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https://www.readbyqxmd.com/read/28735097/protecting-the-heart-through-mk2-modulation-toward-a-role-in-diabetic-cardiomyopathy-and-lipid-metabolism
#1
REVIEW
Matthieu Ruiz, Lise Coderre, Bruce Gordon Allen, Christine Des Rosiers
Various signaling pathways have been identified in the heart as important players during development, physiological adaptation or pathological processes. This includes the MAPK families, particularly p38MAPK, which is involved in several key cellular processes, including differentiation, proliferation, apoptosis, inflammation, metabolism and survival. Disrupted p38MAPK signaling has been associated with several diseases, including cardiovascular diseases (CVD) as well as diabetes and its related complications...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28734639/ffa4-gpr120-pharmacology-and-therapeutic-opportunities
#2
REVIEW
Graeme Milligan, Elisa Alvarez-Curto, Brian D Hudson, Rudi Prihandoko, Andrew B Tobin
Free Fatty Acid receptor 4 (FFA4), also known as GPR120, is a G-protein-coupled receptor (GPCR) responsive to long-chain fatty acids that is attracting considerable attention as a potential novel therapeutic target for the treatment of type 2 diabetes mellitus (T2DM). Although no clinical studies have yet been initiated to assess efficacy in this indication, a significant number of primary publications and patents have highlighted the ability of agonists with potency at FFA4 to improve glucose disposition and enhance insulin sensitivity in animal models...
July 19, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28733937/sequential-extraction-as-novel-approach-to-compare-12-medicinal-plants-from-kenya-regarding-their-potential-to-release-chromium-manganese-copper-and-zinc
#3
R Mogwasi, S Zor, D K Kariuki, M Z Getenga, V Nischwitz
This study is focusing on a novel approach to screen a large number of medicinal plants from Kenya regarding their contents and availability of selected metals potentially relevant for treatment of diabetes patients. For this purpose, total levels of zinc, chromium, manganese, and copper were determined by flame atomic absorption spectrometry and inductively coupled plasma mass spectrometry as well as BCR sequential extraction to fractionate the elemental species in anti-diabetic medicinal plants collected from five natural locations in two sub counties in Nyamira County, Kenya...
July 21, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28733465/the-retinol-binding-protein-receptor-stra6-regulates-diurnal-insulin-responses
#4
Christy M Gliniak, J Mark Brown, Noa Noy
It has long been appreciated that insulin action is closely tied to circadian rhythms. However, mechanisms that dictate diurnal insulin sensitivity in metabolic tissues are not well understood. Retinol binding protein 4 (RBP4) has been implicated as a driver of insulin resistance in rodents and humans, and has become an attractive drug target in type 2 diabetes. RBP4 is synthesized primarily in the liver where it binds retinol and transports it to tissues throughout the body. The retinol-RBP4 complex (holo-RBP) can be recognized by a cell surface receptor known as stimulated by retinoic acid 6 (STRA6) which transports retinol into cells...
July 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28731155/marine-collagen-peptides-reduce-endothelial-cell-injury-in-diabetic-rats-by-inhibiting-apoptosis-and-the-expression-of-coupling-factor-6-and-microparticles
#5
Cuifeng Zhu, Wei Zhang, Jianguo Liu, Bo Mu, Fan Zhang, Nannan Lai, Jianxin Zhou, Aimin Xu, Yong Li
The present study aimed to elucidate the role of marine collagen peptides (MCPs) in protection of carotid artery vascular endothelial cells (CAVECs) in type 2 diabetes mellitus (T2DM), and the mechanism underlying this process. In an in vivo experiment, diabetic Wistar rats were divided randomly into four groups (n=10/group): Diabetes control, and three diabetes groups administered low, medium and high doses of MCPs (2.25, 4.5 and 9.0 g/kg body weight/day, respectively). Another 10 healthy rats served as the control...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28731130/effects-of-reduced-%C3%AE-2-glycoprotein-i-on-high-glucose%C3%A2-induced-cell-death-in-huvecs
#6
Jing-Yun Zhang, Jun Ma, Pei Yu, Guang-Jie Tang, Chun-Jun Li, De-Min Yu, Qiu-Mei Zhang
Reduced β2 glycoprotein I (β2GPI) has been demonstrated to exhibit a beneficial effect in diabetic atherosclerosis and retinal neovascularization. However, the effect of reduced β2GPI on vascular disorders in diabetic mellitus (DM) remains to be elucidated. The present study established a high glucose‑induced injury model using human umbilical cords veins (HUVECs) and evaluated the protective effects of reduced β2GPI against the injury. The data demonstrated that a low concentration of reduced β2GPI (0...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28730726/changes-in-the-extracellular-matrix-surrounding-human-chronic-wounds-revealed-by-2-photon-imaging
#7
Jessica E S Sutcliffe, Christopher Thrasivoulou, Thomas E Serena, Leigh Madden, Toby Richards, Anthony R J Phillips, David L Becker
Chronic wounds are a growing problem worldwide with no effective therapeutic treatments available. Our objective was to understand the composition of the dermal tissue surrounding venous leg ulcers and diabetic foot ulcers (DFU). We used novel 2-photon imaging techniques alongside classical histology to examine biopsies from the edges of two common types of chronic wound, venous leg ulcers and DFU. Compared to normal intact skin, we found that collagen levels are significantly reduced throughout the dermis of venous leg ulcer biopsies and DFU, with a reduction in both fibril thickness and abundance...
July 20, 2017: International Wound Journal
https://www.readbyqxmd.com/read/28728107/developing-potential-agents-against-atherosclerosis-design-synthesis-and-pharmacological-evaluation-of-novel-dual-inhibitors-of-oxidative-stress-and-squalene-synthase-activity
#8
Maria G Katselou, Alexios N Matralis, Angeliki P Kourounakis
For the treatment of multifactorial and complex diseases, it has become increasingly apparent that compounds acting at multiple targets often deliver superior efficacy compared to compounds with high specificity for only a single target. Based on previous studies demonstrating the important antioxidant and anti-hyperlipidemic effect of morpholine and 1,4-benzo(x/thi)azine derivatives (A-E), we hereby present the design, synthesis and pharmacological evaluation of novel dual-acting molecules as a therapeutic approach for atherosclerosis...
June 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28726759/high-resolution-inhibition-profiling-combined-with-hplc-hrms-spe-nmr-for-identification-of-ptp1b-inhibitors-from-vietnamese-plants
#9
Binh Thi Dieu Trinh, Anna K Jäger, Dan Staerk
Protein tyrosine phosphatase 1B (PTP1B) plays a key role as a negative regulator in insulin signal transduction by deactivating the insulin receptor. Thus, PTP1B inhibition has emerged as a potential therapeutic strategy for curing insulin resistance. In this study, 40 extracts from 18 different plant species were investigated for PTP1B inhibitory activity in vitro. The most promising one, the EtOAc extract of Ficus racemosa, was investigated by high-resolution PTP1B inhibition profiling combined with HPLC-HRMS-SPE-NMR analysis...
July 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28726377/a-novel-targeted-mass-spectrometry-approach-enabled-discov-ery-of-o-glycosylated-insulin-and-related-signaling-peptides-in-mouse-and-human-pancreatic-islets
#10
Qing Yu, Alejandra Canales, Matthew S Glover, Rahul Das, Xudong Shi, Yang Liu, Mark P Keller, Alan D Attie, Lingjun Li
O-linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. Despite growing interest in glycoproteins, little attention has been directed to glycosylated signaling peptides, largely due to lack of enabling analytical tools. Here we explore the occurrence of naturally O-linked glycosylation on the signaling peptides extracted from mouse and human pancreatic islets using mass spectrometry (MS). A novel targeted MS-based method is developed to increase the likelihood of capturing these modified signaling peptides and to provide improved sequence coverage and accurate glycosite localization, enabling the first large-scale discovery of O-glycosylation on signaling peptides...
July 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28725914/vascular-complications-in-diabetes-old-messages-new-thoughts
#11
REVIEW
Josephine M Forbes, Amelia K Fotheringham
In parallel with the growing diabetes pandemic, there is an increasing burden of micro- and macrovascular complications, occurring in the majority of patients. The identification of a number of synergistic accelerators of disease, providing therapeutic pathways, has stabilised the incidence of complications in most western nations. However, the primary instigators of diabetic complications and, thus, prevention strategies, remain elusive. This has necessitated a refocus on natural history studies, where tissue and plasma samples are sequentially taken to determine when and how disease initiates...
July 19, 2017: Diabetologia
https://www.readbyqxmd.com/read/28723729/wnt-signaling-in-cardiovascular-disease-opportunities-and-challenges
#12
Austin Gay, Dwight A Towler
PURPOSE OF REVIEW: Cardiometabolic diseases increasingly afflict our aging, dysmetabolic population. Complex signals regulating low-density lipoprotein receptor-related protein (LRP) and frizzled protein family members - the plasma membrane receptors for the cadre of Wnt polypeptide morphogens - contribute to the control of cardiovascular homeostasis. RECENT FINDINGS: Both canonical (β-catenin-dependent) and noncanonical (β-catenin-independent) Wnt signaling programs control vascular smooth muscle (VSM) cell phenotypic modulation in cardiometabolic disease...
July 18, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28723636/redox-dependent-modulation-of-metformin-contributes-to-enhanced-sensitivity-of-esophageal-squamous-cell-carcinoma-to-cisplatin
#13
Pin Dong Li, Zhao Liu, Tian Tian Cheng, Wen Guang Luo, Jing Yao, Jing Chen, Zhen Wei Zou, Li Li Chen, Charlie Ma, Xiao Fang Dai
Glutathione is the major intracellular anti-oxidant against reactive oxygen species and serves as a detoxification essential. The anti-diabetic drug metformin has been showed to exert anti-tumor activity via modulation of redox homeostasis. In this study, we provided evidence that metformin inhibits proliferation and induces apoptosis of esophageal squamous cancer cells. Importantly, we found that metformin acts as pro-oxidant via depletion of intracellular glutathione. Co-treatment with metformin reversed the elevated intracellular glutathione induced by cisplatin and therefore enhanced the sensitivity to cisplatin in vitro and in vivo...
July 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28721687/practical-approach-to-initiating-sglt2-inhibitors-in-type-2-diabetes
#14
REVIEW
Fernando Gomez-Peralta, Cristina Abreu, Albert Lecube, Diego Bellido, Alfonso Soto, Cristóbal Morales, Miguel Brito-Sanfiel, Guillermo Umpierrez
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are an attractive novel therapeutic option for the treatment of type 2 diabetes. They block the reabsorption of filtered glucose in kidneys, mainly in proximal renal tubules, resulting in increased urinary glucose excretion and correction of the diabetes-related hyperglycemia. Beyond improving glucose control, SGLT2 inhibitors offer potential benefits by reducing body weight and blood pressure. On the basis of the efficacy demonstrated in clinical trials, SGLT2 inhibitors are recommended as second- or third-line agents for the management of patients with type 2 diabetes...
July 18, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28721656/circrna-a-novel-type-of-biomarker-for-cancer
#15
REVIEW
He-da Zhang, Lin-Hong Jiang, Da-Wei Sun, Jun-Chen Hou, Zhen-Ling Ji
Circular RNAs (circRNAs) are a class of long, non-coding RNAs molecules that shape a covalently closed continuous loop which have no 5'-3' polarity and contain no polyA tail. CircRNAs also possess relatively jarless framework and are highly tissue-specific expressed in the eukaryotic transcriptome. Emerging evidences have discovered that thousands of endogenous circRNAs are present in mammalian cells and they mediate gene expression at the transcriptional or post-transcriptional level by binding to microRNAs or other molecules and then inhibit their function...
July 18, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28721575/gastroparesis-medical-and-therapeutic-advances
#16
REVIEW
Christopher M Navas, Nihal K Patel, Brian E Lacy
Gastroparesis is a chronic, bothersome, and often disabling neuromuscular disorder of the upper gastrointestinal tract. The most frequently reported symptoms of gastroparesis include nausea, vomiting, epigastric pain, early satiety, and unintentional weight loss. Etiologies of gastroparesis include diabetes, connective tissue disorders, prior infection, mesenteric ischemia, and post-surgical complications. The largest category of gastroparesis patients is comprised of those in whom no definitive cause can be identified (idiopathic gastroparesis)...
July 18, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28721137/beneficial-effects-of-n-3-polyunsaturated-fatty-acids-on-adiponectin-levels-and-adipor-gene-expression-in-patients-with-type-2-diabetes-mellitus-a-randomized-placebo-controlled-double-blind-clinical-trial
#17
Maryam Mazaherioun, Ahmad Saedisomeolia, Mohammad Hassan Javanbakht, Fariba Koohdani, Mohammad Reza Eshraghian, Mahmoud Djalali
INTRODUCTION: There is evidence that n-3 polyunsaturated fatty acids (n-3 PUFAs) exert beneficial effects to improve type 2 diabetes mellitus (T2DM), but its complications remain poorly understood. Hypoadiponectinemia is one of the important mechanisms responsible for T2DM which necessitates developing novel therapeutic strategies. We aimed to determine the effect of n-3 PUFA supplementation on circulating adiponectin and mRNA expression of adiponectin receptors (AdipoR1, AdipoR2) and Sirt-1 in T2DM patients...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28716572/dpph-hplc-ms-assisted-rapid-identification-of-endothelial-protective-substances-from-xiao-ke-an
#18
Zhenzhong Yang, Zhenhao Li, Zheng Li
ETHNOPHARMACOLOGICAL RELEVANCE: Xiao-Ke-An formula (XKA) is a Chinese medicine widely used for treating diabetes and associated complications. Endothelial protection is thought to be one of its therapeutic mechanisms. However, the protective effect of XKA on endothelial cells remains unclear, especially in oxidative injury induced endothelial dysfunction. MATERIALS AND METHODS: A novel strategy to rapidly screen and identify potential endothelial protective substances from XKA was established by combining the 2,2'-diphenyl-1-picrylhydrazyl high performance liquid chromatography coupled with mass spectrometry (DPPH-HPLC-MS) approach with cell-based verification...
July 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28714336/specific-plasma-oxylipins-increase-the-odds-of-cardiovascular-and-cerebrovascular-events-in-patients-with-peripheral-artery-disease
#19
Stephanie Caligiuri, Harold M Aukema, Amir Ravandi, Renee Lavallee, Randolph Guzman, Grant N Pierce
Oxylipins and fatty acids may be novel therapeutic targets for cardiovascular disease. The objective was to determine if plasma oxylipins or fatty acids can influence the odds of cardiovascular/cerebrovascular events. In 98 patients (25 female, 73 male) with peripheral artery disease, the prevalence of transient ischemic attacks, cerebrovascular accidents, stable angina and acute coronary syndrome was n= 16, 10, 16, and 24, respectively. Risk factors such as being male, diagnosed hypertension, diabetes mellitus, and hyperlipidemia were not associated with events...
July 15, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28713160/pathogenic-roles-of-microvesicles-in-diabetic-retinopathy
#20
REVIEW
Wei Zhang, Song Chen, Ming-Lin Liu
Diabetic retinopathy (DR) is a common complication of diabetes and has been recognized as the leading cause of blindness in adults. Several interrelated molecular pathways are involved in the development of DR. Microvesicles (MVs) are cell membrane vesicles, which carry many biologic molecules, such as mRNAs, microRNAs, transcription factors, membrane lipids, membrane receptors, and other proteins. They may be involved in intercellular communication that can promote inflammation, angiogenesis, and coagulation...
July 17, 2017: Acta Pharmacologica Sinica
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