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Pathophysiology diabetic injury

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https://www.readbyqxmd.com/read/28191472/suppression-of-excessive-histone-deacetylases-activity-in-diabetic-hearts-attenuates-myocardial-ischemia-reperfusion-injury-via-mitochondria-apoptosis-pathway
#1
Yang Wu, Yan Leng, Qingtao Meng, Rui Xue, Bo Zhao, Liying Zhan, Zhongyuan Xia
Background. Histone deacetylases (HDACs) play a pivotal role in signaling modification and gene transcriptional regulation that are essential for cardiovascular pathophysiology. Diabetic hearts with higher HDACs activity were more vulnerable to myocardial ischemia/reperfusion (MI/R) injury compared with nondiabetic hearts. We are curious about whether suppression of excessive HDACs activity in diabetic heart protects against MI/R injury. Methods. Diabetic rats were subjected to 45 min of ischemia, followed by 3 h of reperfusion...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28183701/association-of-serum-hmgb2-levels-with-in-stent-restenosis-hmgb2-promotes-neointimal-hyperplasia-in-mice-with-femoral-artery-injury-and-proliferation-and-migration-of-vsmcs
#2
Yu Hu He, Xiao Qun Wang, Jian Zhang, Zhu Hui Liu, Wen Qi Pan, Ying Shen, Zheng Bin Zhu, Ling Jie Wang, Xiao Xiang Yan, Ke Yang, Rui Yan Zhang, Wei Feng Shen, Feng Hua Ding, Lin Lu
OBJECTIVE: In a previous study, we established diabetic and nondiabetic minipig models with coronary artery in-stent restenosis (ISR). Mass spectrometry showed that high-mobility group box (HMGB) 2 level was higher in ISR than in non-ISR tissue from diabetic minipigs. We here investigated whether serum HMGB2 levels were related to ISR in CAD patients. The effect of HMGB2 was evaluated in mice with femoral artery wire injury and in human aortic smooth muscle cells. APPROACH AND RESULTS: From 2513 patients undergoing coronary artery intervention and follow-up angiography at ≈1 year, 262 patients were diagnosed with ISR, and 298 patients with no ISR were randomly included as controls...
February 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28182085/maresin-1-mitigates-high-glucose-induced-mouse-glomerular-mesangial-cell-injury-by-inhibiting-inflammation-and-fibrosis
#3
Shi Tang, Chenlin Gao, Yang Long, Wei Huang, Jiao Chen, Fang Fan, Chunxia Jiang, Yong Xu
Background. Inflammation and fibrosis are the important pathophysiologic processes in diabetic nephropathy (DN). Maresin 1 is a potential anti-inflammatory lipid mediator, which has displayed powerful proresolving activities. Aim. We determine whether maresin 1 has protective effect on mouse glomerular mesangial cells (GMCs) induced by high glucose. Methods. We cultured GMCs stimulated by high glucose and categorized as follows: normal glucose group (5.6 mmol/L), high glucose group (30 mmol/L), mannitol group, maresin 1 intervention group (1, 10, and 100 nmol/L), maresin 1 and normal glucose group, and the N-acetylcysteine (NAC) intervention group (10 μmol/L NAC)...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28176274/microglial-function-during-glucose-deprivation-inflammatory-and-neuropsychiatric-implications
#4
Matthew A Churchward, Devan R Tchir, Kathryn G Todd
Inflammation is increasingly recognized as a contributor to the pathophysiology of neuropsychiatric disorders, including depression, anxiety disorders and autism, though the factors leading to contextually inappropriate or sustained inflammation in pathological conditions are yet to be elucidated. Microglia, as the key mediators of inflammation in the CNS, serve as likely candidates in initiating pathological inflammation and as an ideal point of therapeutic intervention. Glucose deprivation, as a component of the pathophysiology of ischemia or occurring transiently in diabetes, may serve to modify microglial function contributing to inflammatory injury...
February 7, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28121358/ablation-of-carbohydrate-responsive-element-binding-protein-improves-kidney-injury-in-streptozotocin-induced-diabetic-mice
#5
W Zhang, X Li, S-G Zhou
OBJECTIVE: Carbohydrate-responsive element-binding protein (ChREBP) has been reported to regulate glucose and lipids metabolism in the liver. However, its role in the complicated pathophysiology of diabetic nephropathy is not understood. MATERIALS AND METHODS: C57BL/6 mice treated with streptozotocin (STZ) or vehicle control to induce diabetic models. The mRNA and protein levels of ChREBP in kidneys of control and diabetic mice were determined by real-time PCR or Western Blot, respectively...
January 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28119179/the-chronic-kidney-disease-mineral-bone-disorder-ckd-mbd-advances-in-pathophysiology
#6
REVIEW
Keith A Hruska, Toshifumi Sugatani, Olga Agapova, Yifu Fang
The causes of excess cardiovascular mortality associated with chronic kidney disease (CKD) have been attributed in part to the CKD-mineral bone disorder syndrome (CKD-MBD), wherein, novel cardiovascular risk factors have been identified. New advances in the causes of the CKD-MBD are discussed in this review. They demonstrate that repair and disease processes in the kidneys release factors to the circulation that cause the systemic complications of CKD. The discovery of WNT inhibitors, especially Dickkopf 1 (Dkk1), produced during renal repair as participating in the pathogenesis of the vascular and skeletal components of the CKD-MBD implied that additional pathogenic factors are critical...
January 21, 2017: Bone
https://www.readbyqxmd.com/read/28060743/2017-update-on-the-relationship-between-diabetes-and-colorectal-cancer-epidemiology-potential-molecular-mechanisms-and-therapeutic-implications
#7
REVIEW
Nieves González, Isabel Prieto, Laura Del Puerto-Nevado, Sergio Portal-Nuñez, Juan Antonio Ardura, Marta Corton, Beatriz Fernández-Fernández, Oscar Aguilera, Carmen Gomez-Guerrero, Sebastián Mas, Juan Antonio Moreno, Marta Ruiz-Ortega, Ana Belen Sanz, Maria Dolores Sanchez-Niño, Federico Rojo, Fernando Vivanco, Pedro Esbrit, Carmen Ayuso, Gloria Alvarez-Llamas, Jesús Egido, Jesús García-Foncillas, Alberto Ortiz, Diabetes Cancer Connect Consortium
Worldwide deaths from diabetes mellitus (DM) and colorectal cancer increased by 90% and 57%, respectively, over the past 20 years. The risk of colorectal cancer was estimated to be 27% higher in patients with type 2 DM than in non-diabetic controls. However, there are potential confounders, information from lower income countries is scarce, across the globe there is no correlation between DM prevalence and colorectal cancer incidence and the association has evolved over time, suggesting the impact of additional environmental factors...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28027072/spectrum-of-drug-induced-chronic-diarrhea
#8
Nissy A Philip, Nazir Ahmed, Capecomorin S Pitchumoni
The evaluation of a patient with chronic diarrhea can be quite frustrating, as it is expensive and involves multiple diagnostic studies. Moreover, identification of a drug as a cause of chronic diarrhea is a challenge in patients taking multiple medications. The disease may either be associated with intestinal mucosal changes, mimicking diseases such as celiac disease, or purely functional, with no histopathologic change. Drug-induced diarrhea may or may not be associated with malabsorption of nutrients, and a clinical improvement may occur within days of discontinuation of the drug, or may take longer when associated with mucosal injury...
February 2017: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/28003360/down-regulation-of-insulin-receptor-substrate-1-during-hyperglycemia-induces-vascular-smooth-muscle-cell-dedifferentiation
#9
Gang Xi, Christine Wai, Morris F White, David R Clemmons
Diabetes is a major risk factor for the development of atherosclerosis, but the mechanism by which hyperglycemia accelerates lesion development is not well defined. Insulin and insulin-like growth factor I (IGF-I) signal through the scaffold protein insulin receptor substrate 1 (IRS-1). In diabetes, IRS-1 is down-regulated, and cells become resistant to insulin. Under these conditions, the IGF-I receptor signals through an alternate scaffold protein, SHPS-1, resulting in pathophysiologic stimulation of vascular smooth muscle cell (VSMC) migration and proliferation...
February 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27976413/medicinal-chemistry-pharmacology-and-clinical-implications-of-trpv1-receptor-antagonists
#10
REVIEW
Mojgan Aghazadeh Tabrizi, Pier Giovanni Baraldi, Stefania Baraldi, Stefania Gessi, Stefania Merighi, Pier Andrea Borea
Transient receptor potential vanilloid 1 (TRPV1) is an ion channel expressed on sensory neurons triggering an influx of cations. TRPV1 receptors function as homotetramers responsive to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Its phosphorylation increases sensitivity to both chemical and thermal stimuli, while desensitization involves a calcium-dependent mechanism resulting in receptor dephosphorylation. TRPV1 functions as a sensor of noxious stimuli and may represent a target to avoid pain and injury...
December 15, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27974711/skin-wound-healing-an-update-on-the-current-knowledge-and-concepts
#11
Heiko Sorg, Daniel J Tilkorn, Stephan Hager, Jörg Hauser, Ursula Mirastschijski
BACKGROUND: The integrity of healthy skin plays a crucial role in maintaining physiological homeostasis of the human body. The skin is the largest organ system of the body. As such, it plays pivotal roles in the protection against mechanical forces and infections, fluid imbalance, and thermal dysregulation. At the same time, it allows for flexibility to enable joint function in some areas of the body and more rigid fixation to hinder shifting of the palm or foot sole. Many instances lead to inadequate wound healing which necessitates medical intervention...
2017: European Surgical Research. Europäische Chirurgische Forschung. Recherches Chirurgicales Européennes
https://www.readbyqxmd.com/read/27941788/small-molecule-inhibition-of-stoml3-oligomerization-reverses-pathological-mechanical-hypersensitivity
#12
Christiane Wetzel, Simone Pifferi, Cristina Picci, Caglar Gök, Diana Hoffmann, Kiran K Bali, André Lampe, Liudmila Lapatsina, Raluca Fleischer, Ewan St John Smith, Valérie Bégay, Mirko Moroni, Luc Estebanez, Johannes Kühnemund, Jan Walcher, Edgar Specker, Martin Neuenschwander, Jens Peter von Kries, Volker Haucke, Rohini Kuner, James F A Poulet, Jan Schmoranzer, Kate Poole, Gary R Lewin
The skin is equipped with specialized mechanoreceptors that allow the perception of the slightest brush. Indeed, some mechanoreceptors can detect even nanometer-scale movements. Movement is transformed into electrical signals via the gating of mechanically activated ion channels at sensory endings in the skin. The sensitivity of Piezo mechanically gated ion channels is controlled by stomatin-like protein-3 (STOML3), which is required for normal mechanoreceptor function. Here we identify small-molecule inhibitors of STOML3 oligomerization that reversibly reduce the sensitivity of mechanically gated currents in sensory neurons and silence mechanoreceptors in vivo...
February 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/27941647/the-role-of-erk1-2-in-the-development-of-diabetic-cardiomyopathy
#13
REVIEW
Zheng Xu, Jian Sun, Qian Tong, Qian Lin, Lingbo Qian, Yongsoo Park, Yang Zheng
Diabetes mellitus is a chronic metabolic condition that affects carbohydrate, lipid and protein metabolism and may impair numerous organs and functions of the organism. Cardiac dysfunction afflicts many patients who experience the oxidative stress of the heart. Diabetic cardiomyopathy (DCM) is one of the major complications that accounts for more than half of diabetes-related morbidity and mortality cases. Chronic hyperglycemia and hyperlipidemia from diabetes mellitus cause cardiac oxidative stress, endothelial dysfunction, impaired cellular calcium handling, mitochondrial dysfunction, metabolic disturbances, and remodeling of the extracellular matrix, which ultimately lead to DCM...
December 8, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27914709/podocyte-specific-chemokine-c-c-motif-receptor-2%C3%A2-overexpression-mediates-diabetic-renal-injury-in%C3%A2-mice
#14
Hanning You, Ting Gao, Wesley M Raup-Konsavage, Timothy K Cooper, Sarah K Bronson, W Brian Reeves, Alaa S Awad
Inflammation is a central pathophysiologic mechanism that contributes to diabetes mellitus and diabetic nephropathy. Recently, we showed that macrophages directly contribute to diabetic renal injury and that pharmacological blockade or genetic deficiency of chemokine (C-C motif) receptor 2 (CCR2) confers kidney protection in diabetic nephropathy. However, the direct role of CCR2 in kidney-derived cells such as podocytes in diabetic nephropathy remains unclear. To study this, we developed a transgenic mouse model expressing CCR2 specifically in podocytes (Tg[NPHS2-Ccr2]) on a nephropathy-prone (DBA/2J) and CCR2-deficient (Ccr2(-/-)) background with heterozygous Ccr2(+/-) littermate controls...
March 2017: Kidney International
https://www.readbyqxmd.com/read/27896904/contrast-induced-encephalopathy-following-cardiac-catheterization
#15
Roberto Spina, Neil Simon, Romesh Markus, David Wm Muller, Krishna Kathir
OBJECTIVES: To describe the epidemiology, pathophysiology, clinical presentation, and management of contrast-induced encephalopathy (CIE) following cardiac catheterization. BACKGROUND: CIE is an acute, reversible neurological disturbance directly attributable to the intra-arterial administration of iodinated contrast medium. METHODS: The PubMed database was searched and all cases in the literature were retrieved and reviewed. RESULTS: 52 reports of CIE following cardiac catheterization were found...
November 29, 2016: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/27889567/prognostic-value-of-plasma-apelin-concentrations-at-admission-in-patients-with-st-segment-elevation-acute-myocardial-infarction
#16
Jordi Sans-Roselló, Gregori Casals, Xavier Rossello, Bernardino González de la Presa, Montserrat Vila, Albert Duran-Cambra, Manuel Morales-Ruiz, Andreu Ferrero-Gregori, Wladimiro Jiménez, Alessandro Sionis
BACKGROUND: The use of plasma biomarkers is relevant for the prognosis of ST-segment elevation myocardial infarction (STEMI) patients. Apelin, an adipocytokine, plays a pivotal role in the pathophysiology of both ischemia/reperfusion injury and its potential subsequent heart failure. We evaluated apelin concentrations at admission as a biomarker to assess risk of 6-month mortality. METHODS: Consecutive patients with STEMI were recruited from January 2012 to January 2013 (n=250)...
November 24, 2016: Clinical Biochemistry
https://www.readbyqxmd.com/read/27883184/epigenetics-in-reactive-and-reparative-cardiac-fibrogenesis-the-promise-of-epigenetic-therapy
#17
REVIEW
Asish K Ghosh, Rahul Rai, Panagiotis Flevaris, Douglas E Vaughan
Epigenetic changes play a pivotal role in the development of a wide spectrum of human diseases including cardiovascular diseases, cancer, diabetes, and intellectual disabilities. Cardiac fibrogenesis is a common pathophysiological process seen during chronic and stress-induced accelerated cardiac aging. While adequate production of extracellular matrix (ECM) proteins is necessary for post-injury wound healing, excessive synthesis and accumulation of extracellular matrix protein in the stressed or injured hearts causes decreased or loss of lusitropy that leads to cardiac failure...
November 24, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27872031/penile-prosthesis-infections-a-review-of-risk-factors-prevention-and%C3%A2-treatment
#18
REVIEW
Miguel Pineda, Arthur L Burnett
INTRODUCTION: Inflatable penile prosthesis (IPP) surgery has been performed for more than 40 years. IPP infection rates have decreased owing to advances in manufacturing and surgical technique but have remained a devastating complication. AIMS: To describe the pathophysiology of infections, examine evidence associating clinical risk factors with IPP infection, assess the benefit of techniques aimed at preventing and managing infection, and discuss future directions...
October 2016: Sexual Medicine Reviews
https://www.readbyqxmd.com/read/27798458/the-angiotensin-type-2-receptor-and-the-kidney
#19
Antonio A B Peluso, Robson A S Santos, Thomas Unger, U Muscha Steckelings
PURPOSE OF REVIEW: Angiotensin II is a main regulator of kidney function. Renal actions mediated by the angiotensin AT1 receptor have been well known for many years. In contrast, several details of angiotensin AT2 receptor actions in kidney physiology and pathophysiology were only described very recently. These findings are reviewed in this article. RECENT FINDINGS: Regarding the role of the angiotensin AT2 receptor in kidney physiology, a major recent finding was that the AT2 receptor-mediated inhibition of Na-H exchanger-3 and Na/K-ATPase in the renal proximal tubules is caused by internalisation of these transporters, thus reducing reabsorption and increasing natriuresis/diuresis...
January 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27784010/clinical-application-of-biomarkers-in-heart-failure-with-a-preserved-ejection-fraction-a-review
#20
Aakash Garg, Deepti Virmani, Sahil Agrawal, Chirag Agarwal, Abhishek Sharma, Giulio Stefanini, John B Kostis
Heart failure with a preserved ejection fraction (HFpEF) is increasingly prevalent and a leading cause of morbidity and mortality worldwide. HFpEF has a complex pathophysiology, with recent evidence suggesting that an interaction of cardiovascular and noncardiovascular comorbidities (e.g. obesity, hypertension, diabetes, coronary artery disease, and chronic kidney disease) induces an inflammatory state that eventually leads to myocardial structural and functional alterations. Current ACCF/AHA guidelines suggest incorporation of biomarkers along with clinical and imaging tools to establish the diagnosis and disease severity in heart failure (HF)...
2017: Cardiology
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