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

Ectomycorrhizal fungi induce systemic resistance against insects on a non-mycorrhizal plant in a CERK1-dependent manner.

Sun, 31/05/2020 - 12:13
Ectomycorrhizal fungi induce systemic resistance against insects on a non-mycorrhizal plant in a CERK1-dependent manner. New Phytol. 2020 May 30;: Authors: Vishwanathan K, Zienkiewicz K, Liu Y, Janz D, Feussner I, Polle A, Haney CH Abstract Below-ground microbes can induce systemic resistance (ISR) against foliar pests and pathogens on diverse plant hosts. The prevalence of ISR among plant-microbe-pest systems raises the question of host specificity in microbial induction of ISR. To test whether ISR is limited by plant host range, we tested the ISR-inducing ectomycorrhizal fungus Laccaria bicolor on the non-mycorrhizal plant Arabidopsis thaliana. We used the cabbage looper Trichoplusia ni and bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (Pto) as readouts for ISR on Arabidopsis. We found that root inoculation with L. bicolor triggered ISR against T. ni and induced systemic susceptibility (ISS) against the bacterial pathogen Pto. We found that L. bicolor-triggered ISR against T. ni was dependent on jasmonic acid signaling and salicylic acid biosynthesis and signaling. Heat-killed L. bicolor and chitin were sufficient to trigger ISR against T. ni and ISS against Pto. The chitin receptor CERK1 was necessary for L. bicolor-mediated effects on systemic immunity. Collectively our findings suggest that some ISR responses might not require intimate symbiotic association, but rather might be the result of root perception of conserved microbial signals. PMID: 32473606 [PubMed - as supplied by publisher]

Metabolomics in the Development and Progression of rheumatoid arthritis: A Systematic Review.

Sun, 31/05/2020 - 12:13
Metabolomics in the Development and Progression of rheumatoid arthritis: A Systematic Review. Joint Bone Spine. 2020 May 27;: Authors: Li C, Chen B, Fang Z, Leng YF, Wang DW, Chen FQ, Xiao X, Sun ZL Abstract OBJECTIVE: A systematic review and analysis of data from several rheumatoid arthritis metabolomics studies attempts to determine which metabolites can be used as potential biomarkers for the diagnosis of rheumatoid arthritis and to explore the pathogenesis of rheumatoid arthritis. METHODS: We searched all the subject-related documents published by EMBASE, PubMed, Web of Science, and Cochrane Library from the database to the September 2019 publication. Two researchers independently screened the literature and extracted the data. QUADOMICS tool was used to assess the quality of studies included in this systematic review. RESULTS: A total of 10 studies met the inclusion criteria of systematic review, including 502 patients with Rheumatoid arthritis and 373 healthy people. Among them, the biological samples utilized for metabolomic analysis include: serum (n = 8), urine (n = 1) and synovial fluid(n = 1). Some metabolites play an important role in rheumatoid arthritis: glucose, lactic acid, citric acid, leucine, methionine, isoleucine, valine, phenylalanine, threonine, serine, proline, glutamate, histidine, alanine, cholesterol, glycerol, ribose. CONCLUSIONS: Metabolomics provides important new opportunities for further research in rheumatoid arthritis and is expected to elucidate the pathogenesis of rheumatoid arthritis that has not been fully understood before. PMID: 32473419 [PubMed - as supplied by publisher]

STAT5 is required for lipid breakdown and beta-adrenergic responsiveness of brown adipose tissue.

Sun, 31/05/2020 - 12:13
STAT5 is required for lipid breakdown and beta-adrenergic responsiveness of brown adipose tissue. Mol Metab. 2020 May 27;:101026 Authors: Kaltenecker D, Spirk K, Ruge F, Grebien F, Herling M, Rupprecht A, Kenner L, Pohl EE, Mueller KM, Moriggl R Abstract OBJECTIVE: Increasing energy expenditure through activation of brown adipose tissue (BAT) thermogenesis is an attractive approach to counteract obesity. Thus, it is essential to understand the molecular mechanisms that control BAT functions. Until now several members of the Janus kinase (JAK) - signal transducer and activator of transcription (STAT) pathway have been implicated to be relevant for BAT physiology. Yet, whether the STAT family member STAT5 is important for the thermogenic property of adipose tissues is unknown. Here, we investigate the role of STAT5 in thermogenic fat. METHODS: Using mice that harbour an adipocyte-specific deletion of Stat5a/b alleles, we performed metabolic and molecular analyses. RESULTS: We found that STAT5 is necessary for acute cold-induced temperature maintenance and the induction of lipid mobilization in BAT following β3-adrenergic stimulation. Moreover, mitochondrial respiration of primary differentiated brown adipocytes lacking STAT5 was diminished. Increased sensitivity to cold stress upon STAT5 deficiency was associated with reduced expression of thermogenic markers including uncoupling protein 1 (UCP1), while decreased stimulated lipolysis was linked to decreased protein kinase A (PKA) activity. In addition, brown remodeling of white adipose tissue was diminished following chronic β3-adrenergic stimulation, which was accompanied by a decrease in mitochondrial performance. CONCLUSION: We conclude that STAT5 is essential for the functionality and the β-adrenergic responsiveness of thermogenic adipose tissue. PMID: 32473405 [PubMed - as supplied by publisher]

Transcriptome and metabolome integration analysis of mud crab Scylla paramamosain challenged to Vibrio parahaemolyticus infection.

Sun, 31/05/2020 - 12:13
Transcriptome and metabolome integration analysis of mud crab Scylla paramamosain challenged to Vibrio parahaemolyticus infection. Fish Shellfish Immunol. 2020 May 27;: Authors: Kong T, Lin S, Ren X, Li S, Gong Y Abstract Vibrio parahaemolyticus (V. parahaemolyticus) is a common pathogen for marine crustacean, which causes severe illnesses in aquatic animals. Therefore, it is meaningful to explore the mechanism during V. parahaemolyticus infection. In this study, to investigate the immune responses of mud crab Scylla paramamosain (S. paramamosain) to V. parahaemolyticus, we established the metabolic and transcriptional profiles of mud crab hemocytes challenged with V. parahaemolyticus. The results indicated that V. parahaemolyticus infection could induce a series of metabolism alterations at both metabolome and transcriptome levels, including biosynthesis of amino acids and Aminoacyl-tRNA, Purine and pyrimidine metabolism, TCA cycle and glutamine metabolism. In this context, through the integration of metabolomics and transcriptomics, our study provided a more comprehensive understanding of the biological process in mud crab against pathogen infection. PMID: 32473364 [PubMed - as supplied by publisher]

Metabolomics Analysis of the Effect of Hydrogen-Rich Water on Myocardial Ischemia-Reperfusion Injury in Rats.

Sun, 31/05/2020 - 12:13
Related Articles Metabolomics Analysis of the Effect of Hydrogen-Rich Water on Myocardial Ischemia-Reperfusion Injury in Rats. J Bioenerg Biomembr. 2020 May 29;: Authors: Li L, Liu T, Liu L, Zhang Z, Li S, Zhang Z, Zhou Y, Liu F Abstract To investigate the effect of hydrogen-rich water on myocardial tissue metabolism in a myocardial ischemia-reperfusion injury (MIRI) rat model. Twelve rats were randomly divided into a hydrogen-rich water group and a control group of size 6 each. After the heart was removed, it was fixed in the Langendorff device, and the heart was perfused with 37 °C perfusion solution pre-balanced with oxygen. The control group was perfused with Kreb's-Ringers (K-R) solution, and the hydrogen-rich water group was perfused with K-R solution + hydrogen-rich water. Liquid Chromatograph Mass Spectrometer (LC-MS) analysis platform was used for metabolomics research. Principle component analysis (PCA), partial least squares discriminant analysis (PLS-DA), orthogonal partial least squares discriminant analysis (OPLS-DA), Variable importance in projection (VIP) value of OPLS-DA model (threshold value ≥1) were employed with independent sample T Test (p < 0.05) to find differentially expressed metabolites, and screen for differential metabolic pathways. VIP (OPLS-DA) analysis was performed with T test, and the metabolites of the control group and the hydrogen-rich water group were significantly different, and the glycerophospholipid metabolism was screened. Seven myocardial ischemia-reperfusion injury (MIRI)-related signaling pathways were identified, including glycerophospholipid metabolism, glycosylphosphatidylinositol (GPI) anchored biosynthesis, and purine metabolism, as well as 10 biomarkers such as phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine. Hydrogen-rich water regulates the metabolic imbalance that could change MIRI myocardial tissue metabolism, and alleviate ischemia-reperfusion injury in isolated hearts of rats through multiple signaling pathways. PMID: 32472432 [PubMed - as supplied by publisher]

Plasma oxalate: comparison of methodologies.

Sun, 31/05/2020 - 12:13
Related Articles Plasma oxalate: comparison of methodologies. Urolithiasis. 2020 May 29;: Authors: Stokes F, Acquaviva-Bourdain C, Hoppe B, Lieske JC, Lindner E, Toulson G, Vaz FM, Rumsby G Abstract Measurement of oxalate in the blood is essential for monitoring primary hyperoxaluria patients with progressive renal impairment and on dialysis prior to transplantation. As no external quality assurance scheme is available for this analyte, we conducted a sample exchange scheme between six laboratories specifically involved with the investigation of primary hyperoxaluria to compare results. The methodologies compared were gas chromatography/mass spectrometry (GCMS), ion chromatography with mass spectrometry (ICMS), and enzymatic methods using oxalate oxidase and spectrophotometry. Although individual laboratories performed well in terms of reproducibility and linearity, there was poor agreement (absolute values) between centres as illustrated by a longer-term comparison of patient results from two of the participating laboratories. This situation was only partly related to differences in calibration and mainly reflected the lower recoveries seen with the ultrafiltration of samples. These findings lead us to conclude that longitudinal monitoring of primary hyperoxaluria patients with deteriorating kidney function should be performed by a single consistent laboratory and the methodology used should always be defined. In addition, plasma oxalate concentrations reported in registry studies and those associated with the risk of systemic oxalosis in published studies need to be interpreted in light of the methodology used. A reference method and external quality assurance scheme for plasma oxalate analysis would be beneficial. PMID: 32472220 [PubMed - as supplied by publisher]

Redox controls metabolic robustness in the gas-fermenting acetogen Clostridium autoethanogenum.

Sun, 31/05/2020 - 12:13
Related Articles Redox controls metabolic robustness in the gas-fermenting acetogen Clostridium autoethanogenum. Proc Natl Acad Sci U S A. 2020 May 29;: Authors: Mahamkali V, Valgepea K, de Souza Pinto Lemgruber R, Plan M, Tappel R, Köpke M, Simpson SD, Nielsen LK, Marcellin E Abstract Living biological systems display a fascinating ability to self-organize their metabolism. This ability ultimately determines the metabolic robustness that is fundamental to controlling cellular behavior. However, fluctuations in metabolism can affect cellular homeostasis through transient oscillations. For example, yeast cultures exhibit rhythmic oscillatory behavior in high cell-density continuous cultures. Oscillatory behavior provides a unique opportunity for quantitating the robustness of metabolism, as cells respond to changes by inherently compromising metabolic efficiency. Here, we quantify the limits of metabolic robustness in self-oscillating autotrophic continuous cultures of the gas-fermenting acetogen Clostridium autoethanogenum Online gas analysis and high-resolution temporal metabolomics showed oscillations in gas uptake rates and extracellular byproducts synchronized with biomass levels. The data show initial growth on CO, followed by growth on CO and H2 Growth on CO and H2 results in an accelerated growth phase, after which a downcycle is observed in synchrony with a loss in H2 uptake. Intriguingly, oscillations are not linked to translational control, as no differences were observed in protein expression during oscillations. Intracellular metabolomics analysis revealed decreasing levels of redox ratios in synchrony with the cycles. We then developed a thermodynamic metabolic flux analysis model to investigate whether regulation in acetogens is controlled at the thermodynamic level. We used endo- and exo-metabolomics data to show that the thermodynamic driving force of critical reactions collapsed as H2 uptake is lost. The oscillations are coordinated with redox. The data indicate that metabolic oscillations in acetogen gas fermentation are controlled at the thermodynamic level. PMID: 32471945 [PubMed - as supplied by publisher]

Serum Metabolome Changes in Relation to Prothrombotic State Induced by Combined Oral Contraceptives with Drospirenone and Ethinylestradiol.

Sun, 31/05/2020 - 12:13
Related Articles Serum Metabolome Changes in Relation to Prothrombotic State Induced by Combined Oral Contraceptives with Drospirenone and Ethinylestradiol. OMICS. 2020 May 29;: Authors: Swanepoel AC, Bester J, Emmerson O, Soma P, Beukes D, van Reenen M, Loots DT, du Preez I Abstract The association between hypercoagulability and use of drospirenone (DRSP) and ethinylestradiol (EE) containing combined oral contraceptives (COCs) is an important clinical concern. We have previously reported that the two formulations of DRSP combined with EE (namely, DRSP/20EE and DRSP/30EE) bring about a prothrombotic state in hemostatic traits of female users. We report here the serum metabolomic changes in the same study cohort in relation to the attendant prothrombotic state induced by COC use, thus offering new insights on the underlying biochemical mechanisms contributing to the altered coagulatory profile with COC use. A total of 78 healthy women participated in this study and were grouped as follows: control group not using oral contraceptives (n = 25), DRSP/20EE group (n = 27), and DRSP/30EE group (n = 26). Untargeted metabolomics revealed changes in amino acid concentrations, particularly a decrease in glycine and an increase in both cysteine and lanthionine in the serum, accompanied by variations in oxidative stress markers in the COC users compared with the controls. Of importance, this study is the first to link specific amino acid variations, serum metabolites, and the oxidative metabolic profile with DRSP/EE use. These molecular changes could be linked to specific biophysical coagulatory alterations observed in the same individuals. These new findings lend evidence on the metabolomic substrates of the prothrombotic state associated with COC use in women and informs future personalized/precision medicine research. Moreover, we underscore the importance of an interdisciplinary approach to evaluate venous thrombotic risk associated with COC use. PMID: 32471328 [PubMed - as supplied by publisher]

A Translational In Vivo and In Vitro Metabolomic Study Reveals Altered Metabolic Pathways in Red Blood Cells of Type 2 Diabetes.

Sun, 31/05/2020 - 12:13
Related Articles A Translational In Vivo and In Vitro Metabolomic Study Reveals Altered Metabolic Pathways in Red Blood Cells of Type 2 Diabetes. J Clin Med. 2020 May 27;9(6): Authors: Palomino-Schätzlein M, Lamas-Domingo R, Ciudin A, Gutiérrez-Carcedo P, Marés R, Aparicio-Gómez C, Hernández C, Simó R, Herance JR Abstract Clinical parameters used in type 2 diabetes mellitus (T2D) diagnosis and monitoring such as glycosylated haemoglobin (HbA1c) are often unable to capture important information related to diabetic control and chronic complications. In order to search for additional biomarkers, we performed a pilot study comparing T2D patients with healthy controls matched by age, gender, and weight. By using 1H-nuclear magnetic resonance (NMR) based metabolomics profiling of red blood cells (RBCs), we found that the metabolic signature of RBCs in T2D subjects differed significantly from non-diabetic controls. Affected metabolites included glutathione, 2,3-bisphophoglycerate, inosinic acid, lactate, 6-phosphogluconate, creatine and adenosine triphosphate (ATP) and several amino acids such as leucine, glycine, alanine, lysine, aspartate, phenylalanine and tyrosine. These results were validated by an independent cohort of T2D and control patients. An analysis of the pathways in which these metabolites were involved showed that energetic and redox metabolism in RBCs were altered in T2D, as well as metabolites transported by RBCs. Taken together, our results revealed that the metabolic profile of RBCs can discriminate healthy controls from T2D patients. Further research is needed to determine whether metabolic fingerprint in RBC could be useful to complement the information obtained from HbA1c and glycemic variability as well as its potential role in the diabetes management. PMID: 32471219 [PubMed - as supplied by publisher]

Metabolomic Fingerprinting of Potato Cultivars Differing in Susceptibility to Spongospora subterranea f. sp. subterranea Root Infection.

Sun, 31/05/2020 - 12:13
Related Articles Metabolomic Fingerprinting of Potato Cultivars Differing in Susceptibility to Spongospora subterranea f. sp. subterranea Root Infection. Int J Mol Sci. 2020 May 27;21(11): Authors: Lekota M, Modisane KJ, Apostolides Z, van der Waals JE Abstract Plants defend themselves from pathogens by producing bioactive defense chemicals. The biochemical mechanisms relating to quantitative resistance of potato to root infection by Spongospora subterranea f. sp. subterranea (Sss) are, however, not understood, and are not efficiently utilized in potato breeding programs. Untargeted metabolomics using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to elucidate the biochemical mechanisms of susceptibility to Sss root infection. Potato roots and root exudate metabolic profiles of five tolerant cultivars were compared with those of five susceptible cultivars, following Sss inoculation, to identify tolerance-related metabolites. Comparison of the relative metabolite abundance of tolerant versus susceptible cultivars revealed contrasting responses to Sss infection. Metabolites belonging to amino acids, organic acids, fatty acids, phenolics, and sugars, as well as well-known cell wall thickening compounds were putatively identified and were especially abundant in the tolerant cultivars relative to the susceptible cultivars. Metabolites known to activate plant secondary defense metabolism were significantly increased in the tolerant cultivars compared to susceptible cultivars following Sss inoculation. Root-exuded compounds belonging to the chemical class of phenolics were also found in abundance in the tolerant cultivars compared to susceptible cultivars. This study illustrated that Sss infection of potato roots leads to differential expression of metabolites in tolerant and susceptible potato cultivars. PMID: 32471154 [PubMed - as supplied by publisher]

Progression-Dependent Altered Metabolism in Osteosarcoma Resulting in Different Nutrient Source Dependencies.

Sun, 31/05/2020 - 12:13
Related Articles Progression-Dependent Altered Metabolism in Osteosarcoma Resulting in Different Nutrient Source Dependencies. Cancers (Basel). 2020 May 27;12(6): Authors: Fritsche-Guenther R, Gloaguen Y, Kirchner M, Mertins P, Tunn PU, Kirwan JA Abstract Osteosarcoma (OS) is a primary malignant bone tumor and OS metastases are mostly found in the lung. The limited understanding of the biology of metastatic processes in OS limits the ability for effective treatment. Alterations to the metabolome and its transformation during metastasis aids the understanding of the mechanism and provides information on treatment and prognosis. The current study intended to identify metabolic alterations during OS progression by using a targeted gas chromatography mass spectrometry approach. Using a female OS cell line model, malignant and metastatic cells increased their energy metabolism compared to benign OS cells. The metastatic cell line showed a faster metabolic flux compared to the malignant cell line, leading to reduced metabolite pools. However, inhibiting both glycolysis and glutaminolysis resulted in a reduced proliferation. In contrast, malignant but non-metastatic OS cells showed a resistance to glycolytic inhibition but a strong dependency on glutamine as an energy source. Our in vivo metabolic approach hinted at a potential sex-dependent metabolic alteration in OS patients with lung metastases (LM), although this will require validation with larger sample sizes. In line with the in vitro results, we found that female LM patients showed a decreased central carbon metabolism compared to metastases from male patients. PMID: 32471029 [PubMed - as supplied by publisher]

metabolomics; +40 new citations

Sat, 30/05/2020 - 15:05
40 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 2020/05/30PubMed 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; +40 new citations

Sat, 30/05/2020 - 12:05
40 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 2020/05/30PubMed 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; +18 new citations

Fri, 29/05/2020 - 14:56
18 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 2020/05/29PubMed 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

Thu, 28/05/2020 - 14:52
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 2020/05/28PubMed 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.

Metabolomic-/Lipidomic-based Analysis of Plasma to Diagnose Hepatocellular Ballooning in Patients with Nonalcoholic Fatty Liver Disease: A Multicenter Study.

Wed, 27/05/2020 - 14:39
Related Articles Metabolomic-/Lipidomic-based Analysis of Plasma to Diagnose Hepatocellular Ballooning in Patients with Nonalcoholic Fatty Liver Disease: A Multicenter Study. Hepatol Res. 2020 May 26;: Authors: Ogawa Y, Kobayashi T, Honda Y, Kessoku T, Tomeno W, Imajo K, Nakahara T, Oeda S, Nagaoki Y, Amano Y, Ando T, Hirayama M, Isono O, Kamiguchi H, Nagabukuro H, Ogawa S, Satomi Y, Saigusa Y, Takahashi H, Hyogo H, Yoneda M, Saito S, Yamanaka T, Aishima S, Eguchi Y, Kage M, Chayama K, Nakajima A Abstract AIM: Liver biopsy is still required for the diagnosis of hepatocellular ballooning and inflammation, which are important histological feature of nonalcoholic steatohepatitis (NASH). We conducted this multicenter, cross-sectional study to identify novel blood markers for the diagnosis of hepatocellular ballooning. METHODS: We enrolled 176 patients, and 132 patients proven by liver biopsy as having NAFLD were classified as non-ballooning (ballooning grade 0) (n = 83) or ballooning (ballooning grade 1 and 2) (n = 49) by a central pathology review. We performed gas chromatography-mass spectrometry, hydrophilic interaction liquid chromatography tandem mass spectrometry, and lipidomics with plasma. RESULTS: As correlates of hepatocellular ballooning, among the clinical parameters, serum type IV collagen 7S correlated the most significantly with the ballooning grade (correlation coefficient [CC] = 0.463; P < 0.001). Among the metabolic-/lipidomic-markers, phosphatidylcholine (PC)(aa-44:8) correlated the most significantly with the ballooning grade (CC = 0.394; P < 0.001). The area under the receiver operating characteristic curve of type IV collagen 7S, choline, and lysophosphatidylethanolamine (LPE) (e-18:2), was 0.846 (95% confidence interval: 0.772-0.919). CONCLUSIONS: Plasma levels of PC were positively correlated, and those of lysophosphatidylcholine and LPE were negatively correlated with hepatocellular ballooning in NAFLD patients. These noninvasive metabolic-/lipidomic-based plasma tests might be useful to distinguish between cases of NAFLD with and without hepatocellular ballooning. PMID: 32455496 [PubMed - as supplied by publisher]

An unbiased lipidomics approach identifies key lipid molecules as potential therapeutic targets of Dohongsamul-tang against non-alcoholic fatty liver diseases in a mouse model of obesity.

Wed, 27/05/2020 - 14:39
Related Articles An unbiased lipidomics approach identifies key lipid molecules as potential therapeutic targets of Dohongsamul-tang against non-alcoholic fatty liver diseases in a mouse model of obesity. J Ethnopharmacol. 2020 May 23;:112999 Authors: Park SH, Lee JE, Lee SM, Lee J, Seo CS, Hwang GS, Jung J Abstract ETHNOPHARMACOLOGICAL RELEVANCE: . Dohongsamul-tang (DST) is a traditional herbal formula used to promote the blood circulation and inhibit inflammation, and also widely has been used in the treatment of patients with chronic liver diseases in Korea and China. AIM OF THE STUDY: . This study aimed to investigate the effect of DST on regulation of lipid metabolism of chronic liver diseases in mouse model of non-alcoholic fatty liver diseases (NAFLD). MATERIALS AND METHODS: . In this study, we evaluated the effect of DST on high-fat and high-cholesterol diet (HFHC, 40% fat and 1% cholesterol)-induced NAFLD, and applied unbiased lipidomics using ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF MS) coupled with multivariate analysis. RESULTS: . DST improved hepatic morphology and reduced levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). In addition, DST inhibited hepatic lipid accumulation through the downregulation of C/EBPα, PPARγ, and pAMPK. To further elucidate the effect of DST on hepatic lipid metabolism, we applied UPLC/Q-TOF MS-based lipidomics. The score plots of partial least squares-discriminant analysis (PLS-DA) showed that DST changed the lipid metabolic pattern of high-fat and high-cholesterol diet (HFHC) mice. Twenty-two lipid metabolites were selected as biomarkers regulated by DST and pathway analysis revealed that sphingolipid metabolism and glycerophospholipid metabolism were associated with the effect of DST on NAFLD. Among the 22 selected biomarkers, 14 were phospholipids, and DST significantly reversed the increased expression of lysophospholipase 3 (LYPLA3) and neuropathy target esterase (NTE), which are key enzymes in glycerophospholipid metabolism. Given that alterations in sphingolipids and phospholipids can have effects on apoptosis and insulin resistance (IR), we subsequently investigated changes in the expression of apoptosis-related proteins, including Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl2), and IR-related markers after DST treatment. We accordingly found that the ratio of Bax to Bcl-2 expression, a maker of apoptosis, was also elevated in HFHC mice and reduced by DST treatment. In addition, DST enhanced hepatic insulin signaling by upregulating the expression of insulin receptor substrate 1 (IRS-1) and phospho-protein kinase B (pAKT), and oral glucose tolerance test (OGTT) analysis indicated that this herbal preparation also ameliorated systemic IR. CONCLUSIONS: . This study suggested that DST might have an effect on NAFLD by regulating the metabolism of lipids such as phospholipids and sphingolipids and demonstrated that lipidomic profiling is useful to investigate the therapeutic effects of herbal decoctions from traditional Korean and Chinese medicine. PMID: 32454173 [PubMed - as supplied by publisher]

Metabolomics Reveals Altered Hepatic Bile Acids, Gut Microbiome Metabolites, and Cell Membrane Lipids Associated with Marginal Vitamin A Deficiency in a Mongolian Gerbil Model.

Wed, 27/05/2020 - 14:39
Related Articles Metabolomics Reveals Altered Hepatic Bile Acids, Gut Microbiome Metabolites, and Cell Membrane Lipids Associated with Marginal Vitamin A Deficiency in a Mongolian Gerbil Model. Mol Nutr Food Res. 2020 May 26;:e1901319 Authors: La Frano MR, Brito A, Johnson CM, Wilhelmson B, Gannon B, Fanter RK, Pedersen TL, Tanumihardjo SA, Newman JW Abstract SCOPE: This study was designed to provide a broad evaluation of the impacts of vitamin A (VA) deficiency on hepatic metabolism in a gerbil model. METHODS AND RESULTS: After 28d of VA depletion, male Mongolian gerbils (Meriones unguiculatus) were randomly assigned to experimental diets for 28 d. Groups were fed a white maize-based diet with ∼50 μL cottonseed oil vehicle either alone (VA-, n = 10) or containing 40 μg retinyl acetate (VA+, n = 10) for 28 d. Liver retinol was measured by high-performance liquid chromatography (HPLC). Primary metabolomics, aminomics, lipidomics, bile acids, oxylipins, ceramides and endocannabinoids were determined in post-mortem liver samples by liquid chromatography-mass spectrometry (LC-MS). RESULTS: Liver retinol was lower (p < 0.001) in the VA- versus VA+ group, with concentrations indicating marginal VA deficiency. A total of 300 metabolites were identified. Marginal VA deficiency was associated with lower bile acids, trimethylamine N-oxide, and a variety of acyl carnitines, phospholipids and sphingomyelins (p < 0.05). Components of DNA, including purine deoxyribonucleosides, deoxyguanosine, the nucleoside cytidine, and the uracil derivative N-carbomoyl-beta-alanine (p < 0.05), were differentially altered. CONCLUSIONS: Hepatic metabolomics in a marginally VA deficient gerbil model revealed alterations in markers of the gut microbiome, fatty acid and nucleotide metabolism, and cellular structure and signaling. This article is protected by copyright. All rights reserved. PMID: 32453876 [PubMed - as supplied by publisher]

Human-stimulated oocyte extract induces genetic and mitochondrial reprogramming of mesenchymal stromal cells.

Wed, 27/05/2020 - 14:39
Related Articles Human-stimulated oocyte extract induces genetic and mitochondrial reprogramming of mesenchymal stromal cells. PLoS One. 2020;15(5):e0232759 Authors: El-Gammal Z, AlOkda A, Ali SS, Reda A, Magdeldin S, Mansour R, El-Badri N Abstract SUMMARY: Reprogramming autologous adult cells to pluripotent cells allows for relatively safe cell replacement therapy. This can be achieved by nuclear transfer, cell fusion, or induced pluripotent stem cell technology However, the epigenetic memory of the cell is considered as a great challenge facing the complete reprograming of cells by these methods. Introducing oocyte-specific factors into differentiated cells may present a promising approach by mimicking cellular reprogramming during fertilization. METHODS: Human bone marrow mesenchymal stromal cells (hBM-MSCs) were cultured with different concentrations of human metaphase II (M II) oocyte extract (0.1, 1, 5, 10, 30 ng/μl). Reprogramming was assessed at various exposure times (1, 4, 7 days). Cells were tested for their proliferation rate, morphological changes, expression of pluripotency markers, expression of mesenchymal to epithelial transition markers, and mitochondrial rejuvenation. (mitochondrial localization, morphological changes, bioenergetics, transmembrane potential, and levels of reactive oxygen species, ROS). RESULTS: Treatment of human BM-MSCs with 10 ng/μl oocyte extract resulted in increased cell proliferation, which was associated with the upregulation of the pluripotency genes OCT-4, NANOG, and SOX-2 and a concomitant downregulation of mesenchymal-specific genes. MSCs exhibited small, immature round mitochondria with few swollen cristae localized proximal to the cell nucleus. This was accompanied by morphological cell changes, a metabolic shift towards oxidative phosphorylation, a high mitochondrial membrane potential, and increased ROS production. CONCLUSION: These data show that treatment with 10 ng/μl human MII-phase oocyte extract induced genetic and mitochondrial reprogramming of human BM-MSCs to a more embryonic phenotype. PMID: 32453737 [PubMed - as supplied by publisher]

The key points in the pre-analytical procedures of blood and urine samples in metabolomics studies.

Wed, 27/05/2020 - 14:39
Related Articles The key points in the pre-analytical procedures of blood and urine samples in metabolomics studies. Metabolomics. 2020 May 25;16(6):68 Authors: Bi H, Guo Z, Jia X, Liu H, Ma L, Xue L Abstract BACKGROUND: Metabolomics provides measurement of numerous metabolites in human samples, which can be a useful tool in clinical research. Blood and urine are regarded as preferred subjects of study because of their minimally invasive collection and simple preprocessing methods. Adhering to standard operating procedures is an essential factor in ensuring excellent sample quality and reliable results. AIM OF REVIEW: In this review, we summarize the studies about the impacts of various preprocessing factors on metabolomics studies involving clinical blood and urine samples in order to provide guidance for sample collection and preprocessing. KEY SCIENTIFIC CONCEPTS OF REVIEW: Clinical information is important for sample grouping and data analysis which deserves attention before sample collection. Plasma and serum as well as urine samples are appropriate for metabolomics analysis. Collection tubes, hemolysis, delay at room temperature, and freeze-thaw cycles may affect metabolic profiles of blood samples. Collection time, time between sampling and examination, contamination, normalization strategies, and storage conditions may alter analysis results of urine samples. Taking these collection and preprocessing factors into account, this review provides suggestions of standard sample preprocessing. PMID: 32451742 [PubMed - in process]

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