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

Ethnobotanic, Ethnopharmacologic Aspects and New Phytochemical Insights into Moroccan Argan Fruits.

Sat, 09/06/2018 - 12:35
Related Articles Ethnobotanic, Ethnopharmacologic Aspects and New Phytochemical Insights into Moroccan Argan Fruits. Int J Mol Sci. 2017 Oct 30;18(11): Authors: Khallouki F, Eddouks M, Mourad A, Breuer A, Owen RW Abstract This review summarizes available data on argan fruit botany, geographical distribution, traditional uses, environmental interest, socioeconomic role, phytochemistry, as well as health beneficial effects and examination of future prospects. In particular, ethnomedical uses of argan fruits are carried out throughout Morocco where it has been used against various diseases. Different classes of bioactive compounds have been characterized including essential oils, fatty acids, triacylglycerols, flavonoids and their newly reported acylglycosyl derivatives, monophenols, phenolic acids, cinnamic acids, saponins, triterpenes, phytosterols, ubiquinone, melatonin, new aminophenols along with vitamin E among other secondary metabolites. The latter have already shown a wide spectrum of in vitro, and ex vivo biologicalactivities including antioxidant, anti-inflammatory, anti-diabetic, antihypertensive, anti-hypercholesterolemia, analgesic, antimicrobial, molluscicidal anti-nociceptive and anticancer potential. Argan flesh (pulp) contains a broad spectrum of polyphenolic compounds which may have utility for incorporation into nutraceuticals and cosmeceuticals relevant to the food, cosmetic and health industries. Further research is recommended, especially on the health beneficial effects of the aminophenols. PMID: 29084170 [PubMed - indexed for MEDLINE]

Isoprostanes, neuroprostanes and phytoprostanes: An overview of 25years of research in chemistry and biology.

Sat, 09/06/2018 - 12:35
Related Articles Isoprostanes, neuroprostanes and phytoprostanes: An overview of 25years of research in chemistry and biology. Prog Lipid Res. 2017 Oct;68:83-108 Authors: Galano JM, Lee YY, Oger C, Vigor C, Vercauteren J, Durand T, Giera M, Lee JC Abstract Since the beginning of the 1990's diverse types of metabolites originating from polyunsaturated fatty acids, formed under autooxidative conditions were discovered. Known as prostaglandin isomers (or isoprostanoids) originating from arachidonic acid, neuroprostanes from docosahexaenoic acid, and phytoprostanes from α-linolenic acid proved to be prevalent in biology. The syntheses of these compounds by organic chemists and the development of sophisticated mass spectrometry methods has boosted our understanding of the isoprostanoid biology. In recent years, it has become accepted that these molecules not only serve as markers of oxidative damage but also exhibit a wide range of bioactivities. In addition, isoprostanoids have emerged as indicators of oxidative stress in humans and their environment. This review explores in detail the isoprostanoid chemistry and biology that has been achieved in the past three decades. PMID: 28923590 [PubMed - indexed for MEDLINE]

metabolomics; +24 new citations

Fri, 08/06/2018 - 15:20
24 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 2018/06/08PubMed 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; +24 new citations

Fri, 08/06/2018 - 12:20
24 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 2018/06/08PubMed 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; +25 new citations

Thu, 07/06/2018 - 21:02
25 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 2018/06/07PubMed 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; +25 new citations

Thu, 07/06/2018 - 14:57
25 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 2018/06/07PubMed 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; +18 new citations

Wed, 06/06/2018 - 14:36
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 2018/06/06PubMed 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; +18 new citations

Tue, 05/06/2018 - 17:05
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 2018/06/05PubMed 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.

Metabolome changes are induced in the arbuscular mycorrhizal fungus Gigaspora margarita by germination and by its bacterial endosymbiont.

Mon, 04/06/2018 - 13:51
Related Articles Metabolome changes are induced in the arbuscular mycorrhizal fungus Gigaspora margarita by germination and by its bacterial endosymbiont. Mycorrhiza. 2018 Jun 02;: Authors: Dearth SP, Castro HF, Venice F, Tague ED, Novero M, Bonfante P, Campagna SR Abstract Metabolomic profiling is becoming an increasingly important technique in the larger field of systems biology by allowing the simultaneous measurement of thousands of small molecules participating in and resulting from cellular reactions. In this way, metabolomics presents an opportunity to observe the physiological state of a system, which may provide the ability to monitor the whole of cellular metabolism as the technology progresses. The arbuscular mycorrhizal fungus Gigaspora margarita has not previously been explored with regard to metabolite composition. To develop a better understanding of G. margarita and the influences of its endosymbiont Candidatus Glomeribacter gigasporarum, a metabolomic analysis was applied to quiescent and germinated spores with and without endobacteria. Over 100 metabolites were identified and greater than 2600 unique unidentified spectral features were observed. Multivariate analysis of the metabolomes was performed, and a differentiation between all metabolic states of spores and spores hosting the endobacteria was observed. The known metabolites were recruited to many biochemical pathways, with many being involved in maintenance of the antioxidant potential, tyrosine metabolism, and melanin production. Each of the pathways had higher metabolite abundances in the presence of the endosymbiont. These metabolomics data also agree with previously reported transcriptomics results demonstrating the capability of this technique to confirm hypotheses and showing the feasibility of multi-omic approaches for the study of arbuscular mycorrhizal fungi and their endobacterial communities. Challenges still exist in metabolomic analysis, e.g., the identification of compounds is demanding due to incomplete libraries. A metabolomics technique to probe the effects of bacterial endosymbionts on fungal physiology is presented herein, and this method is useful for hypothesis generation as well as testing as noted above. PMID: 29860608 [PubMed - as supplied by publisher]

Glutamine supplementation enhances development of in vitro-produced porcine embryos and increases leucine consumption from the medium.

Mon, 04/06/2018 - 13:51
Related Articles Glutamine supplementation enhances development of in vitro-produced porcine embryos and increases leucine consumption from the medium. Biol Reprod. 2018 May 31;: Authors: Chen PR, Redel BK, Spate LD, Ji T, Salazar SR, Prather RS Abstract Improper composition of culture medium contributes to reduced viability of in vitro-produced embryos. Glutamine (Gln) is a crucial amino acid for preimplantation embryos as it supports proliferation and is involved in many different biosynthetic pathways. Previous transcriptional profiling revealed several upregulated genes related to Gln transport and metabolism in in vitro-produced porcine blastocysts compared to in vivo-produced counterparts, indicating a potential deficiency in the culture medium. Therefore, the objective of this study was to determine the effects of Gln supplementation on in vitro-produced porcine embryo development, gene expression, and metabolism. Cleaved embryos were selected and cultured in MU2 medium supplemented with 1 mM Gln (control), 3.75 mM Gln (+Gln), 3.75 mM GlutaMAX (+Max), or 3.75 mM alanine (+Ala) until day 6. Embryos cultured with +Gln or +Max had increased development to the blastocyst stage and total number of nuclei compared to the control (P < 0.05). Moreover, expression of misregulated transcripts involved in glutamine and glutamate transport and metabolism were corrected when embryos were cultured with +Gln or +Max. Metabolomics analysis revealed increased production of glutamine and glutamate into the medium by embryos cultured with +Max and increased consumption of leucine by embryos cultured with +Gln or +Max. As an indicator of cellular health, mitochondrial membrane potential was increased when embryos were cultured with +Max which was coincident with decreased apoptosis in these blastocysts. Lastly, two embryo transfers by using embryos cultured with +Max resulted in viable piglets, confirming that this treatment is consistent with in vivo developmental competence. PMID: 29860318 [PubMed - as supplied by publisher]

Metabolomics and antioxidant activity of the leaves of Prunus dulcis Mill. (Italian cvs. Toritto and Avola).

Mon, 04/06/2018 - 13:51
Related Articles Metabolomics and antioxidant activity of the leaves of Prunus dulcis Mill. (Italian cvs. Toritto and Avola). J Pharm Biomed Anal. 2018 May 23;158:54-65 Authors: Bottone A, Montoro P, Masullo M, Pizza C, Piacente S Abstract Prunus dulcis leaves have been reported to exert some biological activity, in particular potent free radical-scavenging capacity, but so far there is limited information on their chemical composition. With the aim to achieve deep insight on the chemical constituents of the leaves of P. dulcis cultivars "Toritto" and "Avola", the most appreciated in Italy, an approach based on liquid chromatography-mass spectrometry (LC-MS) combined with isolation and structure elucidation of pure compounds by Nuclear Magnetic Resonance (NMR) analysis was carried out. Results allowed to detect in cv. Toritto leaves phenolics, terpenoids and a cyanogenic glycoside. Successively, various solvent systems were chosen to afford different extracts and an approach based on principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) from LC-MS data sets highlighted eco-friendly methods as selective in extracting phenolics and glycosides. Comparison of LC-MS profiles of the MeOH extracts of cv. Toritto and cvs. Avola (Pizzuta, Fascionello and Romana) leaves and evaluation of their phenolic contents and antioxidant activity were also carried out. PMID: 29860179 [PubMed - as supplied by publisher]

Tracking gene expression and oxidative damage of O2-stressed Clostridioides difficile by a multi-omics approach.

Mon, 04/06/2018 - 13:51
Related Articles Tracking gene expression and oxidative damage of O2-stressed Clostridioides difficile by a multi-omics approach. Anaerobe. 2018 May 31;: Authors: Neumann-Schaal M, Metzendorf NG, Troitzsch D, Nuss AM, Hofmann JD, Beckstette M, Dersch P, Otto A, Sievers S Abstract Clostridioides difficile is the major pathogen causing diarrhea following antibiotic treatment. It is considered to be a strictly anaerobic bacterium, however, previous studies have shown a certain and strain-dependent oxygen tolerance. In this study, the model strain C. difficile 630Δerm was shifted to micro-aerobiosis and was found to stay growing to the same extent as anaerobically growing cells with only few changes in the metabolite pattern. However, an extensive change in gene expression was determined by RNA-Seq. The most striking adaptation strategies involve a change in the reductive fermentation pathways of the amino acids proline, glycine and leucine. But also a far-reaching restructuring in the carbohydrate metabolism was detected with changes in the phosphotransferase system (PTS) facilitated uptake of sugars and a repression of enzymes of glycolysis and butyrate fermentation. Furthermore, a temporary induction in the synthesis of cofactor riboflavin was detected possibly due to an increased demand for flavin mononucleotid (FMN) and flavin adenine dinucleotide (FAD) in redox reactions. However, biosynthesis of the cofactors thiamin pyrophosphate and cobalamin were repressed deducing oxidation-prone enzymes and intermediates in these pathways. Micro-aerobically shocked cells were characterized by an increased demand for cysteine and a thiol redox proteomics approach revealed a dramatic increase in the oxidative state of cysteine in more than 800 peptides after 15 min of micro-aerobic shock. This provides not only a catalogue of oxidation-prone cysteine residues in the C. difficile proteome but also puts the amino acid cysteine into a key position in the oxidative stress response. Our study suggests that tolerance of C. difficile towards O2 is based on a complex and far-reaching adjustment of global gene expression which leads to only a slight change in phenotype. PMID: 29859941 [PubMed - as supplied by publisher]

Adipose Tissue-Derived Stromal Cells for Wound Healing.

Sun, 03/06/2018 - 13:23
Adipose Tissue-Derived Stromal Cells for Wound Healing. Adv Exp Med Biol. 2018 Jun 02;: Authors: Goodarzi P, Alavi-Moghadam S, Sarvari M, Tayanloo Beik A, Falahzadeh K, Aghayan H, Payab M, Larijani B, Gilany K, Rahim F, Adibi H, Arjmand B Abstract Skin as the outer layer covers the body. Wounds can affect this vital organ negatively and disrupt its functions. Wound healing as a biological process is initiated immediately after an injury. This process consists of three stages: inflammation, proliferation, remodeling. Generally, these three stages occur continuously and timely. However, some factors such as infection, obesity and diabetes mellitus can interfere with these stages and impede the normal healing process which results in chronic wounds. Financial burden on both patients and health care systems, negative biologic effect on the patient's general health status and reduction in quality of life are a number of issues which make chronic wounds as a considerable challenge. During recent years, along with advances in the biomedical sciences, various surgical and non-surgical therapeutic methods have been suggested. All of these suggested treatments have their own advantages and disadvantages. Recently, cell-based therapies and regenerative medicine represent promising approaches to wound healing. Accordingly, several types of mesenchymal stem cells have been used in both preclinical and clinical settings for the treatment of wounds. Adipose-derived stromal cells are a cost-effective source of mesenchymal stem cells in wound management which can be easily harvest from adipose tissues through the less invasive processes with high yield rates. In addition, their ability to secrete multiple cytokines and growth factors, and differentiation into skin cells make them an ideal cell type to use in wound treatment. This is a concise overview on the application of adipose-derived stromal cells in wound healing and their role in the treatment of chronic wounds. PMID: 29858972 [PubMed - as supplied by publisher]

Comparative transcription profiling of two fermentation cultures of Xanthomonas campestris pv. campestris B100 sampled in the growth and in the stationary phase.

Sun, 03/06/2018 - 13:23
Comparative transcription profiling of two fermentation cultures of Xanthomonas campestris pv. campestris B100 sampled in the growth and in the stationary phase. Appl Microbiol Biotechnol. 2018 Jun 01;: Authors: Alkhateeb RS, Vorhölter FJ, Steffens T, Rückert C, Ortseifen V, Hublik G, Niehaus K, Pühler A Abstract The ɣ-proteobacterium Xanthomonas campestris pv. campestris (Xcc) is the producer of the biopolymer xanthan, a polysaccharide which is used as a thickener in numerous industrial applications. In this study, we present a global transcriptome profiling of two Xcc strain B100 cultures obtained from fermentation during the growth phase and the subsequent stationary phase associated with xanthan biosynthesis. During the xanthan production phase, highly abundant transcripts belonged to genes encoding for small RNAs, glycogen biosynthesis, and xanthan export. A total of 1850 (40%) genes were differentially transcribed during the stationary phase where 924 were transcriptionally up-regulated and 926 genes were down-regulated. An overview of differentially transcribed genes includes a significant down-regulation of genes involved in transcription, translation, and amino acid biosynthesis pathways. A group of up-regulated genes was involved in cellular response against oxidative stress, such as those coding for superoxide dismutase and catalase. Genes encoding enzymes involved in nucleotide sugar precursor synthesis of xanthan biosynthesis, such as xanA, galU, and ugd, exhibited a transcription pattern that did not change during the growth and stationary phase. Regarding the transcription pattern of the gum gene cluster that govern xanthan biosynthesis, a significant up-regulation of the genes gumB, gumC, and gumD was observed, while the transcript pools of the genes gumG, gumH, gumI, and gumJ were reduced and those of genes gumE, gumF, gumK, gumL, and gumM remained un-changed during the stationary phase compared to the growth phase. The obtained data represents the first analysis of gene expression patterns under xanthan production conditions and provides the bases for future studies aiming at enhancing xanthan yield. PMID: 29858955 [PubMed - as supplied by publisher]

Longitudinal Changes in Cholesterol Efflux Capacities in Patients With Coronary Artery Disease Undergoing Lifestyle Modification Therapy.

Sun, 03/06/2018 - 13:23
Longitudinal Changes in Cholesterol Efflux Capacities in Patients With Coronary Artery Disease Undergoing Lifestyle Modification Therapy. J Am Heart Assoc. 2018 Jun 01;7(11): Authors: Boyer M, Lévesque V, Poirier P, Marette A, Mitchell PL, Mora S, Mathieu P, Després JP, Larose É, Arsenault BJ Abstract BACKGROUND: Our objective was to identify the determinants of high-density lipoprotein cholesterol efflux capacity (HDL-CEC) changes in patients with coronary artery disease who participated in a lifestyle modification program aimed at increasing physical activity levels and improving diet quality. METHODS AND RESULTS: A total of 86 men with coronary artery disease aged between 35 and 80 years participated in a 1-year lifestyle modification program that aimed to achieve a minimum of 150 minutes of aerobic physical activity weekly and improve diet quality. HDL-CECs were measured before and after the 1-year intervention using 3H-cholesterol-labeled J774 and HepG2 cells. Visceral, subcutaneous, and cardiac adipose tissue levels were assessed before and after the intervention using magnetic resonance imaging. Lipoprotein particle size and concentrations were measured by proton nuclear magnetic resonance spectroscopy and a complete lipoprotein-lipid profile was obtained. At baseline, the best correlate of HDL-CECs were apolipoprotein AI (R2=0.35, P<0.0001) and high-density lipoprotein cholesterol (R2=0.21, P<0.0001) for J774-HDL-CECs and HepG2-HDL-CECs, respectively. Baseline and longitudinal changes in HDL-CECs were associated with several lipoprotein size and concentration indices, although high-density lipoprotein cholesterol was the best predictor of longitudinal changes in J774-HDL-CECs (R2=0.18, P=0.002) and apolipoprotein AI was found to be the best predictor of longitudinal changes in HepG2 cholesterol efflux capacities (R2=0.21, P=0.002). CONCLUSIONS: Results of this study suggest that increases in high-density lipoprotein cholesterol and apolipoprotein AI levels typically observed in patients with coronary artery disease undergoing healthy lifestyle modification therapy may be indicative of higher plasma concentrations of functional high-density lipoprotein particles. PMID: 29858367 [PubMed - in process]

Protective effects of Scutellaria baicalensis Georgi extract on D-galactose induced aging rats.

Sat, 02/06/2018 - 12:32
Protective effects of Scutellaria baicalensis Georgi extract on D-galactose induced aging rats. Metab Brain Dis. 2018 May 31;: Authors: Zhao F, Chang Y, Gao L, Qin X, Du G, Zhang X, Zhou Y Abstract Scutellaria baicalensis Georgi (SBG), a traditional Chinese herb, has attracted considerable attention for its wide range of pharmacological activities. This study aimed to investigate the intervention effects of SBG ethanol extract on aging rats induced by D-galactose (D-gal) and to explore potential mechanisms by serum and liver metabolic profiles. The aging rats were induced by the D-gal (100 mg/kg) for 10 weeks continuously with subcutaneous injection, while the control rats received physiological saline. Two other groups of rats were administered with 100 mg/kg/day and 200 mg/kg/day of SBG by oral route following D-gal injections. The abilities of spatial and learning memory were evaluated by open-field test and Morris water maze test. Then, some biochemical indexes related to cognitive ability and aging were measured. Histopathological feature in hippocampal region was observed by Hematoxylin and eosin (HE) staining. The changes of metabolic profiles were evaluated using proton nuclear magnetic resonance (1H NMR) spectroscopy coupled with multivariate data analysis. Results showed that SBG could significantly improve the learning and memory functions, reducing oxidative damage and histological abnormalities of hippocampus neurons. In addition, significant differences in the metabolic profiles were observed both in serum and liver between the model group and the control group. After the treatment using SBG, the levels of these metabolites are significantly changed back to their similar levels in the control group. These metabolic changes are related to the disturbance in amino acid metabolism, glycometabolism and choline metabolism. Hence, SBG may have the potential to improve neurodegeneration and provide brain protection. Graphical abstract A 1H NMR-based metabonomic study was conducted to provide a global view of metabolites related to D-gal induced aging rats and assess the holistic efficacy of Scutellaria baicalensis Georgi. PMID: 29855978 [PubMed - as supplied by publisher]

Tissue Engineered Skin Substitutes.

Sat, 02/06/2018 - 12:32
Tissue Engineered Skin Substitutes. Adv Exp Med Biol. 2018 Jun 01;: Authors: Goodarzi P, Falahzadeh K, Nematizadeh M, Farazandeh P, Payab M, Larijani B, Tayanloo Beik A, Arjmand B Abstract The fundamental skin role is to supply a supportive barrier to protect body against harmful agents and injuries. Three layers of skin including epidermis, dermis and hypodermis form a sophisticated tissue composed of extracellular matrix (ECM) mainly made of collagens and glycosaminoglycans (GAGs) as a scaffold, different cell types such as keratinocytes, fibroblasts and functional cells embedded in the ECM. When the skin is injured, depends on its severity, the majority of mentioned components are recruited to wound regeneration. Additionally, different growth factors like fibroblast growth factor (FGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) are needed to orchestrated wound healing process. In case of large surface area wounds, natural wound repair seems inefficient. Inspired by nature, scientists in tissue engineering field attempt to engineered constructs mimicking natural healing process to promote skin restoration in untreatable injuries. There are three main types of commercially available engineered skin substitutes including epidermal, dermal, and dermoepidermal. Each of them could be composed of scaffold, desired cell types or growth factors. These substitutes could have autologous, allogeneic, or xenogeneic origin. Moreover, they may be cellular or acellular. They are used to accelerate wound healing and recover normal skin functions with pain relief. Although there are a wide variety of commercially available skin substitutes, almost none of them considered as an ideal equivalents required for proper wound healing. PMID: 29855826 [PubMed - as supplied by publisher]

Glutamate mediated metabolic neutralization mitigates propionate toxicity in intracellular Mycobacterium tuberculosis.

Sat, 02/06/2018 - 12:32
Glutamate mediated metabolic neutralization mitigates propionate toxicity in intracellular Mycobacterium tuberculosis. Sci Rep. 2018 May 31;8(1):8506 Authors: Lee JJ, Lim J, Gao S, Lawson CP, Odell M, Raheem S, Woo J, Kang SH, Kang SS, Jeon BY, Eoh H Abstract Metabolic networks in biological systems are interconnected, such that malfunctioning parts can be corrected by other parts within the network, a process termed adaptive metabolism. Unlike Bacillus Calmette-Guérin (BCG), Mycobacterium tuberculosis (Mtb) better manages its intracellular lifestyle by executing adaptive metabolism. Here, we used metabolomics and identified glutamate synthase (GltB/D) that converts glutamine to glutamate (Q → E) as a metabolic effort used to neutralize cytoplasmic pH that is acidified while consuming host propionate carbon through the methylcitrate cycle (MCC). Methylisocitrate lyase, the last step of the MCC, is intrinsically downregulated in BCG, leading to obstruction of carbon flux toward central carbon metabolism, accumulation of MCC intermediates, and interference with GltB/D mediated neutralizing activity against propionate toxicity. Indeed, vitamin B12 mediated bypass MCC and additional supplement of glutamate led to selectively correct the phenotypic attenuation in BCG and restore the adaptive capacity of BCG to the similar level of Mtb phenotype. Collectively, a defective crosstalk between MCC and Q → E contributes to attenuation of intracellular BCG. Furthermore, GltB/D inhibition enhances the level of propionate toxicity in Mtb. Thus, these findings revealed a new adaptive metabolism and propose GltB/D as a synergistic target to improve the antimicrobial outcomes of MCC inhibition in Mtb. PMID: 29855554 [PubMed - in process]

Non-invasive staging of chronic kidney allograft damage using urine metabolomic profiling.

Sat, 02/06/2018 - 12:32
Related Articles Non-invasive staging of chronic kidney allograft damage using urine metabolomic profiling. Pediatr Transplant. 2018 May 31;:e13226 Authors: Landsberg A, Sharma A, Gibson IW, Rush D, Wishart DS, Blydt-Hansen TD Abstract Chronic kidney allograft damage is characterized by IFTA and GS. We sought to identify urinary metabolite signatures associated with severity of IFTA and GS in pediatric kidney transplant recipients. Urine samples (n = 396) from 60 pediatric transplant recipients were obtained at the time of kidney biopsy and assayed for 133 metabolites by mass spectrometry. Metabolite profiles were quantified via PLS-DA. We used mixed-effects regression to identify laboratory and clinical predictors of histopathology. Urine samples (n = 174) without rejection or AKI were divided into training/validation sets (75:25%). Metabolite classifiers trained on IFTA severity and %GS showed strong statistical correlation (r = .73, P < .001 and r = .72; P < .001, respectively) and remained significant on the validation sets. Regression analysis identified additional clinical features that improved prediction: months post-transplant (GS, IFTA); and proteinuria, GFR, and age (GS only). Addition of clinical variables improved performance of the %GS classifier (AUC = 0.9; 95% CI = 0.85-0.96) but not for IFTA (AUC = 0.82; 95% CI = 0.71-0.92). Despite the presence of potentially confounding phenotypes, these findings were further validated in samples withheld for rejection or AKI. We identify urine metabolite classifiers for IFTA and GS, which may prove useful for non-invasive assessment of histopathological damage. PMID: 29855144 [PubMed - as supplied by publisher]

Association Between Newborn Metabolic Profiles and Pediatric Kidney Disease.

Sat, 02/06/2018 - 12:32
Related Articles Association Between Newborn Metabolic Profiles and Pediatric Kidney Disease. Kidney Int Rep. 2018 May;3(3):691-700 Authors: Sood MM, Murphy MSQ, Hawken S, Wong CA, Potter BK, Burns KD, Tsampalieros A, Atkinson KM, Chakraborty P, Wilson K Abstract Introduction: Metabolomics offers considerable promise in early disease detection. We set out to test the hypothesis that routine newborn metabolic profiles at birth, obtained through screening for inborn errors of metabolism, would be associated with kidney disease and add incremental information to known clinical risk factors. Methods: We conducted a population-level cohort study in Ontario, Canada, using metabolic profiles from 1,288,905 newborns from 2006 to 2015. The primary outcome was chronic kidney disease (CKD) or dialysis. Individual metabolites and their ratio combinations were examined by logistic regression after adjustment for established risk factors for kidney disease and incremental risk prediction measured. Results: CKD occurred in 2086 (0.16%, median time 612 days) and dialysis in 641 (0.05%, median time 99 days) infants and children. Individual metabolites consisted of amino acids, acylcarnitines, markers of fatty acid oxidation, and others. Base models incorporating clinical risk factors only provided c-statistics of 0.61 for CKD and 0.70 for dialysis. The addition of identified metabolites to risk prediciton models resulted in significant incremental improvement in the performance of both models (CKD model: c-statistic 0.66 NRI 0.36 IDI 0.04, dialysis model: c-statistic 0.77 NRI 0.57 IDI 0.09). This was consistent after internal validation using bootstrapping and a sensitivity analysis excluding outcomes within the first 30 days. Conclusion: Routinely collected screening metabolites at birth are associated with CKD and the need for dialytic therapies in infants and children, and add incremental information to traditional clinical risk factors. PMID: 29854978 [PubMed]

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