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

metabolomics; +48 new citations

Wed, 17/06/2020 - 15:36
48 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 2020/06/17PubMed 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; +48 new citations

Wed, 17/06/2020 - 12:34
48 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 2020/06/17PubMed 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.

Bariatric surgery decreases oxidative stress and protein glycosylation in patients with morbid obesity.

Mon, 15/06/2020 - 12:11
Bariatric surgery decreases oxidative stress and protein glycosylation in patients with morbid obesity. Eur J Clin Invest. 2020 Jun 14;:e13320 Authors: Carmona-Maurici J, Amigó N, Cuello E, Bermúdez M, Baena-Fustegueras JA, Peinado-Onsurbe J, Pardina E, Vascular and Renal Translational Research Group, IRBLleida, Spain and Spanish Research Network for Renal Diseases (RedInRen. ISCIII) Abstract BACKGROUND: There is growing evidence that oxidative stress (OS) is a critical factor linking obesity with its associated comorbidities, such as cardiovascular diseases. AIM: To evaluate the degree of OS in people with morbid obesity and its relationship with glycoproteins, determined using 1H-NMR spectroscopy, before and after bariatric surgery (BS). METHODS: In this observational cohort study, plasma from 24 patients with BMI ≥ 40 kg/m2 (age: 21-65 years) was used to measure metabolites implicated in OS. We measured glycoprotein (GlycA, GlycB and GlycF) areas and shape factors (H/W = height/width). RESULTS: One year after BS, oxidized low-density lipoprotein had decreased by 49% (p < 0.0001), malondialdehyde by 32% (p = 0.0019) and lipoprotein (a) by 21% (p = 0.0039). The antioxidant enzymes paraoxonase-1 and catalase increased after BS (43%, p < 0.0001 and 54%, p = 0.0002, respectively). Superoxide dismutase-2 had fallen one year after BS (32%, p = 0.0052). After BS, both the glycoprotein areas and shape factors decreased by 20%-26%. These glycoproteins were significantly correlated with OS parameters. The plasma atherogenic index was 63% higher in obese individuals than one year after BS and correlated positively with glycoproteins. For the first time, we here demonstrate the relationship between OS parameters and glycoproteins in people with morbid obesity. So glycoproteins could therefore be a good indicator, together with the oxidative state to assess patient prognosis after BS. PMID: 32535887 [PubMed - as supplied by publisher]

Minimally Invasive Biospecimen Collection for Exposome Research in Children's Health.

Mon, 15/06/2020 - 12:11
Minimally Invasive Biospecimen Collection for Exposome Research in Children's Health. Curr Environ Health Rep. 2020 Jun 13;: Authors: Petrick LM, Arora M, Niedzwiecki MM Abstract PURPOSE OF REVIEW: The advent of low-volume biosampling and novel biomarker matrices offers non- or minimally invasive approaches to sampling in children. These new technologies, combined with advancements in mass spectrometry that provide high sensitivity, robust measurements of low-concentration exposures, facilitate the application of untargeted metabolomics in children's exposome research. Here, we review emerging sampling technologies for alternative biomatrices-dried capillary blood, interstitial fluid, saliva, teeth, and hair-and highlight recent applications of these samplers to drive discovery in population-based exposure research. RECENT FINDINGS: Biosampling and biomarker technologies demonstrate potential to directly measure exposures during key developmental time periods. While saliva is the most traditional of the reported biomatrices, each technology has key advantages and disadvantages. For example, hair and teeth provide retrospective analysis of past exposures, and dried capillary blood provides quantitative measurements of systemic exposures that can be more readily compared with traditional venous blood measurements. Importantly, all technologies can or have the potential to be used at home, increasing the convenience and parental support for children's biosampling. This review describes emerging sample collection technologies that hold promise for children's exposome studies. While applications in metabolomics are still limited, these novel matrices are poised to facilitate longitudinal exposome studies to discover key exposures and windows of susceptibility affecting children's health. PMID: 32535858 [PubMed - as supplied by publisher]

Serum metabolomics identifies metabolite panels that differentiate lame dairy cows from healthy ones.

Mon, 15/06/2020 - 12:11
Serum metabolomics identifies metabolite panels that differentiate lame dairy cows from healthy ones. Metabolomics. 2020 Jun 13;16(6):73 Authors: Zhang G, Zwierzchowski G, Mandal R, Wishart DS, Ametaj BN Abstract INTRODUCTION: Although much is known about lameness application of metabolomics technologies to better understanding its etiology and pathogenesis is of utmost interest. OBJECTIVES: The objective of this study was to investigate serum metabolite alterations in pre-lame, lame and post-lame dairy cows in order to identify potential screening serum metabolite biomarkers for lameness and better understand its pathobiology. METHODS: A combination of direct injection and tandem mass spectrometry (DI-MS/MS) with a reverse-phase liquid chromatography and tandem mass spectrometry (LC-MS/MS) analysis was performed in the serum of six cases of lameness and 20 healthy control cows (CON) at - 8 and - 4 weeks prepartum, at lameness diagnosis week, and at + 4 and + 8 weeks postpartum. RESULTS: Data indicated that pre-lame, lame, and post-lame cows experienced altered concentrations of multiple metabolites. It is interesting to note that throughout the 16-weeks of the study, 7 serum metabolites [e.g., diacyl-phosphatidylcholine (PC aa) C30:0, phosphatidylcholine acyl-alkyl (PC ae) C40:2, sphingomyelin (SM) (OH) C14:1, SM C18:0, isoleucine (Ile), leucine (Leu), and lysine (Lys)] differentiated CON cows from the lame ones. Furthermore, 4 metabolic pathways (i.e., Lys degradation, biotin metabolism, tryptophan (Trp) metabolism, and valine [(Val)-Leu-Ile degradation) were altered in cows with lameness during the onset and progression of the disease. CONCLUSION: Multiple metabolite and pathway alterations were identified in the serum of pre-lame, lame, and post-lame cows that through light into the pathobiology of the disease and that can be used as potential biomarker sets that can predict the risk of lameness in dairy cows. PMID: 32535675 [PubMed - as supplied by publisher]

Early-life exposure to widespread environmental toxicants and maternal-fetal health risk: A focus on metabolomic biomarkers.

Mon, 15/06/2020 - 12:11
Early-life exposure to widespread environmental toxicants and maternal-fetal health risk: A focus on metabolomic biomarkers. Sci Total Environ. 2020 Jun 03;739:139626 Authors: Dai Y, Huo X, Cheng Z, Faas MM, Xu X Abstract Prenatal exposure to widespread environmental toxicants is detrimental to maternal health and fetal development. The effects of environmental toxicants on maternal and fetal metabolic profile changes have not yet been summarized. This systematic review aims to summarize the current studies exploring the association between prenatal exposure to environmental toxicants and metabolic profile alterations in mother and fetus. We searched the MEDLINE (PubMed) electronic database for relevant literature conducted up to September 18, 2019 with some key terms. From the initial 155 articles, 15 articles met the inclusion and exclusion criteria, and consist of highly heterogeneous research methods. Seven studies assessed the effects of multiple environmental pollutants (metals, organic pollutants, nicotine, air pollutants) on the maternal urine and blood metabolomic profile; five studies evaluated the effects of arsenic, polychlorinated biphenyls (PCBs), nicotine, and ambient fine particulate matter (PM2.5) on the cord blood metabolomic profile; and one study assessed the effects of smoking exposure on the amniotic fluid metabolomic profile. The alteration of metabolic pathways in these studies mainly involve energy metabolism, hormone metabolism, oxidative stress and inflammation. No population study investigated the association between environmental toxicants and placental metabolomics. This systematic review provides evidence that prenatal exposure to a variety of environmental pollutants can affect maternal and fetal metabolomic characteristics. Integration of environmental toxicant exposure and metabolomics data in maternal-fetal samples is helpful to understand the interaction between toxicants and metabolites, so as to reveal the pathogenesis of fetal disease or diseases of fetal origin. PMID: 32535459 [PubMed - as supplied by publisher]

Exploration of chemical markers using a metabolomics strategy and machine learning to study the different origins of Ixeris denticulata (Houtt.) Stebb.

Mon, 15/06/2020 - 12:11
Exploration of chemical markers using a metabolomics strategy and machine learning to study the different origins of Ixeris denticulata (Houtt.) Stebb. Food Chem. 2020 Jun 04;330:127232 Authors: Li Y, Wang X, Li C, Huang W, Gu K, Wang Y, Yang B, Li Y Abstract As a generally edible plant, Ixeris denticulata (Houtt.) Stebb is widely distributed in China. Its medicinal value has attracted much attention in recent years. However, the chemical markers that cause quality and taste differences in I. denticulata from different regions are currently unclear. In this study, samples from 8 different origins were collected and analysed by UPLC-Q-TOF/MS. A metabolomics data processing strategy and machine learning method were established to explore the reasons for the difference in quality and taste of different origins from the perspective of chemical composition. With the established strategy, 10 characteristic chemical markers were identified that could be used to distinguish the origins of I. denticulata. The strategy proposed in this study could provide a certain basis for quality control and reasonable consumption of I. denticulata and additional food and medicinal homologous species. PMID: 32535318 [PubMed - as supplied by publisher]

Metabotyping of different soybean genotypes and distinct metabolism in their seeds and leaves.

Mon, 15/06/2020 - 12:11
Metabotyping of different soybean genotypes and distinct metabolism in their seeds and leaves. Food Chem. 2020 Jun 04;330:127198 Authors: Yun DY, Kang YG, Kim M, Kim D, Kim EH, Hong YS Abstract The metabolome of three soybean genotypes, Glycine max Hwangkeum (elite or domesticated cultivar), Glycine max Napjakong (landrace or semi-wild cultivar) and Glycine soja Dolkong (wild cultivar), were characterized in seeds and leaves using a 1H NMR-based metabolomics approach. Expression of primary and secondary metabolites were different in seeds and leaves as well as amongst soybean genotypes. Different kaempferol glycosides were observed in the leaves but not in the seeds, and quercetin derivatives were found only in G. max Napjakong and G. soja Dolkong. Moreover, epicatechin was found only in the seeds of G. max Napjakong and G. soja Dolkong. These results demonstrate distinct adaptations of different soybean genotypes to given environmental conditions. The current study, therefore, provides useful information on global metabolic compositions that might be used to develop soybean-based products through better understanding of the metabolic phenotypes of existing soybean genotypes. PMID: 32535313 [PubMed - as supplied by publisher]

`Untargeted metabolomics study and pro-apoptotic properties of B-norcholesteryl benzimidazole compounds in ovarian cancer SKOV3 cells.

Mon, 15/06/2020 - 12:11
`Untargeted metabolomics study and pro-apoptotic properties of B-norcholesteryl benzimidazole compounds in ovarian cancer SKOV3 cells. J Steroid Biochem Mol Biol. 2020 Jun 11;:105709 Authors: Gan C, Huang X, Wu Y, Zhan J, Zhang X, Liu Q, Huang Y Abstract The current study aims to evaluate the antiproliferative activity of B-norcholesteryl benzimidazole compounds in human ovarian cancer cells (SKOV3). Our experimental data indicates that the tested compounds can induce apoptosis in SKOV3 cells, block S-phase growth, and decrease mitochondrial membrane potential. Western blot results showed that B-norcholesteryl benzimidazole compounds (1 and 2) induced apoptosis in SKOV3 cells via activation of the mitochondrial signaling pathway. Following SKOV3 cells treatment with compounds 1 and 2, the cell metabolism was assessed using the UHPLC-QE-MS (Ultra High Performance Liquid Chromatography-Q Exactive Orbitrap- Mass Spectrometry) non-target metabolomics analysis method. The results showed 10 metabolic pathways that mediated the effects of compound 1, including arginine and proline metabolism; alanine, aspartate, and glutamate metabolism; histidine metabolism; D-glutamine and D-glutamate metabolism; cysteine and methionine metabolism; aminoacyl-tRNA biosynthesis; purine metabolism; Glutathione metabolism; D-Arginine and D-ornithine metabolism; and Nitrogen metabolism. From the perspective of metabolomics, compound 1 inhibits intracellular metabolism, protein synthesis, and slows down energy metabolism in SKOV3 cells. These changes result in the inhibition of proliferation and signal transduction, abrogate invasive and metastatic properties, and induce apoptosis, thus, exerting anti-tumor effects. Application of compound 2 altered activation of metabolic pathways in SKOV3 cells. The main metabolic pathways involved were glycerophospholipid metabolism; arginine and proline metabolism; purine metabolism; glycine, serine, and threonine metabolism; and ether lipid metabolism. The metabolic pathway with the greatest impact and the deepest enrichment was the glycerophospholipid metabolism. In conclusion, compound 2 inhibits proliferation of SKOV3 cells by interfering with glycerate metabolism, which plays a major role in regulation of cell membrane structure and function. Additionally, compound 2 can inhibit the invasion and metastasis of SKOV3 cells and induce apoptosis via interfering with the metabolism of arginine and proline. PMID: 32535031 [PubMed - as supplied by publisher]

Possible metabolic switch between environmental and pathogenic Pseudomonas aeruginosa strains: 1H NMR based metabolomics study.

Sun, 14/06/2020 - 12:01
Possible metabolic switch between environmental and pathogenic Pseudomonas aeruginosa strains: 1H NMR based metabolomics study. J Pharm Biomed Anal. 2020 May 25;188:113369 Authors: Mielko KA, Jabłoński SJ, Wojtowicz W, Milczewska J, Sands D, Łukaszewicz M, Młynarz P Abstract The study aimed to assess whether Pseudomonas aeruginosa strains from different sources can be distinguished by the metabolomic fingerprint and to check whether antibiotic susceptibility distinctions are available through metabolomic analysis. 1H NMR spectroscopy analysis of the bacteria metabolites was performed. Twenty-nine strains were tested (18 isolated form cystic fibrosis patients and 11 environmental). Thirty-one metabolites were identified, 12 were up-regulated in strains from CF patients, while 2 were higher level in strains from the environment. Changed carbohydrate catabolic metabolism and the metabolic shift toward the utilization of amino acids is suggested in strains from CF patients. PMID: 32534405 [PubMed - as supplied by publisher]

TiO2 nanoparticles induced sugar impairments and metabolic pathway shift towards amino acid metabolism in wheat.

Sun, 14/06/2020 - 12:01
TiO2 nanoparticles induced sugar impairments and metabolic pathway shift towards amino acid metabolism in wheat. J Hazard Mater. 2020 May 28;399:122982 Authors: Silva S, Ribeiro TP, Santos C, Pinto DCGA, Silva AMS Abstract TiO2-nanoparticles (TiO2-NP) have the potential to impair plant development. Nevertheless, the metabolic processes behind the physiological responses to TiO2-NP are still far from being fully understood. In this study, Triticum aestivum plants were exposed for 21 days to different concentrations (0; 5; 50; 150 mg L-1) of TiO2-NP (P25). After treatment, the metabolite profiles of roots and leaves were analysed. The content of >70 % of the identified metabolites changed in response to P25 and the impact on metabolic pathways increased with TiO2-NP dose, with leaves showing higher alterations. Roots up-regulated monosaccharides, azelaic acid, and γ-aminobutanoic acid and triggered the tyrosine metabolism, whereas leaves up-regulated the metabolisms of reserve sugars and tocopherol, and the phenylalanine and tryptophan pathways. Both organs (mainly leaves) up-regulated the aspartate family pathway together with serine, alanine and valine metabolisms and the glycerolipids' biosynthesis. In addition, the citrate and glyoxylate metabolisms were down-regulated in both organs (highest dose). Sugar biosynthesis breakdown, due to photosynthetic disturbances, shifted the cell metabolism to use amino acids as an alternative energy source, and both ROS and sugars worked as signalling molecules activating organ dependent antioxidant responses. Concluding, these NP-pollutants severely impact multiple crop metabolic pathways and may ultimately compromise plant performance. PMID: 32534391 [PubMed - as supplied by publisher]

A UPLC-Q-TOF/MS-based plasma metabolomics approach reveals the mechanism of Compound Kushen Injection-based intervention against non-small cell lung cancer in Lewis tumor-bearing mice.

Sun, 14/06/2020 - 12:01
A UPLC-Q-TOF/MS-based plasma metabolomics approach reveals the mechanism of Compound Kushen Injection-based intervention against non-small cell lung cancer in Lewis tumor-bearing mice. Phytomedicine. 2020 Jun 02;76:153259 Authors: Wu H, Wang L, Zhan X, Wang B, Wu J, Zhou A Abstract BACKGROUND: Compound Kushen Injection (CKI), a well-known Chinese Medicine preparation, has been used to treat non-small cell lung cancer (NSCLC) for more than 15 years, and its clinical curative effect is considered to be beneficial. HYPOTHESIS/PURPOSE: This study was designed to evaluate the effects and underlying mechanisms of CKI against NSCLC using an ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based plasma metabolomics approach. METHODS: 4',6-diamidino-2-phenylindole (DAPI) staining and 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) dye reduction assay were employed to assess apoptosis and the viability of A549 cells with and without CKI treatment. The weight/volume of Lewis lung carcinoma (LLC) sarcomas and histopathological examinations were used to evaluate the anti-tumor effects of CKI against NSCLC. A UPLC-Q-TOF/MS method combined with multivariate data analysis was developed to characterize metabolomic fingerprinting and to screen functional biomarkers that are linked to the CKI treatment of LLC mice, and then metabolic pathway analysis was used to investigate the therapeutic mechanism of CKI. RESULTS: DAPI staining and MTT dye reduction assays indicated that CKI-induced apoptosis and inhibited the proliferation of A549 cells, respectively, in a concentration-dependent manner. The sarcoma volumes and weights in LLC tumor-bearing mice in CKI-dosed groups were significantly lower than those in a model group, which was treated with physiological saline. Histopathological analysis of sections of sarcomas and left pulmonary lobes indicated that CKI exerts an ameliorative effect against LLC. Fourteen functional biomarkers that are related to the therapeutic effects of CKI on LLC were screened and identified using a metabolomics study. Analysis of metabolic pathways revealed that the therapeutic effects of CKI on LLC mainly involved glycerophospholipid metabolism, amino acid metabolism and sphingolipid metabolism. As glycerophospholipid metabolism is a crucial feature of cancer-specific metabolism, the enzymes that are involved in 1-acyl-sn-glycero-3-phosphoinositol biosynthesis were further evaluated. Western blotting results indicated that CKI modulated the abnormal biosynthesis pathway of 1-acyl-sn-glycero-3-phosphoinositol by activation of cytidine diphosphate-diacylglycerol-inositol 3-phosphatidyltransferase (CDIPT) and cytosolic phospholipase A2 (cPLA2), and by inhibition of lysophosphatidic acid acyltransferase gamma (AGPAT3). CONCLUSION: This study demonstrated that CKI has a favorable anti-tumor effect and that a UPLC-Q-TOF/MS-based metabolomics method in conjunction with further verifications at the biochemical level is a promising approach for investigating its underlying mechanisms. PMID: 32534358 [PubMed - as supplied by publisher]

Anoectochilus roxburghii polysaccharide prevents carbon tetrachloride-induced liver injury in mice by metabolomic analysis.

Sun, 14/06/2020 - 12:01
Anoectochilus roxburghii polysaccharide prevents carbon tetrachloride-induced liver injury in mice by metabolomic analysis. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Jun 02;1152:122202 Authors: Zeng B, Su M, Chen Q, Chang Q, Wang W, Li H Abstract Anoectochilus roxburghii (Wall.) Lindl, a traditional Chinese medicine, is used for the effective treatment of liver disease in China. Anoectochilus roxburghii polysaccharide (ARPT) is an important constituent of Anoectochilus roxburghii. ARPT exerts a hepatoprotective effect and contributes directly to the therapeutic benefit of Anoectochilus roxburghii. However, the hepatoprotective mechanism of ARPT requires further elucidation. The present study was designed to assess the effects and underlying mechanism of ARPT when used to pretreat carbon tetrachloride (CCl4)-induced liver injury in mice. Mice were randomly divided into three groups: control group (no ARPT treatment or liver injury), model group (liver injury induced with CCl4), and the ARPT group (ARPT pretreatment followed by liver injury). A metabolomic method, based on liquid chromatography combined with mass spectrometry (LC-MS) and pattern recognition analysis, was applied. The data were analyzed with principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), to determine differentiating metabolites in the serum and liver tissue between the experimental groups. The PCA and OPLS-DA scores plots of the serum and liver tissue samples based on the LC-MS data showed a clear separation between the control and liver injury model group, while the ARPT-treated group showed a trend of close with the control. There were eleven metabolites [PS(O-18:0/0:0), phosphocholine, phenylalanine, hippuric acid, α-ketoisovaleric acid, metyrosine, leucinic acid, ketoleucine, Cer(d18:1/19:0), α-kamlolenic acid, and 4-formyl indole] were identified as candidate biomarkers in the serum samples, eight such metabolites (valine, phosphohydroxypyruvic acid, phosphocholine, ornithine, indole, xanthine, uridine, and glucose 6-phosphate) were found in the liver tissue samples, and one metabolite (phosphocholine) was observed in both the serum and liver tissue samples. These endogenous metabolites are considered to be in response to the hepatoprotective effects of ARPT and are involved in amino acid metabolism, lipid metabolism, gut bacteria metabolism, energy metabolism, and the methylation pathway. These findings suggest that ARPT mitigates the metabolic effect of CCl4-induced hepatotoxicity in mice by affecting at least five different pathways. LC-MS-based metabolomics provides a powerful approach for identifying potential biomarkers and for elucidating the protective mechanisms of traditional Chinese medicines against disease. PMID: 32534261 [PubMed - as supplied by publisher]

GC-MS based comparative metabolomic analysis of MCF-7 and MDA-MB-231 cancer cells treated with Tamoxifen and/or Paclitaxel.

Sun, 14/06/2020 - 12:01
GC-MS based comparative metabolomic analysis of MCF-7 and MDA-MB-231 cancer cells treated with Tamoxifen and/or Paclitaxel. J Proteomics. 2020 Jun 10;:103875 Authors: Semreen MH, Alniss H, Cacciatore S, El-Awady R, Mousa M, Almehdi AM, El-Huneidi W, Zerbini L, Soares NC Abstract Breast cancer cells MCF-7 and MDA-MB-231 were treated with Tamoxifen (5 μM) or Paclitaxel (1 μM) or with a combination of the two drugs. Herein, we have employed gas chromatography coupled with mass spectroscopy to identify metabolic changes occurring as response to different drug treatments. We report the identification of sixty-one metabolites and overall the two studied cell lines showed a distinct metabolomic profile from each other. Further data analysis indicates that a total of 30 metabolites were significantly differentially abundant in MCF-7 drug-treated cells, most of the metabolic changes occurred when cells were treated with either Tamoxifen (15) or Paclitaxel (25). On the other side, a total of 31 metabolites were significantly differentially abundant in MDA-MB-31 cells with drug treatment. Similarly, to MCF-7 most of the metabolic changes occurred when cells were treated with either Tamoxifen (19) or Paclitaxel (20). In conclusion, this report demonstrates that Tamoxifen and/or Paclitaxel treatment have a pronounced effect on the main metabolic pathways in both breast cancer (BC) cell lines (MCF-7 and MDA-MB231), which could be used as a foundation for future investigations to understand the possible effect of these drugs on different metabolic pathways. SIGNIFICANCE: Metabolic profiling of cancer cells is a promising tool in tumor diagnosis, biomarker discovery and drug treatment protocols, since cancer cells exhibit altered metabolism when compared to normal cells. Although numerous studies have reported the use of various OMICs applications to investigate breast cancer cells, very few of these have performed thorough screening of metabolites in such cells. Our investigation highlights the first study to characterize MCF7 and MDA-MB-231 cancer cells treated with Tamoxifen and/or Paclitaxel and to identify the affected metabolic pathways. Such findings might play an important role in revealing the molecular bases of the underlying mechanism of action of these two frontline anti-breast cancer drugs. PMID: 32534214 [PubMed - as supplied by publisher]

Effect of traditional Chinese medicine formula GeGen decoction on primary dysmenorrhea: A randomized controlled trial study.

Sun, 14/06/2020 - 12:01
Effect of traditional Chinese medicine formula GeGen decoction on primary dysmenorrhea: A randomized controlled trial study. J Ethnopharmacol. 2020 Jun 10;:113053 Authors: Chai C, Hong F, Yan Y, Yang L, Zong H, Wang C, Liu Z, Yu B Abstract ETHNOPHARMACOLOGICAL RELEVANCE: GeGen Decoction, a well-known Chinese herbal formula, is widely used in China and other Asian countries to treat gynecological diseases, including primary dysmenorrhea. Pharmacological studies have confirmed that GeGen Decoction is able to inhibit spasmodic contractions of the uterus in vivo and in vitro. AIM OF THE STUDY: The objective of this study is to examine the efficacy and safety of GeGen Decoction on primary dysmenorrheic patients. METHODS: This was a randomized, double-blinded, placebo-controlled trial. GeGen Decoction or placebo was administered a week before the expected start of each cycle for three consecutive menstrual periods. Between-group differences in pain intensity were detected by visual analogue scale (VAS). In addition, serum levels of arginine vasopressin (AVP) and estrogen (E) were examined by enzyme-linked immunosorbent assay. Metabolomic analysis was further used to evaluate the influence of GeGen Decoction on the metabolomics of primary dysmenorrheic patients. RESULTS: A total of 71 primary dysmenorrheic women were recruited and 30 participants met the criteria were randomized into GeGen Decoction or placebo group. After three consecutive menstrual cycles' treatment, the VAS score of the GeGen Decoction group was significantly lower than that of the placebo group. Both serum levels of AVP and E decreased after GeGen Decoction administration, while the placebo seemed to have little effect on either of the index. Moreover, after GeGen Decoction treatment, seven important metabolites were identified by metabolomic analysis compared to the placebo group. No abnormalities in blood biochemical and routine physical examination pre and post GeGen Decoction intervention were observed. CONCLUSIONS: GeGen Decoction can remarkably relieve the severity of menstrual pain without obvious adverse effects. Its therapeutic effect on primary dysmenorrhea might be related to the regulation of pituitary hypothalamic ovarian hormones, and interfering with the metabolic change. PMID: 32534120 [PubMed - as supplied by publisher]

Metabolomic study of disease progression in scrapie prion infected mice; validation of a novel method for brain metabolite extraction.

Sun, 14/06/2020 - 12:01
Related Articles Metabolomic study of disease progression in scrapie prion infected mice; validation of a novel method for brain metabolite extraction. Metabolomics. 2020 Jun 12;16(6):72 Authors: Fu ZL, Mercier P, Eskandari-Sedighi G, Yang J, Westaway D, Sykes BD Abstract INTRODUCTION: Prion disease is a form of neurodegenerative disease caused by the misfolding and aggregation of cellular prion protein (PrPC). The neurotoxicity of the misfolded form of prion protein, PrPSc still remains understudied. Here we try to investigate this issue using a metabolomics approach. OBJECTIVES: The intention was to identify and quantify the small-in-size and water-soluble metabolites extracted from mice brains infected with the Rocky Mountain Laboratory isolate of mouse-adapted scrapie prions (RML) and track changes in these metabolites during disease evolution. METHODS: A total of 73 mice were inoculated with RML prions or normal brain homogenate control; brains were harvested at 30, 60, 90, 120 and 150 days post-inoculation (dpi). We devised a high-efficiency metabolite extraction method and used nuclear magnetic resonance spectroscopy to identify and quantify 50 metabolites in the brain extracts. Data were analyzed using multivariate approach. RESULTS: Brain metabolome profiles of RML infected animals displayed continuous changes throughout the course of disease. Among the analyzed metabolites, the most noteworthy changes included increases in myo-inositol and glutamine as well as decreases in 4-aminobutyrate, acetate, aspartate and taurine. CONCLUSION: We report a novel metabolite extraction method for lipid-rich tissue. As all the major metabolites are identifiable and quantifiable by magnetic resonance spectroscopy, this study suggests that tracking of neurochemical profiles could be effective in monitoring the progression of neurodegenerative diseases and useful for assessing the efficacy of candidate therapeutics. PMID: 32533504 [PubMed - as supplied by publisher]

Metabolic reprogramming related to whole-chromosome instability in models for Hürthle cell carcinoma.

Sun, 14/06/2020 - 12:01
Related Articles Metabolic reprogramming related to whole-chromosome instability in models for Hürthle cell carcinoma. Sci Rep. 2020 Jun 12;10(1):9578 Authors: Addie RD, Kostidis S, Corver WE, Oosting J, Aminzadeh-Gohari S, Feichtinger RG, Kofler B, Aydemirli MD, Giera M, Morreau H Abstract Hürthle cell carcinoma (HCC) is a recurrent subtype of non-medullary thyroid cancer. HCC is characterized by profound whole-chromosome instability (w-CIN), resulting in a near-homozygous genome (NHG), a phenomenon recently attributed to reactive oxygen species (ROS) generated during mitosis by malfunctioning mitochondria. We studied shared metabolic traits during standard and glucose-depleted cell culture in thyroid cancer cell lines (TCCLs), with or without a NHG, using quantitative analysis of extra and intracellular metabolites and ROS production following inhibition of complex III with antimycin A. We found that the XTC.UC1 and FTC-236 cell lines (both NHG) are functionally impaired in complex I and produce significantly more superoxide radicals than SW579 and BHP 2-7 (non-NHG) after challenge with antimycin A. FTC-236 showed the lowest levels of glutathione and SOD2. XTC.UC1 and FTC-236 both exhibited reduced glycolytic activity and utilization of alternative sources to meet energy demands. Both cell lines also shared low levels of α-ketoglutarate and high levels of creatine, phosphocreatine, uridine diphosphate-N-acetylglucosamine, pyruvate and acetylcarnitine. Furthermore, the metabolism of XTC.UC1 was skewed towards the de novo synthesis of aspartate, an effect that persisted even in glucose-free media, pointing to reductive carboxylation. Our data suggests that metabolic reprogramming and a subtle balance between ROS generation and scavenging/conversion of intermediates may be involved in ROS-induced w-CIN in HCC and possibly also in rare cases of follicular thyroid cancer showing a NHG. PMID: 32533088 [PubMed - as supplied by publisher]

The zoonotic pathogen Leptospira interrogans mitigates environmental stress through cyclic-di-GMP-controlled biofilm production.

Sun, 14/06/2020 - 12:01
Related Articles The zoonotic pathogen Leptospira interrogans mitigates environmental stress through cyclic-di-GMP-controlled biofilm production. NPJ Biofilms Microbiomes. 2020 Jun 12;6(1):24 Authors: Thibeaux R, Soupé-Gilbert ME, Kainiu M, Girault D, Bierque E, Fernandes J, Bähre H, Douyère A, Eskenazi N, Vinh J, Picardeau M, Goarant C Abstract The zoonotic bacterium Leptospira interrogans is the aetiological agent of leptospirosis, a re-emerging infectious disease that is a growing public health concern. Most human cases of leptospirosis result from environmental infection. Biofilm formation and its contribution to the persistence of virulent leptospires in the environment or in the host have scarcely been addressed. Here, we examined spatial and time-domain changes in biofilm production by L. interrogans. Our observations showed that biofilm formation in L. interrogans is a highly dynamic process and leads to a polarized architecture. We notably found that the biofilm matrix is composed of extracellular DNA, which enhances the biofilm's cohesiveness. By studying L. interrogans mutants with defective diguanylate cyclase and phosphodiesterase genes, we show that biofilm production is regulated by intracellular levels of bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) and underpins the bacterium's ability to withstand a wide variety of simulated environmental stresses. Our present results show how the c-di-GMP pathway regulates biofilm formation by L. interrogans, provide insights into the environmental persistence of L. interrogans and, more generally, highlight leptospirosis as an environment-borne threat to human health. PMID: 32532998 [PubMed - as supplied by publisher]

metabolomics; +26 new citations

Sat, 13/06/2020 - 14:54
26 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 2020/06/13PubMed 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; +30 new citations

Fri, 12/06/2020 - 14:40
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 2020/06/12PubMed 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.

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