PubMed

Automated Analysis of Fluorescence Colocalization: Application to Mitophagy. Methods Enzymol. 2017;588:219-230 Authors: Sauvat A, Zhou H, Leduc M, Gomes-da-Silva LC, Bezu L, Müller K, Forveille S, Liu P, Zhao L, Kroemer G, Kepp O Abstract Mitophagy is a peculiar form of organelle-specific autophagy that targets mitochondria. This process ensures cellular homeostasis, as it fosters the disposal of aged and damaged mitochondria that otherwise would be prone to produce reactive oxygen species and hence endanger genomic stability. Similarly, autophagic clearance of depolarized mitochondria plays a fundamental role in organismal homeostasis as exemplified by the link between Parkinson disease and impaired function of the mitophagy-mediating proteins PINK1 and Parkin. Here, we detail an image-based approach for the quantification of mitochondrial Parkin translocation, which is mechanistically important for the initiation of mitophagy. PMID: 28237103 [PubMed - in process]

Assessment of Glycolytic Flux and Mitochondrial Respiration in the Course of Autophagic Responses. Methods Enzymol. 2017;588:155-170 Authors: Sica V, Bravo-San Pedro JM, Pietrocola F, Izzo V, Maiuri MC, Kroemer G, Galluzzi L Abstract Autophagy is an evolutionarily conserved process that mediates prominent homeostatic functions, both at the cellular and organismal level. Indeed, baseline autophagy not only ensures the disposal of cytoplasmic entities that may become cytotoxic upon accumulation, but also contributes to the maintenance of metabolic fitness in physiological conditions. Likewise, autophagy plays a fundamental role in the cellular and organismal adaptation to homeostatic perturbations of metabolic, physical, or chemical nature. Thus, the molecular machinery for autophagy is functionally regulated by a broad panel of sensors that detect indicators of metabolic homeostasis. Moreover, increases in autophagic flux have a direct impact on core metabolic circuitries including (but not limited to) glycolysis and mitochondrial respiration. Here, we detail a simple methodological approach to monitor these two processes in cultured cancer cells that mount a proficient autophagic response to stress. PMID: 28237099 [PubMed - in process]

Identification and Profiling of Specialized Pro-Resolving Mediators in Human Tears by Lipid Mediator Metabolomics. Prostaglandins Leukot Essent Fatty Acids. 2017 Feb;117:17-27 Authors: English JT, Norris PC, Hodges RR, Dartt DA, Serhan CN Abstract Specialized pro-resolving mediators (SPM), e.g. Resolvin D1, Protectin D1, Lipoxin A₄, and Resolvin E1 have each shown to be active in ocular models reducing inflammation. In general, SPMs have specific agonist functions that stimulate resolution of infection and inflammation in animal disease models. The presence and quantity of SPM in human emotional tears is of interest. Here, utilizing a targeted LC-MS-MS metabololipidomics based approach we document the identification of pro-inflammatory (Prostaglandins and Leukotriene B₄) and pro-resolving lipid mediators (D-series Resolvins, Protectin D1, and Lipoxin A₄) in human emotional tears from 12 healthy individuals. SPMs from the Maresin family (Maresin 1 and Maresin 2) were not present in these samples. Principal Component Analysis (PCA) revealed gender differences in the production of specific mediators within these tear samples as the SPMs were essentially absent in these female donors. These results indicate that specific SPM signatures are present in human emotional tears at concentrations known to be bioactive. Moreover, they will help to further appreciate the mechanisms of production and action of SPMs in the eye, as well as their physiologic roles in human ocular disease resolution. PMID: 28237084 [PubMed - in process]

Related Articles Oxidative stress, metabolomics profiling, and mechanism of local anesthetic induced cell death in yeast. Redox Biol. 2017 Feb 03;12:139-149 Authors: Boone CH, Grove RA, Adamcova D, Seravalli J, Adamec J Abstract The World Health Organization designates lidocaine as an essential medicine in healthcare, greatly increasing the probability of human exposure. Its use has been associated with ROS generation and neurotoxicity. Physiological and metabolomic alterations, and genetics leading to the clinically observed adverse effects have not been temporally characterized. To study alterations that may lead to these undesirable effects, Saccharomyces cerevisiae grown on aerobic carbon sources to stationary phase was assessed over 6h. Exposure of an LC50 dose of lidocaine, increased mitochondrial depolarization and ROS/RNS generation assessed using JC-1, ROS/RNS specific probes, and FACS. Intracellular calcium also increased, assessed by ICP-MS. Measurement of the relative ATP and ADP concentrations indicates an initial 3-fold depletion of ATP suggesting an alteration in the ATP:ADP ratio. At the 6h time point the lidocaine exposed population contained ATP concentrations roughly 85% that of the negative control suggesting the surviving population adapted its metabolic pathways to, at least partially restore cellular bioenergetics. Metabolite analysis indicates an increase of intermediates in the pentose phosphate pathway, the preparatory phase of glycolysis, and NADPH. Oxidative stress produced by lidocaine exposure targets aconitase decreasing its activity with an observed decrease in isocitrate and an increase citrate. Similarly, increases in α-ketoglutarate, malate, and oxaloacetate imply activation of anaplerotic reactions. Antioxidant molecule glutathione and its precursor amino acids, cysteine and glutamate were greatly increased at later time points. Phosphatidylserine externalization suggestive of early phase apoptosis was also observed. Genetic studies using metacaspase null strains showed resistance to lidocaine induced cell death. These data suggest lidocaine induces perpetual mitochondrial depolarization, ROS/RNS generation along with increased glutathione to combat the oxidative cellular environment, glycolytic to PPP cycling of carbon generating NADPH, obstruction of carbon flow through the TCA cycle, decreased ATP generation, and metacaspase dependent apoptotic cell death. PMID: 28236766 [PubMed - as supplied by publisher]

Related Articles Sortilin 1 knockout alters basal adipose glucose metabolism but not diet-induced obesity in mice. FEBS Lett. 2017 Feb 25;: Authors: Li J, Matye DJ, Wang Y, Li T Abstract Sortilin 1 (Sort1) is a trafficking receptor that has been implicated in the regulation of plasma cholesterol in humans and mice. Here, we use metabolomics and hyperinsulinemic-euglycemic clamp approaches to obtain further understanding of the in vivo effects of Sort1 deletion on diet-induced obesity as well as on adipose lipid and glucose metabolism. Results show that Sort1 knockout does not affect Western diet-induced obesity or adipose fatty acid and ceramide concentrations. Under the basal fasting state, chow-fed Sort1 knockout mice have decreased adipose glycolytic metabolites, but Sort1 deletion does not affect insulin-stimulated tissue glucose uptake during the insulin clamp. These results suggest that Sort1 loss-of-function in vivo does not affect obesity development, but differentially modulates adipose glucose metabolism under fasting and insulin-stimulated states. This article is protected by copyright. All rights reserved. PMID: 28236654 [PubMed - as supplied by publisher]

Related Articles The Role of Genomics in Common Variable Immunodeficiency Disorders. Clin Exp Immunol. 2017 Feb 25;: Authors: Kienzler AK, Hargreaves CE, Patel SY Abstract The advent of next generation sequencing (NGS) and 'omic' technologies has revolutionised the field of genetics and its implementation in healthcare has the potential to realise precision medicine. Primary immunodeficiencies (PID) are a group of rare diseases which have benefitted from NGS, with a massive increase in causative genes identified in the past few years. Common Variable Immunodeficiency Disorders (CVID) are a heterogeneous form of PID and the most common form of antibody failure in children and adults. While a monogenic cause of disease has been identified in a small subset of CVID patients, a genome wide association study and whole genome sequencing have found a polygenic cause is likely in the majority. Other NGS technologies such as RNA sequencing and epigenetic studies have further contributed to our understanding of the contribution of altered gene expression in CVID pathogenesis. We believe that to further unravel the complexities of CVID, a multi-omic approach, combining DNA sequencing with gene expression, methylation, proteomic and metabolomics data, will be essential to identify novel disease-associated pathways and therapeutic targets. This article is protected by copyright. All rights reserved. PMID: 28236292 [PubMed - as supplied by publisher]

Related Articles Multivalent Small-Molecule Pan-RAS Inhibitors. Cell. 2017 Feb 23;168(5):878-889.e29 Authors: Welsch ME, Kaplan A, Chambers JM, Stokes ME, Bos PH, Zask A, Zhang Y, Sanchez-Martin M, Badgley MA, Huang CS, Tran TH, Akkiraju H, Brown LM, Nandakumar R, Cremers S, Yang WS, Tong L, Olive KP, Ferrando A, Stockwell BR Abstract Design of small molecules that disrupt protein-protein interactions, including the interaction of RAS proteins and their effectors, may provide chemical probes and therapeutic agents. We describe here the synthesis and testing of potential small-molecule pan-RAS ligands, which were designed to interact with adjacent sites on the surface of oncogenic KRAS. One compound, termed 3144, was found to bind to RAS proteins using microscale thermophoresis, nuclear magnetic resonance spectroscopy, and isothermal titration calorimetry and to exhibit lethality in cells partially dependent on expression of RAS proteins. This compound was metabolically stable in liver microsomes and displayed anti-tumor activity in xenograft mouse cancer models. These findings suggest that pan-RAS inhibition may be an effective therapeutic strategy for some cancers and that structure-based design of small molecules targeting multiple adjacent sites to create multivalent inhibitors may be effective for some proteins. PMID: 28235199 [PubMed - in process]

Related Articles Correction: Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment. PLoS One. 2017;12(2):e0173164 Authors: Scarpellini B, Zanoni M, Sucupira MC, Truong HM, Janini LM, da Silva ID, Diaz RS Abstract [This corrects the article DOI: 10.1371/journal.pone.0161920.]. PMID: 28235085 [PubMed - in process]

Related Articles Diagnosis of a malignant adrenal mass: the role of urinary steroid metabolite profiling. Curr Opin Endocrinol Diabetes Obes. 2017 Feb 23;: Authors: Bancos I, Arlt W Abstract PURPOSE OF REVIEW: Adrenal masses are highly prevalent, found in 5% of the population. Differentiation of benign adrenocortical adenoma from adrenocortical carcinoma is currently hampered by the poor specificity and limited evidence base of imaging tests. This review summarizes the results of studies published to date on urine steroid metabolite profiling for distinguishing benign from malignant adrenal masses. RECENT FINDINGS: Three studies have described cohorts of at least 100 patients with adrenal tumors showing significant differences between urinary steroid metabolite excretions according to the nature of the underlying lesion, suggesting significant value of steroid metabolite profiling as a highly accurate diagnostic test. SUMMARY: Steroid profiling is emerging as a powerful novel diagnostic tool with a significant potential for improving the management for patients with adrenal tumors. Although the current studies use gas chromatography-mass spectrometry for proof of concept, widespread use of the method in routine clinical care will depend on transferring the approach to high-throughput tandem mass spectrometry platforms. The use of computational data analysis in conjunction with urine steroid metabolite profiling, that is, steroid metabolomics, adds accuracy and precision. PMID: 28234802 [PubMed - as supplied by publisher]

Related Articles Metabolite profiling of ascidian Styela plicata using LC-MS with multivariate statistical analysis and their antitumor activity. J Enzyme Inhib Med Chem. 2017 Dec;32(1):614-623 Authors: Palanisamy SK, Trisciuoglio D, Zwergel C, Del Bufalo D, Mai A Abstract To identify the metabolite distribution in ascidian, we have applied an integrated liquid chromatography- tandem mass spectrometry (LC-MS) metabolomics approach to explore and identify patterns in chemical diversity of invasive ascidian Styela plicata. A total of 71 metabolites were reported among these alkaloids, fatty acids and lipids are the most dominant chemical group. Multivariate statistical analysis, principal component analysis (PCA) showed a clear separation according to chemical diversity and taxonomic groups. PCA and partial least square discriminant analysis were applied to discriminate the chemical group of S. plicata crude compounds and classify the compounds with unknown biological activities. In this study, we reported for the first time that a partially purified methanol extract prepared from the ascidian S. plicata and Ascidia mentula possess antitumor activity against four tumor cell lines with different tumor histotype, such as HeLa (cervical carcinoma), HT29 (colon carcinoma), MCF-7 (breast carcinoma) and M14 (melanoma). S. plicata fraction SP-50 showed strong inhibition of cell proliferation and induced apoptosis in HeLa and HT29 cells, thus indicating S. plicata fraction SP-50 a potential lead compound for anticancer therapy. The molecular mechanism of action and chemotherapeutic potential of these ascidian unknown biomolecules need further research. PMID: 28234548 [PubMed - in process]

Related Articles Multi-Omics Reveals that Lead Exposure Disturbs Gut Microbiome Development, Key Metabolites and Metabolic Pathways. Chem Res Toxicol. 2017 Feb 24;: Authors: Gao B, Chi L, Mahbub R, Bian X, Tu P, Ru H, Lu K Abstract Lead exposure remains as a global public health issue and recent Flint water crisis has again raised concern about lead toxicity in the public. The toxicity of lead has been well established in a variety of systems and organs. It has been increasingly appreciated that gut microbiome is highly involved in many critical physiological processes, such as food digestion, immune system development, and metabolic homeostasis, etc. However, despite the key role of gut microbiome in human health, the functional impact of lead exposure on gut microbiome has not been studied yet. This study aims at defining gut microbiome toxicity induced by lead exposure in C57BL/6 mice by multi-omics approaches including 16S rRNA sequencing, whole genome metagenomics sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics profiling. 16S rRNA sequencing revealed that lead exposure altered the gut microbiome trajectory and phylogenetic diversity. Metagenomics sequencing and metabolomics profiling showed that numerous metabolic pathways, including vitamin E and bile acids, nitrogen metabolism, energy metabolism, oxidative stress and defense/detoxification mechanism, were significantly disturbed by lead exposure. These perturbed molecules and pathways may have important implications in lead toxicity in the host. Taken together, we have demonstrated that lead exposure not only alters the gut microbiome community structures/diversity, but also largely affects its metabolic functions, leading to gut microbiome toxicity. PMID: 28234468 [PubMed - as supplied by publisher]

Related Articles Excessive nitrogen application dampens antioxidant capacity and grain filling in wheat as revealed by metabolic and physiological analyses. Sci Rep. 2017 Feb 24;7:43363 Authors: Kong L, Xie Y, Hu L, Si J, Wang Z Abstract In this study, field-grown wheat (Triticum aestivum L.) was treated with normal (Nn) and excessive (Ne) levels of fertilizer N. Results showed that Ne depressed the activity of superoxide dismutase and peroxidase and increased the accumulation of reactive oxygen species (ROS) and malondialdehyde. The normalized difference vegetation index (NDVI) was higher under Ne at anthesis and medium milk but similar at the early dough stage and significantly lower at the hard dough stage than that under Nn. The metabolomics analysis of the leaf responses to Ne during grain filling showed 99 metabolites that were different between Ne and Nn treatments, including phenolic and flavonoid compounds, amino acids, organic acids and lipids, which are primarily involved in ROS scavenging, N metabolism, heat stress adaptation and disease resistance. Organic carbon (C) and total N contents were affected by the Ne treatment, with lower C/N ratios developing after medium milk. Ultimately, grain yields decreased with Ne. Based on these data, compared with the normal N fertilizer treatment, we concluded that excessive N application decreased the ability to scavenge ROS, increased lipid peroxidation and caused significant metabolic changes disturbing N metabolism, secondary metabolism and lipid metabolism, which led to reduced grain filling in wheat. PMID: 28233811 [PubMed - in process]

Related Articles Identification of the compositional changes in Orthosiphon stamineus leaves triggered by different drying techniques using (1) H NMR metabolomics. J Sci Food Agric. 2017 Feb 23;: Authors: Pariyani R, Ismail IS, Azam AA, Abas F, Shaari K Abstract BACKGROUND: Java tea is a well-known herbal infusion prepared from the leaves of Orthosiphon stamineus (OS). The biological properties of tea are in direct correlation with the primary and secondary metabolite composition, which in turn largely depends on the choice of drying methods. Herein, the impact of three commonly used drying methods, i.e., shade, microwave and freeze drying on the metabolite composition and the antioxidant activity of OS leaves were investigated using (1) H NMR spectroscopy combined with multivariate classification and regression analysis tools. RESULTS: A total of 31 constituents comprised of primary and secondary metabolites belonging to the chemical classes of fatty acids, amino acids, sugars, terpenoids and phenolic compounds were identified. Shade dried leaves were identified to possess the highest concentrations of bioactive secondary metabolites such as chlorogenic acid, caffeic acid, luteolin, orthosiphol and apigenin, followed by the microwave dried samples. Freeze dried leaves had higher concentrations of choline, amino acids namely leucine, alanine and glutamine and sugars such as fructose and α-glucose, but, recorded lowest amount of secondary metabolites. CONCLUSION: Metabolite profiling coupled with multivariate analysis identified shade drying as the best method to prepare OS leaves as Java tea or to include in traditional medicine preparation. PMID: 28233369 [PubMed - as supplied by publisher]

Related Articles Abiotic Stress Responses and Microbe-Mediated Mitigation in Plants: The Omics Strategies. Front Plant Sci. 2017;8:172 Authors: Meena KK, Sorty AM, Bitla UM, Choudhary K, Gupta P, Pareek A, Singh DP, Prabha R, Sahu PK, Gupta VK, Singh HB, Krishanani KK, Minhas PS Abstract Abiotic stresses are the foremost limiting factors for agricultural productivity. Crop plants need to cope up adverse external pressure created by environmental and edaphic conditions with their intrinsic biological mechanisms, failing which their growth, development, and productivity suffer. Microorganisms, the most natural inhabitants of diverse environments exhibit enormous metabolic capabilities to mitigate abiotic stresses. Since microbial interactions with plants are an integral part of the living ecosystem, they are believed to be the natural partners that modulate local and systemic mechanisms in plants to offer defense under adverse external conditions. Plant-microbe interactions comprise complex mechanisms within the plant cellular system. Biochemical, molecular and physiological studies are paving the way in understanding the complex but integrated cellular processes. Under the continuous pressure of increasing climatic alterations, it now becomes more imperative to define and interpret plant-microbe relationships in terms of protection against abiotic stresses. At the same time, it also becomes essential to generate deeper insights into the stress-mitigating mechanisms in crop plants for their translation in higher productivity. Multi-omics approaches comprising genomics, transcriptomics, proteomics, metabolomics and phenomics integrate studies on the interaction of plants with microbes and their external environment and generate multi-layered information that can answer what is happening in real-time within the cells. Integration, analysis and decipherization of the big-data can lead to a massive outcome that has significant chance for implementation in the fields. This review summarizes abiotic stresses responses in plants in-terms of biochemical and molecular mechanisms followed by the microbe-mediated stress mitigation phenomenon. We describe the role of multi-omics approaches in generating multi-pronged information to provide a better understanding of plant-microbe interactions that modulate cellular mechanisms in plants under extreme external conditions and help to optimize abiotic stresses. Vigilant amalgamation of these high-throughput approaches supports a higher level of knowledge generation about root-level mechanisms involved in the alleviation of abiotic stresses in organisms. PMID: 28232845 [PubMed - in process]

Related Articles A non-target urinary and serum metabolomics strategy reveals therapeutical mechanism of Radix Astragali on adjuvant-induced arthritis rats. J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Feb 02;1048:94-101 Authors: Xu T, Feng G, Zhao B, Zhao J, Pi Z, Liu S, Song F, Liu Z Abstract Radix Astragali has been used traditionally in China to treat rheumatoid arthritis (RA) in formulas. In this paper, we conducted a holistic evaluation of Radix Astragali acted on adjuvant-induced arthritis (AIA) rats by urinary and serum metabolomic studies. Histological results and hind paw swelling were used to assess the joint damage, while the levels of IL-1β, TNF-α, SOD and MDA in serum were used to assess inflammation injury and oxidative stress. Metabolomic study and multivariate statistical analyses were used to investigate the differences between different groups. After processing with multivariate statistical analysis, 13 and 21 potential biomarkers were respectively found in urine and serum when Radix Astragali treatment group compared with model group. The main metabolism pathways in which Radix Astragali affected on AIA rats were tryptophan metabolism, phenylalanine metabolism, citrate cycle metabolism, fatty acid metabolism, vitamin B6 metabolism and so on. The present study demonstrates that urinary and serum metabolomics method could be a potentially powerful tool to understand the holistic therapeutic effect and the mechanisms of herb medicines. PMID: 28232289 [PubMed - as supplied by publisher]

Related Articles Integrating Multi-Omics Biomarkers and Postprandial Metabolism to Develop Personalized Treatment for Anorexia Nervosa. Prostaglandins Other Lipid Mediat. 2017 Feb 20;: Authors: Shih PB Abstract BACKGROUND: Anorexia Nervosa (AN) is a serious mental illness characterized by emaciation, an intense fear of gaining weight despite being underweight, and distorted body image. Few treatments reverse the core symptoms in AN such as profound aversion to food and food avoidance. Consequently, AN has a chronic and relapsing course and the highest mortality rate of any psychiatric illness. A more complete understanding of the disease pathogenesis is needed in order to develop better treatments and improve AN outcome. The pathogenesis and psychopathophysiology of AN can be better elucidated by combining longitudinal phenotyping with multiple "omics" techniques, including exon sequencing, proteomics, lipidomic, and metabolomics. DESIGN: This paper summarizes the key findings of a series of interrelated studies including new experimental data and previously published data, and describes our current initiatives and future directions. RESULTS: Exon sequencing data was analyzed in 1205 AN and 1948 controls. Metabolomics, lipidomics, and proteomics data were collected in two independent convenience samples consisting of 75 subjects with eating disorders and 61 age-matched healthy controls. Study participants were female and the mean age was 22.9 (4.9 [SD]) years. These exploratory analyses indicated that Epoxide hydrolase 2 (EPHX2) genetic variations were significantly associated with AN and that activity of epoxide hydrolase (sEH) was elevated in AN compared to controls. The polyunsaturated fatty acid (PUFA) and eicosanoids data revealed that Cytochromes P450 pathway was implicated in AN, and AN displayed a dysregulated baseline and postprandial metabolism of sEH-dependent omega-3 and omega-6 PUFA eicosanoids. IMPLICATION AND CURRENT INITIATIVES: Collectively, our data suggest that dietary factors may contribute to the burden of EPHX2-associated AN susceptibility and affect disease outcome. We are implementing new investigations using a longitudinal study design in order to validate and develop an EPHX2 multi-omics biomarker system. We will test whether sEH-associated postprandial metabolism increases AN risk and affects treatment outcome through an ω-6 rich breakfast challenge. Participants will include 100 ill AN patients, 100 recovered AN patients, and 100 age- and race-matched healthy women. These data will allow us to investigate 1) how genetic and dietary factors independently and synergistically contribute to AN risk and progression, and 2) if clinical severity and treatment response in AN are affected by sEH activity and eicosanoid dysregulation. Results of our study will 1) identify clinically relevant biomarkers, 2) unravel mechanistic functions of sEH, and 3) delineate contributory roles of dietary PUFAs and Cytochrome P450 pathway eicosanoids for the purpose of developing novel AN treatments and improving disease prognosis. PMID: 28232135 [PubMed - as supplied by publisher]

Related Articles Increased mean aliphatic lipid chain length in left ventricular hypertrophy secondary to arterial hypertension: A cross-sectional study. Medicine (Baltimore). 2016 Nov;95(46):e4965 Authors: Evaristi MF, Caubère C, Harmancey R, Desmoulin F, Peacock WF, Berry M, Turkieh A, Barutaut M, Galinier M, Dambrin C, Polidori C, Miceli C, Chamontin B, Koukoui F, Roncalli J, Massabuau P, Smih F, Rouet P Abstract About 77.9 million (1 in 4) American adults have high blood pressure. High blood pressure is the primary cause of left ventricular hypertrophy (LVH), which represents a strong predictor of future heart failure and cardiovascular mortality. Previous studies have shown an altered metabolic profile in hypertensive patients with LVH. The goal of this study was to identify blood metabolomic LVH biomarkers by H NMR to provide novel diagnostic tools for rapid LVH detection in populations of hypertensive individuals. This cross-sectional study included 48 hypertensive patients with LVH matched with 48 hypertensive patients with normal LV size, and 24 healthy controls. Two-dimensional targeted M-mode echocardiography was performed to measure left ventricular mass index. Partial least squares discriminant analysis was used for the multivariate analysis of the H NMR spectral data. From the H NMR-based metabolomic profiling, signals coming from methylene (-CH2-) and methyl (-CH3) moieties of aliphatic chains from plasma lipids were identified as discriminant variables. The -CH2-/-CH3 ratio, an indicator of the mean length of the aliphatic lipid chains, was significantly higher (P < 0.001) in the LVH group than in the hypertensive group without LVH and controls. Receiver operating characteristic curve showed that a cutoff of 2.34 provided a 52.08% sensitivity and 85.42% specificity for discriminating LVH (AUC = 0.703, P-value < 0.001). We propose the -CH2-/-CH3 ratio from plasma aliphatic lipid chains as a biomarker for the diagnosis of left ventricular remodeling in hypertension. PMID: 27861330 [PubMed - indexed for MEDLINE]

Related Articles F2-Isoprostanes in HDL are bound to neutral lipids and phospholipids. Free Radic Res. 2016 Dec;50(12):1374-1385 Authors: Proudfoot JM, Barden AE, Croft KD, Galano JM, Durand T, Bultel-Poncé V, Giera M, Mori TA Abstract Low HDL cholesterol (HDL-C) is a risk factor for coronary artery disease (CAD). However, interventions that raise HDL-C have failed to reduce cardiovascular events. We previously reported that HDL is the main carrier of plasma F2-isoprostanes (F2-IsoPs) that are markers of oxidative stress formed upon oxidation of arachidonic acid. F2-IsoPs are predominantly associated with phospholipids. However, there is evidence that F2-IsoPs in the liver of rats treated with carbon tetrachloride associate with the neutral lipids. To date it is not known whether F2-IsoPs are found in the neutral lipids in HDL in humans. Possible candidate neutral lipids include cholesteryl esters, triglycerides, diglycerides, and monoglycerides. This study aimed to identify the lipid classes within native and oxidized HDL that contain F2-IsoPs. We showed that F2-IsoPs in HDL are bound to neutral lipids as well as phospholipids. HDL-3 contained the highest concentration of F2-IsoPs in all lipid classes before and after in vitro oxidation. Using targeted LC/MS and high resolution MS, we were unable to provide conclusive evidence for the presence of the synthesized standards 15(R)-15-F2t-isoP cholesterol and 1-ent-15(RS)-15-F2t-isoprostanoyl-sn-glycerol in the neutral lipids of HDL. Our findings show that oxidized lipids such as F2-IsoPs are found in the core and surface of HDL. However, the exact molecular species remain to be definitively characterized. Future studies are required to determine whether the presence of F2-IsoPs in neutral lipids alters HDL function. PMID: 27750456 [PubMed - indexed for MEDLINE]

Related Articles Secondary metabolites extracted from marine sponge associated Comamonas testosteroni and Citrobacter freundii as potential antimicrobials against MDR pathogens and hypothetical leads for VP40 matrix protein of Ebola virus: an in vitro and in silico investigation. J Biomol Struct Dyn. 2016 Sep;34(9):1865-83 Authors: Skariyachan S, Acharya AB, Subramaniyan S, Babu S, Kulkarni S, Narayanappa R Abstract The current study explores therapeutic potential of metabolites extracted from marine sponge (Cliona sp.)-associated bacteria against MDR pathogens and predicts the binding prospective of probable lead molecules against VP40 target of Ebola virus. The metabolite-producing bacteria were characterized by agar overlay assay and as per the protocols in Bergey's manual of determinative bacteriology. The antibacterial activities of extracted metabolites were tested against clinical pathogens by well-diffusion assay. The selected metabolite producers were characterized by 16S rDNA sequencing. Chemical screening and Fourier Transform Infrared (FTIR) analysis for selected compounds were performed. The probable lead molecules present in the metabolites were hypothesized based on proximate analysis, FTIR data, and literature survey. The drug-like properties and binding potential of lead molecules against VP40 target of Ebola virus were hypothesized by computational virtual screening and molecular docking. The current study demonstrated that clear zones around bacterial colonies in agar overlay assay. Antibiotic sensitivity profiling demonstrated that the clinical isolates were multi-drug resistant, however; most of them showed sensitivity to secondary metabolites (MIC-15 μl/well). The proximate and FTIR analysis suggested that probable metabolites belonged to alkaloids with O-H, C-H, C=O, and N-H groups. 16S rDNA characterization of selected metabolite producers demonstrated that 96% and 99% sequence identity to Comamonas testosteroni and Citrobacter freundii, respectively. The docking studies suggested that molecules such as Gymnastatin, Sorbicillactone, Marizomib, and Daryamide can designed as probable lead candidates against VP40 target of Ebola virus. PMID: 26577929 [PubMed - indexed for MEDLINE]

Related Articles Individual Biomarkers Using Molecular Personalized Medicine Approaches. ORL J Otorhinolaryngol Relat Spec. 2017 Feb 24;79(1-2):7-13 Authors: Zenner HP Abstract Molecular personalized medicine tries to generate individual predictive biomarkers to assist doctors in their decision making. These are thought to improve the efficacy and lower the toxicity of a treatment. The molecular basis of the desired high-precision prediction is modern "omex" technologies providing high-throughput bioanalytical methods. These include genomics and epigenomics, transcriptomics, proteomics, metabolomics, microbiomics, imaging, and functional analyses. In most cases, producing big data also requires a complex biomathematical analysis. Using molecular personalized medicine, the conventional physician's check of biomarker results may no longer be sufficient. By contrast, the physician may need to cooperate with the biomathematician to achieve the desired prediction on the basis of the analysis of individual big data typically produced by omex technologies. Identification of individual biomarkers using molecular personalized medicine approaches is thought to allow a decision-making for the precise use of a targeted therapy, selecting the successful therapeutic tool from a panel of preexisting drugs or medical products. This should avoid the treatment of nonresponders and responders that produces intolerable unwanted effects. PMID: 28231575 [PubMed - as supplied by publisher]