 mM borate buffer and 12.5 mM β-cyclodextrins as chiral selectors and the separation lasts 25 min. The method was optimized and validated for specificity, sensitivity, linearity, accuracy, and precision in murine osteocytes and osteoblasts. LLOQ was 0.25 µmol L-1 for the three D-amino acids and linearity was confirmed with r > 0.995 for all D-and L-amino acids. Accuracy ranged between 81.9% and 111.7% and intra-day precision ranged between 1.8% and 10.9%. Concentrations of D- and L- Asp, Glu, and Ser are given and statistical differences between osteocytes and osteoblasts were found. The highest differences corresponded to L- and D-Glu. This method could play a fundamental role in the study of therapeutic targets in the treatment of bone diseases. PMID: 32769062 [PubMed - as supplied by publisher]

A novel approach combining metabolomics and molecular pharmacology to study the effect of Gei Herba on mouse hematopoietic function.

Mon, 10/08/2020 - 14:02
Related Articles A novel approach combining metabolomics and molecular pharmacology to study the effect of Gei Herba on mouse hematopoietic function. Biomed Pharmacother. 2020 Jul 01;129:110437 Authors: Yang S, Wang X, Duan C, Zhang J Abstract Gei Herba, Chinese named Lanbuzheng (LBZ), is a traditional Chinese medicine promotes hematopoiesis, yet the underlying mechanism for this effect remains largely unknown. In the present study, a novel approach combining LC-MS metabolomics and molecular pharmacology was developed to investigate the hematopoietic effect and mechanism of LBZ on hematopoietic dysfunction (HD) caused by cyclophosphamide (CTX) in treated mice. The results show that LBZ can reduce damage in the spleen, a result consistent with the peripheral hemogram. Fourteen potential biomarkers were identified in the spleen by metabolic profiles analysis, including 5-hydroxymethyluracil, ascorbalamic acid, adenosine 5'-monophosphate, menadiol disulfate, l-homocysteine sulfonic acid and l-carnitine. Change in biomarker levels suggest that LBZ mainly affects β-oxidation of very-long-chain fatty acids, oxidation of branched chain fatty acids and carnitine synthesis, and those metabolites produced along with related metabolic pathways are closely associated with anti-apoptosis. A molecular pharmacology approach was simultaneously developed to examine accompanying cellular signaling mechanisms. LBZ activates PI3K/Akt signaling pathways and granulocyte-colony-stimulating-factor (G-CSF)-mediated Janus kinase 2 (JAK2)/transcription 3 (STAT3), resulting in inhibiting the release of cytochrome c. Further, LBZ inhibits caspase-mediated mitochondrial-dependent apoptosis mediated by caspase-9 and caspase-3. LBZ can thus reduce CTX-induced HD via G-CSF-mediated JAK2/STAT3 signaling and PI3K/Akt mitochondrial-dependent apoptotic pathways. The present study combines metabolomic and molecular pharmacological methods to elucidate mechanisms for the protective effect of LBZ on mouse HD following CTX-induced damage. This approach may be useful for exploring mechanisms of action of other drugs. PMID: 32768939 [PubMed - as supplied by publisher]

Metabonomic analysis of hypophosphatemic laying fatigue syndrome in laying hens.

Mon, 10/08/2020 - 14:02
Related Articles Metabonomic analysis of hypophosphatemic laying fatigue syndrome in laying hens. Theriogenology. 2020 Jul 12;156:222-235 Authors: Xu D, Teng X, Guo R, Shen X, Wan M, Li G, Zhang R, Ge M Abstract Laying fatigue syndrome (LFS) is a common disease in poultry, which is characterized by low egg laying rate, increased broken and soft shell egg rate and osteoporosis, and even death of poultry. Insufficient phosphorus content in feed is one of the major causes of LFS. In this study, a total of 22-week-old Roman white shell hens were randomly divided into two groups, including control (group C) and low dietary phosphorus (group P) groups. The hens of groups C and P were fed with a full mixed diet and a mixed diet containing 0.18% available phosphorus content, respectively. At 25, 29 and 34 weeks, the production performance of hens was detected and the serum samples of hens were collected to detect the changes of serum phosphorus, calcium, osteopelectin (OPG), parathyroid hormone (PTH), estradiol (E2), tartaric acid-resistant phosphatase (TRACP) and alkaline phosphatase (ALP). The keels were removed and x-rayed. In addition, all serum samples were tested by LC-MS metabolomics. Our results showed that low dietary phosphorus decreased the production performance, phosphorus content, and E2 and OPG levels, while increased calcium and PTH levels, and ALP and TRACP activities in laying hens. The hens of group P had bent keels. Besides, small molecular metabolites in serum were enriched in 10 pathways and 17 metabolites were significantly different according to the area under the receiver operating characteristic curve (AUC) analysis. Our results showed that low phosphorus diet could induce LFS. Also, 17 metabolites detected by metabonomics can be used as biomarkers for clinical diagnosis and early warning of hypophosphatemic laying fatigue syndrome (HLFS). This study provides a scientific basis for the early prevention and treatment of HLFS. PMID: 32768871 [PubMed - as supplied by publisher]

Tri-n-butyl phosphate induced earthworm intestinal damage by influencing nutrient absorption and energy homeostasis of intestinal epithelial cells.

Mon, 10/08/2020 - 14:02
Related Articles Tri-n-butyl phosphate induced earthworm intestinal damage by influencing nutrient absorption and energy homeostasis of intestinal epithelial cells. J Hazard Mater. 2020 May 19;398:122850 Authors: Yang Y, Liu P, Li M Abstract Tri-n-butyl phosphate (TnBP) is a typical alkyl organophosphate ester that has been used for decades in various products. However, toxicity on terrestrial organisms induced by TnBP has been rarely reported though soil is a predominant sink for hydrophobic organic compounds. The objective of this study was to investigate the TnBP-induced intestinal toxicity mechanism on earthworm Eisenia fetida as well as the potential role of gut bacteria on host's health. TnBP was found to have high bioconcentrations in earthworm intestinal tract. Digestive tract degradation and digestive enzyme activities disruption associated with nutrients absorption were noticed. Using multi-omics approaches, detailed intestinal toxic mechanism of earthworms under TnBP exposure was provided. Tight junctions between small intestinal epithelial cells and osmotic equilibrium were destroyed under 10 mg/kg TnBP, leading to nutrient absorption disturbance. To satisfy the excessive energy requirements induced by TnBP, amino acids gluconeogenesis and protein degradation were detected. Moreover, TnBP significantly decreased the diversity of gut microbiota and changed their structure and function involved in hosts' health and nutrients supply. Overall, this study provides insight into the molecular mechanism of intestinal toxicity by which earthworms respond to TnBP exposure and offer important information for risk assessment of organophosphate esters on soil ecosystems. PMID: 32768812 [PubMed - as supplied by publisher]

A new perspective on the toxicity of arsenic-contaminated soil: Tandem mass tag proteomics and metabolomics in earthworms.

Mon, 10/08/2020 - 14:02
Related Articles A new perspective on the toxicity of arsenic-contaminated soil: Tandem mass tag proteomics and metabolomics in earthworms. J Hazard Mater. 2020 May 20;398:122825 Authors: Tang R, Lan P, Ding C, Wang J, Zhang T, Wang X Abstract The toxicity of low-level arsenic (As)-contaminated soil is not well understood. An integrated proteomic and metabolomic approach combined with morphological examination was used to investigate the potential biological toxicity of As-contaminated soil based on an exposure experiment with the earthworm Eisenia fetida. The results showed that the earthworm hindgut accumulated high As concentrations resulting in injury to the intestinal epithelia, chloragogenous tissues and coelom tissues. Furthermore, As-contaminated soil induced a significant increase in betaine levels and a decrease in dimethylglycine and myo-inositol levels in the earthworms, suggesting that the osmoregulatory metabolism of the earthworms may have been disturbed. The significantly altered levels of asparagine and dimethylglycine were proposed as potential biomarkers of As-contaminated soil. The upregulation of soluble calcium-binding proteins and profilin, the downregulation of sodium/potassium-transporting ATPase, and the proteins changes identified by gene ontology enrichment analysis confirmed that the earthworms suffered from osmotic stress. In addition, the significant changes in glycine-tRNA ligase activity and coelomic tissue injury revealed that As accumulation may disturb the earthworm immune system. This work provided new insight into the proteomic and metabolic toxicity of low-level As-contaminated soil ecosystems in earthworms, extended our knowledge of dual omics and highlighted the mechanisms underlying toxicity. PMID: 32768809 [PubMed - as supplied by publisher]

Effects of Acanthopanax senticosus (Rupr. & Maxim.) Harms on cerebral ischemia-reperfusion injury revealed by metabolomics and transcriptomics.

Mon, 10/08/2020 - 14:02
Related Articles Effects of Acanthopanax senticosus (Rupr. & Maxim.) Harms on cerebral ischemia-reperfusion injury revealed by metabolomics and transcriptomics. J Ethnopharmacol. 2020 Aug 05;:113212 Authors: Chen RH, Du WD, Wang Q, Li ZF, Wang DX, Yang SL, Feng YL Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral ischemia-reperfusion (CIR) injury is one of the main diseases leading to death and disability. Acanthopanax senticosus (Rupr. & Maxim.) Harms (AS), also known as Panax ginseng, has neuroprotective effects on anti-CIR injury. However, the underlying molecular mechanism of its therapeutic effects is not clear. AIM OF THE STUDY: To systematically study and explore the mechanism of Acanthopanax senticosus (Rupr. & Maxim.) Harms extract (ASE) in the treatment of CIR injury based on metabolomics and transcriptomics. MATERIALS AND METHODS: The pharmacological basis of ASE in the treatment of CIR was evaluated, and samples were used in plasma metabolomics and brain tissue transcriptomics to reveal potential biomarkers. Finally, according to online database, we analyzed biomarkers identified by the two technologies, explained reasons for the therapeutic effect of ASE, and identify therapeutic targets. RESULTS: A total of 53 differential metabolites (DMs) were identified in plasma and 3138 differentially expressed genes (DEGs) were identified in brain tissue from three groups of rats, including sham, ischemia-reperfusion (I/R), and ASE groups. Enrichment analysis showed that Nme6, Tk1, and Pold1 that are involved in the production of deoxycytidine and thymine were significantly up-regulated and Dck was significantly down-regulated by the intervention with ASE. These findings indicated that ASE participates in the pyrimidine metabolism by significantly regulating the balance between dCTP and dTTP. In addition, ASE repaired and promoted the lipid metabolism in rats, which might be due to the significant expression of Dgkz, Chat, and Gpcpd1. CONCLUSIONS: The findings of this study suggest that ASE regulates the significant changes in gene expression in metabolites pyrimidine, and lipid metabolism in CIR rats and plays an active role in the treatment of CIR injury through multiple targets and pathways. PMID: 32768643 [PubMed - as supplied by publisher]

Integrating metabolomics and network pharmacology to explore the protective effect of gross saponins of Tribulus terrestris L. fruit against ischemic stroke in rat.

Mon, 10/08/2020 - 14:02
Related Articles Integrating metabolomics and network pharmacology to explore the protective effect of gross saponins of Tribulus terrestris L. fruit against ischemic stroke in rat. J Ethnopharmacol. 2020 Aug 05;:113202 Authors: Guo W, Wang Y, Fan M, Xie S, Zhao H, Wang J, Liu Y, Xu D, Xu Y Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Tribulus terrestris L. belongs to the family Zygophyllaceae and has been widely used as a folk medicine for a long history in Asian countries. Gross saponins of Tribulus terrestris L. fruit (GSTTF) has an obvious neuroprotective effect on the treatment of ischemic stroke, but its potential therapeutic mechanisms have not been thoroughly studied. AIM OF THE STUDY: To investigate the protective effect of GSTTF against ischemic stroke in rat. MATERIALS AND METHODS: The combination of metabolomics and network pharmacology analysis was applied to investigate the protective effects of GSTTF on ischemic stroke and its putative mechanism. The related pathway of the biomarkers highlighted from metabolomics analysis was explored, then the possible targets of GSTTF were further revealed by network pharmacology analysis. Molecular docking was conducted to investigate the interaction between the active compound and target protein. RESULTS: Metabolomics analysis showed that metabolic disturbances were observed in serum for the rats in middle cerebral artery occlusion (MCAO). These MCAO-induced deviations in serum metabolism can be reversely changed by GSTTF via metabolic pathways regulation. Twenty-four proteins with the connectivity degree larger than 15 were selected by the network pharmacology analysis, which are considered as the possible therapeutic targets of the GSTTF against ischemic stroke. The results of molecular docking showed that the active compounds were capable of binding to the representative potential targets HSD11B1 and AR, respectively. And the docking mode of two compounds with the lowest binding energy to their target protein was illustrated by the ribbon binding map. CONCLUSION: The present study combines metabolomics and network pharmacology analysis to investigate the mechanism of MCAO-induced ischemic stroke and reveal the efficiency and possible mechanisms of GSTTF for ischemic stroke. Further studies on the bioactive saponin as well as their synergistic action on ischemic stroke will be conducted to better reveal the underlying mechanisms. PMID: 32768639 [PubMed - as supplied by publisher]

Sirt2 Inhibition Enhances Metabolic Fitness and Effector Functions of Tumor-Reactive T Cells.

Mon, 10/08/2020 - 14:02
Related Articles Sirt2 Inhibition Enhances Metabolic Fitness and Effector Functions of Tumor-Reactive T Cells. Cell Metab. 2020 Jul 31;: Authors: Hamaidi I, Zhang L, Kim N, Wang MH, Iclozan C, Fang B, Liu M, Koomen JM, Berglund AE, Yoder SJ, Yao J, Engelman RW, Creelan BC, Conejo-Garcia JR, Antonia SJ, Mulé JJ, Kim S Abstract Dysregulated metabolism is a key driver of maladaptive tumor-reactive T lymphocytes within the tumor microenvironment. Actionable targets that rescue the effector activity of antitumor T cells remain elusive. Here, we report that the Sirtuin-2 (Sirt2) NAD+-dependent deacetylase inhibits T cell metabolism and impairs T cell effector functions. Remarkably, upregulation of Sirt2 in human tumor-infiltrating lymphocytes (TILs) negatively correlates with response to TIL therapy in advanced non-small-cell lung cancer. Mechanistically, Sirt2 suppresses T cell metabolism by targeting key enzymes involved in glycolysis, tricarboxylic acid-cycle, fatty acid oxidation, and glutaminolysis. Accordingly, Sirt2-deficient murine T cells exhibit increased glycolysis and oxidative phosphorylation, resulting in enhanced proliferation and effector functions and subsequently exhibiting superior antitumor activity. Importantly, pharmacologic inhibition of Sirt2 endows human TILs with these superior metabolic fitness and effector functions. Our findings unveil Sirt2 as an unexpected actionable target for reprogramming T cell metabolism to augment a broad spectrum of cancer immunotherapies. PMID: 32768387 [PubMed - as supplied by publisher]

Ginseng Omics for Ginsenoside Biosynthesis.

Mon, 10/08/2020 - 14:02
Related Articles Ginseng Omics for Ginsenoside Biosynthesis. Curr Pharm Biotechnol. 2020 Aug 06;: Authors: Yin X, Hu H, Shen X, Li X, Pei J, Xu J Abstract Ginseng, also known as the king of herbs, has been regarded as an important traditional medicine for several millennia. Ginsenosides, a group of triterpenoid saponins, have been characterized as bioactive compounds of ginseng. The complexity of ginsenosides hindered ginseng research and development both in cultivation and in clinical research. Therefore, deciphering the ginsenoside biosynthesis pathway has been a focus of interest for researchers worldwide. The new emergence of biological research tools consisting of omics and bioinformatic tools or computational biology tools are the research trend in the new century. Ginseng is one of the main subjects analyzed using these new quantification tools, including tools of genomics, transcriptomics, and proteomics. Here, we review the current progress of ginseng omics research and provide results for the ginsenoside biosynthesis pathway. Organization and expression of the entire pathway, including the upstream MVA pathway, the cyclization of ginsenoside precursors, and the glycosylation process, are illustrated. Regulatory gene families such as transcriptional factors and transporters are also discussed in this review. PMID: 32767915 [PubMed - as supplied by publisher]

metabolomics; +22 new citations

Sun, 09/08/2020 - 13:47
22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/08/09PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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