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https://www.readbyqxmd.com/read/28749581/prediction-of-transporter-mediated-drug-drug-interactions-for-baricitinib
#1
Maria M Posada, Ellen A Cannady, Christopher D Payne, Xin Zhang, James A Bacon, Y Anne Pak, J William Higgins, Nazila Shahri, Stephen D Hall, Kathleen M Hillgren
Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, undergoes active renal tubular secretion. Baricitinib was not predicted to inhibit hepatic and renal uptake and efflux drug transporters, based on the ratio of the unbound maximum eliminating-organ inlet concentration and the in vitro half-maximal inhibitory concentrations (IC50 ). In vitro, baricitinib was a substrate for organic anion transporter (OAT)3, multidrug and toxin extrusion protein (MATE)2-K, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP)...
July 27, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28749565/melatonin-suppresses-platelet-activation-and-function-against-cardiac-ischemia-reperfusion-injury-via-ppar%C3%AE-fundc1-mitophagy-pathways
#2
Hao Zhou, Dandan Li, Pingjun Zhu, Shunying Hu, Nan Hu, Sai Ma, Ying Zhang, Tianwen Han, Jun Ren, Feng Cao, Yundai Chen
Platelet activation is a major (patho-) physiological mechanism that underlies ischemia/reperfusion (I/R) injury. In this study, we explored the molecular signals for platelet hyperactivity and investigated the beneficial effects of melatonin on platelet reactivity in response to I/R injury. After reperfusion, peroxisome proliferator-activated receptor γ (PPARγ) was progressively downregulated in patients with acute myocardial infarction undergoing coronary artery bypass grafting (CABG) surgery and in mice with I/R injury model...
July 27, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28749562/school-based-systems-change-for-obesity-prevention-in-adolescents-outcomes-of-the-australian-capital-territory-it-s-your-move
#3
Mary Malakellis, Erin Hoare, Andrew Sanigorski, Nicholas Crooks, Steven Allender, Melanie Nichols, Boyd Swinburn, Cal Chikwendu, Paul M Kelly, Solveig Petersen, Lynne Millar
OBJECTIVE: The Australian Capital Territory 'It's Your Move!' (ACT-IYM) was a three-year (2012-2014) systems intervention to prevent obesity among adolescents. METHODS: The ACT-IYM project involved three intervention schools and three comparison schools and targeted secondary students aged 12-16 years. The intervention consisted of multiple initiatives at individual, community, and school policy level to support healthier nutrition and physical activity. Intervention school-specific objectives related to increasing active transport, increasing time spent physically active at school, and supporting mental wellbeing...
July 27, 2017: Australian and New Zealand Journal of Public Health
https://www.readbyqxmd.com/read/28749503/crab-shell-induced-synthesis-of-ordered-macroporous-carbon-nanofiber-arrays-coupled-with-mnco2o4-nanoparticles-as-bifunctional-oxygen-catalysts-for-rechargeable-zn-air-batteries
#4
Duan Bin, Ziyang Guo, Andebet Gedamu Tamirat, Yuanyuan Ma, Yonggang Wang, Yongyao Xia
The oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are traditionally carried out using noble metals (such as Pt) and metal oxides (such as RuO2 and IrO2) as catalysts, respectively. Nevertheless, several key issues such as high cost, poor stability, and detrimental environmental effects limit the catalytic activity of these noble metal- and metal oxide-based catalysts. Herein, we have designed and synthesized macroporous carbon nanofiber arrays by using a natural crab shell template. Subsequently, spinel MnCo2O4 nanoparticles were embedded into the nitrogen-doped macroporous carbon nanofiber arrays (NMCNAs) by a hydrothermal method...
July 27, 2017: Nanoscale
https://www.readbyqxmd.com/read/28749080/cellular-and-genetic-models-of-h6pdh-and-11%C3%AE-hsd1-function-in-skeletal-muscle
#5
Agnieszka E Zielinska, Rachel S Fletcher, Mark Sherlock, Craig L Doig, Gareth G Lavery
Glucocorticoids are important for skeletal muscle energy metabolism, regulating glucose utilization, insulin sensitivity, and muscle mass. Nicotinamide adenine dinucleotide phosphate-dependent 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)-mediated glucocorticoid activation in the sarcoplasmic reticulum (SR) is integral to mediating the detrimental effects of glucocorticoid excess in muscle. 11β-Hydroxysteroid dehydrogenase type 1 activity requires glucose-6-phosphate transporter (G6PT)-mediated G6P transport into the SR for its metabolism by hexose-6-phosphate dehydrogenase (H6PDH) for NADPH generation...
July 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/28749007/reactive-oxygen-species-as-mediators-of-sperm-capacitation-and-pathological-damage
#6
REVIEW
R J Aitken
Oxidative stress plays a major role in the life and death of mammalian spermatozoa. These gametes are professional generators of reactive oxygen species (ROS), which appear to derive from three potential sources: sperm mitochondria, cytosolic L-amino acid oxidases, and plasma membrane nicotinamide adenine dinucleotide phosphate oxidases. The oxidative stress created via these sources appears to play a significant role in driving the physiological changes associated with sperm capacitation through the stimulation of a cyclic adenosine monophosphate/Protein kinase A phosphorylation cascade, including the activation of Extracellular signal regulated kinase-like proteins, massive up-regulation of tyrosine phosphorylation in the sperm tail, as well as the induction of sterol oxidation...
July 27, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28748913/d-chiro-inositol-effectively-attenuates-cholestasis-in-bile-duct-ligated-rats-by-improving-bile-acid-secretion-and-attenuating-oxidative-stress
#7
Shuang-Shuang Zhao, Na-Ren Li, Wu-Li Zhao, Hong Liu, Mao-Xu Ge, Yi-Xuan Zhang, Long-Yin Zhao, Xue-Fu You, Hong-Wei He, Rong-Guang Shao
Cholestatic liver diseases are important causes of liver cirrhosis and liver transplantation, but few drugs are available for treatment. D-chiro-inositol (DCI), an isomer of inositol found in many Leguminosae plants and in animal viscera, is used clinically for the treatment of polycystic ovary syndrome (PCOS) and diabetes mellitus. In this study, we investigated whether DCI exerted an anti-cholestatic effect and its underlying mechanisms. A cholestatic rat model was established via bile duct ligation (BDL)...
July 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28748829/dose-assessment-following-an-overexposure-of-a-worker-at-a-swiss-nuclear-power-plant
#8
Claude J Bailat, Jean-Pascal Laedermann, Sebastien Baechler, Laurent Desorgher, Abbas Aroua, Francois O Bochud
AIM: The aim of this work was to assess the doses received by a diver exposed to a radiation source during maintenance work in the fuel transfer pool at a Swiss nuclear power plant, and to define whether the statutory limit was breached or not. METHOD: Onsite measurements were carried out and different scenarios were simulated using the MicroShield Software and the MCNPX Monte Carlo (MC) radiation transport code to estimate the activity of the irradiating object as well as the doses to the limbs and the effective dose delivered to the operator...
July 27, 2017: Journal of Radiological Protection: Official Journal of the Society for Radiological Protection
https://www.readbyqxmd.com/read/28748435/effects-of-salinity-on-oil-dispersant-toxicity-in-the-eastern-mud-snail-ilyanassa-obsoleta
#9
Marie E DeLorenzo, Brittany N Evans, Katy W Chung, Peter B Key, Michael H Fulton
Chemical dispersants can be a beneficial method for breaking up oil slicks; however, their use in mitigation could pose potential toxic effects on the marine ecosystem. Dispersants may be transported to lower salinity habitats, where toxicity data for aquatic species have not been established. This study examined the effect of salinity on oil dispersant toxicity in the eastern mud snail, Ilyanassa obsoleta, using two dispersants authorized for oil spill response, Corexit® 9500A and Finasol® OSR 52. Median lethal toxicity values (LC50) and sublethal effects were examined at 10, 20, and 30 ppt salinity in adult and larval mud snails...
July 26, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28747976/immunohistochemical-localization-of-glucose-transporter-1-and-3-in-the-scrotal-and-abdominal-testes-of-a-dog
#10
Kyu Ri Hahn, Hyo Young Jung, Dae Young Yoo, Jong Whi Kim, Yang Hee Kim, Young Kwang Jo, Geon A Kim, Jin Young Chung, Jung Hoon Choi, In Koo Hwang, Goo Jang, Yeo Sung Yoon
Glucose is essential for testicular function; the uptake of carbohydrate-derived glucose by cells is mediated by glucose transporters (GLUTs). In the present study, we investigated the activity of GLUT1 and GLUT3, the two main isoforms of GLUTs found in testes, in the left scrotal and right abdominal testes of a German Shepherd dog. Immunohistochemical analysis showed that GLUT1 immunoreactivity was absent in the scrotal and abdominal testes. In contrast, weak to moderate GLUT3 immunoreactivity was observed in mature spermatocytes as well as spermatids in the scrotal testis...
June 2017: Laboratory Animal Research
https://www.readbyqxmd.com/read/28747898/piriformospora-indica-reprograms-gene-expression-in-arabidopsis-phosphate-metabolism-mutants-but-does-not-compensate-for-phosphate-limitation
#11
Madhunita Bakshi, Irena Sherameti, Doreen Meichsner, Johannes Thürich, Ajit Varma, Atul K Johri, Kai-Wun Yeh, Ralf Oelmüller
Piriformospora indica is an endophytic fungus of Sebacinaceae which colonizes the roots of many plant species and confers benefits to the hosts. We demonstrate that approximately 75% of the genes, which respond to P. indica in Arabidopsis roots, differ among seedlings grown on normal phosphate (Pi) or Pi limitation conditions, and among wild-type and the wrky6 mutant impaired in the regulation of the Pi metabolism. Mapman analyses suggest that the fungus activates different signaling, transport, metabolic and developmental programs in the roots of wild-type and wrky6 seedlings under normal and low Pi conditions...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28747869/effect-of-dietary-copper-addition-on-lipid-metabolism-in-rabbits
#12
Liu Lei, Sui Xiaoyi, Li Fuchang
The present study was conducted to investigate the effect of copper supplementation on lipid metabolism in rabbits. Our study showed dietary copper addition (5-45 mg/kg) increased body mass gain, but decreased fat and liver weights compared with those in the control group (P < 0.05). Copper (45 mg/kg) addition significantly increased the skeletal muscle weight, but inhibited cytoplasmic lipid accumulation in liver, skeletal muscle and adipose tissue (P < 0.05). Compared with the control group, dietary copper addition (45 mg/kg) significantly increased plasma triglyceride levels but decreased very low density lipoprotein levels (P < 0...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28747746/one-step-purification-and-immobilization-of-extracellularly-expressed-sortase-a-by-magnetic-particles-to-develop-a-robust-and-recyclable-biocatalyst
#13
Xinrui Zhao, Haofei Hong, Xiaozhong Cheng, Shaozhong Liu, Tao Deng, Zhongwu Guo, Zhimeng Wu
Sortase A (SrtA) is a transpeptidase widely used to site-specifically modify peptides and proteins and shows promise for industrial applications. In this study, a novel strategy was developed for constructing immobilized-SrtA as a robust and recyclable enzyme via direct immobilization of extracellularly expressed SrtA in the fermentation supernatant using magnetic particles. Efficient extracellular SrtA expression was achieved in Escherichia coli through molecular engineering, including manipulation of the protein transport pathway, codon optimization, and co-expression of molecular chaperones to promote expressed SrtA secretion into the medium at high levels...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747540/historical-aspects-chronicling-the-discovery-of-ifnt
#14
Fuller Warren Bazer, William W Thatcher
It has been 42 years since a protein, now known as interferon tau (IFNT), was discovered in ovine conceptus-conditioned culture medium. In 1975, purification and testing of native IFNT revealed its unique antiluteolyic activity to prevent regression of corpora lutea on ovaries of nonpregnant ewes. Antiviral, antiproliferative and immunomodulatory properties of native and recombinant IFNT were also demonstrated. In addition, progesterone and IFNT were found to act cooperatively to silence expression of classical interferon stimulated genes in a cell-specific manner in ovine uterine luminal and superficial glandular epithelia...
July 26, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28747422/suppressing-a-putative-sterol-carrier-gene-reduces-plasmodesmal-permeability-and-activates-sucrose-transporter-genes-during-cotton-fiber-elongation
#15
Zhiyuan Zhang, Yong-Ling Ruan, Na Zhou, Fang Wang, Xueying Guan, Lei Fang, Xiaoguang Shang, Wangzhen Guo, Shuijin Zhu, Tianzhen Zhang
Plasmodesmata (PDs) play vital roles in cell-to-cell communication and plant development. Emerging evidence suggests that sterols are involved in PD activity during cytokinesis. However, whether sterols contribute to PD gating between established cells remains unknown. Here, we isolated GhSCP2D, a putative sterol carrier protein gene from elongating cotton (Gossypium hirsutum) fibers. In contrast to wild-type fiber PDs, which opened at 5-10 days post anthesis (DPA) and closed only at 15-25 DPA, plants with suppressed GhSCP2D expression had reduced sterol contents and closed PDs at 5 through 25 DPA...
July 26, 2017: Plant Cell
https://www.readbyqxmd.com/read/28747251/serca-control-of-cell-death-and-survival
#16
REVIEW
Elie R Chemaly, Luca Troncone, Djamel Lebeche
Intracellular calcium (Ca(2+)) is a critical coordinator of various aspects of cellular physiology. It is increasingly apparent that changes in cellular Ca(2+) dynamics contribute to the regulation of normal and pathological signal transduction that controls cell growth and survival. Aberrant perturbations in Ca(2+) homeostasis have been implicated in a range of pathological conditions, such as cardiovascular diseases, diabetes, tumorigenesis and steatosis hepatitis. Intracellular Ca(2+) concentrations are therefore tightly regulated by a number of Ca(2+) handling enzymes, proteins, channels and transporters located in the plasma membrane and in Ca(2+) storage organelles, which work in concert to fine tune a temporally and spatially precise Ca(2+) signal...
July 12, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28747232/development-of-an-accumulation-assay-and-evaluation-of-the-effects-of-efflux-pump-inhibitors-on-the-retention-of-chlorhexidine-digluconate-in-pseudomonas-aeruginosa-and-staphylococcus-aureus
#17
Molly Mombeshora, Stanley Mukanganyama
BACKGROUND: Chlorhexidine digluconate (CHG) is used as a disinfectant. The emergence of pathogens resistant to the biocide raises health concern. Information on specific efflux mechanisms utilised by bacteria to confer reduced susceptibility to the biocide, may be used to develop ways of preventing the efflux of the biocide from nosocomial pathogens resulting in higher disinfection activity. The aim of the study was to evaluate the role of ATP-binding cassette transporters on the transport of CHG in bacteria...
July 26, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28747093/prochlorperazine-increases-kcc2-function-and-reduces-spasticity-after-spinal-cord-injury
#18
Sylvie Liabeuf, Laetitia Stuhl-Gourmand, Florian Gackière, Renzo Mancuso, Irene Sanchez-Brualla, Philippe Marino, Frédéric Brocard, Laurent Vinay
In mature neurons, low intracellular chloride level required for inhibition is maintained by the potassium-chloride co-transporter KCC2. Impairment of Cl- extrusion following KCC2 dysfunction has been involved in many CNS disorders such as seizures, neuropathic pain or spasticity after a spinal cord injury (SCI). This makes KCC2 an appealing drug target for restoring Cl-homeostasis and inhibition in pathological conditions. In the present study, we screen the Prestwick Chemical Library® and identify conventional antipsychotics phenothiazine derivatives as enhancers of KCC2 activity...
July 26, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28746878/the-type-vi-secretion-system-engages-a-redox-regulated-dual-functional-heme-transporter-for-zinc-acquisition
#19
Meiru Si, Yao Wang, Bing Zhang, Chao Zhao, Yiwen Kang, Haonan Bai, Dawei Wei, Lingfang Zhu, Lei Zhang, Tao G Dong, Xihui Shen
The type VI secretion system was recently reported to be involved in zinc acquisition, but the underlying mechanism remains unclear. Here, we report that Burkholderia thailandensis T6SS4 is involved in zinc acquisition via secretion of a zinc-scavenging protein, TseZ, that interacts with the outer membrane heme transporter HmuR. We find that HmuR is a redox-regulated dual-functional transporter that transports heme iron under normal conditions but zinc upon sensing extracellular oxidative stress, triggered by formation of an intramolecular disulfide bond...
July 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28746873/deletion-of-glut1-and-glut3-reveals-multiple-roles-for-glucose-metabolism-in-platelet-and-megakaryocyte-function
#20
Trevor P Fidler, Robert A Campbell, Trevor Funari, Nicholas Dunne, Enrique Balderas Angeles, Elizabeth A Middleton, Dipayan Chaudhuri, Andrew S Weyrch, E Dale Abel
Anucleate platelets circulate in the blood to facilitate thrombosis and diverse immune functions. Platelet activation leading to clot formation correlates with increased glycogenolysis, glucose uptake, glucose oxidation, and lactic acid production. Simultaneous deletion of glucose transporter (GLUT) 1 and GLUT3 (double knockout [DKO]) specifically in platelets completely abolished glucose uptake. In DKO platelets, mitochondrial oxidative metabolism of non-glycolytic substrates, such as glutamate, increased...
July 25, 2017: Cell Reports
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