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: 2 hours 41 min ago

Effects of RHD gene polymorphisms on distinguishing weak D or DEL from RhD- in blood donation in a Chinese population.

Wed, 27/05/2020 - 14:39
Related Articles Effects of RHD gene polymorphisms on distinguishing weak D or DEL from RhD- in blood donation in a Chinese population. Mol Genet Genomic Med. 2019 06;7(6):e00681 Authors: Shi J, Luo Y Abstract BACKGROUND: Weak D or DEL red blood cell units may be mistyped as RhD- by current serology assays, which can lead to incompatible transfusion to RhD- recipients and further cause anti-D immunization. Molecular RHD blood group typing is a very effective method for overcoming current technical limits. The purpose of this study was to identify RHD single-nucleotide polymorphisms (SNPs) and compare the genotype prevalence among confirmed RhD- individuals in a Chinese population as well as explore effective biomarkers for current weak D or DEL detection before blood transfusion. METHODS: In the present study, 125 weak D (1, 2, 3, and 4.1) or DEL and 185 RhD- blood samples from donors detected by current standard serology were collected. Genotyping system was used to analyze the SNPs of RHD in each sample. RESULTS: Seven SNPs (rs592372, rs11485789, rs6669352, rs3118454, rs1053359, rs590787, and rs3927482) were detected in the RHD region. Rs3118454, rs1053359, rs590787, and rs3927482 showed significant differences between the weak D (1, 2, 3 and 4.1) or DEL and RhD- groups. Further combined analysis of the allelic distribution of these four SNPs revealed their higher frequencies in the RhD- group. CONCLUSION: The SNPs rs3118454, rs1053359, rs590787, and rs3927482 in RHD showed a significantly higher frequency among an RhD- Chinese population and are potential biomarkers. PMID: 30950221 [PubMed - indexed for MEDLINE]

metabolomics; +16 new citations

Tue, 26/05/2020 - 14:23
16 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 2020/05/26PubMed 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.

Application of an in vitro digestion model to study the metabolic profile changes of an herbal extract combination by UHPLC-HRMS.

Mon, 25/05/2020 - 14:11
Application of an in vitro digestion model to study the metabolic profile changes of an herbal extract combination by UHPLC-HRMS. Phytomedicine. 2020 May 01;71:153221 Authors: Thumann TA, Pferschy-Wenzig EM, Aziz-Kalbhenn H, Ammar RM, Rabini S, Moissl-Eichinger C, Bauer R Abstract BACKGROUND: STW 5 is a fixed herbal combination containing extracts from nine medicinal plants: bitter candytuft, greater celandine, garden angelica roots, lemon balm leaves, peppermint leaves, caraway fruits, licorice roots, chamomile flowers, and milk thistle fruit. STW 5 is a clinically proven treatment for functional dyspepsia and irritable bowel syndrome. PURPOSE: Using a static in vitro method, we simulated oral, gastric, and small intestinal digestion and analyzed the metabolic profile changes by UHPLC-HRMS to determine the impact of oro-gastro-intestinal digestion on STW 5 constituents. STUDY DESIGN AND METHODS: STW 5 was incubated according to the InfoGest consensus method. Samples of each digestive phase were analyzed by UHPLC-HRMS in ESI positive and negative modes. After data processing, background subtraction, and normalization, the peak areas of detectable compounds were compared to untreated reference samples and recovery ratios were calculated to monitor the metabolic profile of STW 5 during simulated digestion. RESULTS: Although the levels of some constituents were reduced, we did not observe complete degradation of any of the constituents of STW 5 upon in vitro digestion. We did not detect any new metabolites beyond increased levels of caffeic acid and liquiritigenin due to degradation of progenitor compounds. Changes observed in intestinal bioaccessibility ratios were mainly a result of isomerization, hydrolysis, protein binding, and low water solubility. CONCLUSION: The majority of STW 5 constituents are stable towards simulated in vitro digestion and can reach the colon to interact with gut microbiota if they remain unabsorbed in the upper intestinal tract. PMID: 32447246 [PubMed - as supplied by publisher]

Metabolomic profiling of beers: Combining 1H NMR spectroscopy and chemometric approaches to discriminate craft and industrial products.

Mon, 25/05/2020 - 14:11
Metabolomic profiling of beers: Combining 1H NMR spectroscopy and chemometric approaches to discriminate craft and industrial products. Food Chem. 2020 May 15;327:127025 Authors: Palmioli A, Alberici D, Ciaramelli C, Airoldi C Abstract The authentication and traceability of craft beers is an important issue for both beer consumers and producers. Reliable analytical methods able to identify and discriminate products are needed to protect the craft brew market against fraud and counterfeit. Here, 1H NMR analysis of 31 beer samples, differing for beer style and brewing method (craft or industrial) was combined with multivariate statistical analysis, following both an untargeted and a targeted approach. NMR-based analysis of beer samples was sped developing a specific protocol enabling the automatic identification and quantification of metabolites in approximately thirty seconds per spectrum. A clear discrimination was achieved by exploiting 1H NMR analysis and multivariate chemometric methods and the targeted approach identified the metabolites responsible for the segregation. Overall, this study reports an analytical approach addressing beer traceability and is the starting point for the development of a standardized protocol for the discrimination of industrial and craft beers. PMID: 32447135 [PubMed - as supplied by publisher]

Comparing alpha-cypermethrin induced dose/gender-dependent responses of lizards in hepatotoxicity and nephrotoxicity in a food chain.

Mon, 25/05/2020 - 14:11
Comparing alpha-cypermethrin induced dose/gender-dependent responses of lizards in hepatotoxicity and nephrotoxicity in a food chain. Chemosphere. 2020 May 13;256:127069 Authors: Chen L, Wang D, Zhou Z, Diao J Abstract Pesticides are proposed as one reason for the worldwide decline in the reptile. Effects of pesticides on food intake and organ toxicity could affect wildlife populations dynamics. To explore the hepatotoxicity of alpha-cypermethrin (ACP) in reptiles, we designed a tri-trophic food chain with three concentrations (0, 2, and 20 mg/kgwet weight). Although the enzymes changes were similar between male and female lizards, the significant variations in anti-oxidative enzymes' activities, lactic dehydrogenase activities and acetylcholine esterase activities in liver and kidney suggesting that oxidative stress, decreased metabolic ability and neurotoxicity on lizards. The results of hepatic metabolomics showed that ACP could affect amino acid, energy and lipid metabolism on lizards. Comparing with female lizards, there were more significant changes of metabolites in male lizards. The histopathology analysis in the liver (such as hepatic lobule congestion and hepatocyte vacuolation) and kidney (such as renal tubule necrosis and glomerulus necrosis), dose- and gender dependent changes of lesions suggested the functions of organ were damaged. In summary, the reduction of detoxification and elimination capacities of the liver and kidney showed dose/gender-dependent in lizards. PMID: 32447111 [PubMed - as supplied by publisher]

Toll-like receptor signaling induces a temporal switch towards a resolving lipid profile in monocyte-derived macrophages.

Mon, 25/05/2020 - 14:11
Toll-like receptor signaling induces a temporal switch towards a resolving lipid profile in monocyte-derived macrophages. Biochim Biophys Acta Mol Cell Biol Lipids. 2020 May 21;:158740 Authors: von Hegedus JH, Kahnt AS, Ebert R, Heijink M, Toes REM, Giera M, Ioan-Facsinay A Abstract Inflammation is a tightly regulated process. During the past decade it has become clear that the resolution of inflammation is an active process and its dysregulation can contribute to chronic inflammation. Several cells and soluble mediators, including lipid mediators, regulate the course of inflammation and its resolution. It is, however, unclear which signals and cells are involved in initiating the resolution process. Macrophages are tissue resident cells and key players in regulating tissue inflammation through secretion of soluble mediators, including lipids. We hypothesize that persistent inflammatory stimuli can initiate resolution pathways in macrophages. In this study, we detected 21 lipids in LPS-stimulated human monocyte-derived macrophages by liquid chromatography coupled to tandem mass spectrometry. Cyclooxygenase-derived Prostaglandins were observed in the first six hours of stimulation. Interestingly, a switch towards 15-lipoxygenase products, such as the pro-resolving lipid precursors 15-HEPE and 17-HDHA was observed after 24 h. The RNA and protein expression of cyclooxygenase and 15-lipoxygenase were in line with this trend. Treatment with 17-HDHA increased IL-10 production of monocyte-derived macrophages and decreased LTB4 production by neutrophils, indicating the anti-inflammatory property of this lipid. These data reveal that monocyte-derived macrophages contribute to the resolution of inflammation in time by the production of pro-resolving lipids after an initial inflammatory stimulus. PMID: 32447052 [PubMed - as supplied by publisher]

Selective inhibition of mitochondrial respiratory complexes controls the transition of microglia into a neurotoxic phenotype in situ.

Mon, 25/05/2020 - 14:11
Selective inhibition of mitochondrial respiratory complexes controls the transition of microglia into a neurotoxic phenotype in situ. Brain Behav Immun. 2020 May 21;: Authors: Chausse B, Lewen A, Poschet G, Kann O Abstract Microglia are tissue resident macrophages (innate immunity) and universal sensors of alterations in CNS physiology. In response to pathogen or damage signals, microglia feature rapid activation and can acquire different phenotypes exerting neuroprotection or neurotoxicity. Although transcriptional aspects of microglial phenotypic transitions have been described, the underlying metabolic reprogramming is widely unknown. Employing postnatal organotypic hippocampal slice cultures, we describe that microglia transformed into a mild reactive phenotype by single TLR4 stimulation with lipopolysaccharide (LPS), which was boosted into a severe neurotoxic phenotype by IFN-γ (LPS+INF-γ). The two reactive phenotypes associated with reduction of microglial homeostatic markers, increase of cytokine release (IL-6, TNF-α) as well as enhancement of tissue energy demand and lactate production. These reactive phenotypes differed in the pattern of inhibition of the respiratory chain in mitochondria, however. TLR4 stimulation induced succinate dehydrogenase (complex II) inhibition by the metabolite itaconate. By contrast, TLR4+IFN-γ receptor stimulation mainly resulted in complex IV inhibition by nitric oxide (NO) that also associated with severe oxidative stress, neuronal dysfunction and death. Notably, pharmacological depletion of microglia or treatment with itaconate resulted in effective neuroprotection reflected by well-preserved cytoarchitecture and electrical network activity, i.e., neuronal gamma oscillations (30-70 Hz) that underlie higher cognitive functions in vivo. Our findings provide in situ evidence that (i) proinflammatory microglia can substantially alter brain energy metabolism and (ii) fine-tuning of itaconate and NO metabolism determines microglial reactivity, impairment of neural network function and neurodegeneration. These data add mechanistic insights into microglial activation, with relevance to disorders featuring neuroinflammation and to drug discovery. PMID: 32446944 [PubMed - as supplied by publisher]

metabolomics; +16 new citations

Sun, 24/05/2020 - 13:50
16 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 2020/05/24PubMed 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; +24 new citations

Sat, 23/05/2020 - 13:37
24 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 2020/05/23PubMed 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

Fri, 22/05/2020 - 16:22
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 2020/05/22PubMed 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

Fri, 22/05/2020 - 13:21
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 2020/05/22PubMed 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; +35 new citations

Thu, 21/05/2020 - 16:15
35 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 2020/05/21PubMed 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; +35 new citations

Thu, 21/05/2020 - 13:15
35 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 2020/05/21PubMed 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; +30 new citations

Wed, 20/05/2020 - 15:57
30 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 2020/05/20PubMed 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; +25 new citations

Tue, 19/05/2020 - 15:46
25 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 2020/05/19PubMed 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; +25 new citations

Tue, 19/05/2020 - 12:46
25 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 2020/05/19PubMed 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.

Lizhong decoction ameliorates ulcerative colitis in mice via modulating gut microbiota and its metabolites.

Mon, 18/05/2020 - 12:42
Lizhong decoction ameliorates ulcerative colitis in mice via modulating gut microbiota and its metabolites. Appl Microbiol Biotechnol. 2020 May 17;: Authors: Zou J, Shen Y, Chen M, Zhang Z, Xiao S, Liu C, Wan Y, Yang L, Jiang S, Shang E, Qian D, Duan J Abstract Ulcerative colitis (UC), a kind of inflammatory bowel disease, is generally characterized by chronic, persistent, relapsing, and nonspecific ulceration of the bowel, which is widespread in the world. Although the pathogenesis of UC is multifactorial, growing evidence has demonstrated that gut microbiota and its metabolites are closely related to the development of UC. Lizhong decoction (LZD), a well-known classical Chinese herbal prescription, has been used to clinically treat UC for long time, but its mechanism is not clear. In this study, 16S rRNA gene sequencing combining with untargeted metabolomics profiling was used to investigate how LZD worked. Results indicated that LZD could shape the gut microbiota structure and modify metabolic profiles. The abundance of opportunistic pathogens such as Clostridium sensu stricto 1, Enterobacter, and Escherichia-Shigella correlated with intestinal inflammation markedly decreased, while the levels of beneficial bacteria including Blautia, Muribaculaceae_norank, Prevotellaceae UCG-001, and Ruminiclostridium 9 elevated in various degrees. Additionally, fecal metabolite profiles reflecting microbial activities showed that adenosine, lysoPC(18:0), glycocholic acid, and deoxycholic acid notably decreased, while cholic acid, α-linolenic acid, stearidonic acid, and L-tryptophan significantly increased after LZD treatment. Hence, based on the systematic analysis of 16S rRNA gene sequencing and metabolomics of gut flora, the results provided a novel insight that microbiota and its metabolites might be potential targets for revealing the mechanism of LZD on amelioration of UC.Key Points • The potential mechanism of LZD on the amelioration of UC was firstly investigated.• LZD could significantly shape the structure of gut microbiota.• LZD could notably modulate the fecal metabolic profiling of UC mice. Graphical abstract. PMID: 32418127 [PubMed - as supplied by publisher]

Mechanism of Huang-lian-Jie-du decoction and its effective fraction in alleviating acute ulcerative colitis in mice: Regulating arachidonic acid metabolism and glycerophospholipid metabolism.

Mon, 18/05/2020 - 12:42
Mechanism of Huang-lian-Jie-du decoction and its effective fraction in alleviating acute ulcerative colitis in mice: Regulating arachidonic acid metabolism and glycerophospholipid metabolism. J Ethnopharmacol. 2020 May 14;:112872 Authors: Yuan Z, Yang L, Zhang X, Ji P, Hua Y, Wei Y Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Huang-lian-Jie-du decoction (HLJDD) is a traditional Chinese medicine prescription for clearing away heat, purging fire and detoxifying, which can be used to treat sepsis, stroke, Alzheimer's disease and gastrointestinal diseases. Our previous studies have shown that HLJDD can effectively alleviate acute ulcerative colitis (UC) in mice, and its n-butanol fraction (HLJDD-NBA) is the effective fraction. The aim of this study is to further investigate the mechanism of HLJDD and HLJDD-NBA in relieving UC in mice from a holistic perspective. METHODS: The acute UC model of BABL/c mice was induced by 3.5% (w/v) dextran sodium sulfate drinking water. At the same time of modeling, HLJDD and HLJDD-NBA were given orally for treatment respectively. During the experiment, the clinical symptoms of mice were recorded and the physiological and biochemical indexes of mice were detected after the experiment. In addition, the plasma metabolites of mice in each group were detected and analyzed by ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry and multivariate statistical analysis method. Then, the potential target metabolic pathway of drug intervention was screened through the enrichment analysis of differential metabolites. Finally, we use molecular simulation docking technology to further explore the molecular regulatory mechanism of HLJDD and HLJDD-NBA on potential target metabolic pathways. RESULTS: HLJDD and HLJDD-NBA intervention can significantly reduce the disease activity index of UC mice, inhibit colon length shortening and pathological damage, and relieve the abnormal changes of physiological and biochemical parameters of UC mice. Moreover, HLJDD and HLJDD-NBA can significantly inhibit the metabolic dysfunction of UC mice by reversing the abnormal changes of 24 metabolites in UC mice, and the arachidonic acid metabolic pathway and glycerophospholipid metabolic pathway are the target metabolic pathways regulated by them. Further literature review and molecular simulation docking analysis showed that HLJDD and HLJDD-NBA may inhibit the disorder of arachidonic acid metabolism pathway and glycerophospholipid metabolism pathway by inhibiting COX-2 protein expression and PLA2, 5-LOX activity. CONCLUSIONS: Our experiments revealed that HLJDD and HLJDD-NBA can alleviate UC of mice by regulating arachidonic acid metabolism and glycerophospholipid metabolism, which points out the direction for further research and development of HLJDD as a new anti-ulcer drug. PMID: 32417423 [PubMed - as supplied by publisher]

Use of Single Cell -omic Technologies to Study the Gastrointestinal Tract and Diseases, From Single Cell Identities to Patient Features.

Mon, 18/05/2020 - 12:42
Use of Single Cell -omic Technologies to Study the Gastrointestinal Tract and Diseases, From Single Cell Identities to Patient Features. Gastroenterology. 2020 May 14;: Authors: Islam M, Chen B, Spraggins JM, Kelly RT, Lau KS Abstract Single cells are the building blocks of tissue systems that determine organ phenotypes, behaviors, and function. Understanding the differences between cell types and their activities might provide us with insights into normal tissue functions, development of disease, and new therapeutic strategies. Although -omic level single cell technologies are a relatively recent development that been used only in laboratory studies, these approaches might eventually be used in the clinic. We review the prospects of applying single cell genome, transcriptome, epigenome, proteome, and metabolome analyses to gastroenterology and hepatology research. Combining data from multi-omic platforms and rapid technological developments could lead to new diagnostic, prognostic, and therapeutic approaches. PMID: 32417404 [PubMed - as supplied by publisher]

Psychopharmacological effects of riparin III from Aniba riparia (Nees) Mez. (Lauraceae) supported by metabolic approach and multivariate data analysis.

Mon, 18/05/2020 - 12:42
Psychopharmacological effects of riparin III from Aniba riparia (Nees) Mez. (Lauraceae) supported by metabolic approach and multivariate data analysis. BMC Complement Med Ther. 2020 May 16;20(1):149 Authors: Golzio Dos Santos S, Fernandes Gomes I, Fernandes de Oliveira Golzio AM, Lopes Souto A, Scotti MT, Fechine Tavares J, Chavez Gutierrez SJ, Nóbrega de Almeida R, Barbosa-Filho JM, Sobral da Silva M Abstract BACKGROUND: Currently there is a high prevalence of humor disorders such as anxiety and depression throughout the world, especially concerning advanced age patients. Aniba riparia (Nees) Mez. (Lauraceae), popular known as "louro", can be found from the Amazon through Guianas until the Andes. Previous studies have already reported the isolation of alkamide-type alkaloids such as riparin III (O-methyl-N-2,6-dyhydroxy-benzoyl tyramine) which has demonstrated anxiolytic and antidepressant-like effects in high doses by intraperitoneal administration. METHODS: Experimental protocol was conducted in order to analyze the anxiolytic-like effect of riparin III at lower doses by intravenous administration to Wistar rats (Rattus norvegicus) (n = 5). The experimental approach was designed to last 15 days, divided in 3 distinct periods of five days: control, anxiogenic and treatment periods. The anxiolytic-like effect was evaluated by experimental behavior tests such as open field and elevated plus-maze test, combined with urine metabolic footprint analysis. The urine was collected daily and analyzed by 1H NMR. Generated data were statistically treated by Principal Component Analysis in order to detect patterns among the distinct periods evaluated as well as biomarkers responsible for its distinction. RESULTS: It was observed on treatment group that cortisol, biomarker related to physiological stress was reduced, indicating anxiolytic-like effect of riparin III, probably through activation of 5-HT2A receptors, which was corroborated by behavioral tests. CONCLUSION: 1H NMR urine metabolic footprint combined with multivariate data analysis have demonstrated to be an important diagnostic tool to prove the anxiolytic-like effect of riparin III in a more efficient and pragmatic way. PMID: 32416725 [PubMed - as supplied by publisher]

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