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Pathogenesis diabetic nephropathy

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https://www.readbyqxmd.com/read/29161661/chlorogenic-acid-prevents-diabetic-nephropathy-by-inhibiting-oxidative-stress-and-inflammation-through-modulation-of-the-nrf2-ho-1-and-nf-%C3%A4-b-pathways
#1
Liping Bao, Jushuang Li, Dongqing Zha, Lian Zhang, Ping Gao, Tao Yao, Xiaoyan Wu
Oxidative and inflammatory damage have been suggested to play important roles in the pathogenesis of diabetic nephropathy (DN). Chlorogenic acid (CGA) is one of the most abundant polyphenols and has known immunoprotective, antioxidant and anti-inflammatory properties. In the present study, animal experiments were designed to examine the protective effects of CGA in DN, and cellular experiments were designed to explore the underlying mechanisms. CGA significantly attenuated diabetic renal damage based on histological pathology and molecular biological methods...
November 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29152089/high-glucose-downregulates-myocardin-expression-in-rat-glomerular-mesangial-cells-via-the-erk-signaling-pathway
#2
Ming Li, Lijuan Xu, Guowei Feng, Yan Zhang, Xin Wang, Yuebing Wang
Mesangial cells (MCs), which are vascular smooth muscle-derived cells, occupy the central position in the glomerulus. Diabetic nephropathy (DN) is one of the most common diabetes complications and is likely attributed to the loss of MC contractility. Myocardin stimulates downstream vascular smooth muscle genes and regulates the contractility of vascular smooth muscle cells. Therefore, we hypothesized that myocardin is expressed in MCs and that high glucose is involved in the regulation of myocardin and downstream contractile genes in the context of DN...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29118913/protease-activated-receptor-2-in-diabetic-nephropathy-a-double-edged-sword
#3
Maaike Waasdorp, JanWillem Duitman, Sandrine Florquin, Arnold C Spek
Diabetic nephropathy is a major microvascular complication of diabetes mellitus, and the leading cause of end stage renal disease worldwide. The pathogenesis of diabetic nephropathy is complex, making the development of novel treatments that stop or reverse the progression of microalbuminuria into end stage renal disease a challenge. Protease activated receptor (PAR)-2 has recently been shown to aggravate disease progression in diabetic nephropathy based upon which it was suggested that PAR-2 would be a potential target for the treatment of diabetic nephropathy...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29116339/%C3%AE-arrestin-1-deficiency-ameliorates-renal-interstitial-fibrosis-by-blocking-wnt1-%C3%AE-catenin-signaling-in-mice
#4
Huiyan Xu, Quanxin Li, Jiang Liu, Jiaqing Zhu, Liang Li, Ziying Wang, Yan Zhang, Yu Sun, Jinpeng Sun, Rong Wang, Fan Yi
Despite substantial progress being made in understanding the mechanisms contributing to the pathogenesis of renal fibrosis, there are only a few therapies available to treat or prevent renal fibrosis in clinical use today. Therefore, identifying the key cellular and molecular mediators involved in the pathogenesis of renal fibrosis will provide new therapeutic strategy for treating patients with chronic kidney disease (CKD). β-Arrestin-1, a member of β-arrestin family, not only is a negative adaptor of G protein-coupled receptors (GPCRs), but also acts as a scaffold protein and regulates a diverse array of cellular functions independent of GPCR activation...
November 7, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29108777/antioxidant-for-treatment-of-diabetic-nephropathy-a-systematic-review-and-meta-analysis
#5
REVIEW
Amit D Kandhare, Anwesha Mukherjee, Subhash L Bodhankar
BACKGROUND: Diabetic nephropathy (DN) is one of the leading causes of morbidity and mortality amongst the diabetes mellitus patients. Oxidative stress played a major role in the pathogenesis of DN. Many studies reported that therapies with antioxidant potential have a beneficial effect on DN but there is conflicting evidence amongst them. OBJECTIVE: To elucidate the association between antioxidant and DN and to develop a robust evidence for clinical decisions by conducting systematic reviews and meta-analysis...
November 7, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29108100/association-between-diabetes-mellitus-and-olfactory-dysfunction-current-perspectives-and-future-directions
#6
REVIEW
H Zaghloul, M Pallayova, O Al-Nuaimi, K R Hovis, S Taheri
The increasing global prevalence of diabetes mellitus presents a significant challenge to healthcare systems today. Although diabetic retinopathy, nephropathy and neuropathy are well-established complications of diabetes, there is a paucity of research examining the impact of dysglycaemia on the olfactory system. Olfaction is an important sense, playing a role in the safety, nutrition and quality of life of an individual, but its importance is often overlooked when compared with the other senses. As a result, olfactory dysfunction is often underdiagnosed...
November 6, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/29096857/adma-reduction-does-not-protect-mice-with-streptozotocin-induced-diabetes-mellitus-from-development-of-diabetic-nephropathy
#7
Roman N Rodionov, Annett Heinrich, Silke Brilloff, Natalia Jarzebska, Jens Martens-Lobenhoffer, Stefanie M Bode-Böger, Vladimir T Todorov, Christian P M Hugo, Norbert Weiss, Bernd Hohenstein
BACKGROUND AND AIMS: Cardiovascular disease is the major cause of morbidity and mortality in the world. Diabetes and its complications, such as diabetic nephropathy, dramatically increase cardiovascular risk. Association studies suggest that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases, plays a role in the pathogenesis of diabetic nephropathy. The major pathway of ADMA catabolism is hydrolysis by dimethylarginine dimethylaminohydrolase 1 (DDAH1)...
November 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/29094329/allopurinol-protects-human-glomerular-endothelial-cells-from-high-glucose-induced-reactive-oxygen-species-generation-p53-overexpression-and-endothelial-dysfunction
#8
Theodoros Eleftheriadis, Georgios Pissas, Georgia Antoniadi, Vassilios Liakopoulos, Ioannis Stefanidis
PURPOSE: Mitochondrial reactive oxygen species (ROS) overproduction in capillary endothelial cells is a prerequisite for the development of diabetic nephropathy. Inhibition of xanthine oxidase, another ROS generator, ameliorates experimental diabetic nephropathy. To test the hypothesis that the initial high glucose-induced ROS production by the mitochondria activates xanthine oxidase, which afterward remains as the major source of ROS, we cultured primary human glomerular endothelial cells (GEnC) under normal or high-glucose conditions, with or without the xanthine oxidase inhibitor allopurinol...
November 1, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/29089371/fxr-tgr5-dual-agonist-prevents-progression-of-nephropathy-in-diabetes-and-obesity
#9
Xiaoxin X Wang, Dong Wang, Yuhuan Luo, Komuraiah Myakala, Evgenia Dobrinskikh, Avi Z Rosenberg, Jonathan Levi, Jeffrey B Kopp, Amanda Field, Ashley Hill, Scott Lucia, Liru Qiu, Tao Jiang, Yingqiong Peng, David Orlicky, Gabriel Garcia, Michal Herman-Edelstein, Vivette D'Agati, Kammi Henriksen, Luciano Adorini, Mark Pruzanski, Cen Xie, Kristopher W Krausz, Frank J Gonzalez, Suman Ranjit, Alexander Dvornikov, Enrico Gratton, Moshe Levi
Bile acids are ligands for the nuclear hormone receptor farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5. We have shown that FXR and TGR5 have renoprotective roles in diabetes- and obesity-related kidney disease. Here, we determined whether these effects are mediated through differential or synergistic signaling pathways. We administered the FXR/TGR5 dual agonist INT-767 to DBA/2J mice with streptozotocin-induced diabetes, db/db mice with type 2 diabetes, and C57BL/6J mice with high-fat diet-induced obesity...
October 31, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29080120/clinicopathological-analysis-of-biopsy-proven-diabetic-nephropathy-based-on-the-japanese-classification-of-diabetic-nephropathy
#10
Kengo Furuichi, Miho Shimizu, Yukio Yuzawa, Akinori Hara, Tadashi Toyama, Hiroshi Kitamura, Yoshiki Suzuki, Hiroshi Sato, Noriko Uesugi, Yoshifumi Ubara, Junichi Hohino, Satoshi Hisano, Yoshihiko Ueda, Shinichi Nishi, Hitoshi Yokoyama, Tomoya Nishino, Kentaro Kohagura, Daisuke Ogawa, Koki Mise, Yugo Shibagaki, Hirofumi Makino, Seiichi Matsuo, Takashi Wada
BACKGROUND: The Japanese classification of diabetic nephropathy reflects the risks of mortality, cardiovascular events and kidney prognosis and is clinically useful. Furthermore, pathological findings of diabetic nephropathy are useful for predicting prognoses. In this study, we evaluated the characteristics of pathological findings in relation to the Japanese classification of diabetic nephropathy and their ability to predict prognosis. METHODS: The clinical data of 600 biopsy-confirmed diabetic nephropathy patients were collected retrospectively from 13 centers across Japan...
October 27, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29068452/alleviation-of-oxidative-stress-mediated-nephropathy-by-dietary-fenugreek-trigonella-foenum-graecum-seeds-and-onion-allium-cepa-in-streptozotocin-induced-diabetic-rats
#11
Seetur R Pradeep, Krishnapura Srinivasan
Oxidative stress plays a major role in the progression of diabetes and the pathogenesis of diabetic nephropathy. In this study, the beneficial influence of dietary fenugreek (Trigonella foenum-graecum) seeds and onion (Allium cepa) on oxidative stress-mediated renal injury was evaluated in streptozotocin-induced diabetic rats. Diabetes was induced in adult Wistar rats by the administration of streptozotocin (i.p. 45 mg kg(-1)). Dietary interventions were made with 10% fenugreek seeds or 3% onion (freeze-dried) or their combination for 6 weeks...
October 25, 2017: Food & Function
https://www.readbyqxmd.com/read/29062142/modelling-diabetic-nephropathy-in-mice
#12
REVIEW
Kengo Azushima, Susan B Gurley, Thomas M Coffman
Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in the developed world. Accordingly, an urgent need exists for new, curative treatments as well as for biomarkers to stratify risk of DN among individuals with diabetes mellitus. A barrier to progress in these areas has been a lack of animal models that faithfully replicate the main features of human DN. Such models could be used to define the pathogenesis, identify drug targets and test new therapies. Owing to their tractability for genetic manipulation, mice are widely used to model human diseases, including DN...
October 24, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/29053168/fl-926-16-a-novel-bioavailable-carnosinase-resistant-carnosine-derivative-prevents-onset-and-stops-progression-of-diabetic-nephropathy-in-db-db-mice
#13
Carla Iacobini, Stefano Menini, Claudia Blasetti Fantauzzi, Carlo M Pesce, Andrea Giaccari, Enrica Salomone, Annunziata Lapolla, Marica Orioli, Giancarlo Aldini, Giuseppe Pugliese
BACKGROUND AND PURPOSE: The advanced glycation endproducts (AGEs) participate in the pathogenesis of diabetic nephropathy (DN) by promoting renal inflammation and injury. L-carnosine acts as a quencher of the AGE precursors reactive carbonyl species (RCS), but it is rapidly inactivated by carnosinase. This study evaluated the effect of FL-926-16, a carnosinase-resistant and bioavailable carnosine derivative, on the onset and progression of DN in db/db mice. EXPERIMENTAL APPROACH: Adult male db/db mice and coeval db/m controls were left untreated or treated with FL-926-16 (30 mg·kg(-1) body weight) from week 6 to 20 (prevention protocol) or from week 20 to 34 (regression protocol)...
October 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29039485/calcium-dobesilate-may-alleviate-diabetes%C3%A2-induced-endothelial-dysfunction-and-inflammation
#14
Yijun Zhou, Jiangzi Yuan, Chaojun Qi, Xinghua Shao, Shan Mou, Zhaohui Ni
Diabetic kidney disease (DKD) is a leading cause of end‑stage renal disease. However, the pathogenesis of DKD remains unclear, and no effective treatments for the disease are available. Thus, there is an urgent need to elucidate the pathogenic mechanisms of DKD and to develop more effective therapies for this disease. Human umbilical vein endothelial cells (HUVECs) were cultured using different D‑glucose concentrations to determine the effect of high glucose (HG) on the cells. Alternatively, HUVECs were incubated with 100 µmol/l calcium dobesilate (CaD) to detect its effects...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29038616/sumo-e3-ligase-piasy-mediates-high-glucose-induced-activation-of-nf-%C3%AE%C2%BAb-inflammatory-signaling-in-rat-mesangial-cells
#15
Wei Huang, Yaling Liang, Jianhua Dong, Luping Zhou, Chenlin Gao, Chunxia Jiang, Meijuan Chen, Yang Long, Yong Xu
BACKGROUND: Sumoylation is extensively involved in the regulation of NF-κB signaling. PIASy, as a SUMO E3 ligase, has been proved to mediate sumoylation of IκB kinase γ (IKKγ) and contribute to the activation of NF-κB under genotoxic agent stimulation. However, the association of PIASy and NF-κB signaling in the pathogenesis of diabetic nephropathy (DN) has not been defined. METHODS: Rat glomerular mesangial cells (GMCs) were stimulated by high glucose; siRNA was constructed to silence the expression of PIASy; the expression of PIASy, SUMO isoforms (SUMO1, SUMO2/3), and NF-κB signaling components was analyzed by Western blot; the interaction between IKKγ and SUMO proteins was detected by coimmunoprecipitation; and the release of inflammatory cytokines MCP-1 and IL-6 was assayed by ELISA...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29037450/tissue-expression-of-tubular-injury-markers-is-associated-with-renal-function-decline-in-diabetic-nephropathy
#16
Subin Hwang, Jeeeun Park, Jinhae Kim, Hye Ryoun Jang, Ghee Young Kwon, Wooseong Huh, Yoon-Goo Kim, Dae Joong Kim, Ha Young Oh, Jung Eun Lee
AIMS: The pathogenesis of diabetic kidney disease (DKD) is complex and multifactorial; increasing evidence suggests that tubular injury and inflammatory process are involved in disease progression. We investigated the potential association of renal expression of tubular injury markers, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and inflammatory markers, tumor necrosis factor receptor (TNFR) 1 and 2 with renal progression in pathologically proven diabetic nephropathy (DN)...
August 24, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/29031207/microrna-25-inhibits-high-glucose-induced-apoptosis-in-renal-tubular-epithelial-cells-via-pten-akt-pathway
#17
Huicong Li, Xiaoguang Zhu, Junwei Zhang, Jun Shi
Diabetic nephropathy (DN) has become the major cause of end-stage renal disease (ESRD). It has been demonstrated that apoptosis of renal tubular epithelial cells induced by hyperglycemia contributes to the pathogenesis of DN. Recent researches have corroborated the critical roles of microRNAs (miRNAs) in the apoptosis of various types of cells including renal tubular epithelial cells. However, the eff ; ;ect of miRNAs on the hyperglycemia-induced apoptosis of renal tubular epithelial cells remains unclear...
October 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29022053/glycated-albumin-ga-and-inflammation-role-of-ga-as-a-potential-marker-of-inflammation
#18
REVIEW
H Vernon Roohk, Asad R Zaidi, Dimple Patel
AIMS: Abnormal levels of glycated albumin (GA) are associated with the onset of both diabetes and inflammation. Although inflammation has long been associated with diabetes, this article aims to explore the underlying mechanisms of this relationship as it pertains to the role of GA. METHODS: We have reviewed 52 research articles since the year 2000. Common search terms used were "(inflammatory mediator) and GA" or "inflammation and GA". The findings have been organized according to diabetic complications with respect to the interactions of GA and inflammatory mediators...
October 11, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29020797/extracellular-superoxide-dismutase-attenuates-renal-oxidative-stress-through-the-activation-of-adenosine-monophosphate-activated-protein-kinase-in-diabetic-nephropathy
#19
Yu Ah Hong, Ji Hee Lim, Min Young Kim, Yaeni Kim, Hoon Suk Park, Hyung Wook Kim, Bum Soon Choi, Yoon Sik Chang, Hye Won Kim, Tae-Yoon Kim, Cheol Whee Park
AIMS: Oxidative stress plays a crucial role in the pathogenesis of diabetic nephropathy (DN). We evaluated whether extracellular superoxide dismutase (EC-SOD) has a renoprotective effect through activation of adenosine monophosphate-activated protein kinase (AMPK) in diabetic kidneys. RESULTS: Human recombinant EC-SOD (hEC-SOD) was administered to 8-week-old male C57BLKS/J db/db mice through intraperitoneal injection once a week for 8 weeks. Renal SOD3 expression was suppressed in db/db mice, which was significantly enhanced by hEC-SOD treatment...
November 14, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28987240/protein-tyrosine-phosphatase-1b-deficiency-in-podocytes-mitigates-hyperglycemia-induced-renal-injury
#20
Yoshihiro Ito, Ming-Fo Hsu, Ahmed Bettaieb, Shinichiro Koike, Aline Mello, Miguel Calvo-Rubio, Jose M Villalba, Fawaz G Haj
OBJECTIVE: Diabetic nephropathy is one of the most devastating complications of diabetes, and growing evidence implicates podocyte dysfunction in disease pathogenesis. The objective of this study was to investigate the contribution of protein tyrosine phosphatase 1B (PTP1B) in podocytes to hyperglycemia-induced renal injury. METHODS: To determine the in vivo function of PTP1B in podocytes we generated mice with podocyte-specific PTP1B disruption (hereafter termed pod-PTP1B KO)...
November 2017: Metabolism: Clinical and Experimental
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