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Inflammation diabetic nephropathy

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https://www.readbyqxmd.com/read/28539091/in-silico-identification-of-potential-drug-compound-against-peroxisome-proliferator-activated-receptor-gamma-by-virtual-screening-and-toxicity-studies-for-treatment-of-diabetic-nephropathy
#1
Smrita Singh, Aparajita Mohanty
Diabetic Nephropathy is a serious complication of Diabetes Mellitus. Current therapeutic strategies of Diabetic Nephropathy are based on control of modifiable risks like hypertension, glucose levels, and dyslipidemia. Peroxisome proliferator activated receptor-gamma (PPAR-γ) is implicated in several metabolic syndromes including Diabetic Nephropathy, besides obesity, insulin insensitivity, dislipidemia, inflammation and hypertension. In the present study, virtual screening of 617 compounds from two different public databases was done against PPAR- γ with an objective to find a possible lead compound...
May 24, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28529539/jiangtang-decoction-ameliorate-diabetic-nephropathy-through-the-regulation-of-pi3k-akt-mediated-nf-%C3%AE%C2%BAb-pathways-in-kk-ay-mice
#2
Jin-Ni Hong, Wei-Wei Li, Lin-Lin Wang, Hao Guo, Yong Jiang, Yun-Jia Gao, Peng-Fei Tu, Xue-Mei Wang
BACKGROUND: Jiangtang decoction (JTD) is a China patented drug which contains Euphorbia humifusa Willd, Salvia miltiorrhiza Bunge, Astragalus mongholicus Bunge, Anemarrhena asphodeloides Bunge, and Coptis chinensis Franch. For decades, it has also been used clinically to treat diabetic nephropathy (DN) effectively; however, the associated mechanisms remain unknown. Thus, the present study aimed to examine the protective efficacy of JTD in DN and elucidate the underlying molecular mechanisms...
2017: Chinese Medicine
https://www.readbyqxmd.com/read/28524098/sglt2-inhibitors-as-a-therapeutic-option-for-diabetic-nephropathy
#3
REVIEW
Daiji Kawanami, Keiichiro Matoba, Yusuke Takeda, Yosuke Nagai, Tomoyo Akamine, Tamotsu Yokota, Kazunori Sango, Kazunori Utsunomiya
Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) worldwide. Glycemic and blood pressure (BP) control are important but not sufficient to attenuate the incidence and progression of DN. Sodium-glucose cotransporter (SGLT) 2 inhibitors are a new class of glucose-lowering agent suggested to exert renoprotective effects in glucose lowering-dependent and independent fashions. Experimental studies have shown that SGLT2 inhibitors attenuate DN in animal models of both type 1 diabetes (T1D) and type 2 diabetes (T2D), indicating a potential renoprotective effect beyond glucose reduction...
May 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28520942/emerging-roles-for-micrornas-in-diabetic-microvascular-disease-novel-targets-for-therapy
#4
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/28506912/characterization-and-comparison-of-sglt2-inhibitors-part-3-effects-on-diabetic-complications-in-type-2-diabetic-mice
#5
Atsuo Tahara, Toshiyuki Takasu, Masanori Yokono, Masakazu Imamura, Eiji Kurosaki
In this study, we investigated and compared the effects of all six sodium-glucose cotransporter (SGLT) 2 inhibitors commercially available in Japan on diabetes-related diseases and complications in type 2 diabetic mice. Following 4-week repeated administration to diabetic mice, all SGLT2 inhibitors showed significant improvement in diabetes-related diseases and complications, including obesity; abnormal lipid metabolism; steatohepatitis; inflammation; endothelial dysfunction; and nephropathy. While all SGLT2 inhibitors exerted comparable effects in reducing hyperglycemia, improvement of these diabetes-related diseases and complications was more potent with the two long-acting drugs (ipragliflozin and dapagliflozin) than with the four intermediate-acting four drugs (tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin), albeit without statistical significance...
May 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28506691/urinary-lysophopholipids-are-increased-in-diabetic-patients-with-nephropathy
#6
Jean-Sébastien Saulnier-Blache, Eva Feigerlova, Jean Michel Halimi, Pierre Gourdy, Ronan Roussel, Bruno Guerci, Aude Dupuy, Justine Bertrand-Michel, Jean-Loup Bascands, Samy Hadjadj, Joost P Schanstra
Diabetic nephropathy (DN) is a major cause of chronic kidney disease that frequently leads to end stage renal failure. Lysophosphatidic acid (LPA) and lysophosphatidylcholine (LPC) are lysophospholipid mediators shown to accumulate in kidney and to promote renal inflammation and tubulo-interstitial fibrosis in diabetic rodent models. Here we assessed whether LPA and LPC were associated to the development of nephropathy in diabetic human patients. Several molecular species of LPA and LPC were quantified by LC/MS-MS in urine and plasma from type 2 diabetic patients with (cases; n=41) or without (controls, n=41) nephropathy symptoms (micro/macro-albuminuria and eGFR<60ml/min/1...
May 10, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28497277/brazilin-ameliorates-diabetic-nephropathy-and-inflammation-in-db-db-mice
#7
Zhan-Yuan Li, Yu Zheng, Yan Chen, Min Pan, Shu-Bei Zheng, Wen Huang, Zhi-Hong Zhou, Han-Yang Ye
Hyperglycemia and inflammation play important roles in the pathogenesis of diabetic nephropathy (DN). Brazilin might be an effective pharmacological agent against hyperglycemia and inflammation. In our present study, we explored whether brazilin mitigated pathological progression, inflammation, and extracellular matrix (ECM) accumulation in a mouse model of diabetic nephropathy. Brazilin reduced aggravated biochemical indices of DN (proteinuria and the serum glucose level) and renal hypertrophy. Brazilin also improved renal morphology and inhibited macrophage infiltration, as manifested by different pathological staining methods...
May 11, 2017: Inflammation
https://www.readbyqxmd.com/read/28490956/changes-in-the-nf%C3%AE%C2%BAb-and-e-cadherin-expression-are-associated-to-diabetic-nephropathy-inpsammomys-obesus
#8
Djamila Aroune, Farid Libdiri, Sophie Leboucher, Boubekeur Maouche, Sergio Marco, Salima El-Aoufi
Diabetes mellitus is a major leading cause of end-stage renal failure, characterized by kidney inflammation and glomerular dysfunction, in worldwide. Kidney inflammation is associated to modifications in the expression levels of pro-inflammatory molecules, such as nuclear factor-κB (NFκB) and adhesion molecules, such as E-cadherin, leading to glomerular dysfunction. However, the relationships between these two processes in human diabetic nephropathy remain an open question. Since Psammomys obesus is an ideal animal model to study diabetes mellitus temporal evolution, we have used this model to study the correlation between kidney structural changes and modification on the expression levels of NFκB and E-cadherin over time...
May 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/28466254/celecoxib-alleviates-memory-deficits-by-downregulation-of-cox-2-expression-and-upregulation-of-the-bdnf-trkb-signaling-pathway-in-a-diabetic-rat-model
#9
Ying Yang, Ling Gao
Previous studies conveyed that diabetes causes learning and memory deficits. Data also suggest that celecoxib exerts an anti-hyperalgesic, anti-allodynic, and a plethora of other beneficial effects in diabetic rats. However, whether celecoxib could alleviate memory deficit in diabetic rat is unknown. In the present study, we aimed to examine the potential of celecoxib to counter memory deficits in diabetes. Experimental diabetes was induced by streptozotocin (STZ, 60 mg/kg) in male SD rats. Rats were divided into three groups (n = 16/group): normal control group injected with normal saline, diabetes group injected with STZ, and diabetes + celecoxib group in which diabetic rats were administered with celecoxib by gavage in drinking water (10 mg/kg) for 10 days in terms of which memory performance in animals was measured, hippocampal tissue harvested, and long-term potentiation assessed...
May 2, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28457936/epigallocatechin-gallate-upregulates-nrf2-to-prevent-diabetic-nephropathy-via-disabling-keap1
#10
Weixia Sun, Xiuxia Liu, Haifeng Zhang, Yanyan Song, Tie Li, Xiaona Liu, Yanze Liu, Le Guo, Fuchun Wang, Ting Yang, Weiying Guo, Junduo Wu, Hang Jin, Hao Wu
Epigallocatechin gallate (EGCG) is the most abundant and effective green tea catechin and has been reported to attenuate diabetic nephropathy (DN). However, the mechanism by which EGCG ameliorates DN, till now, has remained unclear. EGCG is known as a potent activator of nuclear factor erythroid 2-related factor 2 (NRF2), which plays a key role in cellular defense against diabetes-induced oxidative stress and in the prevention of DN. In the present study, we tested whether NRF2 is required for EGCG protection against DN...
April 27, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28453961/diabetic-nephropathy-new-insights-into-established-therapeutic-paradigms-and-novel-molecular-targets
#11
REVIEW
Dilip Sharma, Pallab Bhattacharya, Kiran Kalia, Vinod Tiwari
Diabetic nephropathy is one of the most prevalent microvascular complication in patients suffering from diabetes and is reported to be the major cause of renal failure when compared to any other kidney disease. Currently, available therapies provide only symptomatic relief and unable to treat the underlying pathophysiology of diabetic nephropathy. This review will explore new insights into the established therapeutic paradigms targeting oxidative stress, inflammation and endoplasmic reticulum stress with the focus on recent clinical developments...
April 13, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28446168/plasma-matrix-metalloproteinases-are-associated-with-incident-cardiovascular-disease-and-all-cause-mortality-in-patients-with-type-1-diabetes-a-12-year-follow-up-study
#12
S A Peeters, L Engelen, J Buijs, A Jorsal, H-H Parving, L Tarnow, P Rossing, C G Schalkwijk, C D A Stehouwer
BACKGROUND: Altered regulation of extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) may contribute to vascular complications in type 1 diabetes. We investigated associations between plasma MMP-1, -2, -3, -9, -10 and TIMP-1, and cardiovascular events and all-cause mortality in type 1 diabetic patients. METHODS: We prospectively followed 337 type 1 diabetic patients [mean age 41.4 years (9.6), 39% female], 170 with and 167 without diabetic nephropathy, with median follow-up of 12...
April 26, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28438648/the-superoxide-dismutase-mimetic-tempol-blunts-diabetes-induced-upregulation-of-nadph-oxidase-and-endoplasmic-reticulum-stress-in-a-rat-model-of-diabetic-nephropathy
#13
Miles J De Blasio, Anand Ramalingam, Anh H Cao, Darnel Prakoso, Ji-Ming Ye, Raelene Pickering, Anna M D Watson, Judy B de Haan, David M Kaye, Rebecca H Ritchie
Endoplasmic reticulum (ER) stress contributes to progression of diabetic nephropathy, which promotes end-stage renal failure in diabetic patients. This study was undertaken to investigate the actions of tempol and ramipril, pharmacological agents that target the consequences of NADPH oxidase, on diabetic nephropathy in a rat model of type 1 diabetes, with an emphasis on markers of ER stress. Male Sprague-Dawley rats were injected intravenously with a single bolus of streptozotocin (55mg/kg) to induce type 1 diabetes...
April 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28435064/salvianolate-attenuates-renal-fibrosis-in-rat-models-of-diabetic-nephropathy-by-inhibiting-inflammation-and-oxidative-stress-mechanisms
#14
Chongxiang Xiong, Jianrao Lu, Xinhua Wang, Monica V Masucci
OBJECTIVE: Mounting evidence has shown that inflammation and oxidative stress are involved in the development and progression of diabetic nephropathy. Salvianolate is proven to have multiple bioactivities including anti-inflammation and anti-oxidative stress effects in diverse diseases. However, its role in rat models of diabetic nephropathy remains unclear. METHODS: In this study, we examined the renoprotective effect of Salvianolate on rat models of diabetic nephropathy induced by streptozotocin intraperitoneal injection...
April 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28434946/hyperglycemia-induced-renal-p2x7-receptor-activation-enhances-diabetes-related-injury
#15
Robert I Menzies, John W R Booth, John J Mullins, Matthew A Bailey, Frederick W K Tam, Jill T Norman, Robert J Unwin
Diabetes is a leading cause of renal disease. Glomerular mesangial expansion and fibrosis are hallmarks of diabetic nephropathy and this is thought to be promoted by infiltration of circulating macrophages. Monocyte chemoattractant protein-1 (MCP-1) has been shown to attract macrophages in kidney diseases. P2X7 receptors (P2X7R) are highly expressed on macrophages and are essential components of pro-inflammatory signaling in multiple tissues. Here we show that in diabetic patients, renal P2X7R expression is associated with severe mesangial expansion, impaired glomerular filtration (≤40ml/min/1...
April 20, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28426518/pathophysiologic-insight-into-mesoamerican-nephropathy
#16
Magdalena Madero, Fernando E García-Arroyo, Laura-Gabriela Sánchez-Lozada
PURPOSE OF REVIEW: Mesoamerican nephropathy (MeN) is an emerging pathophysiological entity of Chronic kidney desease (CKD) not related to traditional risk factors (diabetes and hypertension) that have caused thousands of deaths in Central America, mainly in sugarcane workers. The focus of this review is to discuss the risk factors and probable mechanisms involved in the initiation and progression of this devastating disease. RECENT FINDINGS: Frequent episodes of subclinical Acute kidney injury caused by repetitive heat stress, dehydration, and strenuous work have been regarded as the main risk factors for MeN...
April 19, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28413612/advances-in-understanding-the-renin-angiotensin-aldosterone-system-raas-in-blood-pressure-control-and-recent-pivotal-trials-of-raas-blockade-in-heart-failure-and-diabetic-nephropathy
#17
REVIEW
Lama Ghazi, Paul Drawz
The renin-angiotensin-aldosterone system (RAAS) plays a fundamental role in the physiology of blood pressure control and the pathophysiology of hypertension (HTN) with effects on vascular tone, sodium retention, oxidative stress, fibrosis, sympathetic tone, and inflammation. Fortunately, RAAS blocking agents have been available to treat HTN since the 1970s and newer medications are being developed. In this review, we will (1) examine new anti-hypertensive medications affecting the RAAS, (2) evaluate recent studies that help provide a better understanding of which patients may be more likely to benefit from RAAS blockade, and (3) review three recent pivotal randomized trials that involve newer RAAS blocking agents and inform clinical practice...
2017: F1000Research
https://www.readbyqxmd.com/read/28409327/heat-shock-proteins-and-kidney-disease-perspectives-of-hsp-therapy
#18
REVIEW
Natalia Chebotareva, Irina Bobkova, Evgeniy Shilov
Heat shock proteins (HSPs) mediate a diverse range of cellular functions, prominently including folding and regulatory processes of cellular repair. A major property of these remarkable proteins, dependent on intracellular or extracellular location, is their capacity for immunoregulation that optimizes immune activity while avoiding hyperactivated inflammation. In this review, recent investigations are described, which examine roles of HSPs in protection of kidney tissue from various traumatic influences and demonstrate their potential for clinical management of nephritic disease...
May 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28404881/tanshinone-iia-attenuates-renal-damage-in-stz-induced-diabetic-rats-via-inhibiting-oxidative-stress-and-inflammation
#19
Xia Chen, Rui Wu, Yiwei Kong, Yuting Yang, Yu Gao, Dandan Sun, Qizhen Liu, Dongjun Dai, Zeyuan Lu, Niansong Wang, Sheng Ge, Feng Wang
Oxidative stress and inflammation have been demonstrated to be involved in the onset and promotion of diabetic nephropathy (DN).Tanshinone IIA (Tan) possesses both antioxidant and anti-inflammatory properties. Here, the aim of the present study was to explore whether Tan could attenuate renal damage in the rats with streptozotocin (STZ)-induced diabetes and its potential mechanisms. Tan was gavaged to STZ-induced diabetic rats at the dose of 10mg/kg once a day for 12 weeks. Tan treatment significantly attenuated albuminuria and renal histopathology in diabetic rats...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28393441/intestinal-alkaline-phosphatase-at-the-crossroad-of-intestinal-health-and-disease-a-putative-role-in-type-1-diabetes
#20
M I Lassenius, C L Fogarty, M Blaut, K Haimila, L Riittinen, A Paju, J Kirveskari, J Järvelä, A J Ahola, D Gordin, M-A Härma, A Kumar, S R Hamarneh, R A Hodin, T Sorsa, T Tervahartiala, S Hörkkö, P J Pussinen, C Forsblom, M Jauhiainen, M-R Taskinen, P-H Groop, M Lehto
BACKGROUND: Patients with type 1 diabetes have shown an increase in circulating cytokines, altered lipoprotein metabolism and signs of vascular dysfunction in response to high-fat meals. Intestinal alkaline phosphatase (IAP) regulates lipid transport and inflammatory responses in the gastrointestinal tract. We therefore hypothesized that changes in IAP activity could have profound effects on gut metabolic homeostasis in patients with type 1 diabetes. METHODS: Faecal samples of 41 nondiabetic controls and 46 patients with type 1 diabetes were analysed for IAP activity, calprotectin, immunoglobulins and short-chain fatty acids (SCFAs)...
April 10, 2017: Journal of Internal Medicine
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