Project description:Kombucha is a traditional fermented beverage obtained from the transformation of sugared black tea by a community of yeasts and bacteria. Kombucha production recently became industrialized, but its quality standards remain poorly defined. Metabolomic analyses were applied using FT-ICR-MS to characterize the impacts of production phases and the type of tea on the non-volatile chemical composition of kombucha. Independently from tea type, the first phase of acidification in open vessel was characterized by the release of gluconate and gallate from acetic acid bacteria metabolism and probably from polymeric polyphenols, respectively. The second phase of carbonation in closed vessel induced a consumption or transformation of oleic acid that could be consecutive of oxygen limitation. The first phase had the most impact on molecular diversity, but tea type mainly influenced the global composition in polyphenol profile. Black tea polyphenols were more impacted by microbial activity compared to green tea polyphenols.
Project description:Populus cathayana × canadansis 'Xinlin 1' ('P.'xin lin 1') with the characteristics of rapid growth and high yield, is frequently attacked by herbivorous insects. However, little is known about how it defenses against Hyphantria cunea (H. cunea) at molecular and biochemical levels. Differences in the transcriptome and metabolome were analyzed after 'P. 'xin lin 1' leaves were fed to H. cunea for 0h, 2h, 4h, 8h, 16h and 24h. In the five comparison groups including 2h vs. CK, 4h vs. CK, 8h vs. CK, 16h vs. CK, and 24h vs. CK, a total of 8925 genes and 842 metabolites were differentially expressed. A total of 825 transcription factors (TFs) were identified, which encoded 56 TF families. The results showed that the top four families with the highest number of TFs were AP2/ERF, MYB, C2C2, bHLH. Analyses of leaves which were fed to H. cunea showed that the differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were significantly enriched in plant hormone signal transduction pathway, MAPK signaling pathway, flavonoid, flavone and flavonol and anthocyanin biosynthesis pathway. Additionally, there were a number of genes significantly up-regulated in MAPK signaling pathway. Some compounds involved in plant hormone signal transduction and flavonoid/flavone and flavonol/ anthocyanin pathways such as jasmonic acid (JA), jasmonoyl-L-Isoleucine (JA-Ile), kaempferol and cyanidin-3-O-glucoside were induced in infested 'P.'xin lin 1'. This study provides a new understanding for exploring the dynamic response mechanism of poplar to the infestation of H. cunea.
Project description:Flavonoids, which are abundant in plants, are recognized for their antioxidant and anticancer roles in clinical applications. However, little is known about the molecular basis of flavonoid biosynthesis in fungi. In this study, we found that inclusion of leachate of Korshinsk peashrub (Caragana korshinskii) in the fermentation medium increased the total flavonoid content of the edible fungus Auricularia cornea by 23.6% relative to that grown in a control medium. Combined transcriptomic and non-targeted metabolomic analysis of the flavonoid biosynthesis pathway in A. cornea illustrated that there are important metabolites in the phenylpropanoid, coumarin and isoflavonoid biosynthesis pathways. In addition, we found that certain homologous genes encode phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO) and chalcone isomerase (CHI) in these biosynthesis pathways. These results, in this study, provide a new line for studying the regulation of flavonoid production in edible fungi.
Project description:L-Arginine/NO pathway is altered in Alzheimer disease (AD). Its clinical relevance and pathway status in vascular dementia (VaD) are unknown. Using targeted metabolomics (a liquid chromatography-mass spectrometry) we assessed L-arginine, L-citrulline, dimethylamine (DMA), asymmetric dimethyl arginine (ADMA) and symmetric dimethylarginine (SDMA) in AD (n = 48), mixed-type dementia (MD; n = 34), VaD (n = 40) and non-demented individuals (n = 140) and determined their clinical relevance (the association with dementia pathology, cognitive impairment, and structural brain damage). L-Arginine, ADMA, L-arginine/ADMA, and L-citrulline levels were decreased in dementia and L-arginine, L-citrulline, age and sex were its independent predictors correctly classifying 91% of cases. L-Arginine and L-arginine/ADMA were differentiating between VaD and AD with moderate accuracy. L-Arginine, L-arginine/ADMA, SDMA, and DMA reflected structural brain changes. DMA and L-citrulline were elevated in patients with strategic infarcts and SDMA, L-arginine/ADMA, and DMA were independent predictors of Hachinski ischemic score. ADMA and SDMA accumulation reflected severity of cognitive impairment. In summary, L-Arginine/NO pathway is altered in neurodegenerative and vascular dementia in association with neurodegenerative and vascular markers of brain damage and severity of cognitive impairment.
Project description:BackgroundCellular metabolism is critical for the host immune function against pathogens, and metabolomic analysis may help understand the characteristic immunopathology of tuberculosis. We performed targeted metabolomic analyses in a large cohort of patients with tuberculous meningitis (TBM), the most severe manifestation of tuberculosis, focusing on tryptophan metabolism.MethodsWe studied 1069 Indonesian and Vietnamese adults with TBM (26.6% HIV-positive), 54 non-infectious controls, 50 with bacterial meningitis, and 60 with cryptococcal meningitis. Tryptophan and downstream metabolites were measured in cerebrospinal fluid (CSF) and plasma using targeted liquid chromatography mass-spectrometry. Individual metabolite levels were associated with survival, clinical parameters, CSF bacterial load and 92 CSF inflammatory proteins.ResultsCSF tryptophan was associated with 60-day mortality from tuberculous meningitis (HR=1.16, 95%CI=1.10-1.24, for each doubling in CSF tryptophan) both in HIV-negative and HIV-positive patients. CSF tryptophan concentrations did not correlate with CSF bacterial load nor CSF inflammation but were negatively correlated with CSF interferon-gamma concentrations. Unlike tryptophan, CSF concentrations of an intercorrelating cluster of downstream kynurenine metabolites did not predict mortality. These CSF kynurenine metabolites did however correlate with CSF inflammation and markers of blood-CSF leakage, and plasma kynurenine predicted death (HR 1.54, 95%CI=1.22-1.93). These findings were mostly specific for TBM, although high CSF tryptophan was also associated with mortality from cryptococcal meningitis.ConclusionTBM patients with a high baseline CSF tryptophan or high systemic (plasma) kynurenine are at increased risk of mortality. These findings may reveal new targets for host-directed therapy.FundingThis study was supported by National Institutes of Health (R01AI145781) and the Wellcome Trust (110179/Z/15/Z and 206724/Z/17/Z).
Project description:Heart failure (HF) has been recognized as a global epidemic with high rates of morbidity, hospitalization, and mortality. The role of amino acids, which provide the body with energy, in the development of HF is still unclear. The aim of this study was to explore changes in serum amino acids in patients with HF and identify potential biomarkers. First, the serum amino acid metabolism profiles of 44 patients with HF and 30 healthy controls (Con) were quantitatively measured. Then, candidate markers were identified through the utilization of T test, multivariate statistical analysis, and receiver operating characteristic (ROC) curve analysis. The results found that there were 11 amino acid levels that were significantly different between patients with HF and Con. Based on ROC curve analysis, the biomarkers of eight amino acids (Glutamic acid, Taurine, L-aspartic acid, L-ornithine, Ethanolamine, L-Serine, L-Sarcosine, and Cysteine) showed high sensitivity and specificity (AUC > 0.90), and binary logistic regression analysis was used in MetaboAnalyst 5.0. Among the amino acids examined, six exhibited notable alterations in accordance with the severity of HF. In conclusion, this study cannot only provide clinicians with an objective diagnostic approach for the early identification of HF, but also enhances comprehension of the underlying mechanisms involved in the pathogenesis of HF.
Project description:BackgroundCellular metabolism is critical for the host immune function against pathogens, and metabolomic analysis may help understand the characteristic immunopathology of tuberculosis. We performed targeted metabolomic analyses in a large cohort of patients with tuberculous meningitis (TBM), the most severe manifestation of tuberculosis, focusing on tryptophan metabolism.MethodsWe studied 1069 Indonesian and Vietnamese adults with TBM (26.6% HIV-positive), 54 non-infectious controls, 50 with bacterial meningitis, and 60 with cryptococcal meningitis. Tryptophan and downstream metabolites were measured in cerebrospinal fluid (CSF) and plasma using targeted liquid chromatography-mass spectrometry. Individual metabolite levels were associated with survival, clinical parameters, CSF bacterial load and 92 CSF inflammatory proteins.ResultsCSF tryptophan was associated with 60-day mortality from TBM (hazard ratio [HR] = 1.16, 95% confidence interval [CI] = 1.10-1.24, for each doubling in CSF tryptophan) both in HIV-negative and -positive patients. CSF tryptophan concentrations did not correlate with CSF bacterial load nor CSF inflammation but were negatively correlated with CSF interferon-gamma concentrations. Unlike tryptophan, CSF concentrations of an intercorrelating cluster of downstream kynurenine metabolites did not predict mortality. These CSF kynurenine metabolites did however correlate with CSF inflammation and markers of blood-CSF leakage, and plasma kynurenine predicted death (HR 1.54, 95% CI = 1.22-1.93). These findings were mostly specific for TBM, although high CSF tryptophan was also associated with mortality from cryptococcal meningitis.ConclusionsTBM patients with a high baseline CSF tryptophan or high systemic (plasma) kynurenine are at increased risk of death. These findings may reveal new targets for host-directed therapy.FundingThis study was supported by National Institutes of Health (R01AI145781) and the Wellcome Trust (110179/Z/15/Z and 206724/Z/17/Z).
Project description:A comparison between a human placental cell line (3A sub E placental, aka, PLC), human choriocarcinoma methotrexate-sensitive JEG3, and methotrexate-resistant JEG3R. This comparison focused on genomic 'hot spot' regions that are frequently mutated in human cancer genes.
Project description:High Flow Nasal Cannula (HFNC) is commonly used for children with respiratory failure, yet no standardized guidelines exist on how to initiate, escalate, and maintain enteral nutrition (EN) for these patients. EN in critically ill children is associated with decreased hospital length of stay, decreased ventilator days, and fewer acquired infections. We aimed to decrease the mean time to EN initiation by 50% after the start of HFNC in 6 months.MethodsThis quality improvement project used the Model for Improvement to inform interventions. A multidisciplinary team created an EN pathway for critically ill patients on HFNC. We conducted Plan-Do-Study-Act cycles related to implementing a standardized pathway for EN on HFNC. The primary outcome was time to EN initiation once on HFNC. Secondary outcomes were time to goal caloric EN, duration of HFNC, and adverse events. Outcomes were plotted on statistical process control charts and analyzed for special cause variation between baseline and intervention periods.ResultsWe included 112 patients in the study. Special cause variation occurred for both primary and secondary outcomes. The mean time to EN initiation decreased from 24.6 hours to 11.7 hours (47.5%). Mean time to goal feeds decreased from 25.8 hours to 15.1 hours (58.5%). Mean HFNC duration did not show any special cause variation. There were no episodes of aspiration.ConclusionImplementation of a standardized pathway for EN on patients receiving HFNC resulted in decreased time to initiation of EN and time to goal caloric EN with no significant increase in adverse events.