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Pathophysiology diabetic injury

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https://www.readbyqxmd.com/read/28323921/emerging-roles-for-micrornas-in-diabetic-microvascular-disease-novel-targets-for-therapy
#1
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, non-coding 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...
February 17, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28298952/insights-for-oxidative-stress-and-mtor-signaling-in-myocardial-ischemia-reperfusion-injury-under-diabetes
#2
REVIEW
Dajun Zhao, Jian Yang, Lifang Yang
Diabetes mellitus (DM) displays a high morbidity. The diabetic heart is susceptible to myocardial ischemia/reperfusion (MI/R) injury. Impaired activation of prosurvival pathways, endoplasmic reticulum (ER) stress, increased basal oxidative state, and decreased antioxidant defense and autophagy may render diabetic hearts more vulnerable to MI/R injury. Oxidative stress and mTOR signaling crucially regulate cardiometabolism, affecting MI/R injury under diabetes. Producing reactive oxygen species (ROS) and reactive nitrogen species (RNS), uncoupling nitric oxide synthase (NOS), and disturbing the mitochondrial quality control may be three major mechanisms of oxidative stress...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28295872/cellular-crosstalk-inflammatory-signals-and-enhanced-microvascular-permeability
#3
Jerome W Breslin
Microvascular leakage remains a significant clinical problem for which there is no specific therapeutic available. This Special Topics issue of the journal Microcirculation features reviews pertaining to the cellular and molecular mechanisms that control the integrity of the microvascular barrier. Meegan et al [1] summarize recent research findings about how neutrophil extracellular traps and how these can cause injury to the microvascular barrier. Zhang et al [2] highlight the microvascular response to advanced glycation end products that are formed as part of the pathophysiology of diabetes mellitus...
March 14, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28267434/dietary-phytochemicals-in-the-protection-against-oxysterol-induced-damage
#4
REVIEW
Antonio Cilla, Amparo Alegría, Alessandro Attanzio, Guadalupe Garcia-Llatas, Luisa Tesoriere, Maria A Livrea
The intake of fruits and vegetables is associated with reduced incidence of many chronic diseases. These foods contain phytochemicals that often possess antioxidant and free radical scavenging capacity and show anti-inflammatory action, which are also the basis of other bioactivities and health benefits, such as anticancer, anti-aging, and protective action for cardiovascular diseases, diabetes mellitus, obesity and neurodegenerative disorders. Many factors can be included in the etiopathogenesis of all of these multifactorial diseases that involve oxidative stress, inflammation and/or cell death processes, oxysterols, i...
March 3, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28259681/stem-cell-laden-hyaluronic-acid-based-spongy-like-hydrogels-for-an-integrated-healing-of-diabetic-wounds-pathophysiologies
#5
Lucília Pereira da Silva, Tírcia Carlos Santos, Daniel Barreira Rodrigues, Rogério Pedro Pirraco, Mariana Teixeira Cerqueira, Rui Luís Reis, Vitor Manuel Correlo, Alexandra Pinto Marques
The correlation between the pathophysiologies of diabetic foot ulcerations is yet to be established and improved treatments are still required. We propose a strategy that directs inflammation, neo-vascularization and neo-innervation of diabetic wounds. Aiming to potentiate a relevant secretome for nerve regeneration, stem cells were pre-cultured in hyaluronic acid-based spongy-like hydrogels under neurogenic/standard media prior transplantation into diabetic mice full-thickness wounds. Acellular spongy-like hydrogels and empty wounds were used as controls...
March 1, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28241825/non-alcoholic-fatty-liver-disease
#6
REVIEW
Brent A Neuschwander-Tetri
Non-alcoholic fatty liver disease has emerged a major challenge because of it prevalence, difficulties in diagnosis, complex pathogenesis, and lack of approved therapies. As the burden of hepatitis C abates over the next decade, non-alcoholic fatty liver disease will become the major form of chronic liver disease in adults and children and could become the leading indication for liver transplantation. This overview briefly summarizes the most recent data on the pathophysiology, diagnosis, and treatment of non-alcoholic fatty liver disease...
February 28, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28230738/clinical-implications-of-20-hydroxyeicosatetraenoic-acid-in-the-kidney-liver-lung-and-brain-an-emerging-therapeutic-target
#7
REVIEW
Osama H Elshenawy, Sherif M Shoieb, Anwar Mohamed, Ayman O S El-Kadi
Cytochrome P450-mediated metabolism of arachidonic acid (AA) is an important pathway for the formation of eicosanoids. The ω-hydroxylation of AA generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in various tissues. In the current review, we discussed the role of 20-HETE in the kidney, liver, lung, and brain during physiological and pathophysiological states. Moreover, we discussed the role of 20-HETE in tumor formation, metabolic syndrome and diabetes. In the kidney, 20-HETE is involved in modulation of preglomerular vascular tone and tubular ion transport...
February 20, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/28223003/treatment-of-metformin-intoxication-complicated-by-lactic-acidosis-and-acute-kidney-injury-the-role-of-prolonged-intermittent-hemodialysis
#8
Giuseppe Regolisti, Riccardo Antoniotti, Filippo Fani, Paolo Greco, Enrico Fiaccadori
Metformin intoxication with lactic acidosis, a potentially lethal condition, may develop in diabetic patients when the drug dose is inappropriate and/or its clearance is reduced. Diagnosis and therapy may be delayed due to nonspecific symptoms at presentation, with severe anion gap metabolic acidosis and elevated serum creatinine values being the most prominent laboratory findings. Confirmation requires measurement of serum metformin by high-performance liquid chromatography-tandem mass spectrometry, but this technique is available only at specialized institutions and cannot be relied on as a guide to immediate treatment...
February 17, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28215037/the-italian-dystonia-registry-rationale-design-and-preliminary-findings
#9
Giovanni Defazio, M Esposito, G Abbruzzese, C L Scaglione, G Fabbrini, G Ferrazzano, S Peluso, R Pellicciari, A F Gigante, G Cossu, R Arca, L Avanzino, F Bono, M R Mazza, L Bertolasi, R Bacchin, R Eleopra, C Lettieri, F Morgante, M C Altavista, L Polidori, R Liguori, S Misceo, G Squintani, M Tinazzi, R Ceravolo, E Unti, L Magistrelli, M Coletti Moja, N Modugno, M Petracca, N Tambasco, M S Cotelli, M Aguggia, A Pisani, M Romano, M Zibetti, A R Bentivoglio, A Albanese, P Girlanda, A Berardelli
The Italian Dystonia Registry is a multicenter data collection system that will prospectively assess the phenomenology and natural history of adult-onset dystonia and will serve as a basis for future etiological, pathophysiological and therapeutic studies. In the first 6 months of activity, 20 movement disorders Italian centres have adhered to the registry and 664 patients have been recruited. Baseline historical information from this cohort provides the first general overview of adult-onset dystonia in Italy...
February 18, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28191472/suppression-of-excessive-histone-deacetylases-activity-in-diabetic-hearts-attenuates-myocardial-ischemia-reperfusion-injury-via-mitochondria-apoptosis-pathway
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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