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

metabolomics; +17 new citations

Wed, 01/04/2020 - 13:40
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 2020/04/01PubMed 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; +17 new citations

Tue, 31/03/2020 - 16:30
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 2020/03/31PubMed 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; +17 new citations

Tue, 31/03/2020 - 13:28
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 2020/03/31PubMed 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.

Integrated omics analysis of sweat reveals an aberrant amino acid metabolism pathway in Vogt-Koyanagi-Harada disease.

Mon, 30/03/2020 - 13:22
Related Articles Integrated omics analysis of sweat reveals an aberrant amino acid metabolism pathway in Vogt-Koyanagi-Harada disease. Clin Exp Immunol. 2020 Mar 28;: Authors: Cui X, Su G, Zhang L, Yi S, Cao Q, Zhou C, Kijlstra A, Yang P Abstract Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disease leading to visual impairment. Its pathogenic mechanisms remain poorly understood. Our purpose was to investigate the distinctive protein and metabolic profiles of sweat in patients with VKH disease. In the present study, proteomics and metabolomics analysis was performed on 60 sweat samples (30 VKH patients and 30 normal controls) using liquid chromatography tandem mass spectrometry. Parallel reaction monitoring (PRM) analysis was used to validate the results of our omics analysis. In total, we were able to detect 716 proteins and 175 metabolites. Among them, 116 proteins (99 decreased and 17 increased) were observed to be significantly different in VKH patients when compared to controls. Twenty-one differentially expressed metabolites were identified in VKH patients, of which eighteen included Choline, L-Tryptophan, Betaine and L-Serine were reduced, while the rest were increased. Our multi-omics strategy reveals an important role for the amino acid metabolic pathway in the pathogenesis of VKH disease. Significant differences in proteins and metabolites were identified in the sweat of VKH patients, and to some extent, an aberrant amino acid metabolism pathway may be a pathogenic factor in the pathogenesis of VKH disease. PMID: 32222072 [PubMed - as supplied by publisher]

Salivary metabolites to detect patients with cancer: a systematic review.

Mon, 30/03/2020 - 13:22
Related Articles Salivary metabolites to detect patients with cancer: a systematic review. Int J Clin Oncol. 2020 Mar 27;: Authors: Assad DX, Mascarenhas ECP, de Lima CL, de Toledo IP, Chardin H, Combes A, Acevedo AC, Guerra ENS Abstract Novel adjunctive screening aids are needed to reduce the morbidity and mortality related to cancer, and every effort should be made for early diagnosis. This systematic review aimed to evaluate salivary metabolites and their diagnostic value in patients with cancer.The systematic review was performed in two phases and included studies that focused on the diagnostic value of salivary metabolites in humans with solid malignant neoplasms. Five electronic databases were searched, and the risk of bias in individual studies was evaluated using the revised Quality Assessment of Diagnostic Accuracy Studies criteria (QUADAS-2). All procedures were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.Of the 1151 studies retrieved, 25 were included; 13 studies used targeted and 12 untargeted metabolomics approaches. Most studies included patients with breast and oral cancer. Except for one, all studies had case-control designs, and none fulfilled all quality assessments. Overall, 140 salivary metabolites were described. The most frequently reported metabolites were alanine, valine, and leucine. Among the 11 studies that reported diagnostic test accuracy (DTA) values, proline, threonine, and histidine in combination and monoacylglycerol alone demonstrated the highest DTA for breast cancer. Combined choline, betaine, pipecolinic acid, and L-carnitine showed better discriminatory performance for early oral cancer.This systematic review highlights the current evidence on salivary metabolites that may be used as a future strategy to diagnose cancer. Further studies including larger sample sizes with confirmation of the results by untargeted analysis are warranted. PMID: 32221803 [PubMed - as supplied by publisher]

Nuclear Magnetic Resonance to Detect Rumen Metabolites Associated with Enteric Methane Emissions from Beef Cattle.

Mon, 30/03/2020 - 13:22
Related Articles Nuclear Magnetic Resonance to Detect Rumen Metabolites Associated with Enteric Methane Emissions from Beef Cattle. Sci Rep. 2020 Mar 27;10(1):5578 Authors: Bica R, Palarea-Albaladejo J, Kew W, Uhrin D, Pacheco D, Macrae A, Dewhurst RJ Abstract This study presents the application of metabolomics to evaluate changes in the rumen metabolites of beef cattle fed with three different diet types: forage-rich, mixed and concentrate-rich. Rumen fluid samples were analysed by 1H-NMR spectroscopy and the resulting spectra were used to characterise and compare metabolomic profiles between diet types and assess the potential for NMR metabolite signals to be used as proxies of methane emissions (CH4 in g/kg DMI). The dataset available consisted of 128 measurements taken from 4 experiments with CH4 measurements taken in respiration chambers. Predictive modelling of CH4 was conducted by partial least squares (PLS) regression, fitting calibration models either using metabolite signals only as predictors or using metabolite signals as well as other diet and animal covariates (DMI, ME, weight, BW0.75, DMI/BW0.75). Cross-validated R2 were 0.57 and 0.70 for the two models respectively. The cattle offered the concentrate-rich diet showed increases in alanine, valerate, propionate, glucose, tyrosine, proline and isoleucine. Lower methane yield was associated with the concentrate-rich diet (p < 0.001). The results provided new insight into the relationship between rumen metabolites, CH4 production and diets, as well as showing that metabolites alone have an acceptable association with the variation in CH4 production from beef cattle. PMID: 32221381 [PubMed - as supplied by publisher]

Serum Metabolites in Hand-Arm Vibration Exposed Workers.

Mon, 30/03/2020 - 13:22
Related Articles Serum Metabolites in Hand-Arm Vibration Exposed Workers. J Occup Environ Med. 2020 Mar 20;: Authors: Vihlborg P, Graff P, Hagenbjörk A, Hadrévi J, Bryngelsson IL, Eriksson K Abstract OBJECTIVE: To investigate whether low molecular organic biomarkers could be identified in blood samples from vibration exposed workers using a metabolomics. METHODS: The study population consisted of 38 metalworkers. All participants underwent a standardized medical examination. Blood samples were collected before and after work shift and analyzed with GC-TOFMS. Multivariate modeling (orthogonal partial least-squares analysis with discriminant analysis [OPLS-DA]) were used to verify differences in metabolic profiles. RESULTS: Twenty-two study participants reported vascular symptoms judged as vibration-related. The metabolic profile from participants with vibration-induced white fingers (VWF) was distinctly separated from participants without VWF, both before and after vibration exposure. CONCLUSION: Metabolites that differed between the groups were identified both before and after exposure. Some of these metabolites might be indicators of health effects from exposure to vibrations. This is the first time that a metabolomic approach has been used in workers exposed to vibrations. PMID: 32221116 [PubMed - as supplied by publisher]

Autophagy induction by thiostrepton improves the efficacy of immunogenic chemotherapy.

Mon, 30/03/2020 - 13:22
Related Articles Autophagy induction by thiostrepton improves the efficacy of immunogenic chemotherapy. J Immunother Cancer. 2020 Mar;8(1): Authors: Wang Y, Xie W, Humeau J, Chen G, Liu P, Pol J, Zhang Z, Kepp O, Kroemer G Abstract BACKGROUND: Immunogenic cell death (ICD) is a peculiar modality of cellular demise that elicits adaptive immune responses and triggers T cell-dependent immunity. METHODS: Fluorescent biosensors were employed for an unbiased drug screen approach aiming at the identification of ICD enhancers. RESULTS: Here, we discovered thiostrepton as an enhancer of ICD able to boost chemotherapy-induced ATP release, calreticulin exposure and high-mobility group box 1 exodus. Moreover, thiostrepton enhanced anticancer immune responses of oxaliplatin (OXA) in vivo in immunocompetent mice, yet failed to do so in immunodeficient animals. Consistently, thiostrepton combined with OXA altered the ratio of cytotoxic T lymphocytes to regulatory T cells, thus overcoming immunosuppression and reinstating anticancer immunosurveillance. CONCLUSION: Altogether, these results indicate that thiostrepton can be advantageously combined with chemotherapy to enhance anticancer immunogenicity. PMID: 32221018 [PubMed - as supplied by publisher]

Metabolic profiling by reversed-phase/ion-exchange mass spectrometry.

Mon, 30/03/2020 - 13:22
Related Articles Metabolic profiling by reversed-phase/ion-exchange mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Mar 16;1143:122072 Authors: Le A, Mak J, Cowan TM Abstract Metabolic profiling is commonly achieved by mass spectrometry (MS) following reversed-phase (RP) and hydrophilic interaction chromatography (HILIC) either performed independently, leading to overlapping datasets, or in a coupled configuration, requiring multiple liquid chromatography (LC) systems. To overcome these limitations, we developed a single, 20-minute chromatographic method using an in-line RP-ion-exchange (IEX) column arrangement and a single LC system. This configuration separates clinically significant polar and non-polar compounds without derivatization or ion-pairing reagents, allowing ionization in both polarities. An in-house library was created with 397 authentic standards, including acylcarnitines, amino acids, bile acids, nucleosides, organic acids, steroid hormones, and vitamins. Analysis of pooled plasma and urine samples revealed 5445 and 4111 ion features, leading to 88 and 82 confirmed metabolite identifications, respectively. Metabolites were detected at clinically relevant concentrations with good precision, and good chromatographic separation was demonstrated for clinically significant isomers including methylmalonic acid and succinic acid, as well as alloisoleucine and isoleucine/leucine. Evaluation of the samples by unsupervised principal component analysis showed excellent analytical quality. PMID: 32220802 [PubMed - as supplied by publisher]

Multi-omics: Differential expression of IFN-γ results in distinctive mechanistic features linking chronic inflammation, gut dysbiosis, and autoimmune diseases.

Mon, 30/03/2020 - 13:22
Related Articles Multi-omics: Differential expression of IFN-γ results in distinctive mechanistic features linking chronic inflammation, gut dysbiosis, and autoimmune diseases. J Autoimmun. 2020 Mar 24;:102436 Authors: Bae HR, Leung PSC, Hodge DL, Fenimore JM, Jeon SM, Thovarai V, Dzutsev A, Welcher AA, Boedigheimer M, Damore MA, Choi MS, Fravell RA, Trinchieri G, Gershwin ME, Young HA Abstract Low grade, chronic inflammation is a critical risk factor for immunologic dysfunction including autoimmune diseases. However, the multiplicity of complex mechanisms and lack of relevant murine models limit our understanding of the precise role of chronic inflammation. To address these hurdles, we took advantage of multi-omics data and a unique murine model with a low but chronic expression of IFN-γ, generated by replacement of the AU-rich element (ARE) in the 3' UTR region of IFN-γ mRNA with random nucleotides. Herein, we demonstrate that low but differential expression of IFN-γ in mice by homozygous or heterozygous ARE replacement triggers distinctive gut microbial alterations, of which alteration is female-biased with autoimmune-associated microbiota. Metabolomics data indicates that gut microbiota-dependent metabolites have more robust sex-differences than microbiome profiling, particularly those involved in fatty acid oxidation and nuclear receptor signaling. More importantly, homozygous ARE-Del mice have dramatic changes in tryptophan metabolism, bile acid and long-chain lipid metabolism, which interact with gut microbiota and nuclear receptor signaling similarly with sex-dependent metabolites. Consistent with these findings, nuclear receptor signaling, encompassing molecules such as PPARs, FXR, and LXRs, was detectable as a top canonical pathway in comparison of blood and tissue-specific gene expression between female homozygous vs heterozygous ARE-Del mice. Further analysis implies that dysregulated autophagy in macrophages is critical for breaking self-tolerance and gut homeostasis, while pathways interact with nuclear receptor signaling to regulate inflammatory responses. Overall, pathway-based integration of multi-omics data provides systemic and cellular insights about how chronic inflammation driven by IFN-γ results in the development of autoimmune diseases with specific etiopathological features. PMID: 32220507 [PubMed - as supplied by publisher]

Systems pharmacology reveals the mechanism of activity of Physalis alkekengi L. var. franchetii against lipopolysaccharide-induced acute lung injury.

Sun, 29/03/2020 - 13:13
Related Articles Systems pharmacology reveals the mechanism of activity of Physalis alkekengi L. var. franchetii against lipopolysaccharide-induced acute lung injury. J Cell Mol Med. 2020 Mar 27;: Authors: Yang Y, Ding Z, Wang Y, Zhong R, Feng Y, Xia T, Xie Y, Yang B, Sun X, Shu Z Abstract Acute lung injury (ALI) is an important cause of mortality of patients with sepsis, shock, trauma, pneumonia, multiple transfusions and pancreatitis. Physalis alkekengi L. var. franchetii (Mast.) Makino (PAF) has been extensively used in Chinese folk medicine because of a good therapeutic effect in respiratory diseases. Here, an integrated approach combining network pharmacology, proton nuclear magnetic resonance-based metabolomics, histopathological analysis and biochemical assays was used to elucidate the mechanism of PAF against ALI induced by lipopolysaccharide (LPS) in a mouse model. We found that the compounds present in PAF interact with 32 targets to effectively improve the damage in the lung undergoing ALI. We predicted the putative signalling pathway involved by using the network pharmacology and then used the orthogonal signal correction partial least-squares discriminant analysis to analyse the disturbances in the serum metabolome in mouse. We also used ELISA, RT-qPCR, Western blotting, immunohistochemistry and TUNEL assay to confirm the potential signalling pathways involved. We found that PAF reduced the release of cytokines, such as TNF-α, and the accumulation of oxidation products; decreased the levels of NF-κB, p-p38, ERK, JNK, p53, caspase-3 and COX-2; and enhanced the translocation of Nrf2 from the cytoplasm to the nucleus. Collectively, PAF significantly reduced oxidative stress injury and inflammation, at the same time correcting the energy metabolism imbalance caused by ALI, increasing the amount of antioxidant-related metabolites and reducing the apoptosis of lung cells. These observations suggest that PAF may be an effective candidate preparation alleviating ALI. PMID: 32220053 [PubMed - as supplied by publisher]

PKA-independent vasopressin signaling in renal collecting duct.

Sun, 29/03/2020 - 13:13
Related Articles PKA-independent vasopressin signaling in renal collecting duct. FASEB J. 2020 Mar 26;: Authors: Datta A, Yang CR, Limbutara K, Chou CL, Rinschen MM, Raghuram V, Knepper MA Abstract Vasopressin regulates renal water excretion by binding to a Gα s-coupled receptor (V2R) in collecting duct cells, resulting in increased water permeability through regulation of the aquaporin-2 (AQP2) water channel. This action is widely accepted to be associated with cAMP-mediated activation of protein kinase A (PKA). Here, we use phosphoproteomics in collecting duct cells in which PKA has been deleted (CRISPR-Cas9) to identify PKA-independent responses to vasopressin. The results show that V2R-mediated vasopressin signaling is predominantly, but not entirely, PKA-dependent. Upregulated sites in PKA-null cells include Ser256 of AQP2, which is critical to regulation of AQP2 trafficking. In addition, phosphorylation changes in the protein kinases Stk39 (SPAK) and Prkci (an atypical PKC) are consistent with PKA-independent regulation of these protein kinases. Target motif analysis of the phosphopeptides increased in PKA-null cells indicates that vasopressin activates one or more members of the AMPK/SNF1-subfamily of basophilic protein kinases. In vitro phosphorylation assays using recombinant, purified SNF1-subfamily kinases confirmed postulated target specificities. Of interest, measured IBMX-dependent cAMP levels were an order of magnitude higher in PKA-null than in PKA-intact cells, indicative of a PKA-dependent feedback mechanism. Overall, the findings support the conclusion that V2-receptor mediated signaling in collecting duct cells is in part PKA-independent. PMID: 32219907 [PubMed - as supplied by publisher]

Identification of endogenous 1-aminopyrene as a novel mediator of progressive chronic kidney disease via aryl hydrocarbon receptor activation.

Sun, 29/03/2020 - 13:13
Related Articles Identification of endogenous 1-aminopyrene as a novel mediator of progressive chronic kidney disease via aryl hydrocarbon receptor activation. Br J Pharmacol. 2020 Mar 26;: Authors: Miao H, Cao G, Wu XQ, Chen YY, Chen DQ, Chen L, Vaziri ND, Feng YL, Su W, Gao Y, Zhuang S, Yu XY, Zhang L, Guo Y, Zhao YY Abstract BACKGROUND AND PURPOSE: Increasing evidence has indicated that the high risk of cardiovascular disease in chronic kidney disease (CKD) patients cannot be sufficiently explained by classic risk factors. EXPERIMENTAL APPROACH: Based on the least absolute shrinkage and selection operator method, we identified significantly altered renal tissue metabolites during progressive CKD in a 5/6 nephrectomised rat model and in CKD patients. KEY RESULTS: Six aryl-containing metabolites (ACM) were significantly increased from week 1 to week 20. They were associated with the activation of aryl hydrocarbon receptor (AhR) and its target genes including CYP1A1, CYP1A2, and CYP1B1, which were further validated by molecular docking. Our study further demonstrated that AhR signalling could be activated by ACM in patients with idiopathic membranous nephropathy, diabetic nephropathy, and immunoglobulin A nephropathy. Most importantly, 1-aminopyrene (AP) showed strong positive and negative correlation with serum creatinine and creatinine clearance, respectively. AP significantly upregulated the mRNA expressions of AhR and its three target genes in both mice and NRK-52E cells, while this effect was partially weakened in AhR shRNA-treated mice and NRK-52E cells. Furthermore, dietary flavonoid supplementation ameliorated CKD and renal fibrosis through partially inhibiting the AhR activity via lowering the ACM levels. The antagonistic effect of flavonoids on AhR was deeply influenced by the number and location of hydroxyl and glycosyl groups. CONCLUSION AND IMPLICATIONS: We uncovered that endogenous AP is a novel mediator of CKD progression via AhR activation; thus, AhR might serve as a promising target for CKD treatment. PMID: 32219844 [PubMed - as supplied by publisher]

Metabolomic profiling of gastric cancer tissues identified potential biomarkers for predicting peritoneal recurrence.

Sun, 29/03/2020 - 13:13
Related Articles Metabolomic profiling of gastric cancer tissues identified potential biomarkers for predicting peritoneal recurrence. Gastric Cancer. 2020 Mar 26;: Authors: Kaji S, Irino T, Kusuhara M, Makuuchi R, Yamakawa Y, Tokunaga M, Tanizawa Y, Bando E, Kawamura T, Kami K, Ohashi Y, Zhang S, Orita H, Lee-Okada HC, Fukunaga T, Terashima M Abstract BACKGROUND: Metabolomics is useful for analyzing the nutrients necessary for cancer progression, as the proliferation is regulated by available nutrients. We studied the metabolomic profile of gastric cancer (GC) tissue to elucidate the associations between metabolism and recurrence. METHODS: Cancer and adjacent non-cancerous tissues were obtained in a pair-wise manner from 140 patients with GC who underwent gastrectomy. Frozen tissues were homogenized and analyzed by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Metabolites were further assessed based on the presence or absence of recurrence. RESULTS: Ninety-three metabolites were quantified. In cancer tissues, the lactate level was significantly higher and the adenylate energy charge was lower than in non-cancerous tissues. The Asp, β-Ala, GDP, and Gly levels were significantly lower in patients with recurrence than in those without. Based on ROC analyses to determine the cut-off values of the four metabolites, patients were categorized into groups at high risk and low risk of peritoneal recurrence. Logistic regression and Cox proportional hazard analyses identified β-Ala as an independent predictor of peritoneal recurrence (hazard ratio [HR] 5.21 [95% confidence interval 1.07-35.89], p = 0.029) and an independent prognostic factor for the overall survival (HR 3.44 [95% CI 1.65-7.14], p < 0.001). CONCLUSIONS: The metabolomic profiles of cancer tissues differed from those of non-cancerous tissues. In addition, four metabolites were significantly associated with recurrence in GC. β-Ala was both a significant predictor of peritoneal recurrence and a prognostic factor. PMID: 32219586 [PubMed - as supplied by publisher]

The protective mechanisms of macroalgae Laminaria japonica consumption against lipid metabolism disorders in high-fat diet-induced hyperlipidemic rats.

Sun, 29/03/2020 - 13:13
Related Articles The protective mechanisms of macroalgae Laminaria japonica consumption against lipid metabolism disorders in high-fat diet-induced hyperlipidemic rats. Food Funct. 2020 Mar 27;: Authors: Zhang Q, Fan XY, Guo WL, Cao YJ, Lin YC, Cheng WJ, Chen LJ, Rao PF, Ni L, Lv XC Abstract Macroalgae Laminaria japonica (MLJ) has been reported to exhibit various biological activities including improving immunity, anti-aging, anti-tumor, anti-atherosclerosis and anti-diabetic, but the protective mechanisms of MLJ consumption against non-alcoholic fatty liver disease (NAFLD) associated with hyperlipidemia remain poorly understood. This study demonstrated that MLJ consumption prevented high-fat diet (HFD)-induced NAFLD associated with hyperlipidemia in a rat model, and improved hyperlipidemia-related parameters, e.g. serum and hepatic lipid profiles. Moreover, histological analysis showed that MLJ reduced lipid deposition in adipocytes and hepatocytes compared with the HFD group. Such beneficial effects may be associated with the modulation of the intestinal microbiota, especially some key microbial phylotypes involved in lipid metabolism homeostasis. The underlying protective mechanisms of MLJ consumption against HFD-induced NAFLD associated with hyperlipidemia were also studied by ultra-high performance liquid chromatography with quadruple-time of flight mass spectrometry (UPLC-QTOF/MS)-based liver metabolomics coupled with pathway analysis. The metabolic pathway enrichment analysis of the differentially abundant hepatic metabolites indicated that primary bile acid biosynthesis metabolism and cysteine and methionine metabolism were the two main metabolic pathways altered by MLJ consumption when compared with the model group. The analysis of the transcription levels of liver-related genes by RT-qPCR and the expressions of liver-related proteins by immunohistochemistry (IHC) showed that MLJ consumption could regulate the levels of mRNA transcription and protein expression related to hepatic lipid metabolism. In short, this study indicates that MLJ could be developed as functional food supplement for the prevention or treatment of NAFLD associated with hyperlipidemia. PMID: 32219261 [PubMed - as supplied by publisher]

Genome Insights of the Plant-Growth Promoting Bacterium Cronobacter muytjensii JZ38 With Volatile-Mediated Antagonistic Activity Against Phytophthora infestans.

Sun, 29/03/2020 - 13:13
Related Articles Genome Insights of the Plant-Growth Promoting Bacterium Cronobacter muytjensii JZ38 With Volatile-Mediated Antagonistic Activity Against Phytophthora infestans. Front Microbiol. 2020;11:369 Authors: Eida AA, Bougouffa S, L'Haridon F, Alam I, Weisskopf L, Bajic VB, Saad MM, Hirt H Abstract Salinity stress is a major challenge to agricultural productivity and global food security in light of a dramatic increase of human population and climate change. Plant growth promoting bacteria can be used as an additional solution to traditional crop breeding and genetic engineering. In the present work, the induction of plant salt tolerance by the desert plant endophyte Cronobacter sp. JZ38 was examined on the model plant Arabidopsis thaliana using different inoculation methods. JZ38 promoted plant growth under salinity stress via contact and emission of volatile compounds. Based on the 16S rRNA and whole genome phylogenetic analysis, fatty acid analysis and phenotypic identification, JZ38 was identified as Cronobacter muytjensii and clearly separated and differentiated from the pathogenic C. sakazakii. Full genome sequencing showed that JZ38 is composed of one chromosome and two plasmids. Bioinformatic analysis and bioassays revealed that JZ38 can grow under a range of abiotic stresses. JZ38 interaction with plants is correlated with an extensive set of genes involved in chemotaxis and motility. The presence of genes for plant nutrient acquisition and phytohormone production could explain the ability of JZ38 to colonize plants and sustain plant growth under stress conditions. Gas chromatography-mass spectrometry analysis of volatiles produced by JZ38 revealed the emission of indole and different sulfur volatile compounds that may play a role in contactless plant growth promotion and antagonistic activity against pathogenic microbes. Indeed, JZ38 was able to inhibit the growth of two strains of the phytopathogenic oomycete Phytophthora infestans via volatile emission. Genetic, transcriptomic and metabolomics analyses, combined with more in vitro assays will provide a better understanding the highlighted genes' involvement in JZ38's functional potential and its interaction with plants. Nevertheless, these results provide insight into the bioactivity of C. muytjensii JZ38 as a multi-stress tolerance promoting bacterium with a potential use in agriculture. PMID: 32218777 [PubMed - as supplied by publisher]

Identifying Protein-metabolite Networks Associated with COPD Phenotypes.

Sun, 29/03/2020 - 13:13
Related Articles Identifying Protein-metabolite Networks Associated with COPD Phenotypes. Metabolites. 2020 Mar 25;10(4): Authors: Mastej E, Gillenwater L, Zhuang Y, Pratte KA, Bowler RP, Kechris K Abstract Chronic obstructive pulmonary disease (COPD) is a disease in which airflow obstruction in the lung makes it difficult for patients to breathe. Although COPD occurs predominantly in smokers, there are still deficits in our understanding of the additional risk factors in smokers. To gain a deeper understanding of the COPD molecular signatures, we used Sparse Multiple Canonical Correlation Network (SmCCNet), a recently developed tool that uses sparse multiple canonical correlation analysis, to integrate proteomic and metabolomic data from the blood of 1008 participants of the COPDGene study to identify novel protein-metabolite networks associated with lung function and emphysema. Our aim was to integrate -omic data through SmCCNet to build interpretable networks that could assist in the discovery of novel biomarkers that may have been overlooked in alternative biomarker discovery methods. We found a protein-metabolite network consisting of 13 proteins and 7 metabolites which had a -0.34 correlation (p-value = 2.5 × 10-28) to lung function. We also found a network of 13 proteins and 10 metabolites that had a -0.27 correlation (p-value = 2.6 × 10-17) to percent emphysema. Protein-metabolite networks can provide additional information on the progression of COPD that complements single biomarker or single -omic analyses. PMID: 32218378 [PubMed - as supplied by publisher]

An Integrative Approach to Assessing Diet-Cancer Relationships.

Sun, 29/03/2020 - 13:13
Related Articles An Integrative Approach to Assessing Diet-Cancer Relationships. Metabolites. 2020 Mar 25;10(4): Authors: Murphy R Abstract The relationship between diet and cancer is often viewed with skepticism by the public and health professionals, despite a considerable body of evidence and general consistency in recommendations over the past decades. A systems biology approach which integrates 'omics' data including metabolomics, genetics, metagenomics, transcriptomics and proteomics holds promise for developing a better understanding of how diet affects cancer and for improving the assessment of diet through biomarker discovery thereby renewing confidence in diet-cancer links. This review discusses the application of multi-omics approaches to studies of diet and cancer. Considerations and challenges that need to be addressed to facilitate the investigation of diet-cancer relationships with multi-omic approaches are also discussed. PMID: 32218376 [PubMed - as supplied by publisher]

Soy Metabolism by Gut Microbiota from Patients with Precancerous Intestinal Lesions.

Sun, 29/03/2020 - 13:13
Related Articles Soy Metabolism by Gut Microbiota from Patients with Precancerous Intestinal Lesions. Microorganisms. 2020 Mar 25;8(4): Authors: Polimeno L, Barone M, Mosca A, Viggiani MT, Joukar F, Mansour-Ghanaei F, Mavaddati S, Daniele A, Debellis L, Bilancia M, Santacroce L, Di Leo A Abstract BACKGROUND: Colorectal cancer (CRC) requires the presence of a variety of factors predisposing a tumorigenic milieu. Excluding familial clustering and hereditary CRC syndromes, the development of sporadic CRC from precancerous lesions is influenced by tissue inflammation, modulation of intestinal immunity, hormones, dietary habits and gut microbiota composition. As concerning the last two aspects, the intestinal presence of equol, the most biologically active metabolite of the soy isoflavone daidzein and the presence of a genetic determinant of gut microbiota able to metabolize daidzein, seem to lower the CRC risk. It has been hypothesized that the anaerobic microorganisms of the Bacteroides genus play a role in equol production. AIM: To evaluate the presence of (i) anaerobic gut microbiota and (ii) the urinary levels of soy isoflavones (daidzein, genistein and equol) in patients with and without precancerous lesions, challenged with a daidzein-rich soy extract. METHODS: Consecutive subjects undergoing colonoscopy participated to the study. Feces were collected from all patients one week before colonoscopy for gut microbiota studies. After the endoscopy examination and the histological evaluation, 40 subjects, 20 with sporadic colorectal adenomas (SCA/P group) and 20 without proliferative lesions (control group) were enrolled for the study. Urine levels of soy isoflavones daidzein, genistein and their metabolite equol, were determined by high performance liquid chromatographic (HPLC) analysis and gut microbiota analysis was performed by Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) procedure. RESULTS: Seventeen different bacterial species were identified in the fecal samples of the forty subjects participating to the study. Ten bacterial species resulted anaerobic Gram-negative bacteria, all belonging to the Bacteroides genus. A significant difference of bacteria species was evidenced in the fecal samples of the two groups of subjects. Particularly important was the evidence of Parabacteroides distasonis, Clostridium clostridioforme and Pediococcus pentasaceus only in control fecal samples, such as the presence of Bacteroides fragilis and Prevotella melaningenica only in SCA/P fecal samples. Concerning the soy isoflavones levels, no statistically significant differences were revealed in the genistein and daidzein urinary levels between the two groups of subjects. On the contrary, urinary equol levels were undetectable in ten SCA/P subjects and in two controls; moreover, when present, the levels of urinary equol were significantly lower in SCA/P subjects compared to controls (0.24 ± 0.27 mg/24 hrs vs. 21.25 ± 4.3 mg/24 hrs, respectively, p = 1.12 × 10-6). CONCLUSIONS: Our results suggest that the presence of anaerobic Bacteroides in the colon, and the production of equol from soy, could determine a milieu able to contrast the development of colonic mucosa proliferative lesions. PMID: 32218321 [PubMed - as supplied by publisher]

Proteomic Analysis of Blood Exosomes from Healthy Females and Breast Cancer Patients Reveals an Association between Different Exosomal Bioactivity on Non-tumorigenic Epithelial Cell and Breast Cancer Cell Migration in Vitro.

Sun, 29/03/2020 - 13:13
Related Articles Proteomic Analysis of Blood Exosomes from Healthy Females and Breast Cancer Patients Reveals an Association between Different Exosomal Bioactivity on Non-tumorigenic Epithelial Cell and Breast Cancer Cell Migration in Vitro. Biomolecules. 2020 Mar 25;10(4): Authors: Tutanov O, Orlova E, Proskura K, Grigor'eva A, Yunusova N, Tsentalovich Y, Alexandrova A, Tamkovich S Abstract Exosomes are important intercellular communication vehicles, secreted into body fluids by multiple cell types, including tumor cells. They contribute to the metastatic progression of tumor cells through paracrine signalling. It has been recently discovered that blood circulating exosomes contain distinguishable fractions of free and cell-surface-associated vesicles. We evaluated the influence of protein cargoes from exosomes from plasma, and exosomes from the total blood of healthy females (HFs) and breast cancer patients (BCPs), on cell motility. We conducted a mass spectrometric analysis of exosomal contents isolated from samples using ultrafiltration and ultracentrifugation approaches and verified their nature using transmission electron microscopy, nanoparticle tracking analysis and flow cytometry. We observed that malignant neoplasm-associated proteins in exosomes from BCP total blood were detected more often than in plasma (66% vs. 59%). FunRich analysis to assess Gene Ontology (GO) enrichment revealed that proteins with catalytic activities, transporter functions and protein metabolism activities were increased in exosomes from BCP blood. Finally, GO analysis revealed that proteomic profiles of exosomes from HF total blood were enriched with proteins inhibiting cell migration and invasion, which explains the low stimulating activity of exosomes from HF total blood on SKBR-3 cancer cell migration velocity. This allows exosomes to act as intermediaries providing intercellular communications through horizontal transfer of RNA and functionally active proteins, potentially affecting the development of both primary neoplasms and distant metastases. PMID: 32218180 [PubMed - as supplied by publisher]

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