PubMed

Plasma Metabolomic Markers of Insulin Resistance and Diabetes and Rate of Incident Parkinson's Disease. J Parkinsons Dis. 2020 Mar 31;: Authors: Molsberry S, Bjornevik K, Hughes KC, Zhang ZJ, Jeanfavre S, Clish C, Healy B, Schwarzschild M, Ascherio A Abstract BACKGROUND: Although there is evidence of shared dysregulated pathways between diabetes and Parkinson's disease, epidemiologic research on an association between the two diseases has produced inconsistent results. OBJECTIVE: We aimed to assess whether known metabolomic markers of insulin resistance and diabetes are also associated with Parkinson's disease development. METHODS: We conducted a nested case-control study among Nurses' Health Study and Health Professionals Follow-up Study participants who had provided blood samples up to twenty years prior to Parkinson's diagnosis. Cases were matched to risk-set sampled controls by age, sex, fasting status, and time of blood collection. Participants provided covariate information via regularly collected cohort questionnaires. We used conditional logistic regression models to assess whether plasma levels of branched chain amino acids, acylcarnitines, glutamate, or glutamine were associated with incident development of Parkinson's disease. RESULTS: A total of 349 case-control pairs were included in this analysis. In the primary analyses, none of the metabolites of interest were associated with Parkinson's disease development. In investigations of the association between each metabolite and Parkinson's disease at different time intervals prior to diagnosis, some metabolites showed marginally significant association but, after correction for multiple testing, only C18 : 2 acylcarnitine was significantly associated with Parkinson's disease among subjects for whom blood was collected less than 60 months prior to case diagnosis. CONCLUSIONS: Plasma levels of diabetes-related metabolites did not contribute to predict risk of Parkinson's disease. Further investigation of the relationship between pre-diagnostic levels of diabetes-related metabolites and Parkinson's disease in other populations is needed to confirm these findings. PMID: 32250318 [PubMed - as supplied by publisher]

An extracytoplasmic protein and a moonlighting enzyme modulate synthesis of c-di-AMP in Listeria monocytogenes. Environ Microbiol. 2020 Apr 06;: Authors: Gibhardt J, Heidemann JL, Bremenkamp R, Rosenberg J, Seifert R, Kaever V, Ficner R, Commichau FM Abstract The second messenger cyclic di-AMP (c-di-AMP) is essential for growth of many bacteria because it controls osmolyte homeostasis. c-di-AMP can regulate the synthesis of potassium uptake systems in some bacteria and also directly inhibits and activates potassium import and export systems, respectively. Therefore, c-di-AMP production and degradation have to be tightly regulated depending on the environmental osmolarity. The Gram-positive pathogen Listeria monocytogenes relies on the membrane-bound diadenylate cyclase CdaA for c-di-AMP production and degrades the nucleotide with two phosphodiesterases. While the enzymes producing and degrading the dinucleotide have been reasonably well examined, the regulation of c-di-AMP production is not well understood yet. Here we demonstrate that the extracytoplasmic regulator CdaR interacts with CdaA via its transmembrane helix to modulate c-di-AMP production. Moreover, we show that the phosphoglucosamine mutase GlmM forms a complex with CdaA and inhibits the diadenylate cyclase activity in vitro. We also found that GlmM inhibits c-di-AMP production in L. monocytogenes when the bacteria encounter osmotic stress. Thus, GlmM is the major factor controlling the activity of CdaA in vivo. GlmM can be assigned to the class of moonlighting proteins because it is active in metabolism and adjusts the cellular turgor depending on environmental osmolarity. This article is protected by copyright. All rights reserved. PMID: 32250026 [PubMed - as supplied by publisher]

Metabolomic alternations of follicular fluid of obese women undergoing in-vitro fertilization treatment. Sci Rep. 2020 Apr 06;10(1):5968 Authors: Song J, Xiang S, Pang C, Guo J, Sun Z Abstract Obesity exerts negative effects on the metabolic homeostasis of cells in various tissues, but how it influences ovum metabolism is not fully understood. Previous studies demonstrate that oocyte genes that regulate oxidative stress, lipid metabolism, and inflammation are highly expressed in obese women. However, the metabolic effects of these genetic variations are not clear. To address this gap, we conducted an exploratory evaluation of follicular fluid (FF) metabolites in underweight, normal-weight, overweight, and obese women undergoing in vitro fertilization (IVF) treatment. The FF samples from the underweight (Group A, n = 40), normal-weight (Group B, n = 40), overweight (Group C, n = 40), and obese women (Group D, n = 40) were analyzed using ultra-performance liquid chromatography high-resolution mass spectrometry. A novel, high-coverage, semi-targeted metabolomics method (SWATH to MRM) and a targeted metabolomics method were employed to identify and verify the differential metabolites between the four groups. Sixteen differentially expressed FF metabolites were identified. Increase of BMI was associated with upregulation of 5 metabolites, ganoderiol H, LPI (18:3), sedoheptulose 1,7-bisphosphate, austalide L and 2 - {[hydroxyl (3-hydroxy-4-methoxyphenylmethylidene] amino} acetic acid, and downregulation of 5 metabolites, 1-phenyl-1,3-elcosanedione, retinol acetate, p-Cresol sulfate, setariol and arachidonyl carnitine. These metabolites were enriched in different metabolic pathways of retinol metabolism and fatty acid metabolism. These obesity-related differential metabolites provide a pathogenesis mechanism that explains the decline of oocyte development during obesity. These results suggest that obesity affects follicular environment prior to pregnancy, a time-window that may be important for lifestyle interventions to decrease obesity levels. PMID: 32249791 [PubMed - in process]

Mass spectrometry-based Food Metabolomics in Routine Applications: A basic Standardization Approach using Housekeeping Metabolites for the Authentication of Asparagus. J Agric Food Chem. 2020 Apr 04;: Authors: Creydt M, Fischer M Abstract The low reproducibility of non-targeted LC-MS-based metabolomics approaches represents a major challenge for their implementation in routine analyses, since it is impossible to compare individual measurements directly with each other, if they were not analysed in the same batch. This study describes a normalization process based on housekeeping metabolites in plant based raw materials, which are present in comparatively constant concentrations and are subject to no or only minor deviations due to exogenous influences. As a model, an authenticity study was selected to determine the origin of white asparagus (asparagus officinalis). Using three model data sets and one test data set, we were able to show that samples that have been measured independently of one another can be correctly assigned in terms of origin after the normalization with housekeeping metabolites. The procedure does not require internal standards or the measurements of further reference samples and can also be applied to other matrices and scientific issues. PMID: 32249560 [PubMed - as supplied by publisher]

Related Articles Analyses of competent and non-competent subpopulations of Bacillus subtilis reveal yhfW, yhxC and ncRNAs as novel players in competence. Environ Microbiol. 2020 Apr 05;: Authors: Boonstra M, Schaffer M, Sousa J, Morawska L, Holsappel S, Hildebrandt P, Sappa PK, Rath H, de Jong A, Lalk M, Mäder U, Völker U, Kuipers OP Abstract Upon competence-inducing nutrient-limited conditions only part of the B. subtilis population becomes competent. Here, we separated the two sub-populations by Fluorescence Assisted Cell Sorting (FACS). Using RNA-seq we confirmed the previously described ComK regulon. We also found for the first time significantly down-regulated genes in the competent sub-population. The down-regulated genes are not under direct control by ComK, but have higher levels of corresponding antisense RNAs in the competent subpopulation. During competence, cell-division and replication are halted. By investigating the proteome during competence we found higher levels of the regulators of cell division, MinD and Noc. The exonucleases SbcC and SbcD were also primarily regulated at the post-transcriptional level. In the competent sub-population yhfW was newly identified as being highly up-regulated. Its absence reduces the expression of comG, and has a modest, but statistically significant effect on the expression of comK. Although expression of yhfW is higher in the competent subpopulation, no ComK-binding site is present in its promoter region. Mutants of yhfW have a small but significant defect in transformation. Metabolomic analyses revealed significant reductions in tricarboxylic acid (TCA) cycle metabolites and several amino acids in a ΔyhfW mutant. RNA-seq analysis of ΔyhfW revealed higher expression of the NAD synthesis genes nadA, nadB and nadC. This article is protected by copyright. All rights reserved. PMID: 32249531 [PubMed - as supplied by publisher]

Related Articles Combined Cohesin-Runx1 Deficiency Synergistically Perturbs Chromatin Looping and Causes Myelodysplastic Syndromes. Cancer Discov. 2020 Apr 05;: Authors: Ochi Y, Kon A, Sakata T, Nakagawa MM, Nakazawa N, Kakuta M, Kataoka K, Koseki H, Nakayama M, Morishita D, Tsuruyama T, Saiki R, Yoda A, Okuda R, Yoshizato T, Yoshida K, Shiozawa Y, Nannya Y, Kotani S, Kogure Y, Kakiuchi N, Nishimura T, Makishima H, Malcovati L, Yokoyama A, Takeuchi K, Sugihara E, Sato TA, Sanada M, Takaori-Kondo A, Cazzola M, Kengaku M, Miyano S, Shirahige K, Suzuki HI, Ogawa S Abstract STAG2 encodes a cohesin component and is frequently mutated in myeloid neoplasms, showing highly significant co-mutation patterns with other drivers, including RUNX1. However, the molecular basis of cohesin-mutated leukemogenesis remains poorly understood. Here we show a critical role of an interplay between Stag2 and Runx1 in the regulation of enhancer-promoter looping and transcription in hematopoiesis. Combined loss of Stag2 and Runx1, which co-localize at enhancer-rich, Ctcf-deficient sites, synergistically attenuates enhancer-promoter loops, particularly at sites enriched for RNA polymerase II and Mediator, and deregulates gene expression, leading to myeloid-skewed expansion of hematopoietic stem/progenitor cells (HSPCs) and myelodysplastic syndromes (MDS). Attenuated enhancer-promoter loops in Stag2/Runx1-deficient cells are associated with downregulation of genes with high basal transcriptional pausing, which are important for regulation of HSPCs. Down-regulation of high-pausing genes is also confirmed in STAG2/cohesin-mutated primary leukemia samples. Our results highlight a unique STAG2/RUNX1 interplay in gene regulation and provide insights into cohesin-mutated leukemogenesis. PMID: 32249213 [PubMed - as supplied by publisher]

Related Articles Quorum sensing inhibition and tobramycin acceleration in Chromobacterium violaceum by two natural cinnamic acid derivatives. Appl Microbiol Biotechnol. 2020 Apr 04;: Authors: Cheng WJ, Zhou JW, Zhang PP, Luo HZ, Tang S, Li JJ, Deng SM, Jia AQ Abstract Chromobacterium violaceum, one free-living Gram-negative bacterium, is abundantly presented in tropics and sub-tropics soil and aquatic environment; it is also an opportunistic human pathogen. Here, two cinnamic acid derivatives, i.e., 4-dimethylaminocinnamic acid (DCA) and 4-methoxycinnamic acid (MCA), were identified as potential quorum sensing (QS) and biofilm inhibitors in C. violaceum ATCC12472. Both DCA (100 μg/mL) and MCA (200 μg/mL) inhibited the levels of N-decanoyl-homoserine lactone (C10-HSL) and reduced the production of certain virulence factors in C. violaceum, including violacein, hemolysin, and chitinase. Metabolomics analysis indicated that QS-related metabolites, such as ethanolamine and L-methionine, were down-regulated after treatment with DCA and MCA. Quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated that DCA and MCA markedly suppressed the expression of two QS-related genes (cviI and cviR). In addition, DCA and MCA also inhibited biofilm formation and enhanced the susceptibility of biofilms to tobramycin, which was evidenced by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Our results indicated that DCA and MCA can serve as QS-based agent for controlling pathogens.Key Points • DCA and MCA inhibited QS and biofilm formation in C. violaceum.• The combination of DCA or MCA and tobramycin removed the preformed biofilm of C. violaceum. • DCA or MCA inhibited virulence factors and expressions of cviI and cviR of C. violaceum.• DCA or MCA are potential antibiotic accelerants for treating C. violaceum infection. PMID: 32248442 [PubMed - as supplied by publisher]

Related Articles Deciphering the mechanism of carbon sources inhibiting recolorization in the removal of refractory dye: Based on an untargeted LC-MS metabolomics approach. Bioresour Technol. 2020 Mar 24;307:123248 Authors: Zheng X, Xie X, Liu Y, Cong J, Fan J, Fang Y, Liu N, He Z, Liu J Abstract In this study, the biological decolorization of reactive black 5 (RB5) by Klebsiella sp. KL-1 in yeast extract (YE) medium was captured the recolorization after exposure to O2, which induced a 15.82% reduction in decolorization efficiency. Similar result was also observed in YE + lactose medium, but not in YE + glucose/xylose media (groups YE + Glu/Xyl). Through biodegradation studies, several degradation intermediates without quinoid structure were produced in groups YE + Glu/Xyl and differential degradation pathways were deduced in diverse groups. Metabolomics analysis revealed significant variations in up-/down-regulated metabolites using RB5 and different carbon sources. Moreover, the underlying mechanism of recolorization inhibition was proposed. Elevated reducing power associated with variable metabolites (2-hydroxyhexadecanoic acid, 9(R)-HODE cholesteryl ester, linoleamide, oleamide) rendered additional reductive cleavage of C-N bond on naphthalene ring. This study provided a new orientation to inhibit recolorization and deepened the understanding of the molecular mechanism of carbon sources inhibiting recolorization in the removal of refractory dyes. PMID: 32248066 [PubMed - as supplied by publisher]

Related Articles Liraglutide attenuates renal tubular ectopic lipid deposition in rats with diabetic nephropathy by inhibiting lipid synthesis and promoting lipolysis. Pharmacol Res. 2020 Apr 02;:104778 Authors: Su K, Yi B, Yao BQ, Xia T, Yang YF, Zhang ZH, Chen C Abstract Liraglutide is a new hypoglycemic drug. The previous studies have shown that liraglutide can improve the renal outcomes of patients with type 2 diabetes. Recently, it was approved by the U.S. FDA for used as a weight-loss drugs. However, the mechanism of its improvements of renal function in diabetic nephropathy patients is unclear. In addition, the effect of liraglutide on lipid metabolism is also not clear. The purpose of this study was to investigate the effects and mechanisms of liraglutide in alleviating ectopic lipid deposition (ELD) in rats with diabetic nephropathy (DN). Male Sprague-Dawley (SD) rats were treated with high-fat diet + unilateral nephrectomy + low-dose STZ combined to establish a DN rat model to evaluate the lipid-lowering effect of liraglutide. Liraglutide at 0.4 mg/kg/d were subcutaneous injected into for 12 weeks (DN + liraglutide group). After the DN rat model was established, body weight loss, 24-h urine volume increasing, serum triglycerides (TG) and serum total cholesterol (TCh) increasing, ectopic lipid droplet deposition in renal tubular increasing, mesangial proliferation in renal tissue were observed in DN rats. The treatment with liraglutide could reduce the body weight and the average daily food intake of the rats, as well as TG, TCh, and ectopic lipid droplet deposition in renal tubular. Metabolomics result showed that serum differential metabolites between the DN - vehicle control group and the DN + liraglutide group mainly included serine, threonine, phenylalanine, oxyproline, threonine, sorbitol, glyceryl monostearate, glycerol monostearate, and β-d-glucuronic acid. Moreover, liraglutide can reduce plasma lipid levels in DN rats by increasing the products of lipolysis including 1-monopalmitin and 1-monoostearin. Immunohistochemistry and Western blot showed that the expression levels of lipid synthesis-related sterol regulatory element binding protein 1 (SREBP-1) and fatty acid synthase (FAS) were significantly increased, and lipolysis-related adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) were significantly decreased both in the renal tissue of DN rats and PA-induced HK-2 cells (lipid droplet accumulation model). However, liraglutide can attenuate renal tubular ectopic lipid deposition in DN rats by inhibiting SREBP-1, FAS and increasing ATGL, HSL protein expression level, and also ameliorated PA-induced lipid accumulation in renal tubular epithelial cells. These lipid metabolism changes were attributed to liraglutide by upregulating AMP-activated protein kinase (AMPK) phosphorylation in the kidney of DN rats. Collectively, these findings confirm that liraglutide inhibits lipid synthesis and promotes lipolysis to attenuate renal ectopic lipid deposition in DN rats by promoting AMPK phosphorylation. PMID: 32247822 [PubMed - as supplied by publisher]

Related Articles Olive oil by-product as functional ingredient in bakery products. Influence of processing and evaluation of biological effects. Food Res Int. 2020 May;131:108940 Authors: Di Nunzio M, Picone G, Pasini F, Chiarello E, Caboni MF, Capozzi F, Gianotti A, Bordoni A Abstract Nowadays, the strong demand for adequate nutrition is accompanied by concern about environmental pollution and there is a considerable emphasis on the recovery and recycling of food by-products and wastes. In this study, we focused on the exploitation of olive pomace as functional ingredient in biscuits and bread. Standard and enriched bakery products were made using different flours and fermentation protocols. After characterization, they were in vitro digested and used for supplementation of intestinal cells (Caco-2), which underwent exogenous inflammation. The enrichment caused a significant increase in the phenolic content in all products, particularly in the sourdough fermented ones. Sourdough fermentation also increased tocol concentration. The increased concentration of bioactive molecules did not reflect the anti-inflammatory effect, which was modulated by the baking procedure. Conventionally fermented bread enriched with 4% pomace and sourdough fermented, not-enriched bread had the greatest anti-inflammatory effect, significantly reducing IL-8 secretion in Caco-2 cells. The cell metabolome was modified only after supplementation with sourdough fermented bread enriched with 4% pomace, probably due to the high concentration of tocopherol that acted synergistically with polyphenols. Our data highlight that changes in chemical composition cannot predict changes in functionality. It is conceivable that matrices (including enrichment) and processing differently modulated bioactive bioaccessibility, and consequently functionality. PMID: 32247504 [PubMed - as supplied by publisher]

Related Articles Revealing the 1H NMR metabolome of mirasol chili peppers (Capsicum annuum) infected by Candidatus Phytoplasma trifolii. Food Res Int. 2020 May;131:108863 Authors: Velásquez-Valle R, Villa-Ruano N, Hidalgo-Martínez D, Zepeda-Vallejo LG, Pérez-Hernández N, Reyes-López CA, Reyes-Cervantes E, Medina-Melchor DL, Becerra-Martínez E Abstract The infection of Capsicum annuum cv. mirasol by Candidatus Phytoplasma trifolii (16SrVI) causes devastating crop losses in northern Mexico. This study addresses the metabolomics profiling of mirasol chili peppers (Capsicum annuum cv. mirasol) infected by Candidatus Phytoplasma trifolii. For this study, 25 diseased fruits and 25 healthy fruits were used. Principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA) revealed dramatic changes in the content of 42 metabolites which were identified in diseased and healthy mirasol chili peppers. The endogenous levels of fructose, glucose and formic acid were substantially decreased in the diseased chili peppers. In the same group of samples, high concentrations of alanine, asparagine, fumaric acid, sucrose and threonine were observed. The content of Choline didńt present a significant difference. This evidence supports the fact that Candidatus Phytoplasma trifolii infection reduces de CO2 fixation into carbohydrates, decreases invertase activity, and inhibits glycolysis in the diseased plant tissues. The levels of ascorbic acid, capsaicin and dihydrocapsaicinin in diseased fruits were dramatically decreased, suggesting that Candidatus Phytoplasma trifolii can reduce the pungency and the nutraceutical value of mirasol chili peppers. PMID: 32247466 [PubMed - as supplied by publisher]

Related Articles Metabolome and proteome of ethylene-treated papayas reveal different pathways to volatile compounds biosynthesis. Food Res Int. 2020 May;131:108975 Authors: Der Agopian RG, Fabi JP, Cordenunsi-Lysenko BR Abstract Papayas undergo fast postharvest changes triggered by the plant hormone ethylene. Some important pathways have been analyzed in limited studies (transcriptomics and targeted metabolomics); however, broad use of proteomics or untargeted metabolomics have not yet been used in papayas. In this study, two groups of green papayas (150 days after anthesis-physiological maturity for papayas) were treated with ethylene at different times (6 and 12 h) and their metabolic changes in fruit pulp were evaluated with untargeted metabolomics (general metabolites and volatile compounds) and proteomics. Polar metabolites exhibited distinct patterns, especially with regard to some amino and fatty acids during stimulated ripening. In particular, glutamate increased through a possible gamma aminobutyric acid (GABA) shunt and/or proteases activity. Moreover, the stimulated ripening altered the volatile compounds and the protein profiles. The results suggest that changes in membrane breakdown and the resulting oxidative processes could be responsible for volatile compound production, altering some sensorial qualities of papayas, such as pulp softening and the specific papaya linalool volatile compound increment. Thus, GABA levels could also be a strong biological marker for papaya development and ripening stages. This study applied two "omic" techniques that provided insight into how the plant hormone ethylene could influence papaya postharvest quality. PMID: 32247445 [PubMed - as supplied by publisher]

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Related Articles Epithelial stem cell marker LGR6 expression identifies a low-risk subgroup in human papillomavirus positive oropharyngeal squamous cell carcinoma. Oral Oncol. 2020 Mar 31;105:104657 Authors: Jank BJ, Kadletz L, Dunkler D, Haas M, Schnoell J, Kenner L, Heiduschka G Abstract OBJECTIVES: R-Spondins (RSPOs) and leucine-rich repeat-containing G-protein coupled receptors (LGRs) play a critical role in embryonic and cancer development through potentiation of WNT/ß-catenin signaling, but their prognostic significance in head and neck squamous cell carcinoma (HNSCC) is still unclear. HNSCC is a group of neoplasms that include, amongst others, oropharyngeal squamous cell carcinoma (OPSCC), some of which are induced by human papillomavirus (HPV). We aimed to investigate the potential prognostic value of RSPO2 and LGR4/5/6 on overall survival (OS) and disease-free survival (DFS) in HNSCC patients. METHODS: We examined RSPO and LGR expression by means of immunohistochemistry in 126 HNSCC patients. Furthermore, in order to validate our findings externally, we examined RSPO2 and LGR6 mRNA expression levels using independent secondary datasets. RESULTS: The five-year OS of our cohort was 59.6%. RSPO2 and LGR4/5/6 expression were not associated with OS or DFS in multivariable analyses. Within the HPV+ cases (n = 26, 33%), however, we observed a difference in OS by RSPO2 expression (5-year OS: RSPO+ 45.4% vs. RSPO2- 84.6%) and LGR6 expression (5-year OS: LGR6+ 52.9% vs. LGR6-100%). Evidence for an interaction of HPV status with RSPO2 and LGR6 was found for OS. Relative to HPV+/LGR6- patients, HPV+/LGR6+ patients were 12 times more likely to die. These results were replicated in the second dataset. CONCLUSION: Our results indicated that the expression status of LGR6 had an influence on the aggressiveness of HPV+ OPSCC, potentially making this receptor a useful marker for identifying patients with a high risk of death. PMID: 32244172 [PubMed - as supplied by publisher]

Related Articles Effect of sulfur-fumigation process on ginseng: Metabolism and absorption evidences. J Ethnopharmacol. 2020 Mar 31;: Authors: Shen H, Zhang L, Xu JD, Ding YF, Zhou J, Wu J, Zhang W, Mao Q, Liu LF, Zhu H, Li SL Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Sulfur-fumigation has been developed to prevent insects and molds during post-harvest handling of Panax ginseng C.A. Mey (ginseng) in the near decades. Our previous study indicated sulfur-fumigation could transform ginsenosides, the active components of ginseng, into sulfur-containing derivatives (SFCDs), the artifacts with unknown toxicity. However, whether the biotransformation could be occurred and absorption characteristics between ginsenosides and SFCDs are still needed to further investigate. AIM OF THE STUDY: To evaluate the effect of sulfur-fumigation process on ginseng through comparing the metabolic profile and absorption characteristics between ginsenoside Rg1, Re and their SFCDs. MATERIALS AND METHODS: Intestinal microflora and liver S9 fraction were utilized to compare the metabolic profile, and single-pass intestinal perfusion and Caco-2 cell models were applied to compare the absorption characteristics, between Rg1, Re and their SFCDs. RESULTS: Rg1 and Re were metabolized to 7 none sulfur-containing metabolites, while their SFCDs were metabolized to 18 sulfur-containing metabolites. The intestinal absorption and transport of Rg1 and Re were much greater than their SFCDs. Besides, the uptakes of Rg1 and Re were transport-dependent, but their SFCDs were non-transport-dependent. CONCLUSION: Ginsenosides and their SFCDs could not be bio-transformed with each other and their absorption characteristics were quite different, which suggested that sulfur-fumigation is not a feasible post-harvest process of ginseng. PMID: 32243989 [PubMed - as supplied by publisher]

Related Articles The metabolism of bile acid and amino acids is correlated with the diagnosis of pancreatic cancer. Clin Chim Acta. 2020 Mar 31;: Authors: Xiong Y, Shi C, Liu X, Yang P Abstract BACKGROUND: Pancreatic cancer (PC) is the fourth leading cause of cancer death because of its subtle clinical symptoms in the early stage. To discover particular serum metabolites as potential biomarkers to differentiate pancreatic carcinoma from begin diseases (BD) is on urgent demand. METHOD: To comprehensively analyze serum metabolites obtained from 14 patients with PC, 10 patients with BD and 10 healthy individuals (normal control, NC), we separated the metabolites using both reversed-phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC), and the data were acquired on a high-resolution quadrupole time-of-flight mass spectrometer operated in the negative (ESI-) and positive (ESI+) electrospray ionization modes, respectively. Differential metabolites were selected by univariate (Student's t test) and multivariate (orthogonal partial least squares-discriminant analysis (OPLS-DA)) statistics. Sequential window acquisition of all theoretical spectra (SWATH) analysis was further utilized to validate metabolites which we have found in the discovery stage. The receiver operator characteristics (ROC) curve analysis was performed to evaluate predictive clinical usefulness of 8 metabolites. RESULTS: A total of 8 metabolites including taurocholic acid, glycochenodexycholic acid, glycocholic acid, L-glutamine, glutamic acid, L-phenylalanine, L-tryptophan, and L-arginine were identified and relatively quantified as differential metabolites for discriminating PC, BD and NC. The 8 metabolites and their combination discriminated PC from BD and NC with well-performed area under the curve (AUC) values, sensitivity and specificity. CONCLUSION: Bile acids (especially taurocholic acid) performed to be potential biomarkers to diagnose PC. And other amino acid (such as L-glutamine, glutamic acid, L-phenylalanine, L-tryptophan, and L-arginine) in the serum samples of PC might provide a sensitive, blood-borne diagnostic signature for the presence of PC or its precursor lesions. PMID: 32243985 [PubMed - as supplied by publisher]

Related Articles The effect of polysaccharides from Cibotium barometz on enhancing temozolomide-induced glutathione exhausted in human glioblastoma U87 cells, as revealed by 1H NMR metabolomics analysis. Int J Biol Macromol. 2020 Mar 31;: Authors: Shi Y, Wang X, Wang N, Li FF, You YL, Wang SQ Abstract Glioblastoma (GBM) is the most malignant central nervous system tumor, with poor prognosis. Temozolomide (TMZ) has been used as a first-line drug for the treatment of GBM for over a decade, but its treatment benefits are limited by acquired resistance. Polysaccharides from Cibotium barometz (CBPs) are polysaccharides purified from the root of Cibotium barometz (L.) J. Sm., possessing sensitizing activity. The purpose of this study was to investigate the anti-cancer effect of CBP from different processing methods on U87 cells using a 1H NMR-based metabolic approach, complemented with qRT-PCR and flow cytometry, to identify potential markers and discover the targets to explore the underlying mechanism. Cibotium barometz is usually processed under sand heating in clinical applications. Polysaccharides from both the processed (PCBP) and raw (RCBP) C. barometz were prepared, and the effect on enhancing the sensitivity to TMZ was investigated in vitro. CBP can significantly increase the toxicity of TMZ to the U87 cell line, promote apoptosis, enhance cell cycle changes, and arrest cells in S phase, and RCBP demonstrated better activity. Multivariate statistical analyses, such as principal component analysis (PCA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA), were used to identify metabolic biomarkers, and 12 metabolites in the cell extract samples were clearly identified as altered after RCBP exposure. NMR-based cell metabolomics provided a holistic method for the identification of CBP's apoptosis-enhancing mechanisms and the exploration of its potential applications in preclinical and clinical studies. PMID: 32243933 [PubMed - as supplied by publisher]

Related Articles Metabolomic Based Approach to Identify Biomarkers of Apple Intake. Mol Nutr Food Res. 2020 Apr 03;:e1901158 Authors: McNamara AE, Collins C, Harsha PSCS, González-Peña D, Gibbons H, McNulty BA, Nugent AP, Walton J, Flynn A, Brennan L Abstract SCOPE: There is an increased interest in developing biomarkers of food intake to address some of the limitations associated with self-reported data. The objective was to identify biomarkers of apple intake, examine dose-response relationships and agreement with self-reported data. METHODS AND RESULTS: Metabolomic data from three studies were examined: an acute intervention, a short-term intervention and a free-living cohort study. Fasting and postprandial urine samples were collected for analysis by 1 H-NMR and LC-MS. Calibration curves were developed to determine apple intake and classify individuals into categories of intake. Multivariate analysis of data revealed that levels of multiple metabolites increased significantly post-apple consumption, compared to the control food- broccoli. In the dose-response study, urinary xylose, epicatechin sulfate and 2, 6-dimethyl-2-(2-hydroxyethyl)-3,4-dihydro-2H-1-benzopyran increased as apple intake increased. Urinary xylose concentrations in a free-living cohort performed poorly at an individual level but were capable of ranking individuals in categories of intake. CONCLUSION: Urinary xylose exhibited a dose-response relationship with apple intake and performed well as a ranking biomarker in the population study. Other potential biomarkers were identified and future work will combine these with xylose in a biomarker panel which may allow for a more objective determination of individual intake This article is protected by copyright. All rights reserved. PMID: 32243719 [PubMed - as supplied by publisher]

Related Articles Effects of Prenatal Exposure to a Mixture of Organophosphate Flame Retardants on Placental Gene Expression and Serotonergic Innervation in the Fetal Rat Brain. Toxicol Sci. 2020 Apr 03;: Authors: Rock KD, St Armour G, Horman B, Phillips A, Ruis M, Stewart AK, Jima D, Muddiman DC, Stapleton HM, Patisaul HB Abstract There is a growing need to understand the potential neurotoxicity of organophosphate ester flame retardants (OPFRs) and plasticizers because use and, consequently, human exposure, is rapidly expanding. We have previously shown in rats that developmental exposure to the commercial FR mixture Firemaster® 550 (FM 550), which contains OPFRs, results in sex-specific behavioral effects, and identified the placenta as a potential target of toxicity. The placenta is a critical coordinator of fetal growth and neurodevelopment, and a source of neurotransmitters (NTs) for the developing brain. We have shown in rats and humans that FRs accumulate in placental tissue, and induce functional changes, including altered neurotransmitter (NT) production. Here we sought to establish if OPFRs (triphenyl phosphate, TPHP, and a mixture of isopropylated triarylphosphate isomers, ITPs) alter placental function and fetal forebrain development, with disruption of tryptophan (Trp) metabolism as a primary pathway of interest. Wistar rat dams were orally exposed to OPFRs (0, 500, 1,000, or 2,000 μg/day) or a serotonin (5-HT) agonist (5-MT) for 14 days during gestation and placenta and fetal forebrain tissues collected for analysis by transcriptomics and metabolomics. Relative abundance of genes responsible for the transport and synthesis of placental 5-HT were disrupted, and multiple neuroactive metabolites in the 5-HT and kynurenine (Kyn) metabolic pathways were upregulated. Additionally, 5-HTergic projections were significantly longer in the fetal forebrains of exposed males. These findings suggest that OPFRs have the potential to impact the 5-HTergic system in the fetal forebrain by disrupting placental Trp metabolism. PMID: 32243540 [PubMed - as supplied by publisher]

Related Articles Advances in disease-modifying pharmacotherapies for the treatment of amyotrophic lateral sclerosis. Expert Opin Pharmacother. 2020 Apr 03;:1-8 Authors: Hergesheimer R, Lanznaster D, Vourc'h P, Andres C, Bakkouche S, Beltran S, Blasco H, Corcia P, Couratier P Abstract Introduction: To date, riluzole and edaravone are the only two drugs that have successfully passed clinical trials for the treatment of Amyotrophic Lateral Sclerosis (ALS). Unfortunately, both drugs exhibit very modest effects. Most other drugs have failed at phase III to show significant effects in phase III when tested in larger cohorts. This pattern necessitates improvements in the approach to ALS pharmacotherapy.Areas covered: The authors discuss the two approved drugs, as well as several examples of drug candidates whose clinical trials did not demonstrate efficacy in phase III. Post-hoc analyses reveal that future clinical trials should include disease-staging procedures, longer-term trials to correctly assess survival, genetic studies of participants to aid in stratification, and more similarity between the protocols on preclinical models and clinical trials. Finally, they discuss the trials in process that demonstrate some of these suggestions and improvements.Expert opinion: The approval of riluzole and edaravone was essentially a desperate attempt to provide urgent pharmacotherapy to the ALS community. To evolve toward more efficient therapies, we must conduct clinical trials with optimal stratification based on rapid/slow progressors and cognitive decline. Pharmaco-metabolomics should allow for the identification of biomarkers that are adapted for a given drug. PMID: 32242755 [PubMed - as supplied by publisher]