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https://www.readbyqxmd.com/read/30554341/renoprotective-effects-of-the-novel-prostaglandin-ep4-receptor-selective-antagonist-asp7657-in-5-6-nephrectomized-chronic-kidney-disease-rats
#1
Kazuhiko Mizukami, Hiroyuki Yoshida, Eisuke Nozawa, Koichi Wada, Tohru Ugawa
Prostaglandins (PGs) are important lipid mediators of numerous physiologic and pathophysiologic processes in the kidney. PGE2 , the most abundant renal PG, plays a major role in renal physiology, including renin release and glomerular hemodynamics. We investigated the renoprotective properties of the novel PGE2 EP4 receptor-selective antagonist ASP7657 in 5/6 nephrectomized rats, a chronic kidney disease (CKD) model. Eight weeks of repeated administration of ASP7657 (0.001-0.1 mg/kg) dose-dependently and significantly reduced urinary protein excretion and attenuated the development of glomerulosclerosis and tubulointerstitial damage, including fibrosis and inflammatory cell infiltration, without affecting blood pressure...
December 15, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/30553290/unilateral-segmental-dysplasia-of-the-vas-deferens
#2
Theodore R Saitz, Anil A Thomas
A healthy 35-year-old male presented for vasectomy after fathering two children. Due to difficulty palpating the left vas, the patient was taken to the operating room for scrotal exploration and vasectomy. The left vas was absent; however, a 1.2 cm pearly nodule was identified in the scrotum along its suspected course. This nodule was excised, found to contain thick white pasty fluid, and confirmed vas deferens by pathology. The patient was found to have normal kidneys on renal ultrasound and was indeed a carrier for cystic fibrosis gene mutations...
December 2018: Canadian Journal of Urology
https://www.readbyqxmd.com/read/30553193/the-renoprotective-effect-of-the-dipeptidyl-peptidase-4-inhibitor-sitagliptin-on-adenine-induced-kidney-disease-in-rats
#3
Aly M Abdelrahman, Yousuf Al Suleimani, Mohammed Al Za'abi, Mohammed Ashique, Priyadarsini Manoj, Christina Hartmann, Abderrahim Nemmar, Nicole Schupp, Badreldin H Ali
We assessed the effect of treatment with the dipeptidyl peptidase-4 inhibitor, sitagliptin, on adenine-induced chronic kidney disease (CKD). Six equal groups of rats were given either normal food or food mixed with adenine (0.25% w/w for five weeks) to induce CKD. Some of these groups were also simultaneously treated with sitagliptin (2.5 and 10 mg/kg/day, by gavage). Rats given adenine showed elevation of blood pressure, decreased body weight and increased relative kidney weight. Adenine also significantly increased plasma urea, creatinine, cystatin C, liver-type fatty acid-binding protein concentrations and neutrophil gelatinase-associated lipocalin activity by 404%, 354%, 667%, 91% and 281% respectively and reduced plasma α-Klotho by 50%...
December 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30551545/dapagliflozin-attenuates-early-markers-of-diabetic-nephropathy-in-fructose-streptozotocin-induced-diabetes-in-rats
#4
Mamdouh A Oraby, Mohammed F El-Yamany, Marwa M Safar, Naglaa Assaf, Hamdy A Ghoneim
Early detection and clinical interference are major challenges for the prevention of diabetic nephropathy (DN) progression. This study investigated the effects of dapagliflozin, a sodium glucose co-transporter 2 inhibitor, on some early markers for DN in fructose-streptozotocin (Fr-STZ)-induced diabetes in rats. Fr-STZ rats were treated with either dapagliflozin (1 mg/kg p.o. daily), metformin (350 mg/kg p.o. daily), or their combination for 6 weeks. Fr-STZ rats displayed marked early tubular renal damage and glomerular podocyte injury as evidenced by renal KIM-1, NGAL, cystatin C, and vanin-1 mRNA, as well as urinary NAG elevation and nephrin mRNA suppression, associated with the development of marked renal interstitial fibrosis and glomerulosclerosis despite the presence of normoalbuminuria...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30551434/pterostilbene-a-bioactive-component-of-blueberries-alleviates-renal-fibrosis-in-a-severe-mouse-model-of-hyperuricemic-nephropathy
#5
Jing Pan, Min Shi, Lingzhi Li, Jing Liu, Fan Guo, Yanhuan Feng, Liang Ma, Ping Fu
Accumulating evidences indicated that hyperuricemia was an independent risk factor for kidney diseases and contributed to kidney fibrosis. Preventing and treating renal fibrosis was an optimal treatment for hyperuricemia-induced kidney diseases. In the study, pterostilbene (PTE) as a bioactive component of blueberries was confirmed to possess lowering serum uric acid and renal protective functions by the decrease of serum creatinine, BUN, urine albumin, and urine albumin-to-creatinine ratio (uACR) in a mouse model of hyperuricemic nephropathy (HN)...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30551415/kaempferol-attenuates-diabetic-nephropathy-by-inhibiting-rhoa-rho-kinase-mediated-inflammatory-signalling
#6
Dilip Sharma, Piyush Gondaliya, Vinod Tiwari, Kiran Kalia
RhoA/Rho-associated coiled-coil forming protein serine/threonine kinase (ROCK) has appeared as a potential therapeutic target in numerous diseases, because of its preventing action on various enzymes providing antioxidant and cytoprotective action. Progression and pathophysiology of diabetic nephropathy have also shown potential involvement of oxidative stress and inflammatory pathways. In the present study, we investigated the effect of kaempferol on hyperglycemia-induced activation of RhoA kinase and associated inflammatory signaling cascade...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30551358/mechanistic-role-of-camp-and-hepatocyte-growth-factor-signaling-in-thioacetamide-induced-nephrotoxicity-unraveling-the-role-of-platelet-rich-plasma
#7
Walaa Arafa Keshk, Samer Mahmoud Zahran
Chronic kidney diseases occur as result of exposure to wide range of deleterious agents as environmental pollutants, toxins and drug. Currently, there is no effective protective therapy against renal damage, fibrosis and its sequel of end stage renal disease. Platelet-rich plasma (PRP) has a progressively gained consideration in wound healing, repair/regeneration of damaged tissues and conservation of organ function. However, its impact on thioacetamide (TAA) induced chronic renal damage has not been elucidated yet...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30551123/aerobic-exercise-training-alleviates-renal-injury-by-interfering-with-mitochondrial-function-in-type-1-diabetic-mice
#8
Lin-Xia Tang, Bin Wang, Zhi-Kun Wu
BACKGROUND Diabetic nephropathy was one of the most serious and harmful diabetic complications, characterized by progressive loss of renal function and renal fibrosis. Aerobic exercise training is an important non-pharmacologic method to prevent and treat diabetes mellitus and diabetic complications. MATERIAL AND METHODS Intraperitoneal (i.p.) injection of streptozocin (STZ) was used to construct a type 1 diabetic mouse model. Renal function and mitochondrial function were measured by urinary protein level, Masson staining and ATP, superoxide production, and membrane potential, respectively...
December 14, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/30546836/inhibition-of-heparanase-protects-against-chronic-kidney-dysfunction-following-ischemia-reperfusion-injury
#9
Valentina Masola, Gloria Bellin, Gisella Vischini, Luigi Dall'Olmo, Simona Granata, Giovanni Gambaro, Antonio Lupo, Maurizio Onisto, Gianluigi Zaza
Renal ischemia/reperfusion (I/R) injury occurs in patients undergoing renal transplantation and with acute kidney injury and is responsible for the development of chronic allograft dysfunction as characterized by parenchymal alteration and fibrosis. Heparanase (HPSE), an endoglycosidase that regulates EMT and macrophage polarization, is an active player in the biological response triggered by ischemia/reperfusion (I/R) injury. I/R was induced in vivo by clamping left renal artery for 30 min in wt C57BL/6J mice...
November 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/30545984/expression-profiling-of-fibroblasts-in-chronic-and-acute-disease-models-reveals-novel-pathways-in-kidney-fibrosis
#10
Atsuko Y Higashi, Bruce J Aronow, Gregory R Dressler
BACKGROUND: Renal interstitial fibrosis results from activation and proliferation of fibroblasts to myofibroblasts, secretion and accumulation of extracellular matrix, and displacement of normal renal tubules. In contrast to chronic renal disease, acute injury may be repaired, a process that includes a decrease in the number of myofibroblasts in the interstitium and degradation of the accumulated extracellular matrix, leaving little evidence of prior injury. METHODS: To investigate whether activated fibroblasts demonstrate changes in gene expression that correspond with regression after acute injury but are not observed in chronic models of fibrosis, we used microarrays to analyze gene expression patterns among fibroblast populations at different stages of injury or repair...
December 13, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/30545632/autophagy-in-foxd1-stroma-derived-cells-regulates-renal-fibrosis-through-tgf-%C3%AE-and-nlrp3-inflammasome-pathway
#11
Sun Ah Nam, Wan-Young Kim, Jin-Won Kim, Min Gyu Kang, Sang Hee Park, Myung-Shik Lee, Hyung Wook Kim, Chul Woo Yang, Jin Kim, Yong Kyun Kim
Renal fibrosis is the final common pathway of various renal injuries and it leads to chronic kidney disease. Recent studies reported that FOXD1-lineage pericyte plays a critical role in tubulointerstitial fibrosis (TIF). However the regulatory mechanisms remain unclear. Autophagy is a cellular process of degradation of damaged cytoplasmic components that regulates cell death and proliferation. To investigate the role of autophagy in FOXD1-lineage pericytes on renal TIF, we generated the FOXD1-lineage stromal cell-specific Atg7 deletion (Atg7△FOXD1 ) mice...
December 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/30543420/design-and-synthesis-of-potent-long-acting-lipidated-relaxin-2-analogs
#12
Avinash Muppidi, Sang Jun Lee, Che-Hsiung Hsu, Huafei Zou, Candy Lee, Elsa Pflimlin, Madhupriya Mahankali, Pengyu Yang, Elizabeth Chao, Insha Ahmad, Andreas Crameri, Danling Wang, Ashley Woods, Weijun Shen
Peptide hormone relaxin-2, a member of the insulin family of peptides, plays a key role in hemodynamics and renal function and has shown preclinical efficacy in multiple disease models, including acute heart failure, fibrosis, preeclampsia, and corneal wound healing. Recently, serelaxin, a recombinant version of relaxin-2, has been studied in a large phase 3 clinical trial (RELAX-AHF-2) for acute decompensated heart failure patients with disappointing outcome. The poor in vivo half-life of relaxin-2 may have limited its therapeutic efficacy and long-term cardiovascular benefit...
December 13, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/30541245/mediterranean-fever-mefv-gene-mutations-in-glomerulonephritides-a-clinicopathological-study
#13
Ufuk İlgen, Gökhan Nergizoğlu
Background/aim: The aim of this study is to determine the ME diterranean F e V er ( MEFV ) gene mutation carrier rate in patients with glomerulonephritis and to investigate the association between disease features and MEFV variants. Materials and methods: Medical records regarding clinical, laboratory, histopathological, and prognostic features of 200 adult patients with biopsy-proven glomerulonephritis were evaluated retrospectively. Exons 2 and 10 of the MEFV gene of each patient were sequenced by next-generation sequencing...
December 12, 2018: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/30540645/combination-of-st2-and-b-type-natriuretic-peptide-in-diabetic-patients-with-acute-heart-failure-relation-with-ventricular-stiffness-and-outcome
#14
Gaetano Ruocco, Isabella Evangelista, Beatrice Franci, Barbara Lucani, Simona Martini, Ranuccio Nuti, Alberto Palazzuoli
BACKGROUND: Diabetes is a common disease in heart failure and its prevalence ranges from 10 to 30%. ST-2 is a novel biomarker of myocardial fibrosis and remodelling in heart failure and may be involved in the inflammatory process of diabetes mellitus. In this study, we sought: to evaluate levels of ST-2 and B-type natriuretic peptide (BNP) in groups with acute heart failure with and without diabetes; to analyse the prognostic impact of ST-2 over a 6-month follow-up period. METHODS: We performed an echocardiographic examination and measured ST-2 and BNP within 24 h of hospital admission...
December 11, 2018: Journal of Cardiovascular Medicine
https://www.readbyqxmd.com/read/30539697/generation-of-a-primary-hyperoxaluria-type-1-disease-model-via-crispr-cas9-system-in-rats
#15
Rui Zheng, Xiaoliang Fang, Lei He, Yanjiao Shao, Nana Guo, Liren Wang, Mingyao Liu, Dali Li, Hongquan Geng
BACKGROUND: Primary hyperoxaluria type 1 (PH1) is an inherited disease caused by mutations in alanine-glyoxylate aminotransferase (AGXT). It is characterized by abnormal metabolism of glyoxylic acid in liver leading to endogenous oxalate overproduction and deposition of oxalate in multiple organs, mainly the kidney. Patients of PH1 often suffer from recurrent urinary tract stones, and finally renal failure. There is no effective treatment other than combined liver-kidney transplantation...
December 11, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/30539648/unravelling-reno-protective-effects-of-sglt2-inhibition-in-human-proximal-tubular-cells
#16
Markus Pirklbauer, Ramona Schupart, Lisa Christina Fuchs, Petra Staudinger, Ulrike Corazza, Sebastian Sallaberger, Johannes Leierer, Gert Mayer, Herbert Schramek
Large clinical trials demonstrated that SGLT2 inhibitors (SGLT2i) slow the progression of kidney function decline in type 2 diabetes. As the underlying molecular mechanisms are largely unknown, we studied the effects of SGLT2i on gene expression in two human proximal tubular (PT) cell lines under normoglycemic conditions, utilizing two SGLT2i, namely empagliflocin and canagliflocin. Genome-wide expression analysis did not reveal substantial differences between these two SGLT2i. Microarray hybridization analysis identified 94 genes that were both upregulated by TGF-ß1 and downregulated by either of the two SGLT2i in HK-2 and RPTEC/TERT1 cells...
December 12, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/30538643/preventing-peritoneal-dialysis-associated-fibrosis-by-therapeutic-blunting-of-peritoneal-toll-like-receptor-activity
#17
REVIEW
Anne-Catherine Raby, Mario O Labéta
Peritoneal dialysis (PD) is an essential daily life-saving treatment for end-stage renal failure. PD therapy is limited by peritoneal inflammation, which leads to peritoneal membrane failure as a result of progressive fibrosis. Peritoneal infections, with the concomitant acute inflammatory response and membrane fibrosis development, worsen PD patient outcomes. Patients who remain infection-free, however, also show evidence of inflammation-induced membrane damage and fibrosis, leading to PD cessation. In this case, uraemia, prolonged exposure to bio-incompatible PD solutions and surgical catheter insertion have been reported to induce sterile peritoneal inflammation and fibrosis as a result of cellular stress or tissue injury...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/30537019/lipophagy-in-nonliver-tissues-and-some-related-diseases-pathogenic-and-therapeutic-implications
#18
REVIEW
Kebing Zhou, Pingbo Yao, Jun He, Hong Zhao
Lipid autophagy (lipophagy) is defined as a selective autophagy process in which some intracellular lipid droplets are selectively degraded by autophagic lysosomes pathway. The occurrence of lipophagy was first discovered in liver tissues. Additionally, abundant evidence indicated that the occurrence of hepatic lipophagy has been implicated in many liver diseases including fatty liver diseases, nonalcoholic fatty liver diseases, liver fibrosis, and liver cirrhosis. However, recent studies suggested that hepatic lipophagy occurs not only in liver tissue but also in other nonliver tissues and cells...
December 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30536302/hgf-alleviates-renal-interstitial-fibrosis-via-inhibiting-the-tgf-%C3%AE-1-smad-pathway
#19
J Xu, T-T Yu, K Zhang, M Li, H-J Shi, X-J Meng, L-S Zhu, L-K Zhu
OBJECTIVE: To study the role of HGF (stem cell growth factor) in renal interstitial fibrosis and to explore its underlying mechanism. MATERIALS AND METHODS: A unilateral ureteral obstruction (UUO) mouse model was first constructed, and kidney samples of mice were then collected. Fibrosis-related indicators in UUO mice kidney were detected by Western blot. The mRNA and protein levels of HGF in UUO mice were detected by quantitative Real-time-polymerase chain reaction (qRT-PCR) and Western blot, respectively...
November 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/30536131/the-mirna-184-drives-renal-fibrosis-by-targeting-hif1an-in-vitro-and-in-vivo
#20
Bin Chen
Progressive renal fibrosis is the last phase of chronic kidney disease and results in renal failure. Micro-RNA has been demonstrated as important agent to drive organ fibrosis. However, the precise mechanisms are not fully understood. Here, we found miRNA-184 as a critical mediator to promote the renal fibrosis by targeting HIF1AN. In Vivo, miRNA-184 expression levels remarkably increased both in patients' serum and in unilateral ureteral obstruction kidneys, as well as induced the expression of COL1A1 and COL3A1...
December 10, 2018: International Urology and Nephrology
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