Development of gene silencer pyrrole-imidazole polyamides targeting GSK3β for treatment of polycystic kidney diseases.

The cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB)-glycogen synthase kinase 3β (GSK3β) signaling pathway was reported to be involved in the progression of autosomal dominant polycystic kidney diseases (ADPKD). We designed and synthesized pyrrole-imidazole (PI) polyamides as novel gene-silencers to prevent binding of CREB on the GSK3β gene promoter and examined the effects of the PI polyamides on proliferation and cyst formation of mouse collecting duct M1 cells. The GSK3β PI polyamides significantly inhibited expression of GSK3β mRNA in M1 cells with forskolin.

Transcriptional Suppression of Diabetic Nephropathy with Novel Gene Silencer Pyrrole-Imidazole Polyamides Preventing USF1 Binding to the TGF-β1 Promoter.

Upstream stimulatory factor 1 (USF1) is a transcription factor that is increased in high-glucose conditions and activates the transforming growth factor (TGF)-β1 promoter. We examined the effects of synthetic pyrrole-imidazole (PI) polyamides in preventing USF1 binding on the TGF-β1 promoter in Wistar rats in which diabetic nephropathy was established by intravenous administration of streptozotocin (STZ). High glucose induced nuclear localization of USF1 in cultured mesangial cells (MCs).

Correlation between Aortic Calcification Score and Biochemical Parameters in Hemodialysis Patients.

Background: The purpose of this study was to determine the correlation between aortic calcification and demographic and biochemical parameters in hemodialysis patients.

Summary: Calcification scores of the aortic arch and abdominal aorta were determined from multi-slice computed tomography scans and evaluated according to the Agatston score. The associations between demographic and biochemical parameters and aortic calcification score were determined.

Prevalence of Carnitine Deficiency and Decreased Carnitine Levels in Patients on Hemodialysis.

Background: Patients on hemodialysis (HD) are known to be at risk of carnitine deficiency. The aims of this study were to investigate the prevalence of carnitine deficiency in patients on dialysis and to compare the likelihood of a reduction in the serum carnitine level on HD with that on hemodiafiltration (HDF).

Methods: The prevalence of carnitine deficiency, defined as a serum free carnitine level < 20 μmol/L, and that of carnitine insufficiency, defined as an acyl/free carnitine ratio > 0.