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https://www.readbyqxmd.com/read/28448553/a-computational-toxicogenomics-approach-identifies-a-list-of-highly-hepatotoxic-compounds-from-a-large-microarray-database
#1
Héctor A Rueda-Zárate, Iván Imaz-Rosshandler, Roberto A Cárdenas-Ovando, Juan E Castillo-Fernández, Julieta Noguez-Monroy, Claudia Rangel-Escareño
The liver and the kidney are the most common targets of chemical toxicity, due to their major metabolic and excretory functions. However, since the liver is directly involved in biotransformation, compounds in many currently and normally used drugs could affect it adversely. Most chemical compounds are already labeled according to FDA-approved labels using DILI-concern scale. Drug Induced Liver Injury (DILI) scale refers to an adverse drug reaction. Many compounds do not exhibit hepatotoxicity at early stages of development, so it is important to detect anomalies at gene expression level that could predict adverse reactions in later stages...
2017: PloS One
https://www.readbyqxmd.com/read/28447033/prokineticin-is-a-new-linker-between-obesity-and-cardiovascular-diseases
#2
REVIEW
Canan G Nebigil
Obesity is a fast growing epidemic event worldwide. Fatness is associated with a number of comorbidities, including cardiovascular diseases (CVDs). Although obesity can be heredity in 30-70% cases, the environmental contributions also play an important role in the increasing prevalence of obesity. The relationship between development of obesity and CVD is poorly characterized. Obesity and CVD can also be resulted from a common mechanism such as metabolic, inflammatory, and neurohormonal changes. Prokineticins are defined as cytokines (immunoregulatory proteins), adipokines (adipocyte-secreted hormone), angiogenic (increasing vessel formation), or aneroxic (lowering food intake) hormones...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28446807/increased-blood-pressure-in-nesfatin-nuclebindin-2-transgenic-mice
#3
Yusaku Mori, Hiroyuki Shimizu, Hideki Kushima, Munenori Hiromura, Michishige Terasaki, Michitaka Tanaka, Aya Osaki, Tsutomu Hirano
Nesfatin/nucleobindin-2 (nesf/NUCB2), a precursor of the anorexigenic protein nesfatin-1, is selectively expressed in the hypothalamic nuclei, which are central to the regulation of the autonomic nervous system. The present study sought to investigate the involvement of nesf/NUCB2 in the regulation of blood pressure and ingestive behavior, by using nesf/NUCB2-transgenic (Tg) mice. Blood pressure and heart rates were measured under conscious and unconscious conditions. Twenty-four-hour water intake and urine volume of male nesf/NUCB2-Tg mice and their littermates in metabolic cages were measured...
April 27, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/28445717/hepatic-elovl6-mrna-is-regulated-by-the-gga-mir-22-3p-in-egg-laying-hen
#4
Zheng Ma, Hong Li, Hang Zheng, Keren Jiang, Fengbin Yan, Yadong Tian, Xiangtao Kang, Yanbin Wang, Xiaojun Liu
The elongation of very long chain fatty acids protein 6 (ELOVL6) encodes a fatty acid elongase that is responsible for the final step in endogenous saturated fatty acid synthesis and involves in de novo lipogenesis. Though the regulatory mechanism of ELOVL6 expression has been studied extensively, little is known about the role of miRNA in regulating ELOVL6 gene expression in chicken until now. To investigate the regulatory mechanism of miRNA on the expression of ELOVL6 gene, bioinformatics analysis was employed to predict the potential miRNAs that binding with the 3'untranslated region (3'UTR) of ELOVL6...
April 23, 2017: Gene
https://www.readbyqxmd.com/read/28445053/sulfotransferases-and-breast-cancer-resistance-protein-determine-the-disposition-of-calycosin-in-vitro-and-in-vivo
#5
Jia Yu, Lijun Zhu, Haihui Zheng, Xia Gong, Jianghuang Yu, Jiamei Chen, Yuhuan Li, Hongming Zheng, Xiaoxiao Qi, Ying Wang, Ming Hu, Linlin Lu, Zhong Qiu Liu
Sulfation is a key process of drugs disposition that generally regulates the drug effectiveness and toxicity. Calycosin derived from the dry root extract of Radix Astragali exhibits a variety of biological effects that easily undergo extensive phase II metabolism. However, the sulfation pathway of calycosin lacks information. We investigated the disposition mechanisms of calycosin sulfate in vitro and in vivo. We characterized the sulfation metabolism and excretion of calycosin using bi-directional transport studies...
April 26, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28444472/the-effect-of-sodium-glucose-co-transporter-2-sglt-2-inhibitors-on-cardiometabolic-profile-beyond-the-hypoglycaemic-action
#6
Eirini Lioudaki, Emmanouil S Androulakis, Martin Whyte, Konstantinos G Stylianou, Eugenios K Daphnis, Emmanouil S Ganotakis
Type 2 diabetes mellitus (T2DM) has growing prevalence worldwide and major clinical implications, chiefly cardiovascular (CV) and renal disease burden. Sodium-glucose co-transporter (SGLT)-2 inhibitors are a new drug class in the management of T2DM with a mechanism of action independent of insulin. In addition to their hypoglycaemic effect, SGLT-2 inhibitors appear to have haemodynamic and nephroprotective effects. Studies have consistently showed a modest but significant blood pressure (BP) reduction. Metabolic benefits are also attributed to SGLT-2 inhibitors with a modest but consistent body weight decrease recorded along with improvements in lipid profile and uric acid levels...
April 25, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28443535/effects-of-immunocastration-and-%C3%AE-adrenergic-agonists-on-the-performance-and-carcass-traits-of-feedlot-finished-nellore-cattle
#7
D S Antonelo, M R Mazon, K E Z Nubiato, J F M Gómez, D J Brigida, R C Gomes, A S Netto, P R Leme, S L Silva
β-Adrenergic agonists (β-AA) are non-hormonal growth promoters which promote muscle hypertrophy in supplemented animals. The effects of two β-AA in combination with the immunocastration technique on the performance and carcass traits were evaluated using 96 feedlot Nellore males in a randomized complete block design with two sex conditions (immunocastrated (IC) v. non-castrated (NC)) and three treatments: CON (no β-agonists added), RH (300 mg of ractopamine hydrochloride/day, for 33 days) or ZH (80 mg of zilpaterol·hydrochloride animal/day for 30 days, removed 3 days for required withdrawal period)...
April 26, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/28443030/mitochondrial-reactive-oxygen-species-and-kidney-hypoxia-in-the-development-of-diabetic-nephropathy
#8
REVIEW
Tomas A Schiffer, Malou Friederich-Persson
The underlying mechanisms in the development of diabetic nephropathy are currently unclear and likely consist of a series of dynamic events from the early to late stages of the disease. Diabetic nephropathy is currently without curative treatments and it is acknowledged that even the earliest clinical manifestation of nephropathy is preceded by an established morphological renal injury that is in turn preceded by functional and metabolic alterations. An early manifestation of the diabetic kidney is the development of kidney hypoxia that has been acknowledged as a common pathway to nephropathy...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28442752/zika-virus-infection-reprograms-global-transcription-of-host-cells-to-allow-sustained-infection
#9
Shashi Kant Tiwari, Jason Dang, Yue Qin, Gianluigi Lichinchi, Vikas Bansal, Tariq M Rana
Zika virus (ZIKV) is an emerging virus causally linked to neurological disorders, including congenital microcephaly and Guillain-Barré syndrome. There are currently no targeted therapies for ZIKV infection. To identify novel antiviral targets and to elucidate the mechanisms by which ZIKV exploits the host cell machinery to support sustained replication, we analyzed the transcriptomic landscape of human microglia, fibroblast, embryonic kidney and monocyte-derived macrophage cell lines before and after ZIKV infection...
April 26, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28442280/kidney-disease-in-patients-with-obesity-it-is-not-always-obesity-related-glomerulopathy-alone
#10
Steven P Salvatore, James M Chevalier, Sheng F Kuo, Pat F Audia, Surya V Seshan
OBJECTIVE: Patients with obesity are at risk for chronic kidney disease. The aim is to characterize the spectrum of kidney disease in these patients, which may be related to obesity, termed obesity-related glomerulopathy (ORG), or may have other diseases secondary to associated or unassociated medical conditions. METHODS: Native kidney biopsies from 2000 to 2012 were retrospectively reviewed from all patients with body mass index >30kg/m(2). Glomerular diameter was measured using a standard micrometer and clinicopathologic characteristics were analyzed...
April 22, 2017: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/28441657/involvement-of-the-multidrug-and-toxic-compound-extrusion-transporter-in-testosterone-release-from-cultured-pig-leydig-cells
#11
Mitsuhiro Goda, Kana Oda, Atsuko Oda, Naoki Kobayashi, Masato Otsuka
Testosterone is considered to be released from Leydig cells via passive diffusion because of its hydrophobicity; however, the exact mechanism underlying testosterone secretion and the transporter involved are both unknown. Multidrug and toxic compound extrusion (MATE) transporters are predominantly found in the kidneys and liver and are thought to function in the elimination of metabolic organic cations during the final step of excretion in the kidney. In contrast, mMATE2 has been shown to be predominantly expressed in testicular Leydig cells...
April 26, 2017: Pharmacology
https://www.readbyqxmd.com/read/28441380/comparison-of-general-obesity-and-measures-of-body-fat-distribution-in-older-adults-in-relation-to-cancer-risk-meta-analysis-of-individual-participant-data-of-seven-prospective-cohorts-in-europe
#12
Heinz Freisling, Melina Arnold, Isabelle Soerjomataram, Mark George O'Doherty, José Manuel Ordóñez-Mena, Christina Bamia, Ellen Kampman, Michael Leitzmann, Isabelle Romieu, Frank Kee, Konstantinos Tsilidis, Anne Tjønneland, Antonia Trichopoulou, Paolo Boffetta, Vassiliki Benetou, H B As Bueno-de-Mesquita, José María Huerta, Hermann Brenner, Tom Wilsgaard, Mazda Jenab
BACKGROUND: We evaluated the associations of anthropometric indicators of general obesity (body mass index, BMI), an established risk factor of various cancer, and body fat distribution (waist circumference, WC; hip circumference, HC; and waist-to-hip ratio, WHR), which may better reflect metabolic complications of obesity, with total obesity-related and site-specific (colorectal and postmenopausal breast) cancer incidence. METHODS: This is a meta-analysis of seven prospective cohort studies participating in the CHANCES consortium including 18 668 men and 24 751 women with a mean age of 62 and 63 years, respectively...
April 25, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28441075/autophagy-and-kidney-inflammation
#13
Tomonori Kimura, Yoshitaka Isaka, Tamotsu Yoshimori
Inflammation plays a pivotal role in pathophysiological processes of kidney diseases. Macroautophagy/autophagy plays multiple roles in inflammatory responses, and the regulation of inflammation by autophagy has great potential as a treatment for damaged kidneys. A growing body of evidence suggests autophagy protects kidney from versatile kidney inflammatory insults, including those that are acute, chronic, metabolic, and aging-related. Noteworthy is that, in kidney, mitophagy is active, and damaged lysosomes are removed by autophagy...
April 25, 2017: Autophagy
https://www.readbyqxmd.com/read/28439641/data-driven-metabolic-subtypes-predict-future-adverse-events-in-individuals-with-type-1-diabetes
#14
Raija Lithovius, Iiro Toppila, Valma Harjutsalo, Carol Forsblom, Per-Henrik Groop, Ville-Petteri Mäkinen
AIMS/HYPOTHESIS: Previously, we proposed that data-driven metabolic subtypes predict mortality in type 1 diabetes. Here, we analysed new clinical endpoints and revisited the subtypes after 7 years of additional follow-up. METHODS: Finnish individuals with type 1 diabetes (2059 men and 1924 women, insulin treatment before 35 years of age) were recruited by the national multicentre FinnDiane Study Group. The participants were assigned one of six metabolic subtypes according to a previously published self-organising map from 2008...
April 24, 2017: Diabetologia
https://www.readbyqxmd.com/read/28439468/a-link-between-central-kynurenine-metabolism-and-bone-strength-in-rats-with-chronic-kidney-disease
#15
Bartlomiej Kalaska, Krystyna Pawlak, Ewa Oksztulska-Kolanek, Tomasz Domaniewski, Beata Znorko, Malgorzata Karbowska, Aleksandra Citkowska, Joanna Rogalska, Alicja Roszczenko, Malgorzata M Brzoska, Dariusz Pawlak
BACKGROUND: Disturbances in mineral and bone metabolism represent one of the most complex complications of chronic kidney disease (CKD). Serotonin, a monoamine synthesized from tryptophan, may play a potential role in bone metabolism. Brain-derived serotonin exerts a positive effect on the bone structure by limiting bone resorption and enhancing bone formation. Tryptophan is the precursor not only to the serotonin but also and primarily to kynurenine metabolites. The ultimate aim of the present study was to determine the association between central kynurenine metabolism and biomechanical as well as geometrical properties of bone in the experimental model of the early stage of CKD...
2017: PeerJ
https://www.readbyqxmd.com/read/28438763/the-performing-animal-causes-and-consequences-of-body-remodelling-and-metabolic-adjustments-in-red-knots-facing-contrasting-thermal-environments
#16
François Vézina, Alexander R Gerson, Christopher G Guglielmo, Theunis Piersma
Using red knots (Calidris canutus) as a model, we determined how changes in mass and metabolic activity of organs relate to temperature-induced variation in metabolic performance. In cold-acclimated birds, we expected large muscles and heart, improved oxidative capacity and lipid transport, and we predicted that this would explain variation in maximal thermogenic capacity (Msum). We also expected larger digestive and excretory organs in these birds and predicted that this would explain variation in basal metabolic rate (BMR)...
April 24, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28438436/effects-of-dextran-sulfate-sodium-induced-experimental-colitis-on-cytochrome-p450-activity-in-rat-liver-kidney-and-intestine
#17
Nan Hu, Yanjuan Huang, Xuejiao Gao, Sai Li, Zhixiang Yan, Bin Wei, Ru Yan
Dextran sulfate sodium (DSS) induced experimental colitis presents a histologic resemblance to human ulcerative colitis (UC). Altered cytochrome P450s (CYPs) have been reported in this model and patients with UC. In this study, six CYPs activities were quantitatively determined in microsomes of liver (RLMs), kidney (RRMs) and intestine (RIMs) from rats with colitis at acute (5% DSS for 7 days, UCA) and remission (7-day DSS treatment followed by 7-day cessation, UCR) phases and compared with normal rats. Generally, CYPs activities varied with isoform, organ, and disease status...
April 21, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28437620/american-association-of-clinical-endocrinologists-and-american-college-of-endocrinology-guidelines-for-management-of-dyslipidemia-and-prevention-of-cardiovascular-disease
#18
Paul S Jellinger, Yehuda Handelsman, Paul D Rosenblit, Zachary T Bloomgarden, Vivian A Fonseca, Alan J Garber, George Grunberger, Chris K Guerin, David S H Bell, Jeffrey I Mechanick, Rachel Pessah-Pollack, Kathleen Wyne, Donald Smith, Eliot A Brinton, Sergio Fazio, Michael Davidson
OBJECTIVE: The development of these guidelines is mandated by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs). METHODS: Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols...
April 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28437467/mutant-uromodulin-expression-leads-to-altered-homeostasis-of-the-endoplasmic-reticulum-and-activates-the-unfolded-protein-response
#19
Céline Schaeffer, Stefania Merella, Elena Pasqualetto, Dejan Lazarevic, Luca Rampoldi
Uromodulin is the most abundant urinary protein in physiological conditions. It is exclusively produced by renal epithelial cells lining the thick ascending limb of Henle's loop (TAL) and it plays key roles in kidney function and disease. Mutations in UMOD, the gene encoding uromodulin, cause autosomal dominant tubulointerstitial kidney disease uromodulin-related (ADTKD-UMOD), characterised by hyperuricemia, gout and progressive loss of renal function. While the primary effect of UMOD mutations, retention in the endoplasmic reticulum (ER), is well established, its downstream effects are still largely unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28436957/pyruvate-kinase-m2-activation-may-protect-against-the-progression-of-diabetic-glomerular-pathology-and-mitochondrial-dysfunction
#20
Weier Qi, Hillary A Keenan, Qian Li, Atsushi Ishikado, Aimo Kannt, Thorsten Sadowski, Mark A Yorek, I-Hsien Wu, Samuel Lockhart, Lawrence J Coppey, Anja Pfenninger, Chong Wee Liew, Guifen Qiang, Alison M Burkart, Stephanie Hastings, David Pober, Christopher Cahill, Monika A Niewczas, William J Israelsen, Liane Tinsley, Isaac E Stillman, Peter S Amenta, Edward P Feener, Matthew G Vander Heiden, Robert C Stanton, George L King
Diabetic nephropathy (DN) is a major cause of end-stage renal disease, and therapeutic options for preventing its progression are limited. To identify novel therapeutic strategies, we studied protective factors for DN using proteomics on glomeruli from individuals with extreme duration of diabetes (ł50 years) without DN and those with histologic signs of DN. Enzymes in the glycolytic, sorbitol, methylglyoxal and mitochondrial pathways were elevated in individuals without DN. In particular, pyruvate kinase M2 (PKM2) expression and activity were upregulated...
April 24, 2017: Nature Medicine
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