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https://www.readbyqxmd.com/read/28535482/multiple-metal-exposures-and-their-correlation-with-monoamine-neurotransmitter-metabolism-in-chinese-electroplating-workers
#1
Lin-Lin Wu, Wei Gong, Si-Peng Shen, Zhong-He Wang, Jia-Xi Yao, Jun Wang, Jing Yu, Rong Gao, Gang Wu
Excessive metal exposure has been recognized as one of the detrimental factors for brain damage. However, the potential adverse effects induced by heavy metals on monoamine neurotransmitter pathways remains poorly understood. Our study aimed to investigate the possible association between metal exposure and neurotransmitter metabolism. By a cross-sectional investigation, 224 electroplating workers and 213 non-electroplating exposure workers were recruited in the exposure and control groups. Metal exposure levels were analyzed using inductively-coupled plasma mass spectrometry and monoamine neurotransmitter pathway metabolites were measured by ultra-performance liquid chromatography tandem mass spectrometry in human urine samples...
April 26, 2017: Chemosphere
https://www.readbyqxmd.com/read/28535441/enantioselective-metabolism-of-triadimefon-and-its-chiral-metabolite-triadimenol-in-lizards
#2
Qiuxuan Shen, Jitong Li, Peng Xu, Wei Li, Guoqiang Zhuang, Yinghuan Wang
Chinese lizards (Eremias argus) were exposed to separated R-(-)-triadimefon, S-(+)-triadimefon and racemic triadimefon to evaluate enantioselective accumulation of triadimefon. After single oral administration of R-(-)-triadimefon, S-(+)-triadimefon and racemic triadimefon, the time-concentration curves in different tissues were found to be different. Triadimefon enantiomers crossed the blood-brain barrier and brain is a main target organ. The residues of triadimefon enantiomers in fat were highest after 24h indicating that fat was the main tissue of accumulation...
May 20, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28535410/effect-of-enzyme-inhibition-on-perampanel-pharmacokinetics-why-study-design-matters
#3
Barry E Gidal, Rama Maganti, Antonio Laurenza, Haichen Yang, David A Verbel, Edgar Schuck, Jim Ferry
OBJECTIVES: Perampanel, a selective, noncompetitive AMPA receptor antagonist, is indicated as adjunctive therapy for the treatment of partial seizures with or without secondarily generalized seizures and primary generalized tonic-clonic seizures in patients with epilepsy aged 12years and older. In vitro studies and Phase I trials indicate that perampanel is metabolized almost exclusively by CYP3A, with an elimination half-life (t1/2) averaging approximately 105h. Understanding of pharmacokinetic (PK) interactions-enzyme inhibition or induction-and anticipating their occurrence are important for management of patients with epilepsy...
April 26, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28535369/packing-on-the-pounds-in-response-to-bacterial-growth-conditions
#4
Sabih Rashid, Lesley T MacNeil
Reporting in Nature Cell Biology, Lin and Wang (2017) show that bacterial methyl metabolism impacts host mitochondrial dynamics and lipid storage in C. elegans. The authors propose a model whereby bacterial metabolic products regulate a nuclear hormone receptor that promotes lipid accumulation through expression of a secreted Hedgehog-like protein.
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28535269/increased-retinal-oxygen-metabolism-precedes-microvascular-alterations-in-type-1-diabetic-mice
#5
Wenzhong Liu, Shoujian Wang, Brian Soetikno, Ji Yi, Kevin Zhang, Siyu Chen, Robert A Linsenmeier, Christine M Sorenson, Nader Sheibani, Hao F Zhang
Purpose: To investigate inner retinal oxygen metabolic rate (IRMRO2) during early stages of type 1 diabetes in a transgenic mouse model. Methods: In current study, we involved seven diabetic mice (Akita/+, TSP1-/-) and seven control mice (TSP1-/-), and applied visible-light optical coherence tomography (vis-OCT) to image functional parameters including retinal blood flow rate, oxygen saturation (sO2) and the IRMRO2 value longitudinally from 5 weeks of age to 13 weeks of age...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28535199/genotype-phenotype-correlation-in-patients-with-isovaleric-acidemia-comparative-structural-modelling-and-computational-analysis-of-novel-variants
#6
Osama K Zaki, George Priya Doss C, Salsabil A Ali, Ghadeer G Murad, Shaima A Elashi, Maryam Sa Ebnou, D Thirumal Kumar, Ola Khalifa, Radwa Gamal, Heba S A El Abd, Bilal N Nasr, Hatem Zayed
Isovaleric acidemia (IVA) is an autosomal recessive inborn error of leucine metabolism. It is caused by a deficiency in the mitochondrial isovaleryl-CoA dehydrogenase (IVD) enzyme. In this study, we investigated eight patients with IVA. The patients diagnoses were confirmed by urinary organic acid analysis and the blood C5-Carnitine value. A molecular genetic analysis of the IVD gene revealed nine different variants: five were missense variants (c.1193G>A; p. R398Q, c.1207T>A; p. Y403N, c.872C>T; p...
May 23, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28535147/mechanics-of-post-fusion-exocytotic-vesicle
#7
Thomas Stephens, Zhanghan Wu, Jian Liu
Exocytosis is an important cellular process controlled by metabolic signaling. It involves vesicle fusion to the plasma membrane, followed by the opening of a fusion pore, and the subsequent release of the vesicular lumen content into the extracellular space. While most modeling efforts focus on the events leading to membrane fusion, how the vesicular membrane remodels after fusing to plasma membrane remains unclear. This latter event dictates the nature and the efficiency of exocytotic vesicular secretions, and is thus critical for exocytotic function...
May 23, 2017: Physical Biology
https://www.readbyqxmd.com/read/28534956/effects-of-octreotide-on-hepatic-glycogenesis-in-rats-with-high-fat-diet%C3%A2-induced-obesity
#8
Xiao-Xia Wang, Ting Ye, Mao Li, Xian Li, Ou Qiang, Cheng-Wei Tang, Rui Liu
Reduced hepatic glycogenesis is one of the most important causes of metabolic abnormalities in non‑alcoholic fatty liver disease. Octreotide, a somatostatin analogue, has been demonstrated to promote weight loss and improve metabolic disorders in mice with high fat diet (HFD)‑induced obesity. However, whether octreotide affects hepatic glycogenesis is unknown. The aim of the present study was to verify the effects of octreotide on hepatic glycogenesis in rats with HFD‑induced obesity. Male Sprague‑Dawley rats were fed a standard diet or a HFD for 24 weeks...
May 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28534854/methodical-challenges-and-a-possible-resolution-in-the-assessment-of-receptor-reserve-for-adenosine-an-agonist-with-short-half-life
#9
Judit Zsuga, Tamas Erdei, Katalin Szabó, Nora Lampe, Csaba Papp, Akos Pinter, Andras Jozsef Szentmiklosi, Bela Juhasz, Zoltán Szilvássy, Rudolf Gesztelyi
The term receptor reserve, first introduced and used in the traditional receptor theory, is an integrative measure of response-inducing ability of the interaction between an agonist and a receptor system (consisting of a receptor and its downstream signaling). The underlying phenomenon, i.e., stimulation of a submaximal fraction of receptors can apparently elicit the maximal effect (in certain cases), provides an opportunity to assess the receptor reserve. However, determining receptor reserve is challenging for agonists with short half-lives, such as adenosine...
May 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28534261/the-role-of-drug-metabolites-in-the-inhibition-of-cytochrome-p450-enzymes
#10
Momir Mikov, Maja Đanić, Nebojša Pavlović, Bojan Stanimirov, Svetlana Goločorbin-Kon, Karmen Stankov, Hani Al-Salami
Following the drug administration, patients are exposed not only to the parent drug itself, but also to the metabolites generated by drug-metabolizing enzymes. The role of drug metabolites in cytochrome P450 (CYP) inhibition and subsequent drug-drug interactions (DDIs) have recently become a topic of considerable interest and scientific debate. The list of metabolites that were found to significantly contribute to clinically relevant DDIs is constantly being expanded and reported in the literature. New strategies have been developed for better understanding how different metabolites of a drug candidate contribute to its pharmacokinetic properties and pharmacological as well as its toxicological effects...
May 22, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28533932/metabolic-parameters-and-responsiveness-of-isolated-iliac-artery-in-ldlr-mice-role-of-aerobic-exercise-training
#11
Nádia F Garcia, Amanda Cs Sponton, Maria A Delbin, Juliana M Parente, Michele M Castro, Angelina Zanesco, Camila de Moraes
Physical inactivity and dyslipidemia are considered risk factors for cardiovascular diseases. There are few studies evaluating the effects of physical exercise in small-caliber artery in a model that mimics familial hypercholesterolemia. The aim of this study was to examine the effect of exercise training, at moderate intensity, on metabolic parameters and iliac artery responsiveness in LDL(-/-) mice. Sedentary (SD) and trained (TR) mice performed AET (5 days/week, 60 minutes/day at 60-70% of maximum speed) during 8 weeks...
2017: American Journal of Cardiovascular Disease
https://www.readbyqxmd.com/read/28533787/genome-wide-analysis-of-gene-expression-provides-new-insights-into-cold-responses-in-thellungiella-salsuginea
#12
Jiangshan Wang, Quan Zhang, Feng Cui, Lei Hou, Shuzhen Zhao, Han Xia, Jingjing Qiu, Tingting Li, Ye Zhang, Xingjun Wang, Chuanzhi Zhao
Low temperature is one of the major environmental stresses that affects plant growth and development, and leads to decrease in crop yield and quality. Thellungiella salsuginea (salt cress) exhibits high tolerance to chilling, is an appropriate model to investigate the molecular mechanisms of cold tolerance. Here, we compared transcription changes in the roots and leaves of T. salsuginea under cold stress using RNA-seq. We identified 2,782 and 1,430 differentially expressed genes (DEGs) in leaves and roots upon cold treatment, respectively...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28533752/protocatechuic-acid-a-phenolic-from-sansevieria-roxburghiana-leaves-suppresses-diabetic-cardiomyopathy-via-stimulating-glucose-metabolism-ameliorating-oxidative-stress-and-inhibiting-inflammation
#13
Niloy Bhattacharjee, Tarun K Dua, Ritu Khanra, Swarnalata Joardar, Ashis Nandy, Achintya Saha, Vincenzo De Feo, Saikat Dewanjee
Persistent hyperglycemia, impairment of redox status and establishment of inflammatory pathophysiology integrally play important role in the pathogenesis of diabetic cardiomyopathy (DC). Present study examined the therapeutic potential of protocatechuic acid isolated from the Sansevieria roxburghiana rhizomes against DC employing rodent model of type 2 diabetes (T2D). T2D was induced by high fat diet + a low-single dose of streptozotocin (35 mg/kg, i.p.). T2D rats exhibited significantly (p < 0.01) high fasting blood glucose level...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28533737/the-alpha-1a-adrenergic-receptor-agonist-a61603-reduces-cardiac-polyunsaturated-fatty-acid-and-endocannabinoid-metabolites-associated-with-inflammation-in-vivo
#14
Monte S Willis, Amro Ilaiwy, Megan D Montgomery, Paul C Simpson, Brian C Jensen
INTRODUCTION: Alpha-1-adrenergic receptors (α1-ARs) are G-protein coupled receptors (GPCRs) with three highly homologous subtypes (α1A, α1B, and α1D). Of these three subtypes, only the α1A and α1B are expressed in the heart. Multiple pre-clinical models of heart injury demonstrate cardioprotective roles for the α1A. Non-selective α1-AR activation promotes glycolysis in the heart, but the functional α1-AR subtype and broader metabolic effects have not been studied. OBJECTIVES: Given the high metabolic demands of the heart and previous evidence indicating benefit from α1A activation, we chose to investigate the effects of α1A activation on the cardiac metabolome in vivo...
October 2016: Metabolomics: Official Journal of the Metabolomic Society
https://www.readbyqxmd.com/read/28533546/prostaglandin-e2-inhibits-matrix-mineralization-by-human-bone-marrow-stromal-cell-derived-osteoblasts-via-epac-dependent-camp-signaling
#15
Ali Mirsaidi, André N Tiaden, Peter J Richards
The osteoinductive properties of prostaglandin E2 (PGE2) and its signaling pathways have led to suggestions that it may serve as a potential therapeutic strategy for bone loss. However, the prominence of PGE2 as an inducer of bone formation is attributed primarily to findings from studies using rodent models. In the current study, we investigated the effects of PGE2 on human bone marrow stromal cell (hBMSC) lineage commitment and determined its mode of action. We demonstrated that PGE2 treatment of hBMSCs significantly altered the expression profile of several genes associated with osteoblast differentiation (RUNX2 and ALP) and maturation (BGLAP and MGP)...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28533544/sex-specific-metabolic-profiles-of-androgens-and-its-main-binding-protein-shbg-in-a-middle-aged-population-without-diabetes
#16
Uwe Piontek, Henri Wallaschofski, Gabi Kastenmüller, Karsten Suhre, Henry Völzke, Kieu Trinh Do, Anna Artati, Matthias Nauck, Jerzy Adamski, Nele Friedrich, Maik Pietzner
The role of androgens in metabolism with respect to sex-specific disease associations is poorly understood. Therefore, we aimed to provide molecular signatures in plasma and urine of androgen action in a sex-specific manner using state-of-the-art metabolomics techniques. Our study population consisted of 430 men and 343 women, aged 20-80 years, who were recruited for the cross-sectional population-based Study of Health in Pomerania (SHIP-TREND), Germany. We used linear regression models to identify associations between testosterone, androstenedione and dehydroepiandrosterone-sulfate (DHEAS) as well as sex hormone-binding globulin and plasma or urine metabolites measured by mass spectrometry...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28533471/the-atypical-response-regulator-atvr-is-a-new-player-in-pseudomonas-aeruginosa-response-to-hypoxia-and-virulence
#17
Gilberto Hideo Kaihami, Leandro Carvalho Dantas Breda, José Roberto Fogaça de Almeida, Thays de Oliveira Pereira, Gianlucca Gonçalves Nicastro, Ana Laura Boechat, Sandro Rogério de Almeida, Regina Lúcia Baldini
Two-component systems are widespread in bacteria, allowing adaptation to environmental changes. The classical pathway is composed by a histidine kinase that phosphorylates an aspartate residue in the cognate response regulator (RR). RRs lacking the phosphorylable aspartate also occur, but their function and contribution during host-pathogen interaction are poorly characterized. AtvR (PA14_26570) is the only atypical response regulator with a DNA-binding domain in the opportunistic pathogen Pseudomonas aeruginosa Macrophage infection with the atvR mutant strain resulted in higher TNF-α secretion as well as increased bacterial clearance as compared to macrophages infected with the wild-type strain...
May 22, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28533437/metformin-inhibits-cellular-proliferation-and-bioenergetics-in-colorectal-cancer-patient-derived-xenografts
#18
Nur-Afidah Mohamed Suhaimi, Wai Min Phyo, Hao Yun Yap, Sharon Heng Yee Choy, Xiaona Wei, Yukti Choudhury, Wai Jin Tan, Luke Anthony Peng Yee Tan, Roger Sik Yin Foo, Suzanne Hui San Tan, Zenia Tiang, Chin Fong Wong, Poh Koon Koh, Min-Han Tan
There is increasing pre-clinical evidence suggesting that metformin, an anti-diabetic drug, has anti-cancer properties against various malignancies including colorectal cancer (CRC). However, majority of evidence which were derived from cancer cell lines and xenografts are likely to overestimate the benefit of metformin since these models are inadequate and require supraphysiological levels of metformin. Here, we generated patient-derived xenografts (PDX) lines from 2 CRC patients to assess the properties of metformin and 5-fluorouracil (5-FU), the first-line drug treatment for CRC...
May 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28533395/integrative-modeling-of-gene-and-genome-evolution-roots-the-archaeal-tree-of-life
#19
Tom A Williams, Gergely J Szöllősi, Anja Spang, Peter G Foster, Sarah E Heaps, Bastien Boussau, Thijs J G Ettema, T Martin Embley
A root for the archaeal tree is essential for reconstructing the metabolism and ecology of early cells and for testing hypotheses that propose that the eukaryotic nuclear lineage originated from within the Archaea; however, published studies based on outgroup rooting disagree regarding the position of the archaeal root. Here we constructed a consensus unrooted archaeal topology using protein concatenation and a multigene supertree method based on 3,242 single gene trees, and then rooted this tree using a recently developed model of genome evolution...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533366/mechanism-of-h2s-mediated-protection-against-oxidative-stress-in-escherichia-coli
#20
Alexander Mironov, Tatyana Seregina, Maxim Nagornykh, Lyly G Luhachack, Natalya Korolkova, Liubov Errais Lopes, Vera Kotova, Gennady Zavilgelsky, Rustem Shakulov, Konstantin Shatalin, Evgeny Nudler
Endogenous hydrogen sulfide (H2S) renders bacteria highly resistant to oxidative stress, but its mechanism remains poorly understood. Here, we report that 3-mercaptopyruvate sulfurtransferase (3MST) is the major source of endogenous H2S in Escherichia coli Cellular resistance to H2O2 strongly depends on the activity of mstA, a gene that encodes 3MST. Deletion of the ferric uptake regulator (Fur) renders ∆mstA cells hypersensitive to H2O2 Conversely, induction of chromosomal mstA from a strong pLtetO-1 promoter (P tet -mstA) renders ∆fur cells fully resistant to H2O2 Furthermore, the endogenous level of H2S is reduced in ∆fur or ∆sodA ∆sodB cells but restored after the addition of an iron chelator dipyridyl...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
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