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Related Articles APOE2 orchestrated differences in transcriptomic and lipidomic profiles of postmortem AD brain. Alzheimers Res Ther. 2019 12 30;11(1):113 Authors: Lefterov I, Wolfe CM, Fitz NF, Nam KN, Letronne F, Biedrzycki RJ, Kofler J, Han X, Wang J, Schug J, Koldamova R Abstract BACKGROUND: The application of advanced sequencing technologies and improved mass-spectrometry platforms revealed significant changes in gene expression and lipids in Alzheimer's disease (AD) brain. The results so far have prompted further research using "multi-omics" approaches. These approaches become particularly relevant, considering the inheritance of APOEε4 allele as a major genetic risk factor of AD, disease protective effect of APOEε2 allele, and a major role of APOE in brain lipid metabolism. METHODS: Postmortem brain samples from inferior parietal lobule genotyped as APOEε2/c (APOEε2/carriers), APOEε3/3, and APOEε4/c (APOEε4/carriers), age- and gender-matched, were used to reveal APOE allele-associated changes in transcriptomes and lipidomes. Differential gene expression and co-expression network analyses were applied to identify up- and downregulated Gene Ontology (GO) terms and pathways for correlation to lipidomics data. RESULTS: Significantly affected GO terms and pathways were determined based on the comparisons of APOEε2/c datasets to those of APOEε3/3 and APOEε4/c brain samples. The analysis of lists of genes in highly correlated network modules and of those differentially expressed demonstrated significant enrichment in GO terms associated with genes involved in intracellular proteasomal and lysosomal degradation of proteins, protein aggregates and organelles, ER stress, and response to unfolded protein, as well as mitochondrial function, electron transport, and ATP synthesis. Small nucleolar RNA coding units important for posttranscriptional modification of mRNA and therefore translation and protein synthesis were upregulated in APOEε2/c brain samples compared to both APOEε3/3 and APOEε4/c. The analysis of lipidomics datasets revealed significant changes in ten major lipid classes (exclusively a decrease in APOEε4/c samples), most notably non-bilayer-forming phosphatidylethanolamine and phosphatidic acid, as well as mitochondrial membrane-forming lipids. CONCLUSIONS: The results of this study, despite the advanced stage of AD, point to the significant differences in postmortem brain transcriptomes and lipidomes, suggesting APOE allele associated differences in pathogenic mechanisms. Correlations within and between lipidomes and transcriptomes indicate coordinated effects of changes in the proteasomal system and autophagy-canonical and selective, facilitating intracellular degradation, protein entry into ER, response to ER stress, nucleolar modifications of mRNA, and likely myelination in APOEε2/c brains. Additional research and a better knowledge of the molecular mechanisms of proteostasis in the early stages of AD are required to develop more effective diagnostic approaches and eventually efficient therapeutic strategies. PMID: 31888770 [PubMed - indexed for MEDLINE]

Related Articles One-carbon metabolism supplementation improves outcome after stroke in aged male MTHFR-deficient mice. Neurobiol Dis. 2019 12;132:104613 Authors: Jadavji NM, Mosnier H, Kelly E, Lawrence K, Cruickshank S, Stacey S, McCall A, Dhatt S, Arning E, Bottiglieri T, Smith PD Abstract The prevalence of stroke increases with age and the ability to absorb all nutrients from our diets decreases with age. Nutrition is a modifiable risk factor for stroke, which is a leading cause of death and disability in world-wide. Deficiencies in one‑carbon metabolism, including in methyltetrahydrofolate reductase (MTHFR), have been linked to increased risk of stroke. The Mthfr+/- mice mouse model mimic the phenotype of the MTHFR677C➔T polymorphism, such as elevated levels of homocystine. Using this mouse model, the aim of this study was to investigate the impact of dietary supplementation with 5-methylTHF, vitamin B12, and choline after ischemic stroke. Male Mthfr+/- and wildtype littermate control mice were aged (~1.5-year-old) and were placed on control diet (CD) 4-weeks prior to sensorimotor cortex damage using photothrombosis (PT), a model for ischemic stroke. Post-operatively, one group of Mthfr+/- and wildtype littermate mice were placed on 5-methylTHF, vitamin B12, and choline supplemented diet (SD). Four weeks after PT and SD motor function was assessed using the accelerating rotarod, forepaw asymmetry, and ladder beam walking tasks. Total homocysteine and cysteine levels were measured in blood. Brain tissue was processed to assess lesion volume and investigate biochemical and molecular changes. After PT and SD, Mthfr+/- mice were able to stay on the accelerating rotarod longer and used their impaired forepaw to explore more when compared to CD animals. Furthermore, total homocysteine levels in plasma and lesion volume were reduced in Mthfr+/+ and Mthfr+/- SD mice. Within the damage site, there were reduced levels of apoptotic cell death and increased neuroprotective cellular response in the brains of SD treated Mthfr+/- mice. This study reveals a critical role for one‑carbon supplementation, with 5-methylTHF, vitamin B12, and choline, in supporting improvement after ischemic stroke damage. PMID: 31525435 [PubMed - indexed for MEDLINE]

Related Articles Generation of a multiplex mutagenesis population via pooled CRISPR-Cas9 in soya bean. Plant Biotechnol J. 2020 03;18(3):721-731 Authors: Bai M, Yuan J, Kuang H, Gong P, Li S, Zhang Z, Liu B, Sun J, Yang M, Yang L, Wang D, Song S, Guan Y Abstract The output of genetic mutant screenings in soya bean [Glycine max (L.) Merr.] has been limited by its paleopolypoid genome. CRISPR-Cas9 can generate multiplex mutants in crops with complex genomes. Nevertheless, the transformation efficiency of soya bean remains low and, hence, remains the major obstacle in the application of CRISPR-Cas9 as a mutant screening tool. Here, we report a pooled CRISPR-Cas9 platform to generate soya bean multiplex mutagenesis populations. We optimized the key steps in the screening protocol, including vector construction, sgRNA assessment, pooled transformation, sgRNA identification and gene editing verification. We constructed 70 CRISPR-Cas9 vectors to target 102 candidate genes and their paralogs which were subjected to pooled transformation in 16 batches. A population consisting of 407 T0 lines was obtained containing all sgRNAs at an average mutagenesis frequency of 59.2%, including 35.6% lines carrying multiplex mutations. The mutation frequency in the T1 progeny could be increased further despite obtaining a transgenic chimera. In this population, we characterized gmric1/gmric2 double mutants with increased nodule numbers and gmrdn1-1/1-2/1-3 triple mutant lines with decreased nodulation. Our study provides an advanced strategy for the generation of a targeted multiplex mutant population to overcome the gene redundancy problem in soya bean as well as in other major crops. PMID: 31452351 [PubMed - indexed for MEDLINE]

Related Articles T-cell bispecific antibodies in node-positive breast cancer: novel therapeutic avenue for MHC class I loss variants. Ann Oncol. 2019 06 01;30(6):934-944 Authors: Messaoudene M, Mourikis TP, Michels J, Fu Y, Bonvalet M, Lacroix-Trikki M, Routy B, Fluckiger A, Rusakiewicz S, Roberti MP, Cotteret S, Flament C, Poirier-Colame V, Jacquelot N, Ghiringhelli F, Caignard A, Eggermont AMM, Kroemer G, Marabelle A, Arnedos M, Vicier C, Dogan S, Jaulin F, Sammut SJ, Cope W, Caldas C, Delaloge S, McGranahan N, André F, Zitvogel L Abstract BACKGROUND: Tumor-infiltrating lymphocytes (TILs) represent a prognostic factor for survival in primary breast cancer (BC). Nonetheless, neoepitope load and TILs cytolytic activity are modest in BC, compromising the efficacy of immune-activating antibodies, which do not yet compete against immunogenic chemotherapy. PATIENTS AND METHODS: We analyzed by functional flow cytometry the immune dynamics of primary and metastatic axillary nodes [metastatic lymph nodes (mLN)] in early BC (EBC) after exposure to T-cell bispecific antibodies (TCB) bridging CD3ε and human epidermal growth factor receptor 2 (HER2) or Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 (CEACAM5), before and after chemotherapy. Human leukocyte antigen (HLA) class I loss was assessed by whole exome sequencing and immunohistochemistry. One hundred primary BC, 64 surrounding 'healthy tissue' and 24 mLN-related parameters were analyzed. RESULTS: HLA loss of heterozygosity was observed in EBC, at a clonal and subclonal level and was associated with regulatory T cells and T-cell immunoglobulin and mucin-domain-3 expression restraining the immuno-stimulatory effects of neoadjuvant chemotherapy. TCB bridging CD3ε and HER2 or CEACAM5 could bypass major histocompatibility complex (MHC) class I loss, partially rescuing T-cell functions in mLN. CONCLUSION: TCB should be developed in BC to circumvent low MHC/peptide complexes. PMID: 30924846 [PubMed - indexed for MEDLINE]

Related Articles Chemical Tagging in Mass Spectrometry for Systems Biology. Anal Chem. 2019 01 02;91(1):109-125 Authors: Huang T, Armbruster MR, Coulton JB, Edwards JL PMID: 30392353 [PubMed - indexed for MEDLINE]

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 2020/08/06PubMed 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.

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 2020/08/05PubMed 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.

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 2020/08/05PubMed 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.

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/08/04PubMed 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.

Lipidomics in Non-alcoholic Fatty Liver Disease: Exploring Serum Lipids as Biomarkers for Pediatric NAFLD. J Pediatr Gastroenterol Nutr. 2020 Jul 30;: Authors: Draijer LG, Froon-Torenstra D, van Weeghel M, Vaz FM, Bohte AE, Holleboom AG, Benninga MA, Koot BGP Abstract OBJECTIVES: Disturbances in lipid metabolism play an important role in the pathogenesis of Non-alcoholic Fatty Liver Disease (NAFLD). Using lipidomics, an analytical technique that is used to broadly survey lipid metabolism, we searched for biomarkers in plasma that are correlated with the presence of hepatic steatosis in children with obesity. METHODS: Lipidomics was performed in plasma samples of 21 children with obesity in whom steatosis was detected using proton magnetic resonance spectroscopy (H-MRS) and were compared to the lipidome of 21 samples of non-steatotic subjects with obesity. RESULTS: Forty-two samples were analyzed (57% male; median age 15 years). A total of 18 lipid classes comprising 839 different lipid species were identified. A statistically significant increase in alkyldiacylglycerol (TG[O]) and phosphatidylethanolamine (PE) species and a significant decrease in alkyl/alkenyl-phosphatidylethanolamine (PE[O]), alkyl/alkenyl-lysophosphatidylethanolamine (LPE[O]) and alkyl/alkenyl-phosphatidylcholine (PC[O]) was observed in children with hepatic steatosis compared to controls. Twelve individual lipid species of three lipid classes were significantly increased in steatotic subjects compared to controls. CONCLUSIONS: In this pilot study we found statistically significant alterations in 5 major lipid classes and twelve individual lipid species in children with steatosis. These might be potential biomarkers for pediatric NAFLD. Lipidomic studies in larger cohorts of children are needed to determine the diagnostic value of these lipids and determine whether results can be generalized for different age groups and ethnic backgrounds. PMID: 32740539 [PubMed - as supplied by publisher]

Comparison of flavonoids and phenylpropanoids compounds in Chinese water chestnut processed with different methods. Food Chem. 2020 Jul 25;335:127662 Authors: Nie H, Chen H, Li G, Su K, Song M, Duan Z, Li X, Cao X, Huang J, Huang S, Luo Y Abstract Different processing methods of Chinese water chestnut (CWC; Eleocharis dulcis (Burm.f.) Trin. ex Hensch.) steaming with skin (WPC), cooking with skin (WPS), steaming with peeling (PS), fresh cutting (FF) and cooking with peeling (PC) were compared. Liquid chromatography-mass spectrometry was used to analyze the metabolic profiles of the processed samples. A total of 454 metabolites, including 123 flavonoids and 57 phenylpropanoids, were characterized. The flavonoid and phenylpropanoid profiles were distinguished using PCA. Eighteen flavonoids and six phenylpropanoids were detected and quantitated in the WPC and WPS samples but not in the FF, PC and PS samples. In addition to the O-hexoside of tricin, kaempferol and luteolin were the predominant flavonoids in the WPC and WPS samples, and all three compounds were higher in the WPC and WPS samples than in the FF sample. This study provides new results regarding differences in the metabolite profile of CWC processed with different methods. PMID: 32739819 [PubMed - as supplied by publisher]

Treasure from garden: Bioactive compounds of buckwheat. Food Chem. 2020 Jul 24;335:127653 Authors: Huda MN, Lu S, Jahan T, Ding M, Jha R, Zhang K, Zhang W, Georgiev MI, Park SU, Zhou M Abstract Buckwheat is a gluten-free crop under the family Polygonaceae abundant with beneficial phytochemicals that provide significant health benefits. It is cultivated and adapted in diverse ecological zones all over the world. Recently its popularity is expanding as a nutrient-rich healthy food with low-calories. The bioactive compounds in buckwheat are flavonoids (i.e., rutin, quercetin, orientin, isoorientin, vitexin, and isovitexin), fatty acids, polysaccharides, proteins, and amino acids, iminosugars, dietary fiber, fagopyrins, resistant starch, vitamins, and minerals. Buckwheat possesses high nutritional value due to these bioactive compounds. Additionally, several essential bioactive factors that have long been gaining interest because these compounds are beneficial for healing and preventing several human diseases. The present review demonstrates an overview of the recent researches regarding buckwheat phytochemicals and particularly focusing on the distinct function of bioactive components with their health benefits. PMID: 32739818 [PubMed - as supplied by publisher]

Metabolomics research on the hepatoprotective effect of cultured bear bile powder in α-naphthylisothiocyanate-induced cholestatic mice. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Jul 16;1153:122269 Authors: Wu J, Fang S, Li W, Li Y, Li Y, Wang T, Yang L, Liu S, Wang Z, Ma Y Abstract Natural bear bile powder (NBBP) is a famous traditional medicine and has been widely used in clinic. However, access to the sources of bear bile is restricted; hence, it is essential to discover new substitutes for NBBP. Cultured bear bile powder (CBBP) is transformed from chicken bile and contains main ingredients as to NBBP. In the present study, the effect and potential mechanism of action of CBBP on cholestatic liver injury in-naphthylisothiocyanate (ANIT)-induced mouse model was explored using metabolomics. CBBP treatment ameliorated impaired hepatic dysfunction and tissue damage that induced by ANIT. Metabolomics showed there were 28 different metabolites induced by ANIT as compared with control mice, and 18 of which was reversed by CBBP. Pathway analysis revealed that those 18 metabolites are mainly involved in bile acid (BA) biosynthesis and D-glutamine and D-glutamate metabolism. Further LC-MS/MS analysis showed that CBBP and NBBP both reduced serum and liver levels of BAs, but increased their biliary levels. Additionally, CBBP and NBBP upregulated expression of BA efflux transporters, Mrp2, Mrp3, and Mrp4, and metabolic enzymes, Cyp2b10 and Ugt1a1 of liver tissue of cholestatic mice, increased the BA excretion and metabolism. Moreover, CBBP and NBBP treatment upregulated GCLc/GCLm expression, and restored glutathione metabolism. In conclusion, the protective effects of CBBP against cholestatic liver injury were similar to those of NBBP. Mechanistically, both CBBP and NBBP reversed the disruption in homeostasis of BAs and glutathione, alleviating damage to hepatocytes. PMID: 32739790 [PubMed - as supplied by publisher]

Metabolic profiling of organic acids in urine samples of Cri Du Chat syndrome individuals by gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Jul 14;1153:122267 Authors: Araújo BR, Furtado DZS, de Moura Leite FBV, de Assunção NA, Carrilho E Abstract Cri Du Chat (CDC) syndrome is a rare genetic condition caused by the deletion of genetic material on the small arm (the p arm) of chromosome 5. A high-pitched cry that sounds like that of a cat, dysmorphic characteristics, and cytogenetic methods are often used for diagnosing the syndrome. In this study, we applied GC-MS analysis for determining organic acids in urine from 17 control volunteers without CDC syndrome, and from 16 individuals with the CDC syndrome in order to determine the profile of organic acids and biochemical pathways alterations resulting from this genetic condition. First, performing multivariate data analysis selected the best method for extracting organic acids with greater signal intensities and good reproducibility. After selection, multivariate (PLS-DA) and univariate (Mann-Whitney test) data analysis discriminated the metabolites responsible for separation between groups. Nine organic acid metabolites had values of VIP ≥ 1.0 and p-values ≤ 0.05, with highest intensities in the samples from CDC individuals, indicating the strongest discriminative power (tricarballylic acid, indoleacetic acid, anthranilic acid, 4-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, 4-hydroxyhippuric acid, pantothenic acid, homovanillic acid, and vanillylmandelic acid). These metabolites are involved in several biochemical pathways like in the tyrosine and phenylalanine metabolism, as well as the tryptophan metabolism, which could be associated (i) to some neuropsychiatric alterations commonly observed in CDC individuals, (ii) to exogenous compounds related to transformation products by intestinal microbial, and (iii) to a possible deficiency in enzyme activity due to the syndrome. PMID: 32739788 [PubMed - as supplied by publisher]

Modulatory effects of Xihuang Pill on lung cancer treatment by an integrative approach. Biomed Pharmacother. 2020 Jul 30;130:110533 Authors: Li C, Chen W, Zhang M, Zhang C, Cao B, Dong B, Qi S, Zhang Y, Fei X, Li X, Li R, Wang J, Li G Abstract Lung cancer has a rapidly increasing incidence and remains the highest ranked cancer in terms of mortality worldwide. Xihuang Pill(XHW), a famous four-herb traditional Chinese formulation, has been used to treat lung cancer in China for more than 100 years. It is usually prescribed as a complementary and alternative medicine for cancer therapy. However, the main active ingredients of XHW that treat lung cancer and their regulatory effects remain unclear. Here, we revealed modulatory effects effects of XHW on lung cancer in a mouse model of Lewis lung cancer (LLC) by a comprehensive strategy combining network pharmacology with metabolomics. The results demonstrated that XHW inhibited tumour growth in this model. Additionally, 11 differentially expressed metabolites were identified in the XHW group compared to those in the model group or normal group by untargeted metabolomics. They were enriched in amino acid-related metabolic pathways, and the top three pathways were phenylalanine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis; and aminoacyl-tRNA biosynthesis. A total of 107 active components derived from Niuhuang, Shexiang, Ruxiang and Moyao, directly acted on 13 important targets (NR3C2, AKR1D1, MPO, PNP, NT5E, TAAR1, ADRB2, ADRB1, ADRA1A, ADRA2B, ADRA2A, MAOA and MAOB) to regulate 4 metabolites (L-phenylalanine, l-adrenaline, corticosterone and guanosine). Our results suggested that the key metabolites of XHW involved in the treatment of lung cancer were regulated by a multi-component and multi-target interaction network. This research elucidated the modulatory effect and therapeutic advantages of XHW treatment for lung tumours through an integrated approach. PMID: 32739739 [PubMed - as supplied by publisher]

The synergistic mechanism of total saponins and flavonoids in Notoginseng-Safflower pair against myocardial ischemia uncovered by an integrated metabolomics strategy. Biomed Pharmacother. 2020 Jul 30;130:110574 Authors: Meng Y, Du Z, Li Y, Gao P, Song J, Lu Y, Tu P, Jiang Y, Guo X Abstract The Notoginseng-Safflower pair composed of Panax notoginseng (Burk.) F. H. Chen and Carthamus tinctorius L. has remarkable clinical efficacy for preventing and treating cardiovascular diseases in China. Notoginseng total saponins (NS) and Safflower total flavonoids (SF) are the major effective ingredients in Notoginseng and Safflower, respectively. Though our previous study showed that the combination of NS and SF (NS-SF) exhibits significant cardioprotective effects for myocardial ischemia (MI), there might be difference in their action mechanisms. However, the anti-MI characteristics of individual NS and SF remains unclear. Herein, an integrated metabolomics strategy coupled with multiple biological methods were employed to investigate the cardioprotective effects of NS and SF alone or in combination against isoproterenol (ISO)-induced MI and to further explore the synergistic relationship between NS and SF. Our results demonstrated that pretreatments with NS, SF, and NS-SF all showed cardioprotective effects against MI injury and NS-SF exhibited to be the best. Interestingly, the results demonstrated that NS and SF exhibited differentiated metabolic targets and mediators in the glycerophospholipid metabolism. Furthermore, administration of NS alone exhibited greater effects on reversing the elevated the proinflammatory metabolites and mediators in MI rats compared to SF alone. However, individual SF showed greater amelioration of MI-disturbed antioxidant and prooxidative metabolites and better inhibition of the oxidative stress than NS alone. Collectively, our study demonstrated that the capability of NS-SF to regulate both metabolic targets of NS and SF might be the basis of NS-SF to produce a cooperative effect greater than their individual effects that enhance the anti-MI efficacy and provided valuable information for the clinical application of Notoginseng-Safflower pair. PMID: 32739736 [PubMed - as supplied by publisher]

Effects of the Suxiao Jiuxin pill on acute myocardial infarction assessed by comprehensive metabolomics. Phytomedicine. 2020 Jul 25;77:153291 Authors: Wu G, Zhong J, Chen L, Gu Y, Hong Y, Ma J, Zheng N, Liu AJ, Sheng L, Zhang W, Li H Abstract BACKGROUND: SJP is the commercial Chinese medicine included in the Chinese Pharmacopoeia, with well-established cardiovascular protective effects in the clinic. However, the mechanisms underlying the protective effects of SJP on cardiovascular disease have not yet been clearly elucidated. AIMS: To investigate the underlying protective mechanisms of SJP in an acute myocardial infarction (AMI) rat model using comprehensive metabolomics. MATERIALS AND METHODS: The rat model of AMI was generated by ligating the left anterior descending coronary artery. After 2 weeks treatment with SJP, the entire metabolic changes in the serum, heart, urine and feces of the rat were profiled by HPLC-QTOF-MS/MS. RESULTS: The metabolic profiles in different biological samples (heart, serum, urine and feces) were significantly different among groups, in which a total of 112 metabolites were identified. AMI caused comprehensive metabolic changes in amino acid metabolism, galactose metabolism and fatty acid metabolism, while SJP reversed more than half of the differential metabolic changes, mainly affecting amino acid metabolism and fatty acid metabolism. Correlation analysis found that SJP could significantly alter the metabolic activity of 12 key metabolites, regarded as potential biomarkers of SJP treatment. According to the results of network analysis, 6 biomarkers were considered to be hub metabolites, which means that these metabolites may have a major relationship with the SJP therapeutic effects on AMI. CONCLUSION: The combined comprehensive metabolomics and network analysis, indicated that the protective effect of SJP on cardiovascular disease was associated with systemic metabolic modulation, in particular regulation of amino acid and fatty acid metabolism. PMID: 32739572 [PubMed - as supplied by publisher]

EARLY PREGNANCY METABOLITES PREDICT GESTATIONAL DIABETES MELLITUS: IMPLICATIONS FOR FETAL PROGRAMMING. Am J Obstet Gynecol. 2020 Jul 30;: Authors: Koos BJ, Gornbein JA Abstract BACKGROUND: Aberrant fetal programming in gestational diabetes (GDM) appears to increase the risk for obesity, type 2 diabetes, and cardiovascular disease. The inability to identify accurately GDM in the first trimester has thwarted ascertaining whether early therapeutic interventions reduce the predisposition to these prevalent medical disorders. OBJECTIVE: A metabolomics study was conducted to determine whether advanced analytical methods could identify accurate predictors of GDM in early pregnancy. STUDY DESIGN: This nested, observational case-control study comprised 46 GDM and 46 control (CON) gravidas in early gestation who were matched by maternal age, body mass index (BMI), and gestational age at urine collection. GDM was diagnosed according to community standards. A comprehensive metabolomics platform measured 626 endogenous metabolites in randomly collected urine. Consensus multivariate criteria or most important by one method identified low-molecular weight metabolites independently associated with GDM, and a classification tree selected a subset most predictive of GDM. RESULTS: Urine for both groups was collected at a mean gestational age of 12 weeks (range: 6-19 weeks). Consensus multivariate analysis identified 11 metabolites independently linked to GDM. Classification tree analysis selected a seven-metabolite subset that predicted GDM with an accuracy of 96.7%, independent of maternal age, BMI, and time of urine collection. CONCLUSION: Validation of this high-accuracy model by a larger study is now needed to support future studies to determine whether first-trimester therapeutic interventions in GDM reduce short- and long-term morbidity. PMID: 32739399 [PubMed - as supplied by publisher]

Tracking the potential involvement of metabolic disease in Alzheimer's disease-Biomarkers and beyond. Int Rev Neurobiol. 2020;154:51-77 Authors: Luchsinger JA, Zetterberg H Abstract There is a vast literature linking systemic metabolic conditions to dementia due to Alzheimer's disease (AD). Advances in in vivo measurements of AD neuropathology using brain imaging, cerebrospinal fluid (CSF), and/or blood biomarkers have led to research in AD that uses in vivo biomarkers as outcomes, focusing primarily on amyloid, tau, and neurodegeneration as constructs. Studies of Type 2 Diabetes Mellitus (T2DM) and AD biomarkers seem to show that T2DM is not related to amyloid deposition, but is related to neurodegeneration and tau deposition. There is a dearth of studies examining adiposity, insulin resistance, and metabolic syndrome in relation to AD biomarkers and the associations in these studies are inconsistent. Metabolomics studies have reported associations of unsaturated fatty acids with AD neuropathology at autopsy, and sphingolipids and glycerophospholipids in relation to neurodegeneration and amyloid and tau. There are other neurodegenerative diseases, such as Lewy body disease that may overlap with AD, and specific biomarkers for these pathologies are being developed and should be integrated into AD biomarker research. More longitudinal studies are needed with concurrent assessment of metabolic factors and AD biomarkers in order to improve the opportunity to assess causality. Ideally, AD biomarkers should be integrated into clinical trials of interventions that affect metabolic factors. Advances in blood-based AD biomarkers, which are less costly and invasive compared with CSF and brain imaging biomarkers, could facilitate widespread implementation of AD biomarkers in studies examining the metabolic contribution to AD. PMID: 32739014 [PubMed - as supplied by publisher]

Elucidation of metabolic responses in mud crab Scylla paramamosain challenged to WSSV infection by integration of metabolomics and transcriptomics. Dev Comp Immunol. 2020 Jul 29;:103799 Authors: Kong T, Ren X, Lin S, Li S, Gong Y Abstract White spot syndrome virus (WSSV) is a severe pathogen of mud crab Scylla paramamosain (S. paramamosain). Hemolymph, containing three types of hemocytes, is the key immunoregulatory tool of mud crab in response to pathogens. Herein, the metabonomics and transcriptomics analysis of hemocytes were adopted to investigate the immune response of S. paramamosain challenged to WSSV. We established the metabolic and transcriptional profiles of mud crab hemocytes with different treatments, including the control group (WT), WSSV early infected group (WSSV-6 h) and WSSV later infected group (WSSV-72 h). The results showed that 68 metabolites were dysregulated both in WSSV-infected mud crab of early stage and later stage, while 4452 genes were up-regulated and 9746 genes were down-regulated in WSSV-6 h, and 2016 genes were up-regulated and 6229 genes were down-regulated compared in WSSV-72 h. We found that several pathways were dysregulated at both metabolic and transcriptional levels, including ABC transporters, purine metabolism,taurine and hypotaurine metabolism in the WSSV early infected group, cysteine metabolism,methionine metabolism and biosynthesis of unsaturated fatty acids in the WSSV later infected group. 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 viral invasion. PMID: 32738334 [PubMed - as supplied by publisher]