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

PubMed

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 22 min 6 sec ago

Comprehensive metabolic profiling of Parkinson's disease by liquid chromatography-mass spectrometry.

Tue, 26/01/2021 - 09:15
Related Articles Comprehensive metabolic profiling of Parkinson's disease by liquid chromatography-mass spectrometry. Mol Neurodegener. 2021 Jan 23;16(1):4 Authors: Shao Y, Li T, Liu Z, Wang X, Xu X, Li S, Xu G, Le W Abstract BACKGROUND: Parkinson's disease (PD) is a prevalent neurological disease in the elderly with increasing morbidity and mortality. Despite enormous efforts, rapid and accurate diagnosis of PD is still compromised. Metabolomics defines the final readout of genome-environment interactions through the analysis of the entire metabolic profile in biological matrices. Recently, unbiased metabolic profiling of human sample has been initiated to identify novel PD metabolic biomarkers and dysfunctional metabolic pathways, however, it remains a challenge to define reliable biomarker(s) for clinical use. METHODS: We presented a comprehensive metabolic evaluation for identifying crucial metabolic disturbances in PD using liquid chromatography-high resolution mass spectrometry-based metabolomics approach. Plasma samples from 3 independent cohorts (n = 460, 223 PD, 169 healthy controls (HCs) and 68 PD-unrelated neurological disease controls) were collected for the characterization of metabolic changes resulted from PD, antiparkinsonian treatment and potential interferences of other diseases. Unbiased multivariate and univariate analyses were performed to determine the most promising metabolic signatures from all metabolomic datasets. Multiple linear regressions were applied to investigate the associations of metabolites with age, duration time and stage of PD. The combinational biomarker model established by binary logistic regression analysis was validated by 3 cohorts. RESULTS: A list of metabolites including amino acids, acylcarnitines, organic acids, steroids, amides, and lipids from human plasma of 3 cohorts were identified. Compared with HC, we observed significant reductions of fatty acids (FFAs) and caffeine metabolites, elevations of bile acids and microbiota-derived deleterious metabolites, and alterations in steroid hormones in drug-naïve PD. Additionally, we found that L-dopa treatment could affect plasma metabolome involved in phenylalanine and tyrosine metabolism and alleviate the elevations of bile acids in PD. Finally, a metabolite panel of 4 biomarker candidates, including FFA 10:0, FFA 12:0, indolelactic acid and phenylacetyl-glutamine was identified based on comprehensive discovery and validation workflow. This panel showed favorable discriminating power for PD. CONCLUSIONS: This study may help improve our understanding of PD etiopathogenesis and facilitate target screening for therapeutic intervention. The metabolite panel identified in this study may provide novel approach for the clinical diagnosis of PD in the future. PMID: 33485385 [PubMed - in process]

Metabolomics analysis of the effects of temperature on the growth and development of juvenile European seabass (Dicentrarchus labrax).

Sun, 24/01/2021 - 14:54
Related Articles Metabolomics analysis of the effects of temperature on the growth and development of juvenile European seabass (Dicentrarchus labrax). Sci Total Environ. 2021 Jan 14;769:145155 Authors: Zhang Z, Zhou C, Fan K, Zhang L, Liu Y, Liu PF Abstract Temperature variations have significant impacts on the growth and development of fish. In this study, the effects of temperature on the growth and development of European seabass (Dicentrarchus labrax) were investigated using ultra-performance liquid chromatography-tandem mass spectrometry-based metabolomics. Three groups of fish were exposed to various temperatures for 60 days: T1-E (10 °C), T2-E (15 °C), and T3-E (20 °C). Afterward, the temperature of all groups was increased to 20 °C and maintained for 62 days (T1-S, T2-S, T3-S). The livers were extracted for subsequent analysis. In the first stage of the experiment, the growth rate was highest in the T3-E group, followed by the T1-E and T2-E groups. The following metabolites identified by comparative analysis were found to be elevated: L-thyroxine, cysteamine, uridine diphosphate (UDP)-glucose, α-ketoglutaric acid, carbamoyl phosphate, and guanidine acetic acid of the T1-E group. Pathway analysis of the altered metabolites suggested changes in glucose metabolism, arginine and proline metabolism, the tricarboxylic acid cycle, the ornithine cycle, histidine metabolism, and taurine metabolism, which were involved with growth and development. Meanwhile, partial compensatory growth was observed in fish in the T1-S and T2-S groups. Metabolites identified as potential markers of growth included L-cysteine, taurocholic acid, UDP-glucose, and L-thyroxine. The significantly changed metabolic pathways were cysteine and methionine metabolism, bile secretion, tyrosine metabolism, and hypotaurine metabolism. We screened out the marker metabolites and metabolic pathway could provide important insights into the potential mechanisms of temperature affects the growth and development of European seabass. All in all, our research can provide theoretical basis and technical guidance for efficiently culturing European seabass. PMID: 33485208 [PubMed - as supplied by publisher]

Traumatic brain injury metabolome and mitochondrial impact after early stage Ru360 treatment.

Sun, 24/01/2021 - 14:54
Related Articles Traumatic brain injury metabolome and mitochondrial impact after early stage Ru360 treatment. Mitochondrion. 2021 Jan 20;: Authors: Chitturi J, Santhakumar V, Kannurpatti SS Abstract Ru360, a mitochondrial Ca2+ uptake inhibitor, was tested in a unilateral fluid percussion TBI model in developing rats (P31). Vehicle and Ru360 treated TBI rats underwent sensorimotor behavioral monitoring between 24 to 72 hours, thereafter which 185 brain metabolites were analyzed postmortem using LC/MS. Ru360 treatment after TBI improved sensorimotor behavioral recovery, upregulated glycolytic and pentose phosphate pathways, mitigated oxidative stress and prevented NAD+ depletion across both hemispheres. While neural viability improved ipsilaterally, it reduced contralaterally. Ru360 treatment, overall, had a global impact with most benefit near the strongest injury impact areas, while perturbing mitochondrial oxidative energetics in the milder TBI impact areas. PMID: 33484870 [PubMed - as supplied by publisher]

Dietary table grape protects against UV photodamage in humans: 2. molecular biomarker studies.

Sun, 24/01/2021 - 14:54
Related Articles Dietary table grape protects against UV photodamage in humans: 2. molecular biomarker studies. J Am Acad Dermatol. 2021 Jan 20;: Authors: Oak ASW, Shafi R, Elsayed M, Mishra B, Bae S, Barnes S, Kashyap MP, Slominski AT, Wilson LS, Athar M, Elmets CA PMID: 33484768 [PubMed - as supplied by publisher]

Oxoeicosanoid receptor inhibition alleviates acute myocardial infarction through activation of BCAT1.

Sun, 24/01/2021 - 14:54
Related Articles Oxoeicosanoid receptor inhibition alleviates acute myocardial infarction through activation of BCAT1. Basic Res Cardiol. 2021 Jan 23;116(1):3 Authors: Lai Q, Yuan G, Shen L, Zhang L, Fu F, Liu Z, Zhang Y, Kou J, Liu S, Yu B, Li F Abstract 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is an arachidonic acid metabolite produced along with leukotrienes via the 5-lipoxygenase pathway. Metabolomics studies have shown that 5-oxo-ETE level is elevated in the serum in acute myocardial infarction (AMI). The actions of 5-oxo-ETE are mediated by the highly selective oxoeicosanoid receptor (OXE-R). Moreover, increased OXE-R content was verified in AMI patients and mice. However, the precise role of OXE-R in AMI is unclear. In the present study, we demonstrate that 5-oxo-ETE triggered myocardial injury in mice. Pathway enrichment analysis identified branched chain amino acid transaminase 1/2 (BCAT1/2) as potential mediators of this effect. Western blot and immunohistochemical analyses showed that BCAT1/BCAT2 expression was significantly reduced by AMI in vitro and in vivo, while pharmacologic inhibition of BCAT1/BCAT2 accelerated myocardial injury. Conversely, heart-specific overexpression of BCAT1/BCAT2 in mice protected against ischemic myocardial injury. Treatment with the selective OXE-R inhibitor Gue1654 alleviated coronary artery ligation-induced ischemic myocardial injury in mice and oxygen/glucose deprivation-induced injury in cardiomyocytes through activation of BCAT1, while inhibiting OXE-R suppressed protein kinase C-ε (PKC-ε)/nuclear factor κB (NF-κB) signaling and cardiomyocyte apoptosis. Overall, our study confirmed a novel target OXE-R for the treatment of AMI based on metabolomics, and targeting OXE-R may represent unrecognized therapeutic intervention for cardiovascular diseases through activation of BCAT1. PMID: 33484341 [PubMed - as supplied by publisher]

Correction to: Metabolic characterisation of disturbances in the APOC3/triglyceride‑rich lipoprotein pathway through sample‑based recall by genotype.

Sun, 24/01/2021 - 14:54
Related Articles Correction to: Metabolic characterisation of disturbances in the APOC3/triglyceride‑rich lipoprotein pathway through sample‑based recall by genotype. Metabolomics. 2021 Jan 23;17(2):15 Authors: Corbin LJ, Hughes DA, Chetwynd AJ, Taylor AE, Southam AD, Jankevics A, Weber RJM, Groom A, Dunn WB, Timpson NJ PMID: 33484338 [PubMed - as supplied by publisher]

Lilikoi V2.0: a deep learning-enabled, personalized pathway-based R package for diagnosis and prognosis predictions using metabolomics data.

Sun, 24/01/2021 - 14:54
Related Articles Lilikoi V2.0: a deep learning-enabled, personalized pathway-based R package for diagnosis and prognosis predictions using metabolomics data. Gigascience. 2021 Jan 23;10(1): Authors: Fang X, Liu Y, Ren Z, Du Y, Huang Q, Garmire LX Abstract BACKGROUND: previously we developed Lilikoi, a personalized pathway-based method to classify diseases using metabolomics data. Given the new trends of computation in the metabolomics field, it is important to update Lilikoi software. RESULTS: here we report the next version of Lilikoi as a significant upgrade. The new Lilikoi v2.0 R package has implemented a deep learning method for classification, in addition to popular machine learning methods. It also has several new modules, including the most significant addition of prognosis prediction, implemented by Cox-proportional hazards model and the deep learning-based Cox-nnet model. Additionally, Lilikoi v2.0 supports data preprocessing, exploratory analysis, pathway visualization, and metabolite pathway regression. CONCULSION: Lilikoi v2.0 is a modern, comprehensive package to enable metabolomics analysis in R programming environment. PMID: 33484242 [PubMed - as supplied by publisher]

The contributions of metabolomics in the discovery of new therapeutic targets in Alzheimer's disease.

Sun, 24/01/2021 - 14:54
Related Articles The contributions of metabolomics in the discovery of new therapeutic targets in Alzheimer's disease. Fundam Clin Pharmacol. 2021 Jan 23;: Authors: Altiné-Samey R, Antier D, Mavel S, Dufour-Rainfray D, Balageas AC, Beaufils E, Emond P, Foucault-Fruchard L, Chalon S Abstract Alzheimer's disease (AD) leads to the progressive loss of memory and other cognitive functions. It is the most common form of dementia in the elderly and has become a major public health problem due to the increase in life expectancy. Although the detection of AD is based on several neuropsychological tests, imaging and biological analyses, none of these biomarkers allows a clear understanding of the pathophysiological mechanisms involved in the disease, and no efficient treatment is currently available. Metabolomics, which allows the study of biochemical alterations underlying pathological processes, could help to identify these mechanisms, to discover new therapeutic targets and to monitor the therapeutic response and disease progression. In this review, we have summarized and analyzed the results from a number of studies on metabolomics analyses performed in biological samples originated from the central nervous system, in AD subjects and in animal models of this disease. This synthesis revealed modified expression of specific metabolites in pathological conditions which allowed the identification of significantly impacted metabolic pathways both in animals and humans, such as the arginine biosynthesis and the alanine, aspartate and glutamate metabolism. We discuss the potential biochemical mechanisms involved, the extent to which they could impact the specific hallmarks of AD, and the therapeutic approaches which could be proposed as a result. PMID: 33484165 [PubMed - as supplied by publisher]

Chemical comparison of the raw and processed Farfarae Flos by liquid chromatography-mass spectrometry based metabolomic approach.

Sun, 24/01/2021 - 14:54
Related Articles Chemical comparison of the raw and processed Farfarae Flos by liquid chromatography-mass spectrometry based metabolomic approach. J Mass Spectrom. 2021 Feb;56(2):e4697 Authors: Cao J, Lu Z, Qin X, Li Z Abstract Farfarae Flos (FF) has been used in China for a long time as an anti-tussive and expectorant herbal drugs, and it was usually honey-fried FF (HFF). To clarify the mechanism of honey processing, it is important to know the chemical difference between FF and HFF firstly. In this study, UHPLC-Orbitrap-MS was used to characterize the chemical compounds in FF, honey and HFF. Then the metabolomic approach based on UHPLC-Orbitrap-MS revealed 68 differential compounds between the FF and HFF, and chemical reactions occurring during processing were also proposed to elucidate the honey processing mechanisms of FF. In order to investigate the chemical difference between FF and HFF comprehensively and accurately, the components derived from the honey and the moisture content in FF and HFF were considered for the first time. In summary, this study investigated the chemical differences between FF and HFF in a holistic way, which laid the basis for the quality control of HFF and further explaining the honey processing mechanisms of FF. In addition, eight native compounds derived from the honey could be used as the index to authenticate the HFF prepared by the genuine honey. PMID: 33484014 [PubMed - as supplied by publisher]

Mouse Quantitative Proteomics Knowledgebase: reference protein concentration ranges in 20 mouse tissues using 5000 quantitative proteomics assays.

Sun, 24/01/2021 - 14:54
Related Articles Mouse Quantitative Proteomics Knowledgebase: reference protein concentration ranges in 20 mouse tissues using 5000 quantitative proteomics assays. Bioinformatics. 2021 Jan 23;: Authors: Mohammed Y, Bhowmick P, Michaud SA, Sickmann A, Borchers CH Abstract Laboratory mouse is the most used animal model in biological research, largely due to its high conserved synteny with human. Researchers use mice to answer various questions ranging from determining a pathological effect of knocked out/in gene to understanding drug metabolism. Our group developed >5000 quantitative targeted proteomics assays for 20 mouse tissues and determined the concentration ranges of a total of more than 1600 proteins using heavy labelled internal standards. We describe here MouseQuaPro; a knowledgebase that hosts this collection of carefully curated experimental data. The Web-based application includes protein concentrations from >700 mouse tissue samples from three common research strains, corresponding to more than 200k experimentally determined concentrations. The knowledgebase integrates the assay and protein concentration information with their human orthologs, functional and molecular annotations, biological pathways, related human diseases, and known gene expressions. At its core are the protein concentration ranges, which provide insights into (dis)similarities between tissues, strains, and sexes. MouseQuaPro implements advanced search as well as filtering functionalities with a simple interface and interactive visualization. This information-rich resource provides an initial map of protein absolute concentration in mouse tissues and allows guided design of proteomics phenotyping experiments. The knowledgebase is available at mousequapro.proteincentre.com. (Reviewer access username and password: mousequapro_reviewer1234567). PMID: 33483739 [PubMed - as supplied by publisher]

Cognitive analysis of metabolomics data for systems biology.

Sun, 24/01/2021 - 14:54
Related Articles Cognitive analysis of metabolomics data for systems biology. Nat Protoc. 2021 Jan 22;: Authors: Majumder EL, Billings EM, Benton HP, Martin RL, Palermo A, Guijas C, Rinschen MM, Domingo-Almenara X, Montenegro-Burke JR, Tagtow BA, Plumb RS, Siuzdak G Abstract Cognitive computing is revolutionizing the way big data are processed and integrated, with artificial intelligence (AI) natural language processing (NLP) platforms helping researchers to efficiently search and digest the vast scientific literature. Most available platforms have been developed for biomedical researchers, but new NLP tools are emerging for biologists in other fields and an important example is metabolomics. NLP provides literature-based contextualization of metabolic features that decreases the time and expert-level subject knowledge required during the prioritization, identification and interpretation steps in the metabolomics data analysis pipeline. Here, we describe and demonstrate four workflows that combine metabolomics data with NLP-based literature searches of scientific databases to aid in the analysis of metabolomics data and their biological interpretation. The four procedures can be used in isolation or consecutively, depending on the research questions. The first, used for initial metabolite annotation and prioritization, creates a list of metabolites that would be interesting for follow-up. The second workflow finds literature evidence of the activity of metabolites and metabolic pathways in governing the biological condition on a systems biology level. The third is used to identify candidate biomarkers, and the fourth looks for metabolic conditions or drug-repurposing targets that the two diseases have in common. The protocol can take 1-4 h or more to complete, depending on the processing time of the various software used. PMID: 33483720 [PubMed - as supplied by publisher]

Artemisinin-resistant K13 mutations rewire Plasmodium falciparum's intra-erythrocytic metabolic program to enhance survival.

Sun, 24/01/2021 - 14:54
Related Articles Artemisinin-resistant K13 mutations rewire Plasmodium falciparum's intra-erythrocytic metabolic program to enhance survival. Nat Commun. 2021 Jan 22;12(1):530 Authors: Mok S, Stokes BH, Gnädig NF, Ross LS, Yeo T, Amaratunga C, Allman E, Solyakov L, Bottrill AR, Tripathi J, Fairhurst RM, Llinás M, Bozdech Z, Tobin AB, Fidock DA Abstract The emergence and spread of artemisinin resistance, driven by mutations in Plasmodium falciparum K13, has compromised antimalarial efficacy and threatens the global malaria elimination campaign. By applying systems-based quantitative transcriptomics, proteomics, and metabolomics to a panel of isogenic K13 mutant or wild-type P. falciparum lines, we provide evidence that K13 mutations alter multiple aspects of the parasite's intra-erythrocytic developmental program. These changes impact cell-cycle periodicity, the unfolded protein response, protein degradation, vesicular trafficking, and mitochondrial metabolism. K13-mediated artemisinin resistance in the Cambodian Cam3.II line was reversed by atovaquone, a mitochondrial electron transport chain inhibitor. These results suggest that mitochondrial processes including damage sensing and anti-oxidant properties might augment the ability of mutant K13 to protect P. falciparum against artemisinin action by helping these parasites undergo temporary quiescence and accelerated growth recovery post drug elimination. PMID: 33483501 [PubMed - as supplied by publisher]

metabolomics; +17 new citations

Sat, 23/01/2021 - 14:45
17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2021/01/23PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Synergistic effects of glyphosate and multiwall carbon nanotubes on Arabidopsis thaliana physiology and metabolism.

Fri, 22/01/2021 - 14:35
Related Articles Synergistic effects of glyphosate and multiwall carbon nanotubes on Arabidopsis thaliana physiology and metabolism. Sci Total Environ. 2021 Jan 15;769:145156 Authors: Ke M, Ye Y, Zhang Z, Gillings M, Qu Q, Xu N, Xu L, Lu T, Wang J, Qian H Abstract Agricultural chemicals have the potential to become pollutants that adversely affect plant growth. Interactions between these compounds are likely, but potential synergies are under-researched. Multiwall carbon nanotubes are increasingly finding novel uses in agriculture, as delivery mechanisms and as slow-release fertilizers. There is potential for nanotubes to interact with other agricultural chemicals in unpredictable ways. To investigate this possibility, we examined interactions with glyphosate, a widely used herbicide that is also attracting increasing concern over its potential for non-target effects. Here we examined potential synergistic effects on hydroponically grown Arabidopsis thaliana. Single treatments did not affect plant growth significantly, or did only mildly. However, combined treatment significantly affected both plant root and shoot growth. High-level content of malondialdehyde and up-regulated of metabolic antioxidant molecules in plant indicated that combined group caused the strong oxidative damage, while the decreased of antioxidant enzyme activities indicated an imbalance between reactive oxygen species (ROS)and the antioxidant defense system due to the continuously generated ROS. Besides, several intermediate metabolites of unsaturated fatty acids synthesis pathways were up-regulated in combined treatment, which clarified that combined group changed membrane components. The increase of intermediate metabolites in combined group also reflected more energy consumption in the repairment of the disrupt of combined treatment. The synergistic effect observed was attributed to the accumulation of glyphosate resulting from permeability and transportability of the carbon nanotubes. Overall, the risk of nanotube-herbicide interaction suggests a caution use of nanotubes in agricultural applications. PMID: 33477045 [PubMed - as supplied by publisher]

Artificial light at night interacts with predatory threat to alter reef fish metabolite profiles.

Fri, 22/01/2021 - 14:35
Related Articles Artificial light at night interacts with predatory threat to alter reef fish metabolite profiles. Sci Total Environ. 2021 Jan 05;769:144482 Authors: Hillyer KE, Beale DJ, Shima JS Abstract Light cycles and predatory threat define activity patterns (e.g. feeding/sleeping, activity/rest) in most diurnal fish species. Artificial light at night (ALAN) may disrupt natural cycles and biochemical processes, a mismatch which can eventually reduce condition and fitness. We evaluate the separate and joint effects of ALAN and predator threat on metabolism within brain, liver and muscle tissue of a common, wild caught damselfish, blue green chromis (Chromis viridis). The effects of ALAN varied according to tissue type and predator exposure. In all tissues we observed changes in metabolic pathways associated with increased activity under continuous light (despite provision of shelter), specifically those associated with energy metabolism, cell signalling, responses to oxidative stress and markers of cellular damage. In both the brain and liver tissues, predator threat served to moderate the influence of ALAN on metabolic change, likely due to increased sheltering behaviour. However, no interaction of predator threat with ALAN was observed in metabolism of the muscle tissue. Our results highlight complex sub-acute effects of ALAN exposure on tissue specific and whole organism energy metabolism. Collectively these effects indicate that ALAN has significant scope to reduce fitness of coastal fishes and potentially threaten ecosystem services, but that these changes are highly complex and may be altered by biotic drivers of activity. PMID: 33477042 [PubMed - as supplied by publisher]

Uncovering the antitumor effects and mechanisms of Shikonin against colon cancer on comprehensive analysis.

Fri, 22/01/2021 - 14:35
Related Articles Uncovering the antitumor effects and mechanisms of Shikonin against colon cancer on comprehensive analysis. Phytomedicine. 2021 Jan 08;82:153460 Authors: Chen Y, Si L, Zhang J, Yu H, Liu X, Chen Y, Wu Y Abstract BACKGROUND: Shikonin, a naphthoquinone compound extracted from the root of Lithospermum erythrorhizon, has been extensively studied for its antitumor activity. However, the systematic pathways involved in Shikonin intervention in human colon cancer has not yet clearly defined. PURPOSE: This study was to evaluate the cytotoxic effects of Shikonin in colon cancer, as well as investigate the potential biomarkers from a global perspective and the possible antitumor mechanisms involved. METHODS: In this work, cell viability, cell cycle and cell apoptosis in human colon cancer cells were assessed to evaluate the antitumor activity of Shikonin. Transcriptomics and metabolomics were integrated to provide the perturbed pathways and explore the potential mechanisms. The crucial proteins and genes involved were further validated by immunohistochemistry and real-time quantitative PCR. RESULTS: Shikonin revealed a remarkable antitumor potency in colon cancer. Cell cycle was significantly arrested at the S phase as well as apoptosis was induced in SW480 cell line. Furthermore, a total of 1642 differentially expressed genes and 40 metabolites were detected after Shikonin intervention. The integrated analysis suggested that the antitumor effect was mainly attributed to purine metabolism, arginine biosynthesis, pyrimidine metabolism, urea cycle and metabolism of amino acids. The up-regulated expression of proteins vital for arginine biosynthesis was subsequently validated by immunohistochemistry in xenograft mice. Notably, supplemental dNTPs and arginine could significantly reverse the cytotoxic effect induced by Shikonin and the genes participating in purine metabolism and arginine biosynthesis were further determined by RT-qPCR. CONCLUSION: Our findings provide a systematic perspective in the therapeutic effect of Shikonin which might lay a foundation for further research on Shikonin in colon cancer. PMID: 33476976 [PubMed - as supplied by publisher]

Rosmarinic acid attenuates obesity and obesity-related inflammation in human adipocytes.

Fri, 22/01/2021 - 14:35
Related Articles Rosmarinic acid attenuates obesity and obesity-related inflammation in human adipocytes. Food Chem Toxicol. 2021 Jan 18;:112002 Authors: Vasileva LV, Savova MS, Tews D, Wabitsch M, Georgiev MI Abstract Chronic low-grade inflammation is a hallmark of obesity and its related metabolic disorders. At the same time signaling from pro-inflammatory factors such as transforming growth factor beta (TGF-β) or interleukin 17A (IL-17A) are proposed as crucial for the commitment of fibroblast progenitor cells towards adipogenic differentiation. Modulation of inflammation during adipogenic differentiation is incompletely explored as a potential approach to prevent metabolic disorders. Rosmarinic acid (RA) is a caffeic acid derivative known for its anti-inflammatory effects. Experimental studies of its activity on adipogenic factors or in vivo obesity models are, however, controversial and hence insufficient. Here, we investigated the anti-adipogenic action of RA in human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. Gene expression levels of key players in adipogenesis and lipid metabolism were assessed. Furthermore, a molecular mechanism of action was proposed. The most prominent effect was found on the translation of C/EBPα, PPARγ and adiponectin, as well as on the modulation of TGF1B and IL17A. Interestingly, involvement of NRF2 signaling was identified upon RA treatment. In summary, our findings indicate that RA prevents inflammation and excessive lipid accumulation in human adipocytes. Data from the molecular analysis demonstrates that RA has potential for treatment of obesity and obesity-related inflammation. PMID: 33476690 [PubMed - as supplied by publisher]

Plasma metabolomics of presymptomatic PSEN1-H163Y mutation carriers: a pilot study.

Fri, 22/01/2021 - 14:35
Related Articles Plasma metabolomics of presymptomatic PSEN1-H163Y mutation carriers: a pilot study. Ann Clin Transl Neurol. 2021 Jan 21;: Authors: Natarajan K, Ullgren A, Khoshnood B, Johansson C, Laffita-Mesa JM, Pannee J, Zetterberg H, Blennow K, Graff C Abstract BACKGROUND AND OBJECTIVE: PSEN1-H163Y carriers, at the presymptomatic stage, have reduced 18 FDG-PET binding in the cerebrum of the brain (Scholl et al., Neurobiol Aging 32:1388-1399, 2011). This could imply dysfunctional energy metabolism in the brain. In this study, plasma of presymptomatic PSEN1 mutation carriers was analyzed to understand associated metabolic changes. METHODS: We analyzed plasma from noncarriers (NC, n = 8) and presymptomatic PSEN1-H163Y mutation carriers (MC, n = 6) via untargeted metabolomics using gas and liquid chromatography coupled with mass spectrometry, which identified 1199 metabolites. All the metabolites were compared between MC and NC using univariate analysis, as well as correlated with the ratio of Aβ1-42/A β 1-40 , using Spearman's correlation. Altered metabolites were subjected to Ingenuity Pathway Analysis (IPA). RESULTS: Based on principal component analysis the plasma metabolite profiles were divided into dataset A and dataset B. In dataset A, when comparing between presymptomatic MC and NC, the levels of 79 different metabolites were altered. Out of 79, only 14 were annotated metabolites. In dataset B, 37 metabolites were significantly altered between presymptomatic MC and NC and nine metabolites were annotated. In both datasets, annotated metabolites represent amino acids, fatty acyls, bile acids, hexoses, purine nucleosides, carboxylic acids, and glycerophosphatidylcholine species. 1-docosapentaenoyl-GPC was positively correlated, uric acid and glucose were negatively correlated with the ratio of plasma Aβ1-42 /Aβ1-40 (P < 0.05). INTERPRETATION: This study finds dysregulated metabolite classes, which are changed before the disease symptom onset. Also, it provides an opportunity to compare with sporadic Alzheimer's Disease. Observed findings in this study need to be validated in a larger and independent Familial Alzheimer's Disease (FAD) cohort. PMID: 33476461 [PubMed - as supplied by publisher]

Blood plasma metabolomics of children and adolescents with sickle cell anaemia treated with hydroxycarbamide: a new tool for uncovering biochemical alterations.

Fri, 22/01/2021 - 14:35
Related Articles Blood plasma metabolomics of children and adolescents with sickle cell anaemia treated with hydroxycarbamide: a new tool for uncovering biochemical alterations. Br J Haematol. 2021 Jan 21;: Authors: Ribeiro PR, Teixeira RDS, Souza AR, Pereira TCS, Boffo EF, Carosio MGA, Ferreira AG, Oliveira RV, Rodrigues LEA, Silva JJ, de Souza AJ, Ladeia AMT Abstract Sickle cell anaemia (SCA) is a debilitating genetic haemoglobinopathy predominantly affecting the disenfranchised strata of society in Africa and the Americas. The most common pharmacological treatment for this disease is the administration of hydroxycarbamide (HC) for which questions remain regarding its mechanism of action, efficacy and long-term toxicity specifically in paediatric individuals. A multiplatform metabolomics approach was used to assess the metabolome of plasma samples from a population of children and adolescents with SCA with and without HC treatment along with non-SCA individuals. Fifty-three metabolites were identified by ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) and 1 H nuclear magnetic resonance (NMR) with a predominance of membrane lipids, amino acids and organic acids. The partial least-squares discriminant analysis (PLS-DA) analysis allowed a clear discrimination between the different studied groups, revealing clear effects of the HC treatment in the patients' metabolome including rescue of specific metabolites to control levels. Increased creatine/creatinine levels under HC treatment suggests a possible increase in the arginine pool and increased NO synthesis, supporting existing models for HC action in SCA. The metabolomics results extend the current knowledge on the models for SCA pathophysiology including impairment of Lands' cycle and increased synthesis of sphingosine 1-phosphate. Putative novel biomarkers are suggested. PMID: 33476407 [PubMed - as supplied by publisher]

Microalgal-bacterial consortia unveil distinct physiological changes to facilitate growth of microalgae.

Fri, 22/01/2021 - 14:35
Related Articles Microalgal-bacterial consortia unveil distinct physiological changes to facilitate growth of microalgae. FEMS Microbiol Ecol. 2021 Jan 21;: Authors: Perera IA, Abinandan S, Subashchandrabose SR, Venkateswarlu K, Naidu R, Megharaj M Abstract Physiological changes that drive the microalgal-bacterial consortia are poorly understood so far. In the present novel study, we initially assessed five morphologically distinct microalgae for their ability in establishing consortia in Bold's basal medium with a bacterial strain, Variovorax paradoxus IS1, all isolated from wastewaters. Tetradesmus obliquus IS2 and Coelastrella sp. IS3 were further selected for gaining insights into physiological changes including those of metabolomes in consortia involving V. paradoxus IS1. The distinct parameters investigated were pigments (chlorophyll a, b, and carotenoids), reactive oxygen species (ROS), lipids, and metabolites that are implicated in major metabolic pathways. There was a significant increase (>1.2-fold) in pigments, viz., chlorophyll a, b and carotenoids, decrease in ROS, and enhanced lipid yield (>2-fold) in consortia than in individual cultures. In addition, the differential regulation of cellular metabolites such as sugars, amino acids, organic acids, and phytohormones was distinct among the two microalgal-bacterial consortia. Our results thus indicate that the selected microalgal strains, T. obliquus IS2 and Coelastrella sp. IS3, developed efficient consortia with V. paradoxus IS1 by effecting the required physiological changes including metabolomics. Such microalgal-bacterial consortia could largely be used in wastewater treatment and for production of value-added metabolites. PMID: 33476378 [PubMed - as supplied by publisher]

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