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https://www.readbyqxmd.com/read/29155147/selective-and-membrane-permeable-small-molecule-inhibitors-of-nicotinamide-n-methyltransferase-reverse-high-fat-diet-induced-obesity-in-mice
#1
Harshini Neelakantan, Virginia Vance, Michael D Wetzel, Hua-Yu Leo Wang, Stanton F McHardy, Celeste C Finnerty, Jonathan D Hommel, Stanley J Watowich
There is a critical need for new mechanism-of-action drugs that reduce the burden of obesity and associated chronic metabolic comorbidities. A potentially novel target to treat obesity and type 2 diabetes is nicotinamide-N-methyltransferase (NNMT), a cytosolic enzyme with newly identified roles in cellular metabolism and energy homeostasis. To validate NNMT as an anti-obesity drug target, we investigated the permeability, selectivity, mechanistic, and physiological properties of a series of small molecule NNMT inhibitors...
November 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29154802/microrna-profiling-in-mda-mb-231-human-breast-cancer-cell-exposed-to-the-phaleria-macrocarpa-boerl-fruit-ethyl-acetate-fraction-pmeaf-through-iilumina-hi-seq-technologies-and-various-in-silico-bioinformatics-tools
#2
Nowroji Kavitha, Soundararajan Vijayarathna, Shanmugapriya, Chern Ein Oon, Yeng Chen, Jagat R Kanwar, Vasu Punj, Sreenivasan Sasidharan
ETHNOPHARMACOLOGICAL RELEVANCE: Phaleria macrocarpa (Scheff) Boerl, is a famous traditional medicinal plant which exhibited cytotoxicity against various cancerous cells. Traditionally, P. macrocarpa has been used to control cancer, impotency, hemorrhoids, diabetes mellitus, allergies, liver and heart disease, kidney disorders, blood diseases, acne, stroke, migraine, and various skin diseases. AIM OF THE STUDY: Recent studies have demonstrated a potent anticancer potential of P...
November 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29149824/gene-therapy-and-retinal-diseases
#3
Claudio Campa, Carla Enrica Gallenga, Elena Bolletta, Paolo Perri
Background Gene therapy represents the therapeutic delivery of nucleic acid polymers into a patient's cells with the aim of treating an underlying disease. Over the past 2 decades this new therapy has made substantial progress owing to better understanding of the pathobiologic basis of various diseases coupled with growth of gene transfer biotechnologies. The eye, in particular, represents a suitable target for such therapy due to the immune privilege provided by the blood-ocular barrier, the ability to directly visualize, access and locally treat the cells and the minimal amount of vector needed given the size of this organ...
November 16, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/29142980/effectiveness-of-multifaceted-care-approach-on-adverse-clinical-outcomes-in-nondiabetic-ckd-a-systematic-review-and-meta-analysis
#4
Aminu K Bello, Bilal Qarni, Arian Samimi, Julius Okel, Trish Chatterley, Ikechi G Okpechi, Ben Vandermeer, Branko Braam
Introduction: The risk of major adverse events associated with chronic kidney disease (CKD) could potentially be reduced with effective medical interventions. The impact of multifaceted interventions as compared with usual care in patients with nondiabetic CKD is unclear. We performed a systematic review to analyze the impact of multifaceted interventions on reducing the risk of major adverse events in this population. Methods: Systematic review and meta-analysis...
July 2017: KI Reports
https://www.readbyqxmd.com/read/29140125/diabetes-area-patent-participation-analysis-part-ii-years-2011-2016
#5
Markus Boehm, Matthew Crawford, Jamie E Moscovitz, Philip A Carpino
Diabetes is a metabolic disease characterized by elevated levels of plasma glucose. When untreated, diabetes increases the risk of developing co-morbidities such as cardiovascular disease. Several drugs, often used as part of combination therapies, have been approved to treat the disease, but these drugs will eventually fail to effectively control blood glucose levels, at which point insulin replacement therapy is required. A medical need exists for new anti-diabetic drugs that exhibit good efficacy with improved safety/toleration profiles and can be added on top of existing therapies, or that can provide additional benefits beyond glucose lowering such as pancreatic beta (β)-cell protection...
November 15, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/29137966/clinical-outcomes-of-complex-real-world-diabetic-patients-treated-with-amphilimus-sirolimus-eluting-stents-or-zotarolimus-eluting-stents-a-single-center-registry
#6
Rik Rozemeijer, Daniela Benedetto, Adriaan O Kraaijeveld, Michiel Voskuil, Mèra Stein, Leo Timmers, Saskia Z Rittersma, Pierfrancesco Agostoni, Pieter A Doevendans, Pieter R Stella
OBJECTIVE: To assess clinical outcomes of Amphilimus Sirolimus-Eluting Stents (A-SES) as compared to Zotarolimus-Eluting Stents (ZES) in complex real-world diabetic patients. BACKGROUND: Patients with diabetes mellitus represent one of the most challenging scenarios with high rates of restenosis and stent thrombosis in the current era of drug-eluting stents. Hence, we assessed the safety of A-SES versus ZES in complex diabetic patients. METHODS: In this observational study, we analyzed all consecutive patients with diabetes mellitus referred to our center from November 2012 to November 2014...
October 26, 2017: Cardiovascular Revascularization Medicine: Including Molecular Interventions
https://www.readbyqxmd.com/read/29137713/trpv1-a-potential-therapeutic-target-in-type-2-diabetes-and-comorbidities
#7
REVIEW
Dorte X Gram, Jens J Holst, Arpad Szallasi
With an estimated 422 million affected patients worldwide in 2016, type 2 diabetes (T2D) has reached pandemic proportions and represents a major unmet medical need. T2D is a polygenic disease with a chronic, low-grade inflammatory component. Second-generation transient receptor potential vanilloid-1 (TRPV1) antagonists are potent anti-inflammatory agents with proven clinical safety. In rodent models of T2D, TRPV1 blockade was shown to halt disease progression and improve glucose metabolism. Thus, we propose that TRPV1 antagonists merit further study as novel therapeutic approaches to potentially treat T2D and its comorbidities...
November 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29134229/decursin-and-decursinol-angelate-molecular-mechanism-and-therapeutic-potential-in-inflammatory-diseases
#8
REVIEW
Adeeb Shehzad, Sajida Parveen, Munibah Qureshi, Fazli Subhan, Young Sup Lee
Epidemiological studies have shown that inflammation plays a critical role in the development and progression of various chronic diseases, including cancers, neurological diseases, hepatic fibrosis, diabetic retinopathy, and vascular diseases. Decursin and decursinol angelate (DA) are pyranocoumarin compounds obtained from the roots of Angelica gigas. Several studies have described the anti-inflammatory effects of decursin and DA. Decursin and DA have shown potential anti-inflammatory activity by modulating growth factors such as vascular endothelial growth factor, transcription factors such as signal transducer and activator of transcription 3 and nuclear factor kappa-light-chain-enhancer of activated B cells, cellular enzymes including matrix metalloproteinases cyclooxygenase, and protein kinases such as extracellular receptor kinase, phosphatidylinositol-3-kinase, and protein kinase C...
November 13, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29133778/glucagon-like-peptide-1-glp-1-receptor-agonist-liraglutide-alters-bone-marrow-exosome-mediated-mirna-signal-pathways-in-ovariectomized-rats-with-type-2-diabetes
#9
Jin Li, Ling-Zhi Fu, Lu Liu, Fen Xie, Ru-Chun Dai
BACKGROUND Compared with normal postmenopausal women, estrogen deficiency and hyperglycemia in postmenopausal women with type 2 diabetes (T2DM) lead to more severe bone property degradation. Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has been reported to improve bone condition among people with T2DM but the precise mechanisms remain unclear. Exosomes work as mediators in cell-to-cell communication, delivering functional miRNAs between cells. We aimed to explore the role of exosomes in T2DM-related bone metabolic disorders and the bone protective mechanisms of liraglutide...
November 14, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29133606/effects-of-bariatric-surgery-in-obese-patients-with-hypertension-the-gateway-randomized-trial-gastric-bypass-to-treat-obese-patients-with-steady-hypertension
#10
Carlos Aurelio Schiavon, Angela Cristine Bersch-Ferreira, Eliana Vieira Santucci, Juliana Dantas Oliveira, Camila Ragne Torreglosa, Priscila Torres Bueno, Julia Caldas Frayha, Renato Nakagawa Santos, Lucas Petri Damian, Patricia Malvina Noujaim, Helio Halpern, Frederico L J Monteiro, Ricardo Vitor Cohen, Carlos H Uchoa, Marcio Gonçalves de Souza, Celso Amodeo, Luiz Bortolotto, Dimas Ikeoka, Luciano F Drager, Alexandre Biasi Cavalcanti, Otavio Berwanger
BACKGROUND : Recent research efforts on bariatric surgery have focused on metabolic and diabetes mellitus resolution. Randomized trials designed to assess the impact of bariatric surgery in patients with obesity and hypertension are needed. METHODS : In this randomized, single-center, nonblinded trial, we included patients with hypertension (using ≥2 medications at maximum doses or >2 at moderate doses) and a body mass index between 30.0 and 39.9 kg/m(2) Patients were randomized to Roux-en-Y gastric bypass plus medical therapy or medical therapy alone...
November 13, 2017: Circulation
https://www.readbyqxmd.com/read/29130053/treatment-gaps-found-in-the-management-of-type-2-diabetes-at-a-community-health-centre-in-johannesburg-south-africa
#11
Yacob Pinchevsky, Neil Butkow, Tobias Chirwa, Frederick Raal
Aims: The management of cardiometabolic goals or "ABCs" (HbA1c, blood pressure (BP), and cholesterol) ultimately determines the morbidity and mortality outcomes in patients with type 2 diabetes mellitus (T2DM). We sought to determine if patients with T2DM attending an urbanized public sector community health centre (CHC) were having their ABCs measured, were treated with appropriate cardioprotective agents and finally, were achieving guideline-based targets. Methods and Results: A cross-sectional record review of 519 patients was conducted between May and August 2015...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29129773/gambogic-acid-ameliorates-diabetes-induced-proliferative-retinopathy-through-inhibition-of-the-hif-1%C3%AE-vegf-expression-via-targeting-pi3k-akt-pathway
#12
Jianyi Cui, Rui Gong, Shuiqing Hu, Ling Cai, Lei Chen
AIMS: Gambogic acid (GA) is one of active components of Chinese medicine gamboges resin. Diabetic retinopathy (DR) is a most serious microvascular complication of diabetes and also the leading cause of blindness. The aim of this study is to evaluate the beneficial effect of GA on diabetes-induced retinal angiogenesis and further explore the potential mechanisms. MATERIAL AND METHODS: High glucose (HG)-treated RF/6A cells and STZ-induced diabetic mice were used as in vitro and in vivo models...
November 9, 2017: Life Sciences
https://www.readbyqxmd.com/read/29128603/optimal-blood-pressure-control-after-coronary-events-the-challenge-remains
#13
Elise Sverre, Kari Peersen, Jan Erik Otterstad, Lars Gullestad, Joep Perk, Erik Gjertsen, Torbjørn Moum, Einar Husebye, Toril Dammen, John Munkhaugen
We identified sociodemographic, medical, and psychosocial factors associated with unfavorable blood pressure (BP) control in 1012 patients, hospitalized with myocardial infarction and/or a coronary revascularization procedure. This cross-sectional study collected data from hospital records, a comprehensive self-report questionnaire, clinical examination, and blood samples after 2-36 (mean 17) months follow-up. Forty-six percent had unfavorable BP control (≥140/90 [80 in diabetics] mm Hg) at follow-up. Low socioeconomic status and psychosocial factors did not predict unfavorable BP control...
October 28, 2017: Journal of the American Society of Hypertension: JASH
https://www.readbyqxmd.com/read/29118927/topical-insulin-accelerates-cutaneous-wound-healing-in-insulin-resistant-diabetic-rats
#14
Tianyi Yu, Min Gao, Peilang Yang, Qing Pei, Dan Liu, Di Wang, Xiong Zhang, Yan Liu
Insulin signaling defects could lead to insulin resistance in insulin target organs: typically, in the muscler, liver, and adipose tissue. We have observed that insulin accelerated diabetic wound healing in our previous works; to further elucidate the mechanism, we investigated the expression and activation of insulin and insulin-like growth factor (IGF)-1 signaling, compared insulin sensitivity in skin tissue with that in liver tissue, and also observed the regulation of insulin on inflammatory response of wounds during the healing process...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29117876/the-role-of-gender-and-anxiety-in-the-association-between-somatic-diseases-and-depression-findings-from-three-combined-epidemiological-studies-in-primary-care
#15
E Asselmann, J Venz, L Pieper, H-U Wittchen, D Pittrow, K Beesdo-Baum
AIMS: Although associations between various somatic diseases and depression are well established, findings concerning the role of gender and anxiety disorders for these associations remain fragmented and partly inconsistent. Combining data from three large-scaled epidemiological studies in primary care, we aim to investigate interactions of somatic diseases with gender and anxiety disorders in the association with depression. METHODS: Self-reported depression according to the International Classification of Diseases, Tenth Edition (ICD-10) was assessed in n = 83 737 patients from three independent studies [DETECT (Diabetes Cardiovascular Risk Evaluation: Targets and Essential Data for Commitment of Treatment), Depression-2000 and Generalized Anxiety and Depression in Primary Care (GAD-P)] using the Depression Screening Questionnaire (DSQ)...
November 9, 2017: Epidemiology and Psychiatric Sciences
https://www.readbyqxmd.com/read/29115401/inhibitors-targeting-the-sumoylation-pathway-a-patent-review-2012%C3%A2-2015-review
#16
Yanjun Zhou, Chunmei Ji, Mengda Cao, Miao Guo, Wen Huang, Weiwei Ni, Ling Meng, Haiwei Yang, Ji-Fu Wei
Small ubiquitin‑related modifier (SUMO) proteins bind to the lysine residue of target proteins to produce functionally mature proteins. The abnormal SUMOylation of certain target proteins is associated with diseases including cancer, heart disease, diabetes, arthritis, degenerative diseases and brain ischemia/stroke. Thus, there has been growing appreciation for the potential importance of the SUMO conjugation pathway as a target for treating these diseases. This review introduces the important steps in the reversible SUMOylation pathway...
November 1, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29111280/akt-activation-a-potential-strategy-to-ameliorate-insulin-resistance
#17
REVIEW
Zhengyi Zhang, Huadong Liu, Jiankang Liu
Insulin resistance is a hallmark of type 2 diabetes and obesity while the mechanism remains unclear. Current therapy to treat type 2 diabetes is metformin, the 5'-monophosphate-activated protein kinase (AMPK) activator, owing to the ability to augment peripheral glucose uptake. However, metformin also displays limitations, as AMPK activation remains intact and regular in most type 2 diabetes and metformin does not seem to facilitate peripheral insulin resistance. Evidence has shown that PI3K-Akt/PKB pathway could be induced via insulin and act as an important effector...
October 27, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29110972/patient-reported-outcomes-in-patients-with-type-2-diabetes-treated-with-dulaglutide-added-to-titrated-insulin-glargine-award-9
#18
Maria Yu, Kate Van Brunt, Zvonko Milicevic, Oralee Varnado, Kristina S Boye
PURPOSE: This 28-week, randomized, double-blind study compared a once-weekly injection of dulaglutide 1.5 mg to placebo, both added to titrated once-daily insulin glargine (with or without metformin), in patients with type 2 diabetes mellitus and inadequate glycemia control (control defined as hemoglobin A1c, ≥7% and ≤10.5%). Patient-reported outcomes were assessed as an exploratory objective to further understand patients' physical, psychological, and social aspects of well-being and injection-device experience...
October 27, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/29110801/enhanced-electrical-field-stimulated-nitrergic-and-purinergic-vasoreactivity-in-distal-vs-proximal-internal-pudendal-arteries
#19
Michael R Odom, Elena S Pak, David A Brown, Johanna L Hannan
BACKGROUND: The internal pudendal arteries (IPAs) supply blood to the penis and are highly susceptible to vascular remodeling in rodent models of diabetes, hypertension, aging, and chronic kidney disease, thus contributing to erectile dysfunction. Interestingly, vascular remodeling primarily occurs in the distal and not in the proximal IPA, suggesting distinct local physiologic signaling differences within the IPA. AIM: To examine the role of purinergic signaling and neurotransmitter release by electrical field stimulation (EFS) in the regulation of proximal and distal IPA vascular tone...
November 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/29106816/insulin-glargine-300-u-ml-is-associated-with-less-weight-gain-while-maintaining-glycemic-control-and-low-risk-of-hypoglycemia-compared-with-insulin-glargine-100-u-ml-in-an-aging-population-with-type-2-diabetes
#20
Medha N Munshi, Jasvinder Gill, Jason Chao, Elena V Nikonova, Meenakshi Patel
OBJECTIVE: Assess efficacy, hypoglycemia and weight gain in patients with type 2 diabetes (T2D) treated with insulin glargine 300 U/mL (Gla-300) or 100 U/mL (Gla-100) across different age groups. METHODS: Pooled data were generated for patients randomized to Gla-300 or Gla-100 in the EDITION 2 (NCT01499095) and 3 (NCT01676220) studies. In four age groups (<55, ≥55 to <60, ≥60 to <65, ≥65 years), glycated hemoglobin A1C (A1C), percentage of patients reaching A1C <7...
November 6, 2017: Endocrine Practice
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