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https://www.readbyqxmd.com/read/28544245/ghrelin-receptor-inverse-agonists-as-a-novel-therapeutic-approach-against-obesity-related-metabolic-disease
#1
Kathrin Abegg, Lara Bernasconi, Melanie Hutter, Lynda Whiting, Claudio Pietra, Claudio Giuliano, Thomas A Lutz, Thomas Riediger
AIMS: Ghrelin is implicated in the control of energy balance and glucose homeostasis. The ghrelin receptor exhibits ligand independent constitutive activity, which can be pharmacologically exploited to induce inverse ghrelin actions. Since ghrelin receptor inverse agonists (GHSR-IA) might be effective for the treatment of obesity-related metabolic disease, we tested two novel synthetic compounds GHSR-IA1 and GHSR-IA2. MATERIALS AND METHODS: In functional cell assays, electrophysiogical and immunohistochemical experiments, we demonstrated inverse agonist activity for GHSR-IA1 and GHSR-IA2...
May 24, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28543947/%C3%AE-1-adrenoceptor-but-not-%C3%AE-2-adrenoceptor-subtype-regulates-heart-rate-in-type-2-diabetes-rats-in-vivo
#2
Rosalind F Cook, Carol T Bussey, Kimberley M Mellor, Patricia A Cragg, Regis R Lamberts
BACKGROUND: β-Adrenoceptor blockers are widely used to reduce heart rate, the strongest predictor of mortality in cardiac patients, but are less effective in diabetic patients. This study aimed to determine the specific β1 - and β2 -adrenoceptor subtype contributions to chronotropic responses in type 2 diabetes in vivo, which are currently unknown. METHODS: Type 2 diabetic and non-diabetic rats were implanted with radio-telemeters to measure arterial blood pressure and derive heart rate under conscious conditions...
May 22, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28541811/future-drug-discovery-in-renin-angiotensin-aldosterone-system-intervention
#3
Maria Tamargo, Juan Tamargo
Renin-angiotensin- aldosterone system inhibitors (RAASIs), including angiotensin-converting enzyme inhibitors, angiotensin AT1 receptor blockers and mineralocorticoid receptor antagonists (MRAs), are the cornerstone for the treatment of cardiovascular and renal diseases. Areas covered: The authors searched MEDLINE, PubMed and ClinicalTrials.gov to identify eligible full-text English language papers. Herein, the authors discuss AT2-receptor agonists and ACE2/angiotensin-(1- 7)/Mas-receptor axis modulators, direct renin inhibitors, brain aminopeptidase A inhibitors, biased AT1R blockers, chymase inhibitors, multitargeted drugs, vaccines and aldosterone receptor antagonists as well as aldosterone synthase inhibitors...
May 25, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28540676/micrornas-biomarkers-diagnostics-and-therapeutics
#4
Weili Huang
MicroRNAs (miRNAs) are small noncoding RNAs (21-23 nucleotides in length) that regulate gene expression at translational or posttranslational levels. The major regulatory mechanisms include translational repression or mRNA degradation (Filipowicz et al., Curr Opin Struct Biol 15:331-341, 2005).Aberrant expression of miRNAs has been found to be associated with a variety of human diseases such as cancers/tumors, diabetes, viral infections, cardiovascular diseases, neurodegenerative diseases, and other diseases (Wang et al...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28540228/research-in-pharmacotherapy-for-erectile-dysfunction
#5
REVIEW
Ji-Kan Ryu, Jun-Kyu Suh, Arthur L Burnett
Although oral phosphodiesterase-5 (PDE5) inhibitors are generally accepted as an effective therapy for erectile dysfunction (ED), men with ED from diabetes or radical prostatectomy respond poorly to these drugs. Many researchers have tried to develop novel therapeutics that target alternative molecular pathways. A group of therapeutics belongs to centrally acting agents that target dopamine and melanocortin receptors. The other one is the peripherally acting agents that target soluble guanylate cyclase, Rho-kinase pathway, and Maxi-K channel, etc...
April 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28540143/association-between-coronary-artery-disease-and-microrna-literature-review-and-clinical-perspective
#6
Rehan Malik, Raja S Mushtaque, Usman A Siddiqui, Adnan Younus, Muhammad A Aziz, Choudhry Humayun, Kanaan Mansoor, Muhammad A Latif, Salman Waheed, Salman Assad, Idrees Khan, Syed M Bukhari, Daniel DelCampo, Ali Adus, Swetha Gannarapu
BACKGROUND: Until recently, circulating micro-RNAs (miRNAs) have attracted major interest as novel biomarkers for the early diagnosis of coronary artery disease (CAD). This review article summarizes the available evidence on the correlation of micro-RNAs with both the clinical and subclinical coronary artery disease and highlights the necessity for exploring miRNAs as a potential diagnostic and prognostic biomarker of early CAD in an adult population. METHODS: A systematic literature analysis and retrieval online systems Public/Publisher MEDLINE/ Excerpta Medica Database /Medical Literature Analysis and Retrieval System Online,(PUBMED/EMBASE/MEDLINE) search were conducted for relevant information...
April 23, 2017: Curēus
https://www.readbyqxmd.com/read/28536423/fam3b-mediates-high-glucose-induced-vascular-smooth-muscle-cell-proliferation-and-migration-via-inhibition-of-mir-322-5p
#7
Wenxiang Zhang, Siyu Chen, Zhao Zhang, Chen Wang, Chang Liu
The proliferation and migration of vascular smooth muscle cells (VSMCs) play an essential role during the development of cardiovascular diseases (CVDs). While many factors potentially contribute to the abnormal activation of VSMCs, hyperglycemia is generally believed to be a major causative factor. On the other hand, FAM3B (named PANDER for its secretory form) is a uniquely structured protein strongly expressed within and secreted from the endocrine pancreas. FAM3B is co-secreted with insulin from the β-cell upon glucose stimulation and regulates glucose homeostasis...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28534138/a-chemically-modified-curcumin-cmc-2-24-inhibits-nuclear-factor-%C3%AE%C2%BAb-activation-and-inflammatory-bone-loss-in-murine-models-of-lps-induced-experimental-periodontitis-and-diabetes-associated-natural-periodontitis
#8
Muna S Elburki, Carlos Rossa, Morgana R Guimarães-Stabili, Hsi-Ming Lee, Fabiana A Curylofo-Zotti, Francis Johnson, Lorne M Golub
The purpose of this study was to assess the effect of a novel chemically modified curcumin (CMC 2.24) on NF-κB and MAPK signaling and inflammatory cytokine production in two experimental models of periodontal disease in rats. Experimental model I: Periodontitis was induced by repeated injections of LPS into the gingiva (3×/week, 3 weeks); control rats received vehicle injections. CMC 2.24, or the vehicle, was administered by daily oral gavage for 4 weeks. Experimental model II: Diabetes was induced in adult male rats by streptozotocin injection; periodontal breakdown then results as a complication of uncontrolled hyperglycemia...
May 22, 2017: Inflammation
https://www.readbyqxmd.com/read/28529328/perivascular-adipose-tissue-epiphenomenon-or-local-risk-factor
#9
REVIEW
K Schäfer, I Drosos, S Konstantinides
Obesity is associated with an increased cardiovascular risk, but the mechanisms underlying the link between increased body weight and vascular disease are incompletely understood. Over the past 15 years, perivascular adipose tissue has emerged as active component of the vessel wall involved in vascular homeostasis. However, perivascular adipose tissue can adopt detrimental properties under the influence of obesity and other factors and contribute actively to the pathophysiology of cardiovascular disease. Conversely, changes of the vessel wall may negatively affect perivascular adipose tissue qualities...
May 22, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28529319/therapeutic-targeting-of-the-angiopoietin-tie-pathway
#10
REVIEW
Pipsa Saharinen, Lauri Eklund, Kari Alitalo
The endothelial angiopoietin (ANG)-TIE growth factor receptor pathway regulates vascular permeability and pathological vascular remodelling during inflammation, tumour angiogenesis and metastasis. Drugs that target the ANG-TIE pathway are in clinical development for oncological and ophthalmological applications. The aim is to complement current vascular endothelial growth factor (VEGF)-based anti-angiogenic therapies in cancer, wet age-related macular degeneration and macular oedema. The unique function of the ANG-TIE pathway in vascular stabilization also renders this pathway an attractive target in sepsis, organ transplantation, atherosclerosis and vascular complications of diabetes...
May 19, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28528753/healthcare-access-and-quality-index-based-on-mortality-from-causes-amenable-to-personal-health-care-in-195-countries-and-territories-1990-2015-a-novel-analysis-from-the-global-burden-of-disease-study-2015
#11
(no author information available yet)
BACKGROUND: National levels of personal health-care access and quality can be approximated by measuring mortality rates from causes that should not be fatal in the presence of effective medical care (ie, amenable mortality). Previous analyses of mortality amenable to health care only focused on high-income countries and faced several methodological challenges. In the present analysis, we use the highly standardised cause of death and risk factor estimates generated through the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to improve and expand the quantification of personal health-care access and quality for 195 countries and territories from 1990 to 2015...
May 18, 2017: Lancet
https://www.readbyqxmd.com/read/28526214/high-glucose-environment-induced-intracellular-o-glcnac-glycosylation-and-reduced-galectin-7-expression-in-keratinocytes-implications-on-impaired-diabetic-wound-healing
#12
Shu-Mei Huang, Ching-Shuang Wu, Min-Hsi Chiu, Hui-Jun Yang, Gwo-Shing Chen, Cheng-Che E Lan
BACKGROUND: Diabetes is an important global health issue due to its increasing prevalence and association with various complications. Impaired wound healing is a serious complication associated with diabetes that frequently results in infection and amputation. Galectin-7 (Gal-7) has been reported to play an important role during skin wound healing. Previously, we had demonstrated that high glucose environment alters physiologic functions of keratinocytes and contributes to impaired wound healing in diabetic condition...
April 30, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28525362/fgf21-receptor-agonists-an-emerging-therapeutic-class-for-obesity-related-diseases
#13
Junichiro Sonoda, Mark Z Chen, Amos Baruch
Fibroblast growth factor 21 (FGF21) analogs and FGF21 receptor agonists (FGF21RAs) that mimic FGF21 ligand activity constitute the new "FGF21-class" of anti-obesity and anti-diabetic molecules that improve insulin sensitivity, ameliorate hepatosteatosis and promote weight loss. The metabolic actions of FGF21-class proteins in obese mice are attributed to stimulation of brown fat thermogenesis and increased secretion of adiponectin. The therapeutic utility of this class of molecules is being actively investigated in clinical trials for the treatment of type 2 diabetes and non-alcoholic steatohepatitis (NASH)...
May 19, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28522407/high-throughput-screening-and-bioinformatic-analysis-to-ascertain-compounds-that-prevent-saturated-fatty-acid-induced-%C3%AE-cell-apoptosis
#14
Seung-Hee Lee, Daniel Cunha, Carlo Piermarocchi, Giovanni Paternostro, Anthony Pinkerton, Laurence Ladriere, Piero Marchetti, Decio L Eizirik, Miriam Cnop, Fred Levine
Pancreatic β-cell lipotoxicity is a central feature of the pathogenesis of type 2 diabetes. To study the mechanism by which fatty acids cause β-cell death and develop novel approaches to prevent it, a high-throughput screen on the β-cell line INS1 was carried out. The cells were exposed to palmitate to induce cell death and compounds that reversed palmitate-induced cytotoxicity were ascertained. Hits from the screen were analyzed by an increasingly more stringent testing funnel, ending with studies on primary human islets treated with palmitate...
May 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28521289/role-of-transgelin-2-in-diabetes-associated-pancreatic-ductal-adenocarcinoma
#15
Yan Sun, Weiwei He, Man Luo, Yuhong Zhou, Guilin Chang, Weiying Ren, Kefen Wu, Xi Li, Jiping Shen, Xiaoping Zhao, Yu Hu
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis. Diabetes is a significant risk factor for PDAC and >50% of PDAC patients have concomitant diabetes. How diabetes influences the initiation and progression of PDAC remains elusive. Here, we show that transgelin-2 is dominantly expressed in PDAC tissues compared with adjacent normal tissues. The high level of transgelin-2 indicates poor survival of patients with PDAC. Remarkably, transgelin-2 expression is correlated with diabetic status...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28520942/emerging-roles-for-micrornas-in-diabetic-microvascular-disease-novel-targets-for-therapy
#16
Yu Zhang, Xinghui Sun, Basak Icli, Mark W Feinberg
Chronic, low-grade systemic inflammation and impaired microvascular function are critical hallmarks in the development of insulin resistance. Accordingly, insulin resistance is a major risk factor for type 2 diabetes and cardiovascular disease. Accumulating studies demonstrate that restoration of impaired function of the diabetic macro- and microvasculature may ameliorate a range of cardiovascular disease states and diabetes-associated complications. In this review, we focus on the emerging role of microRNAs (miRNAs), noncoding RNAs that fine-tune target gene expression and signaling pathways, in insulin-responsive tissues and cell types important for maintaining optimal vascular homeostasis and preventing the sequelae of diabetes-induced end organ injury...
April 1, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28520887/apolipoprotein-c-iii-and-high-density-lipoprotein-subspecies-defined-by-apolipoprotein-c-iii-in-relation-to-diabetes-risk
#17
Sarah A Aroner, Ming Yang, Junlong Li, Jeremy D Furtado, Frank M Sacks, Anne Tjønneland, Kim Overvad, Tianxi Cai, Majken K Jensen
Apolipoprotein C-III (apoC-III) is a potential novel biomarker that may play an important role in the pathogenesis of diabetes, particularly when present on high-density lipoprotein (HDL). In a case-cohort design among 3,101 non-cases and 434 incident diabetes cases occurring before 2007 in the Danish Diet, Cancer, and Health study, we examined associations of baseline (1993-1997) plasma concentrations of apoC-III and subspecies of HDL defined by the presence or absence of apoC-III with risk of diabetes using Cox regression...
May 18, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28514232/ppar%C3%AE-agonists-attenuate-trigeminal-neuropathic-pain
#18
Danielle N Lyons, Liping Zhang, Robert J Danaher, Craig S Miller, Karin N Westlund
The aim of this study is to investigate the role of peroxisome proliferator-activated receptor-gamma isoform (PPARγ), in trigeminal neuropathic pain utilizing a novel mouse trigeminal inflammatory compression (TIC) injury model. The study determined that the PPARγ nuclear receptor plays a significant role in trigeminal nociception transmission, evidenced by: (1) Intense PPARγ immunoreactivity is expressed 3 weeks after TIC nerve injury in the spinal trigeminal caudalis, the termination site of trigeminal nociceptive nerve fibers...
May 16, 2017: Clinical Journal of Pain
https://www.readbyqxmd.com/read/28512432/whole-body-cryotherapy-in-athletes-from-therapy-to-stimulation-an-updated-review-of-the-literature
#19
REVIEW
Giovanni Lombardi, Ewa Ziemann, Giuseppe Banfi
Nowadays, whole-body cryotherapy is a medical physical treatment widely used in sports medicine. Recovery from injuries (e.g., trauma, overuse) and after-season recovery are the main purposes for application. However, the most recent studies confirmed the anti-inflammatory, anti-analgesic, and anti-oxidant effects of this therapy by highlighting the underlying physiological responses. In addition to its therapeutic effects, whole-body cryotherapy has been demonstrated to be a preventive strategy against the deleterious effects of exercise-induced inflammation and soreness...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28507818/screening-of-a-natural-compound-library-identifies-emodin-a-natural-compound-from-rheum-palmatum-linn-that-inhibits-dpp4
#20
Zhaokai Wang, Longhe Yang, Hu Fan, Peng Wu, Fang Zhang, Chao Zhang, Wenjie Liu, Min Li
Historically, Chinese herbal medicines have been widely used in the treatment of hyperglycemia, but the mechanisms underlying their effectiveness remain largely unknown. Here, we screened a compound library primarily comprised of natural compounds extracted from herbs and marine organisms. The results showed that emodin, a natural compound from Rheum palmatum Linn, inhibited DPP4 activity with an in vitro IC50 of 5.76 µM without inhibiting either DPP8 or DPP9. A docking model revealed that emodin binds to DPP4 protein through Glu205 and Glu206, although with low affinity...
2017: PeerJ
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