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

Untargeted LC-HRMS-based metabolomics to identify novel biomarkers of metastatic colorectal cancer.

Sun, 29/12/2019 - 18:00
Related Articles Untargeted LC-HRMS-based metabolomics to identify novel biomarkers of metastatic colorectal cancer. Sci Rep. 2019 Dec 27;9(1):20198 Authors: Martín-Blázquez A, Díaz C, González-Flores E, Franco-Rivas D, Jiménez-Luna C, Melguizo C, Prados J, Genilloud O, Vicente F, Caba O, Pérez Del Palacio J Abstract Colorectal cancer is one of the main causes of cancer death worldwide, and novel biomarkers are urgently needed for its early diagnosis and treatment. The utilization of metabolomics to identify and quantify metabolites in body fluids may allow the detection of changes in their concentrations that could serve as diagnostic markers for colorectal cancer and may also represent new therapeutic targets. Metabolomics generates a pathophysiological 'fingerprint' that is unique to each individual. The purpose of our study was to identify a differential metabolomic signature for metastatic colorectal cancer. Serum samples from 60 healthy controls and 65 patients with metastatic colorectal cancer were studied by liquid chromatography coupled to high-resolution mass spectrometry in an untargeted metabolomic approach. Multivariate analysis revealed a separation between patients with metastatic colorectal cancer and healthy controls, who significantly differed in serum concentrations of one endocannabinoid, two glycerophospholipids, and two sphingolipids. These findings demonstrate that metabolomics using liquid-chromatography coupled to high-resolution mass spectrometry offers a potent diagnostic tool for metastatic colorectal cancer. PMID: 31882610 [PubMed - in process]

Untargeted UPLC-MS metabolomics reveals multiple changes of urine composition in healthy adult volunteers after consumption of curcuma longa L. extract.

Sun, 29/12/2019 - 18:00
Related Articles Untargeted UPLC-MS metabolomics reveals multiple changes of urine composition in healthy adult volunteers after consumption of curcuma longa L. extract. Food Res Int. 2020 Jan;127:108730 Authors: Peron G, Sut S, Dal Ben S, Voinovich D, Dall'Acqua S Abstract Curcuma longa L. is used as food supplement to prevent diseases, although limited studies have been performed on healthy subjects up to now. In the present work, an untargeted UPLC-MS metabolomics approach was applied to study the changes of 24-hours urinary composition on healthy volunteers due to a 28-days daily consumption of a dried C. longa extract containing a standardized amount of curcuminoids. Changes in the excretion of different metabolites were observed after supplementation. Curcumin and two metabolic derivatives (hexahydrocurcumin and dihydrocurcumin) were detected in urine, indicating the absorption of the main curcuminoid from the extract and its further metabolism by liver and gut microbiota. For the first time ar-turmerone, the main apolar constituent of curcuma, was detected in urine in intact form, and its presence was confirmed by a targeted GC-MS analysis. The increase of tetranor-PGJM and tetranor-PGDM, two prostaglandin-D2 metabolites, was observed, being related to the anti-inflammatory effect exerted by curcuma. The variation of the amounts of HPAG, PAG, proline-betaine and hydroxyphenyllactic acid indicate that the supplementation induced changes to the activity of gut microbiota. Finally, the reduced excretion of niacin metabolites (nicotinuric acid, trigonelline and 2PY) and medium- and short-chain acylcarnitines suggests that curcuma could induce the mitochondrial β-oxidation of fatty acids for energy production in healthy subjects. Overall, the results indicate that a prolonged daily consumption of a dried curcuma extract exerts multiple effects on healthy subjects, furthermore they show the opportunity offered by untargeted metabolomics for the study of the bioactivity of natural extracts in healthy human volunteers. PMID: 31882111 [PubMed - in process]

Phenolic profiling and in vitro bioactivity of Moringa oleifera leaves as affected by different extraction solvents.

Sun, 29/12/2019 - 18:00
Related Articles Phenolic profiling and in vitro bioactivity of Moringa oleifera leaves as affected by different extraction solvents. Food Res Int. 2020 Jan;127:108712 Authors: Rocchetti G, Pagnossa JP, Blasi F, Cossignani L, Hilsdorf Piccoli R, Zengin G, Montesano D, Cocconcelli PS, Lucini L Abstract In this work the (poly)-phenolic profile of Moringa oleifera leaves was comprehensively investigated through untargeted metabolomics, following a homogenizer-assisted extraction (HAE) using three solvent systems, i.e. methanol (HAE-1), methanol-water 50:50 v/v (HAE-2) and ethyl acetate (HAE-3). This approach allowed to putatively annotate 291 compounds, recording mainly flavonoids and phenolic acids. Thereafter, antioxidant capacity, antimicrobial activity and enzyme inhibition were assayed in the different extracts. HAE-1 extract showed the highest total phenolic content (31.84 mg/g), followed by HAE-2 (26.95 mg/g) and HAE-3 (14.71 mg/g). In addition, HAE-1 and HAE-2 extracts exhibited an expressive activity against Bacillus cereus and Listeria innocua. The HAE-2 leaf extract was characterized by the highest DPPH and ABTS values (being 49.55 and 45.26 mgTE/g), while ferric reducing antioxidant power was found to be higher in HAE-1 (58.26 mgTE/g). Finally, the enzyme inhibitory effects of M. oleifera leaf extracts were investigated against five enzymes, namely acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, α-amylase and α-glucosidase. All of the tested extracts exhibited inhibitory effects on AChE and BChE with a higher activity for HAE-3 and HAE-1, whilst HAE-1 showed the higher impact on tyrosinase, glucosidase and amylase activities. Taken together, these findings suggest that M. oleifera leaf extracts are a good source of bioactive polyphenols with a potential use in food and pharma industries. PMID: 31882101 [PubMed - in process]

Hepatotoxicity and the role of the gut-liver axis in rats after oral administration of titanium dioxide nanoparticles.

Sun, 29/12/2019 - 18:00
Related Articles Hepatotoxicity and the role of the gut-liver axis in rats after oral administration of titanium dioxide nanoparticles. Part Fibre Toxicol. 2019 Dec 27;16(1):48 Authors: Chen Z, Zhou D, Han S, Zhou S, Jia G Abstract BACKGROUND: Due to its excellent physicochemical properties and wide applications in consumer goods, titanium dioxide nanoparticles (TiO2 NPs) have been increasingly exposed to the environment and the public. However, the health effects of oral exposure of TiO2 NPs are still controversial. This study aimed to illustrate the hepatotoxicity induced by TiO2 NPs and the underlying mechanisms. Rats were administered with TiO2 NPs (29 nm) orally at exposure doses of 0, 2, 10, 50 mg/kg daily for 90 days. Changes in the gut microbiota and hepatic metabolomics were analyzed to explore the role of the gut-liver axis in the hepatotoxicity induced by TiO2 NPs. RESULTS: TiO2 NPs caused slight hepatotoxicity, including clear mitochondrial swelling, after subchronic oral exposure at 50 mg/kg. Liver metabolomics analysis showed that 29 metabolites and two metabolic pathways changed significantly in exposed rats. Glutamate, glutamine, and glutathione were the key metabolites leading the generation of energy-related metabolic disorders and imbalance of oxidation/antioxidation. 16S rDNA sequencing analysis showed that the diversity of gut microbiota in rats increased in a dose-dependent manner. The abundance of Lactobacillus_reuteri increased and the abundance of Romboutsia decreased significantly in feces of TiO2 NPs-exposed rats, leading to changes of metabolic function of gut microbiota. Lipopolysaccharides (LPS) produced by gut microbiota increased significantly, which may be a key factor in the subsequent liver effects. CONCLUSIONS: TiO2 NPs could induce slight hepatotoxicity at dose of 50 mg/kg after long-term oral exposure. The indirect pathway of the gut-liver axis, linking liver metabolism and gut microbiota, played an important role in the underlying mechanisms. PMID: 31881974 [PubMed - in process]

Green and White Asparagus (Asparagus officinalis): A Source of Developmental, Chemical and Urinary Intrigue.

Sun, 29/12/2019 - 18:00
Related Articles Green and White Asparagus (Asparagus officinalis): A Source of Developmental, Chemical and Urinary Intrigue. Metabolites. 2019 Dec 25;10(1): Authors: Pegiou E, Mumm R, Acharya P, de Vos RCH, Hall RD Abstract Asparagus (Asparagus officinalis) is one of the world's top 20 vegetable crops. Both green and white shoots (spears) are produced; the latter being harvested before becoming exposed to light. The crop is grown in nearly all areas of the world, with the largest production regions being China, Western Europe, North America and Peru. Successful production demands high farmer input and specific environmental conditions and cultivation practices. Asparagus materials have also been used for centuries as herbal medicine. Despite this widespread cultivation and consumption, we still know relatively little about the biochemistry of this crop and how this relates to the nutritional, flavour, and neutra-pharmaceutical properties of the materials used. To date, no-one has directly compared the contrasting compositions of the green and white crops. In this short review, we have summarised most of the literature to illustrate the chemical richness of the crop and how this might relate to key quality parameters. Asparagus has excellent nutritional properties and its flavour/fragrance is attributed to a set of volatile components including pyrazines and sulphur-containing compounds. More detailed research, however, is needed and we propose that (untargeted) metabolomics should have a more prominent role to play in these investigations. PMID: 31881716 [PubMed]

metabolomics; +19 new citations

Sat, 28/12/2019 - 14:54
19 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 2019/12/28PubMed 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.

Synergistic effect of Aconiti Lateralis Radix Praeparata water-soluble alkaloids and Ginseng Radix et Rhizoma total ginsenosides compatibility on acute heart failure rats.

Fri, 27/12/2019 - 14:49
Related Articles Synergistic effect of Aconiti Lateralis Radix Praeparata water-soluble alkaloids and Ginseng Radix et Rhizoma total ginsenosides compatibility on acute heart failure rats. J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Dec 09;1137:121935 Authors: Liu M, Li Y, Tang Y, Zheng L, Peng C Abstract The aim of this study was to investigate the synergistic effect and underlying mechanism of compatibility of Aconiti Lateralis Radix Praeparata water-soluble alkaloids (FWA) and Ginseng Radix et Rhizoma total ginsenosides (RTG) on propafenone hydrochloride induced acute heart failure (AHF) rats. Firstly, hemodynamics and serum biochemical indexes were measured to observe the therapeutic effect of FWA, RTG and their compatibility on AHF rats. Non-target serum metabolomics and multicomponent pharmacokinetic experiments were then performed to reveal the mechanism from the two aspects of body reaction and drug behavior in vivo. Data showed the haemodynamics indexes (maximum change rate of left ventricular pressure, heart rate) and neuroendocrine cytokines (TNF-α and Nt-proBNP) levels in rats treated by compatibility of FWA and RTG were improved more significantly than that treated by single drug. Through metabolomics analysis, six metabolites, including L-pipecolic acid, L-arginine, uric acid, N-benzoylglycine, sphingosine-1-phosphate and phosphatidylinositol lyso 16:0, were selected and identified as the potential biomarkers of the synergistic effect. Furthermore, lysine degradation, arginine and proline metabolism, purine metabolism, sphingolipid metabolism, etc. were the differential pathways involved. The results of pharmacokinetics showed Cmax, AUClast and t1/2 of the four components (uracil, salsolinol, guanosine, higenamine) of FWA in compatibility group were obviously higher than that in single drug group, which indicated the absorption and bioavailability of these alkaloids were increased, and the residence time was prolonged after FWA combined with RTG. In conclusion, the therapeutic effect of FWA-RTG on AHF rats was enhanced and that might because the compatibility of FWA-RTG affected the process of some metabolites in AHF rats, and pharmacokinetic behavior of components in FWA was obviously influenced after co-administered with RTG. PMID: 31877430 [PubMed - as supplied by publisher]

Perspective: Cell Danger Response Biology-The New Science that Connects Environmental Health with Mitochondria and the Rising Tide of Chronic Illness.

Fri, 27/12/2019 - 14:49
Related Articles Perspective: Cell Danger Response Biology-The New Science that Connects Environmental Health with Mitochondria and the Rising Tide of Chronic Illness. Mitochondrion. 2019 Dec 23;: Authors: Naviaux RK Abstract This paper is written for non-specialists in mitochondrial biology to provide access to an important area of science that has broad implications for all people. The cell danger response (CDR) is a universal response to environmental threat or injury. Once triggered, healing cannot be completed until the choreographed stages of the CDR are returned to an updated state of readiness. Although the CDR is a cellular response, it has the power to change human thought and behavior, child development, physical fitness and resilience, fertility, and the susceptibility of entire populations to disease. Mitochondria regulate the CDR by monitoring and responding to the physical, chemical, and microbial conditions within and around the cell. In this way, mitochondria connect cellular health to environmental health. Over 7,000 chemicals are now made or imported to the US for industrial, agricultural, and personal care use in amounts ranging from 25,000 to over 1 million pounds each year, and plastic waste now exceeds 83 billion pounds/year. This chemical load creates a rising tide of manmade pollutants in the oceans, air, water, and food chain. Fewer than 5% of these chemicals have been tested for developmental toxicity. In the 1980s, 5-10% of children lived with a chronic illness. As of 2018, 40% of children, 50% of teens, 60% of adults under age 65, and 90% of adults over 65 live with chronic illness. Several studies now report the presence of dozens to hundreds of manmade chemicals and pollutants in placenta, umbilical cord blood, and newborn blood spots. New methods in metabolomics and exposomics allow scientists to measure thousands of chemicals in blood, air, water, soil, and the food chain. Systematic measurements of environmental chemicals can now be correlated with annual and regional patterns of childhood illness. These data can be used to prepare a prioritized list of molecules for congressional action, ranked according to their impact on human health. "When a deep injury is done to us, we never heal until we forgive." --Nelson Mandela (1918-2013). PMID: 31877376 [PubMed - as supplied by publisher]

Metabolites in a mouse cancer model enhance venous thrombogenicity through the aryl hydrocarbon receptor-tissue factor axis.

Fri, 27/12/2019 - 14:49
Related Articles Metabolites in a mouse cancer model enhance venous thrombogenicity through the aryl hydrocarbon receptor-tissue factor axis. Blood. 2019 Dec 26;134(26):2399-2413 Authors: Belghasem M, Roth D, Richards S, Napolene MA, Walker J, Yin W, Arinze N, Lyle C, Spencer C, Francis JM, Thompson C, Andry C, Whelan SA, Lee N, Ravid K, Chitalia VC Abstract Patients with malignancy are at 4- to 7-fold higher risk of venous thromboembolism (VTE), a potentially fatal, yet preventable complication. Although general mechanisms of thrombosis are enhanced in these patients, malignancy-specific triggers and their therapeutic implication remain poorly understood. Here we examined a colon cancer-specific VTE model and probed a set of metabolites with prothrombotic propensity in the inferior vena cava (IVC) ligation model. Athymic mice injected with human colon adenocarcinoma cells exhibited significantly higher IVC clot weights, a biological readout of venous thrombogenicity, compared with the control mice. Targeted metabolomics analysis of plasma of mice revealed an increase in the blood levels of kynurenine and indoxyl sulfate (tryptophan metabolites) in xenograft-bearing mice, which correlated positively with the increase in the IVC clot size. These metabolites are ligands of aryl hydrocarbon receptor (AHR) signaling. Accordingly, plasma from the xenograft-bearing mice activated the AHR pathway and augmented tissue factor (TF) and plasminogen activator inhibitor 1 (PAI-1) levels in venous endothelial cells in an AHR-dependent manner. Consistent with these findings, the endothelium from the IVC of xenograft-bearing animals revealed nuclear AHR and upregulated TF and PAI-1 expression, telltale signs of an activated AHR-TF/PAI-1 axis. Importantly, pharmacological inhibition of AHR activity suppressed TF and PAI-1 expression in endothelial cells of the IVC and reduced clot weights in both kynurenine-injected and xenograft-bearing mice. Together, these data show dysregulated tryptophan metabolites in a mouse cancer model, and they reveal a novel link between these metabolites and the control of the AHR-TF/PAI-1 axis and VTE in cancer. PMID: 31877217 [PubMed - in process]

Dried blood spot N-glycome analysis by MALDI mass spectrometry.

Fri, 27/12/2019 - 14:49
Related Articles Dried blood spot N-glycome analysis by MALDI mass spectrometry. Talanta. 2019 Dec 01;205:120104 Authors: Vreeker GCM, Bladergroen MR, Nicolardi S, Mesker WE, Tollenaar RAEM, van der Burgt YEM, Wuhrer M Abstract Body fluid N-glycome analysis as well as glyco-proteoform profiling of existing protein biomarkers potentially provides a stratification layer additional to quantitative, diagnostic protein levels. For clinical omics applications, the collection of a dried blood spot (DBS) is increasingly pursued as an alternative to sampling milliliters of peripheral blood. Here we evaluate DBS cards as a blood collection strategy for protein N-glycosylation analysis aiming for high-throughput clinical applications. A protocol for facile N-glycosylation profiling from DBS is developed that includes sialic acid linkage differentiation. This protocol is based on a previously established total plasma N-glycome mass spectrometry (MS) method, with adjustments for the analysis of DBS specimens. After DBS-punching and protein solubilization N-glycans are released, followed by chemical derivatization of sialic acids and MS-measurement of N-glycan profiles. With this method, more than 80 different glycan structures are identified from a DBS, with RSDs below 10% for the ten most abundant glycans. N-glycan profiles of finger-tip blood and venous blood are compared and short-term stability of DBS is demonstrated. This method for fast N-glycosylation profiling of DBS provides a minimally invasive alternative to conventional serum and plasma protein N-glycosylation workflows. With simplified blood sampling this DBS approach has vast potential for clinical glycomics applications. PMID: 31450448 [PubMed - indexed for MEDLINE]

A single-cell platform for reconstituting and characterizing fatty acid elongase component enzymes.

Fri, 27/12/2019 - 14:49
Related Articles A single-cell platform for reconstituting and characterizing fatty acid elongase component enzymes. PLoS One. 2019;14(3):e0213620 Authors: Campbell AA, Stenback KE, Flyckt K, Hoang T, Perera MAD, Nikolau BJ Abstract Fatty acids of more than 18-carbons, generally known as very long chain fatty acids (VLCFAs) are essential for eukaryotic cell viability, and uniquely in terrestrial plants they are the precursors of the cuticular lipids that form the organism's outer barrier to the environment. VLCFAs are synthesized by fatty acid elongase (FAE), which is an integral membrane enzyme system with multiple components. The genetic complexity of the FAE system, and its membrane association has hampered the biochemical characterization of FAE. In this study we computationally identified Zea mays genetic sequences that encode the enzymatic components of FAE and developed a heterologous expression system to evaluate their functionality. The ability of the maize components to genetically complement Saccharomyces cerevisiae lethal mutants confirmed the functionality of ZmKCS4, ZmELO1, ZmKCR1, ZmKCR2, ZmHCD and ZmECR, and the VLCFA profiles of the resulting strains were used to infer the ability of each enzyme component to determine the product profile of FAE. These characterizations indicate that the product profile of the FAE system is an attribute shared among the KCS, ELO, and KCR components of FAE. PMID: 30856216 [PubMed - indexed for MEDLINE]

Akt-mediated phosphorylation of MICU1 regulates mitochondrial Ca2+ levels and tumor growth.

Fri, 27/12/2019 - 14:49
Related Articles Akt-mediated phosphorylation of MICU1 regulates mitochondrial Ca2+ levels and tumor growth. EMBO J. 2019 01 15;38(2): Authors: Marchi S, Corricelli M, Branchini A, Vitto VAM, Missiroli S, Morciano G, Perrone M, Ferrarese M, Giorgi C, Pinotti M, Galluzzi L, Kroemer G, Pinton P Abstract Although mitochondria play a multifunctional role in cancer progression and Ca2+ signaling is remodeled in a wide variety of tumors, the underlying mechanisms that link mitochondrial Ca2+ homeostasis with malignant tumor formation and growth remain elusive. Here, we show that phosphorylation at the N-terminal region of the mitochondrial calcium uniporter (MCU) regulatory subunit MICU1 leads to a notable increase in the basal mitochondrial Ca2+ levels. A pool of active Akt in the mitochondria is responsible for MICU1 phosphorylation, and mitochondrion-targeted Akt strongly regulates the mitochondrial Ca2+ content. The Akt-mediated phosphorylation impairs MICU1 processing and stability, culminating in reactive oxygen species (ROS) production and tumor progression. Thus, our data reveal the crucial role of the Akt-MICU1 axis in cancer and underscore the strategic importance of the association between aberrant mitochondrial Ca2+ levels and tumor development. PMID: 30504268 [PubMed - indexed for MEDLINE]

Metabolic profiling of acromegaly using a GC-MS-based nontargeted metabolomic approach.

Thu, 26/12/2019 - 14:43
Related Articles Metabolic profiling of acromegaly using a GC-MS-based nontargeted metabolomic approach. Endocrine. 2019 Dec 24;: Authors: Yu H, Zhao Y, Zhang Y, Zhong L Abstract PURPOSE: Acromegaly is a rare disease caused by chronic hypersecretion of growth hormone, which leads to multiple comorbidities and reduced life expectancy. The objective of this study was to characterize the serum metabolic profiles of acromegaly patients and identify metabolic biomarkers using metabolomics. METHODS: Twenty-nine active acromegaly patients and age- and sex-matched normal controls were recruited. Serum samples were collected, and serum metabolites were analyzed using gas chromatography-mass spectrometry coupled with a series of multivariate statistical analyses. RESULTS: The orthogonal projections to latent structures-discriminate analysis (OPLS-DA) model identified and validated significant metabolic differences between individuals with acromegaly and normal controls (R2Y = 0.908 and Q2Y = 0.601). Compared with normal controls, acromegaly patients had elevated levels of 5-aminovaleric acid, glyceric acid, L-dithiothreitol, dihydrocoumarin, N-acetyl-L-glutamic acid, gluconic acid, and monoolein (P < 0.05) and reduced serum levels of D-erythronolactone, taurine, carbamoyl-aspartic acid, and mucic acid (P < 0.01). Furthermore, glyceric acid and taurine possessed higher area under the receiver operating characteristic curve values (AUC values, 0.914 and 0.931, respectively), suggesting an excellent clinical ability to distinguish acromegaly patients from normal controls. Pathway analysis revealed that the pentose phosphate pathway and the taurine and hypotaurine metabolic pathway are significant pathways (P = 0.002 and 0.004, respectively). CONCLUSIONS: Metabolic activity is significantly altered in the serum of individuals with active acromegaly. Glyceric acid and taurine may be considered potential biomarkers for distinguishing acromegaly patients from normal controls. PMID: 31875304 [PubMed - as supplied by publisher]

Comparative Genomics for the Elucidation of Multidrug Resistance in Candida lusitaniae.

Thu, 26/12/2019 - 14:43
Related Articles Comparative Genomics for the Elucidation of Multidrug Resistance in Candida lusitaniae. MBio. 2019 Dec 24;10(6): Authors: Kannan A, Asner SA, Trachsel E, Kelly S, Parker J, Sanglard D Abstract Multidrug resistance (MDR) has emerged in hospitals due to the use of several agents administered in combination or sequentially to the same individual. We reported earlier MDR in Candida lusitaniae during therapy with amphotericin B (AmB), azoles, and candins. Here, we used comparative genomic approaches between the initial susceptible isolate and 4 other isolates with different MDR profiles. From a total of 18 nonsynonymous single nucleotide polymorphisms (NSS) in genome comparisons with the initial isolate, six could be associated with MDR. One of the single nucleotide polymorphisms (SNPs) occurred in a putative transcriptional activator (MRR1) resulting in a V668G substitution in isolates resistant to azoles and 5-fluorocytosine (5-FC). We demonstrated by genome editing that MRR1 acted by upregulation of MFS7 (a multidrug transporter) in the presence of the V668G substitution. MFS7 itself mediated not only azole resistance but also 5-FC resistance, which represents a novel resistance mechanism for this drug class. Three other distinct NSS occurred in FKS1 (a glucan synthase gene that is targeted by candins) in three candin-resistant isolates. Last, two other NSS in ERG3 and ERG4 (ergosterol biosynthesis) resulting in nonsense mutations were revealed in AmB-resistant isolates, one of which accumulated the two ERG NSS. AmB-resistant isolates lacked ergosterol and exhibited sterol profiles, consistent with ERG3 and ERG4 defects. In conclusion, this genome analysis combined with genetics and metabolomics helped decipher the resistance profiles identified in this clinical case. MDR isolates accumulated six different mutations conferring resistance to all antifungal agents used in medicine. This case study illustrates the capacity of C. lusitaniae to rapidly adapt under drug pressure within the host.IMPORTANCE Antifungal resistance is an inevitable phenomenon when fungal pathogens are exposed to antifungal drugs. These drugs can be grouped in four distinct classes (azoles, candins, polyenes, and pyrimidine analogs) and are used in different clinical settings. Failures in therapy implicate the sequential or combined use of these different drug classes, which can result in some cases in the development of multidrug resistance (MDR). MDR is particularly challenging in the clinic since it drastically reduces possible treatment alternatives. In this study, we report the rapid development of MDR in Candida lusitaniae in a patient, which became resistant to all known antifungal agents used until now in medicine. To understand how MDR developed in C. lusitaniae, whole-genome sequencing followed by comparative genome analysis was undertaken in sequential MDR isolates. This helped to detect all specific mutations linked to drug resistance and explained the different MDR patterns exhibited by the clinical isolates. PMID: 31874914 [PubMed - in process]

Transcutaneous Blood VOC Imaging System (Skin-Gas Cam) with Real-Time Bio-Fluorometric Device on Rounded Skin Surface.

Thu, 26/12/2019 - 14:43
Related Articles Transcutaneous Blood VOC Imaging System (Skin-Gas Cam) with Real-Time Bio-Fluorometric Device on Rounded Skin Surface. ACS Sens. 2019 Dec 24;: Authors: Iitani K, Toma K, Arakawa T, Mitsubayashi K Abstract A skin-gas cam that allows continuous imaging of transcutaneous blood volatile organic compounds (VOCs) emanated from human skin was developed. The skin-gas cam is able to reveal the relationship between the local skin conditions and transcutaneous blood VOCs in the field of volatile metabolomics (volatolomics). A ring-type ultraviolet (UV) light-emitting diode was mounted around a camera lens as an excitation light source, which enabled the simultaneous excitation and imaging of fluorescence. A nicotinamide adenine dinucleotide (NAD)-dependent alcohol dehydrogenase (ADH) was used to detect ethanol as a model sample. When gaseous ethanol was applied to an ADH-immobilized mesh that was wetted with an oxidized NAD solution placed in front of the camera, a reduced form of NAD (NADH) was produced through an ADH-mediated reaction. NADH emits fluorescence by UV excitation, and thus, the concentration distribution of ethanol was visualized by measuring the distribution of the fluorescence light intensity from NADH on the ADH-immobilized mesh surface. In this study, a new gas application method that mimicked the release mechanism of transcutaneous gas for quantification of the transcutaneous gas concentration was evaluated. Also, spatiotemporal changes of transcutaneous ethanol for various body parts were measured. As a result, we revealed a relationship between local skin conditions and VOCs that could not be observed previously. In particular, we demonstrated the facile measurement of transdermal gases from around the ear where capillaries are densely distributed below a thin stratum corneum. PMID: 31874557 [PubMed - as supplied by publisher]

Serum proteome profiles to differentiate Crohn disease from intestinal tuberculosis and primary intestinal lymphoma: A pilot study.

Thu, 26/12/2019 - 14:43
Related Articles Serum proteome profiles to differentiate Crohn disease from intestinal tuberculosis and primary intestinal lymphoma: A pilot study. Medicine (Baltimore). 2019 Dec;98(50):e18304 Authors: Ning L, Shan G, Sun Z, Lou X, Zhang F, Li S, Du H, Yu J, Chen H, Xu G Abstract The differential diagnosis of Crohn disease (CD) from intestinal tuberculosis (ITB) and primary intestinal lymphoma (PIL) is challenging in patients who exhibit atypical clinical characteristics. The aim of the present study was to explore the serum proteome profiles of CD, PIL and ITB and to identify their differentiations.Treatment-naïve patients with CD (n = 10), PIL (n = 10) and ITB (n = 10) were enrolled in the present study. Differentially expressed proteins (DEPs) in patient serum samples were compared between groups using tandem mass tag labeled proteomic technology. A principal component analysis (PCA) plot and volcano maps were also visualized. Functional pathway analysis was performed using Reactome. The Area under the Curve (AUC) was calculated for each DEP.A total of 818 proteins were identified through proteomic quantification. Among them, 108 DEPs were identified to be differentiated between CD and ITB, 105 proteins between CD and PIL and 55 proteins between ITB and PIL. The proteome from the three groups was distinguishable in the PCA plot. The results revealed that 19, 12, and 10 proteins (AUC ≥ 0.95) were differentially expressed between CD and PIL, CD and ITB, and PIL and ITB, respectively. Among these DEPs, tumor necrosis factor ligand superfamily member 13 was higher in CD than in ITB and PIL. Peroxiredoxin-5, T-complex protein 1 subunit Gamma, CutA, and Fibulin-5 were increased in CD and PIL when compared with ITB. The levels of fibrinogen chains were also significantly higher in patients with PIL compared with CD.The current study demonstrated that serum proteome was distinguishable among patients with CD, PIL, and ITB. The identified proteins may assist in the clinical differentiation among them. PMID: 31852111 [PubMed - indexed for MEDLINE]

metabolomics; +23 new citations

Wed, 25/12/2019 - 14:36
23 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 2019/12/25PubMed 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; +16 new citations

Tue, 24/12/2019 - 14:24
16 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 2019/12/24PubMed 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.

The lipidome of endometrial fluid differs between implantative and non-implantative IVF cycles.

Mon, 23/12/2019 - 14:17
Related Articles The lipidome of endometrial fluid differs between implantative and non-implantative IVF cycles. J Assist Reprod Genet. 2019 Dec 21;: Authors: Matorras R, Martinez-Arranz I, Arretxe E, Iruarrizaga-Lejarreta M, Corral B, Ibañez-Perez J, Exposito A, Prieto B, Elortza F, Alonso C Abstract OBJECTIVE: To characterize the most relevant changes in the lipidome of endometrial fluid aspirate (EFA) in non-implantative cycles. DESIGN: Lipidomics in a prospective cohort study. SETTINGS: Reproductive unit of a university hospital. PATIENTS: Twenty-nine women undergoing an IVF cycle. Fifteen achieved pregnancy and 14 did not. INTERVENTION: Endometrial fluid aspiration immediately before performing embryo transfer. MAIN OUTCOME MEASURES: Clinical pregnancy rate and lipidomic profiles obtained on an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based analytical platform. RESULTS: The comparative analysis of the lipidomic patterns of endometrial fluid in implantative and non-implantative IVF cycles revealed eight altered metabolites: seven glycerophospholipids and an omega-6 polyunsaturated fatty acid. Then, women with a non-implantative cycle were accurately classified with a support vector machine algorithm including these eight lipid metabolites. The diagnostic performances of the algorithm showed an area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy of 0.893 ± 0.07, 85.7%, 80.0%, and 82.8%, respectively. CONCLUSION: A predictive lipidomic signature linked to the implantative status of the endometrial fluid has been found. PMID: 31865491 [PubMed - as supplied by publisher]

Rhizobacteria-induced systemic tolerance against drought stress in Sorghum bicolor (L.) Moench.

Mon, 23/12/2019 - 14:17
Related Articles Rhizobacteria-induced systemic tolerance against drought stress in Sorghum bicolor (L.) Moench. Microbiol Res. 2019 Nov 30;232:126388 Authors: Carlson R, Tugizimana F, Steenkamp PA, Dubery IA, Hassen AI, Labuschagne N Abstract Induction of systemic tolerance in sorghum [Sorghum bicolor (L.) Moench] against drought stress was studied by screening a large collection of rhizobacterial isolates for their potential to exhibit this essential plant growth-promoting trait. This was done by means of a greenhouse assay that measured the relative change in both plant height and -biomass (roots and shoots) between rhizobacteria-primed versus non-primed (naïve) plants under drought stress conditions. In order to elucidate the metabolomic changes in S. bicolor that conferred the drought stress tolerance after treatment (priming) with selected isolates, untargeted ultra-high performance liquid chromatography-high definition mass spectrometry (UHPLC-HDMS)-based metabolomics was carried out. Intracellular metabolites were methanol-extracted from rhizobacteria-primed and naïve S. bicolor roots and shoots. Extracts were analysed on a UHPLC-HDMS system and the generated data were chemometrically mined to determine signatory metabolic profiles and bio-markers related to induced systemic tolerance. The metabolomic results showed significant treatment-related differential metabolic reprogramming between rhizobacteria-primed and naïve plants, correlating to the ability of the selected isolates to protect S. bicolor against drought stress. The selected isolates, identified by means of 16S rRNA gene sequencing as members of the genera Bacillus and Pseudomonas, were screened for 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity by means of an in vitro assay and the presence of the acdS gene was subsequently confirmed by PCR for strain N66 (Pseudomonas sp.). The underlying key metabolic changes in the enhanced drought stress tolerance observed in rhizobacteria-primed S. bicolor plants included (1) augmented antioxidant capacity; (2) growth promotion and root architecture modification as a result of the upregulation of the hormones gibberellic acid, indole acetic acid and cytokinin; (3) the early activation of induce systemic tolerance through the signalling hormones brassinolides, salicylic acid and jasmonic acid and signalling molecules sphingosine and psychosine; (4) the production of the osmolytes proline, glutamic acid and choline; (5) the production of the epicuticular wax docosanoic acid and (6) ACC deaminase activity resulting in lowered ethylene levels. These results unravelled key molecular details underlying the PGPR-induced systemic tolerance in sorghum plants, providing insights for the plant priming for abiotic stress. PMID: 31865223 [PubMed - as supplied by publisher]

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