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

The application of pseudotargeted metabolomics method for fruit juices discrimination.

Mon, 10/02/2020 - 14:09
Related Articles The application of pseudotargeted metabolomics method for fruit juices discrimination. Food Chem. 2020 Jan 22;316:126278 Authors: Xu L, Xu Z, Wang X, Wang B, Liao X Abstract To optimize and evaluate the pseudotargeted metabolomics for juice discrimination and authentication, five widely consumed fruit (apple, orange, pear, purple grape and mandarin) juices were selected. SWATH-MS data was acquired by various windows being calculated based on total ion current, and then 2310 and 2292 MRM transitions were generated. Most of them (1522 and 1872) were detected in positive and negative modes. Distinctive separation among these juices could be observed from principal component analysis and hierarchical clustering analysis. After analysis of variance, fold change analysis and orthogonal projection to latent structures discriminant analysis, 57 potential markers were defined. Subsequently, 33 markers were putatively annotated, which could be used for juice discrimination and authentication. And 7 markers including l-phenylalanine, ascorbic acid, adenosine, epicatechin, glutathione, chlorogenic acid and nobiletin, were confirmed by standards. It is clearly indicated that pseudotargeted metabolomics could make great contribution to food industry as a new emerging technique. PMID: 32036184 [PubMed - as supplied by publisher]

Physiochemical properties, protein and metabolite profiles of muscle exudate of chicken meat affected by wooden breast myopathy.

Mon, 10/02/2020 - 14:09
Related Articles Physiochemical properties, protein and metabolite profiles of muscle exudate of chicken meat affected by wooden breast myopathy. Food Chem. 2020 Jan 23;316:126271 Authors: Xing T, Zhao X, Xu X, Li J, Zhang L, Gao F Abstract The current study was designed to investigate the physiochemical properties, protein and metabolite profiles of muscle exudate obtained from chicken breast fillets affected by wooden breast (WB) myopathy. Twenty-four fillets were categorized into varying degrees of WB condition including normal, moderate and severe. Results indicated that exudate loss, free hemoglobin concentration, protein and lipid oxidation were affected by WB myopathy. Electrophoresis analysis showed eight distinct protein bands of differential relative abundance in WB samples compared with the normal, and the identified proteins were mostly involved in carbohydrate metabolic process. 1H nuclear magnetic resonance-based metabolomics identified eleven metabolites including amino acids, nucleotides and organic acid as the most influential metabolites affected by WB myopathy. Overall, this study shows differential molecular profiles of myopathic chicken muscle exudate, and provides a valuable resource for further recognition of WB myopathy. PMID: 32036178 [PubMed - as supplied by publisher]

Metabolomics analysis to evaluate the antibacterial activity of the essential oil from the leaves of Cinnamomum camphora (Linn.) Presl.

Mon, 10/02/2020 - 14:09
Related Articles Metabolomics analysis to evaluate the antibacterial activity of the essential oil from the leaves of Cinnamomum camphora (Linn.) Presl. J Ethnopharmacol. 2020 Feb 06;:112652 Authors: Chen J, Tang C, Zhang R, Ye S, Zhao Z, Huang Y, Xu X, Lan W, Yang D Abstract ETHNOPHARMACOLOGY RELEVANCE: Cinnamomum camphora (Linn.) Presl (C. camphora) is one of the oldest herbal medicines used as a traditional medicine, owning a wide range of biological functions including anti-bacterial, anti-oxidative, anti-fungal, anti-inflammatory, insecticidal and repellent activities. OBJECTIVE: The aim of this study was to investigate the antibacterial activity and mechanism of action of the essential oil (EO) from C. camphora. MATERIALS AND METHODS: The EO was isolated from the leaves of C. camphora by hydrodistillation, and the chemical compositions of the EO were analyzed by gas chromatography-mass spectrometry (GC-MS). The minimum inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) values of the EO were estimated by the microbroth dilution method. Growth curve was investigated by turbidimetry. Apoptosis was measured by flow cytometry. Morphological change of bacteria was observed by field emission scanning electron microscopy and transmission electron microscopy. The integrity of cell membrane was evaluated by NanoDrop and BCA Protein Assay Kit. The methicillin-resistant Staphylococcus aureus (MRSA) metabolic profile in the presence of the EO was explored by GC-MS-based metabolomics. Isocitrate dehydrogenase (ICDH), α-ketoglutarate dehydrogenase (α-KGDH), succinic dehydrogenase (SDH) and malic dehydrogenase (MDH) activities were detected by commercial kits. RESULTS: The main components of the EO from the leaves of C. camphora were identified to be linalool (26.6%), eucalyptol (16.8%), α-terpineol (8.7%), isoborneol (8.1%), β-phellandrene (5.1%), and camphor (5.0%). The EO had good activity against MRSA, Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis, Salmonella gallinarum and Escherichia coli. MRSA was selected as the model bacterium to illustrate antibacterial mechanism of action of the EO, and the MIC and MBC values was 0.8 and 1.6 mg/mL, respectively. Apoptosis rate of MRSA increased in a concentration-dependent manner after the addition of EO. The cell morphology was damaged by the EO. There were 74 significantly different metabolites, including 29 upregulated and 45 downregulated metabolites in the result of metabolomics evaluation. Seven pathways were enriched by shared differential metabolites. The EO enhanced the activity of ICDH by 47.35%, while weaken MDH, SDH and α-KGDH by 72.63%, 31.52% and 63.29%, respectively. CONCLUSIONS: The EO from C. camphora showed anti-MRSA activity via damaging cell membranes and disturbing the amino metabolism. PMID: 32035880 [PubMed - as supplied by publisher]

Unraveling the metabolite signature of citrus showing defense response towards Candidatus Liberibacter asiaticus after application of endophyte Bacillus subtilis L1-21.

Sun, 09/02/2020 - 13:53
Related Articles Unraveling the metabolite signature of citrus showing defense response towards Candidatus Liberibacter asiaticus after application of endophyte Bacillus subtilis L1-21. Microbiol Res. 2020 Jan 31;234:126425 Authors: Munir S, Li Y, He P, He P, Ahmed A, Wu Y, He Y Abstract Huanglongbing (HLB) is one of the most serious citrus diseases, caused by phloem limited endophytic bacteria Candidatus Liberibacter asiaticus (Clas), affecting worldwide citrus production. Metabolomics approaches were employed to gain insight into mechanisms involved in defense against Clas in endophyte Bacillus subtilis L1-21 treated diseased and healthy citrus plants. Using LC-ESI-MS/MS, we compared the metabolic profile of citrus plants before and after treatment with endophyte L1-21. Our analysis indicated large differences in citrus metabolites after endophyte L1-21 application. In total, seven hundred and fourty two metabolites were detected with highest percentage recorded for organic acids, flavone, amino acid derivatives, flavone C-glycosides, nucleotide derivatives, and flavonol. Interestingly, differentially expressed metabolites (DEMs) analysis revealed the amino acids, such as lysine and tyrosine which are involved in plant defense agianst pathogen attack were regulated in diseased citrus plants after endophyte application (padj<0.05). In addition, other important metabolites up-regulated were xanthine, leucic acid, and α-Linolenic acid implicated in different plant defense pathways against Clas. Furhter, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed important pathways related to purine metabolism, biotin metabolism, and betalain biosynthesis, terpenoid-quinone biosynthesis, phenylalanine, tyrosine and lysine biosynthesis, isoflavonoid biosynthesis (padj<0.05). Taken together, this is the first study using native endophytes in diseased and healthy state of citrus which has proven to be useful in disease management by strengthening the defense of citrus to Clas pathogen. PMID: 32035248 [PubMed - as supplied by publisher]

Plasma lipid profile associates with the improvement of psychological well-being in individuals with perceived stress symptoms.

Sun, 09/02/2020 - 13:53
Related Articles Plasma lipid profile associates with the improvement of psychological well-being in individuals with perceived stress symptoms. Sci Rep. 2020 Feb 07;10(1):2143 Authors: Noerman S, Klåvus A, Järvelä-Reijonen E, Karhunen L, Auriola S, Korpela R, Lappalainen R, Kujala UM, Puttonen S, Kolehmainen M, Hanhineva K Abstract Psychological stress is a suggested risk factor of metabolic disorders, but molecular mediators are not well understood. We investigated the association between the metabolic profiles of fasting plasma and the improvement of psychological well-being using non-targeted liquid chromatography-mass spectrometry (LC-MS) platform. The metabolic profiles of volunteers participating in the face-to-face intervention group (n = 60) in a randomised lifestyle intervention were compared to ones of controls (n = 64) between baseline and 36-week follow-up. Despite modest differences in metabolic profile between groups, we found associations between phosphatidylcholines (PCs) and several parameters indicating stress, adiposity, relaxation, and recovery. The relief of heart-rate-variability-based stress had positive, while improved indices of recovery and relaxation in the intervention group had an inverse association with the reduction of e.g. lysophosphatidylcholines (LPC). Interleukin-1 receptor antagonist and adiposity correlated positively with the suppressed PCs and negatively with the elevated plasmalogens PC(P-18:0/22:6) and PC(P-18:0/20:4). Also, we found changes in an unknown class of lipids over time regardless of the intervention groups, which also correlated with physiological and psychological markers of stress. The associations between lipid changes with some markers of psychological wellbeing and body composition may suggest the involvement of these lipids in the shared mechanisms between psychological and metabolic health. PMID: 32034255 [PubMed - in process]

G protein-coupled kisspeptin receptor induces metabolic reprograming and tumorigenesis in estrogen receptor-negative breast cancer.

Sun, 09/02/2020 - 13:53
Related Articles G protein-coupled kisspeptin receptor induces metabolic reprograming and tumorigenesis in estrogen receptor-negative breast cancer. Cell Death Dis. 2020 Feb 07;11(2):106 Authors: Dragan M, Nguyen MU, Guzman S, Goertzen C, Brackstone M, Dhillo WS, Bech PR, Clarke S, Abbara A, Tuck AB, Hess DA, Pine SR, Zong WX, Wondisford FE, Su X, Babwah AV, Bhattacharya M Abstract Triple-negative breast cancer (TNBC) is a highly metastatic and deadly disease. TNBC tumors lack estrogen receptor (ERα), progesterone receptor (PR), and HER2 (ErbB2) and exhibit increased glutamine metabolism, a requirement for tumor growth. The G protein-coupled kisspeptin receptor (KISS1R) is highly expressed in patient TNBC tumors and promotes malignant transformation of breast epithelial cells. This study found that TNBC patients displayed elevated plasma kisspeptin levels compared with healthy subjects. It also provides the first evidence that in addition to promoting tumor growth and metastasis in vivo, KISS1R-induced glutamine dependence of tumors. In addition, tracer-based metabolomics analyses revealed that KISS1R promoted glutaminolysis and nucleotide biosynthesis by increasing c-Myc and glutaminase levels, key regulators of glutamine metabolism. Overall, this study establishes KISS1R as a novel regulator of TNBC metabolism and metastasis, suggesting that targeting KISS1R could have therapeutic potential in the treatment of TNBC. PMID: 32034133 [PubMed - in process]

Gastric bypass surgery in a rat model alters the community structure and functional composition of the intestinal microbiota independently of weight loss.

Sun, 09/02/2020 - 13:53
Related Articles Gastric bypass surgery in a rat model alters the community structure and functional composition of the intestinal microbiota independently of weight loss. Microbiome. 2020 Feb 07;8(1):13 Authors: Haange SB, Jehmlich N, Krügel U, Hintschich C, Wehrmann D, Hankir M, Seyfried F, Froment J, Hübschmann T, Müller S, Wissenbach DK, Kang K, Buettner C, Panagiotou G, Noll M, Rolle-Kampczyk U, Fenske W, von Bergen M Abstract BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery is a last-resort treatment to induce substantial and sustained weight loss in cases of severe obesity. This anatomical rearrangement affects the intestinal microbiota, but so far, little information is available on how it interferes with microbial functionality and microbial-host interactions independently of weight loss. METHODS: A rat model was employed where the RYGB-surgery cohort is compared to sham-operated controls which were kept at a matched body weight by food restriction. We investigated the microbial taxonomy and functional activity using 16S rRNA amplicon gene sequencing, metaproteomics, and metabolomics on samples collected from theileum, the cecum, and the colon, and separately analysed the lumen and mucus-associated microbiota. RESULTS: Altered gut architecture in RYGB increased the relative occurrence of Actinobacteria, especially Bifidobacteriaceae and Proteobacteria, while in general, Firmicutes were decreased although Streptococcaceae and Clostridium perfringens were observed at relative higher abundances independent of weight loss. A decrease of conjugated and secondary bile acids was observed in the RYGB-gut lumen. The arginine biosynthesis pathway in the microbiota was altered, as indicated by the changes in the abundance of upstream metabolites and enzymes, resulting in lower levels of arginine and higher levels of aspartate in the colon after RYGB. CONCLUSION: The anatomical rearrangement in RYGB affects microbiota composition and functionality as well as changes in amino acid and bile acid metabolism independently of weight loss. The shift in the taxonomic structure of the microbiota after RYGB may be mediated by the resulting change in the composition of the bile acid pool in the gut and by changes in the composition of nutrients in the gut. Video abstract. PMID: 32033593 [PubMed - in process]

Nicotinamide attenuates the decrease in dendritic spine density in hippocampal primary neurons from 5xFAD mice, an Alzheimer's disease animal model.

Sun, 09/02/2020 - 13:53
Related Articles Nicotinamide attenuates the decrease in dendritic spine density in hippocampal primary neurons from 5xFAD mice, an Alzheimer's disease animal model. Mol Brain. 2020 Feb 07;13(1):17 Authors: Kim H, Kim B, Kim HS, Cho JY Abstract Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by memory loss and the presence of amyloid plaques and neurofibrillary tangles in the patients' brains. In this study, we investigated the alterations in metabolite profiles of the hippocampal tissues from 6, 8, and 12 month-old wild-type (WT) and 5xfamiliar AD (5xFAD) mice, an AD mouse model harboring 5 early-onset familiar AD mutations, which shows memory loss from approximately 5 months of age, by exploiting the untargeted metabolomics profiling. We found that nicotinamide and adenosine monophosphate levels have been significantly decreased while lysophosphatidylcholine (LysoPC) (16:0), LysoPC (18:0), and lysophosphatidylethanolamine (LysoPE) (16:0) levels have been significantly increased in the hippocampi from 5xFAD mice at 8 months or 12 months of age, compared to those from age-matched wild-type mice. In the present study, we focused on the role of nicotinamide and examined if replenishment of nicotinamide exerts attenuating effects on the reduction in dendritic spine density in hippocampal primary neurons from 5xFAD mice. Treatment with nicotinamide attenuated the deficits in spine density in the hippocampal primary neurons derived from 5xFAD mice, indicating a potential role of nicotinamide in the pathogenesis of AD. Taken together, these findings suggest that the decreased hippocampal nicotinamide level could be linked with AD pathogenesis and be a useful therapeutic target for AD. PMID: 32033569 [PubMed - in process]

Biosynthesis of Saxitoxin in Marine Dinoflagellates: An Omics Perspective.

Sun, 09/02/2020 - 13:53
Related Articles Biosynthesis of Saxitoxin in Marine Dinoflagellates: An Omics Perspective. Mar Drugs. 2020 Feb 05;18(2): Authors: Akbar MA, Mohd Yusof NY, Tahir NI, Ahmad A, Usup G, Sahrani FK, Bunawan H Abstract Saxitoxin is an alkaloid neurotoxin originally isolated from the clam Saxidomus giganteus in 1957. This group of neurotoxins is produced by several species of freshwater cyanobacteria and marine dinoflagellates. The saxitoxin biosynthesis pathway was described for the first time in the 1980s and, since then, it was studied in more than seven cyanobacterial genera, comprising 26 genes that form a cluster ranging from 25.7 kb to 35 kb in sequence length. Due to the complexity of the genomic landscape, saxitoxin biosynthesis in dinoflagellates remains unknown. In order to reveal and understand the dynamics of the activity in such impressive unicellular organisms with a complex genome, a strategy that can carefully engage them in a systems view is necessary. Advances in omics technology (the collective tools of biological sciences) facilitated high-throughput studies of the genome, transcriptome, proteome, and metabolome of dinoflagellates. The omics approach was utilized to address saxitoxin-producing dinoflagellates in response to environmental stresses to improve understanding of dinoflagellates gene-environment interactions. Therefore, in this review, the progress in understanding dinoflagellate saxitoxin biosynthesis using an omics approach is emphasized. Further potential applications of metabolomics and genomics to unravel novel insights into saxitoxin biosynthesis in dinoflagellates are also reviewed. PMID: 32033403 [PubMed - in process]

Beneficial Effects of a Low-dose of Conjugated Linoleic Acid on Body Weight Gain and other Cardiometabolic Risk Factors in Cafeteria Diet-fed Rats.

Sun, 09/02/2020 - 13:53
Related Articles Beneficial Effects of a Low-dose of Conjugated Linoleic Acid on Body Weight Gain and other Cardiometabolic Risk Factors in Cafeteria Diet-fed Rats. Nutrients. 2020 Feb 04;12(2): Authors: Martín-González MZ, Palacios H, Rodríguez MA, Arola L, Aragonès G, Muguerza B Abstract Conjugated linoleic acid (CLA) is a dietary supplement that has been shown to improve obesity. However, some authors have associated high doses of CLA supplementation with liver impairment and insulin resistance. The aim of this study was to assess whether the consumption of low doses of CLA maintained the beneficial effects on the main metabolic disturbances associated with metabolic syndrome (MetS) but prevented the occurrence of non-desirable outcomes associated with its consumption. Male Wistar rats, fed standard or cafeteria (CAF) diet for 12 weeks, were supplemented with three different low doses of CLA in the last three weeks. Both biochemical and H1 NMR-based metabolomics profiles were analysed in serum and liver. The consumption of 100 mg/kg CLA, but not doses of 200 and 300 mg/kg, ameliorated the increase in body weight gain as well as the serum concentrations of glucose, insulin, cholesterol, triglyceride, diglyceride, and total phospholipid induced by a CAF diet. In turn, CLA reverted the increase in lactate, alanine, and glucose concentrations in the liver of these animals, but enhanced hepatic cholesterol accumulation without any detrimental effect on liver function. In conclusion, a low dose of CLA corrected the adverse effects associated with MetS without compromising other metabolic parameters. PMID: 32033223 [PubMed - in process]

metabolomics; +18 new citations

Sat, 08/02/2020 - 13:45
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 2020/02/08PubMed 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; +26 new citations

Fri, 07/02/2020 - 13:34
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 2020/02/07PubMed 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; +56 new citations

Thu, 06/02/2020 - 16:11
56 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 2020/02/06PubMed 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.

metabolomics; +56 new citations

Thu, 06/02/2020 - 13:11
56 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 2020/02/06PubMed 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.

metabolomics; +37 new citations

Wed, 05/02/2020 - 22:08
37 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 2020/02/05PubMed 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.

Metabolomic profiling to evaluate the efficacy of proxalutamide, a novel androgen receptor antagonist, in prostate cancer cells.

Mon, 03/02/2020 - 12:43
Metabolomic profiling to evaluate the efficacy of proxalutamide, a novel androgen receptor antagonist, in prostate cancer cells. Invest New Drugs. 2020 Feb 01;: Authors: Qu F, Gu Y, Wang Q, He M, Zhou F, Sun J, Wang G, Peng Y Abstract Proxalutamide is a newly developed androgen receptor (AR) antagonist for the treatment of castration-resistant prostate cancer (PCa) that has entered phase III clinical trials. In the present study, we intended to elucidate the antitumor efficacy of proxalutamide through the metabolomic profiling of PCa cells. Two AR-positive PCa cell lines and two AR-negative PCa cell lines were investigated. Cell viability assays based on ATP quantitation were conducted. LC-Q/TOF-MS was used to analyze intracellular metabolites before or after the administration of proxalutamide and two other clinical AR antagonists (bicalutamide and enzalutamide). The results of this study showed that the inhibitory effect of proxalutamide on PCa cell proliferation was better than that of bicalutamide and enzalutamide, and proxalutamide preferentially affected AR-positive PCa cells over AR-negative cells. The metabolic composition of PCa cells changed significantly after proxalutamide administration, and these changes in response to proxalutamide were significantly different from those in the presence of the two other AR antagonists. In AR-positive cells, proxalutamide significantly decreased the intracellular levels of glutamine, glutamate, glutathione, cysteine, glycine, aspartate, uridine, cytidine and thymidine. However, the effects of the two other antagonists on these discriminant metabolites were ambiguous, and no changes in these metabolites were found in AR-negative cells. Our findings indicate that proxalutamide has inhibitory effects on glutamine metabolism, redox homeostasis and de novo pyrimidine synthesis in AR-positive PCa cells that enhance the cellular sensitivity to proxalutamide. PMID: 32008178 [PubMed - as supplied by publisher]

Metabolic Profiles Help Discriminate Mild Cognitive Impairment from Dementia Stage in Alzheimer's Disease.

Mon, 03/02/2020 - 12:43
Metabolic Profiles Help Discriminate Mild Cognitive Impairment from Dementia Stage in Alzheimer's Disease. J Alzheimers Dis. 2020 Jan 28;: Authors: Jääskeläinen O, Hall A, Tiainen M, van Gils M, Lötjönen J, Kangas AJ, Helisalmi S, Pikkarainen M, Hallikainen M, Koivisto A, Hartikainen P, Hiltunen M, Ala-Korpela M, Soininen P, Soininen H, Herukka SK Abstract Accurate differentiation between neurodegenerative diseases is developing quickly and has reached an effective level in disease recognition. However, there has been less focus on effectively distinguishing the prodromal state from later dementia stages due to a lack of suitable biomarkers. We utilized the Disease State Index (DSI) machine learning classifier to see how well quantified metabolomics data compares to clinically used cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD). The metabolic profiles were quantified for 498 serum and CSF samples using proton nuclear magnetic resonance spectroscopy. The patient cohorts in this study were dementia (with a clinical AD diagnosis) (N = 359), mild cognitive impairment (MCI) (N = 96), and control patients with subjective memory complaints (N = 43). DSI classification was conducted for MCI (N = 51) and dementia (N = 214) patients with low CSF amyloid-β levels indicating AD pathology and controls without such amyloid pathology (N = 36). We saw that the conventional CSF markers of AD were better at classifying controls from both dementia and MCI patients. However, quantified metabolic subclasses were more effective in classifying MCI from dementia. Our results show the consistent effectiveness of traditional CSF biomarkers in AD diagnostics. However, these markers are relatively ineffective in differentiating between MCI and the dementia stage, where the quantified metabolomics data provided significant benefit. PMID: 32007958 [PubMed - as supplied by publisher]

Metabolomic study of raw and bran-fried Atractylodis Rhizoma on rats with spleen deficiency.

Mon, 03/02/2020 - 12:43
Metabolomic study of raw and bran-fried Atractylodis Rhizoma on rats with spleen deficiency. J Pharm Biomed Anal. 2019 Dec 30;182:112927 Authors: Zhang BX, Qi XJ, Cai Q Abstract Atractylodis Rhizoma, a classical Chinese medicine, exhibits unambiguous therapeutic effect on spleen deficiency in China for decades. The aim of the present study was to explore the different effects on the composition and level of endogenous metabolites in rats with spleen deficiency after oral administration of raw and bran-fired Atractylodis Rhizoma, and to explain the mechanism of pharmacodynamic enhancement of the bran-fried Atractylodis Rhizoma from the perspective of metabolomics. With this purpose, spleen deficiency model was established by diet, excessive fatigue and bitter cold diarrhea. Then, Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of vasoactive intestinal peptide (VIP), Somatostatin (SS), substance P (SP) and succinodehydrogenase (SDH) in rats of each group, and to compare the contents of VIP, SS, SP and SDH among groups. UHPLC-Q-TOF-MS based metabolomics was adopted to analyze the plasma from spleen deficiency rats and control rats. Principle component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were utilized to identify differences of metabolic profiles in rats among the control group and the model group;The OPLS-DA were used to analyze the effects of raw and bran-fried Atractylodis Rhizoma on the same metabolites. The results showed that compared with the control group, the contents of VIP, SS, SP and SDH in the plasma of model group decreased, which proved the success of the model group. Compared with model group, the contents of VIP, SS, SP and SDH in the plasma of raw and bran-fried Atractylodis Rhizoma increased, and the effect of bran-fried Atractylodis Rhizoma was better than that of raw Atractylodis Rhizoma. Metabolomics results showed that seventeen different metabolites of spleen deficiency were screened out in the plasma of rats with spleen deficiency compared with the control group. Among them, Nicotinic acid, Dihydrofolic acid, Pantetheine 4'-phosphate and Photophatidylcholine (PC) were the metabolites significantly associated with spleen deficiency, and bran-fried Atractylodis Rhizoma had better intervention and regulation. Through the analysis of metabolic pathways related to these different metabolites of spleen deficiency, and primarily involved in glucosamine metabolism, one carbon pool by folate and so on. This study showed that Atractylodis Rhizoma could provide satisfactory therapeutic effects on spleen deficiency and metabolomics study can be utilized to further understand the molecular mechanisms. PMID: 32007825 [PubMed - as supplied by publisher]

The impact of phenanthrene on membrane phospholipids and its biodegradation by Sphingopyxis soli.

Mon, 03/02/2020 - 12:43
The impact of phenanthrene on membrane phospholipids and its biodegradation by Sphingopyxis soli. Ecotoxicol Environ Saf. 2020 Jan 30;192:110254 Authors: Shon JC, Noh YJ, Kwon YS, Kim JH, Wu Z, Seo JS Abstract The direct interactions of bacterial membranes and polycyclic aromatic hydrocarbons (PAHs) strongly influence the biological processes, such as metabolic activity and uptake of substrates due to changes in membrane lipids. However, the elucidation of adaptation mechanisms as well as membrane phospholipid alterations in the presence of phenanthrene (PHE) from α-proteobacteria has not been fully explored. This study was conducted to define the degradation efficiency of PHE by Sphingopyxis soli strain KIT-001 in a newly isolated from Jeonju river sediments and to characterize lipid profiles in the presence of PHE in comparison to cells grown on glucose using quantitative lipidomic analysis. This strain was able to respectively utilize 1-hydroxy-2-naphthoic acid and salicylic acid as sole carbon source and approximately 90% of PHE (50 mg/L) was rapidly degraded via naphthalene route within 1 day incubation. In the cells grown on PHE, strain KIT-001 appeared to dynamically change profiles of metabolite and lipid in comparison to cells grown on glucose. The levels of primary metabolites, phosphatidylethanolamines (PE), and phosphatidic acids (PA) were significantly decreased, whereas the levels of phosphatidylcholines (PC) and phosphatidylglycerols (PG) were significantly increased. The adaptation mechanism of Sphingopyxis sp. regarded mainly the accumulation of bilayer forming lipids and anionic lipids to adapt more quickly under restricted nutrition and toxicity condition. Hence, these findings are conceivable that strain KIT-001 has a good adaptive ability and biodegradation for PHE through the alteration of phospholipids, and will be helpful for applications for effective bioremediation of PAHs-contaminated sites. PMID: 32007746 [PubMed - as supplied by publisher]

Dose-escalation trial of budesonide in surfactant for prevention of bronchopulmonary dysplasia in extremely low gestational age high-risk newborns (SASSIE).

Sun, 02/02/2020 - 12:27
Related Articles Dose-escalation trial of budesonide in surfactant for prevention of bronchopulmonary dysplasia in extremely low gestational age high-risk newborns (SASSIE). Pediatr Res. 2020 Feb 01;: Authors: McEvoy CT, Ballard PL, Ward RM, Rower JE, Wadhawan R, Hudak ML, Weitkamp JH, Harris J, Asselin J, Chapin C, Ballard RA Abstract BACKGROUND: Initial trials of lung-targeted budesonide (0.25 mg/kg) in surfactant to prevent bronchopulmonary dysplasia (BPD) in premature infants have shown benefit; however, the optimal safe dose is unknown. METHODS: Dose-escalation study of budesonide (0.025, 0.05, 0.10 mg/kg) in calfactatant in extremely low gestational age neonates (ELGANs) requiring intubation at 3-14 days. Tracheal aspirate (TA) cytokines, blood budesonide concentrations, and untargeted blood metabolomics were measured. Outcomes were compared with matched infants receiving surfactant in the Trial Of Late SURFactant (TOLSURF). RESULTS: Twenty-four infants with mean gestational age 25.0 weeks and 743 g birth weight requiring mechanical ventilation were enrolled at mean age 6 days. Budesonide was detected in the blood of all infants with a half-life of 3.4 h. Of 11 infants with elevated TA cytokine levels at baseline, treatment was associated with sustained decrease (mean 65%) at all three dosing levels. There were time- and dose-dependent decreases in blood cortisol concentrations and changes in total blood metabolites. Respiratory outcomes did not differ from the historic controls. CONCLUSIONS: Budesonide/surfactant had no clinical respiratory benefit at any dosing levels for intubated ELGANs. One-tenth the dose used in previous trials had minimal systemic metabolic effects and appeared effective for lung-targeted anti-inflammatory action. PMID: 32006953 [PubMed - as supplied by publisher]

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