Improving the ability of kidney to tolerate ischemic injury has important implications. We investigated effect recombinant human erythropoietin (rHuEPO) treatment on subsequent ischemia/reperfusion (I/R) and evaluated role heat shock protein (HSP) 70 in rHuEPO-induced renal protection. rHuEPO (3000 U/kg) was administered 24 h before I/R injury, rats were killed at 24, 48, 72 after injury. Pretreatment resulted following: i) decreased serum creatinine level; ii) tubular cell apoptosis...

There is growing evidence of a role the immune system in pathophysiology ischemia-reperfusion (I/R) injury, but influence I/R injury on innate immunity still undetermined.Sprague-Dawley rats were used. was induced by clamping both renal arteries for 45 min, and killed 1, 3, 5, 7 days later. Activation evaluated terms expression toll-like receptor (TLR) 2 or TLR4 mRNAs protein, level TLR ligand (heat shock protein [HSP] 70), maturation dendritic cells double-label immunohistochemistry major...

Mammalian members of the forkhead box protein O (FoxO) class transcription factors are implicated in regulation oxidative stress, and FoxO proteins negatively regulated by phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway. We examined effect Klotho on PI3K/AKT pathway manganese superoxide dismutase (MnSOD) during tacrolimus (Tac)-induced stress. Klotho-treated mice showed decreased Tac-induced stress accompanied functional histological improvements. inhibited PI3K/AKT-mediated...

Peroxisome proliferator–activated receptor (PPAR)α, a member of the ligand-activated nuclear superfamily, plays an important role in lipid metabolism and glucose homeostasis is highly expressed kidney. The present studies were aimed at determining PPARα pathogenesis diabetic nephropathy using PPARα-knockout mice cultured murine mesangial cells. Diabetes was induced low-dose streptozotocin protocol 8-week-old male 129 SvJ wild-type mice. Diabetic developed elevated fasting blood (P <...

We investigated the effects of pravastatin, a competitive inhibitor 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, on interstitial inflammation and fibrosis, using an animal model chronic cyclosporine (CsA)-induced nephropathy. Sprague-Dawley rats were maintained low-salt diet (0.05% sodium) treated daily for 1 or 4 wk with vehicle (olive oil; ml/kg sc), CsA (15 mg/kg both pravastatin (5 20 in drinking water). Anti-inflammatory antifibrotic studied by evaluating concentrations...

An inhibitor of sodium glucose co-transporter type 2 (SGLT-2) is recommended in diabetes mellitus (DM) but its use still undetermined tacrolimus (TAC)-induced DM. We evaluated the effect empagliflozin (Em) on TAC-induced pancreatic islet dysfunction and renal injury an experimental model DM vitro. TAC induced a twofold increase SGLT-2 expression, while Em decreased expression further increased urinary excretion compared to group. reduced hyperglycemia plasma insulin level, size,...

Growing evidence suggests that GLP-1 protects beta cells against various cellular injuries by modulating autophagy. In this study, we examined whether exendin-4 (Ex-4), a analog, had preventive effects on tacrolimus (Tac)-induced cell injury improving autophagy clearance. Rats with Tac-induced diabetes mellitus exhibited increased autophagy-associated protein expression, light chain 3B levels, and autophagic vacuole numbers in pancreatic cells. Additionally, Tac dose- time-dependent manner...

Abstract Objectives To explore the possibility of kidney organoids generated using patient derived human induced pluripotent stem cells (hiPSC) for modeling Fabry disease nephropathy (FDN). Methods First, we hiPSC line peripheral blood mononuclear (PBMCs) from two male FD-patients with different types GLA mutation: a classic type mutation (CMC-Fb-001) and non-classic (CMC-Fb-003) mutation. Second, wild-type (WT) (WTC-11) mutant hiPSCs (CMC-Fb-001 CMC-Fb-003). We then compared...

<i>Background/Aims:</i> Apoptosis contributes to cyclosporine (CsA)-induced renal cell death. This study tested the effects of CsA-induced endoplasmic reticulum (ER) stress on apoptotic death in an experimental model chronic CsA nephropathy. <i>Methods:</i> (15 mg/kg per day) was given rats for 7 or 28 days. The ER response evaluated with BiP expression, and proapoptotic assessed CHOP caspase 12 expression. structure by transmission electron microscopy, detected TUNEL...

TonEBP (tonicity-responsive enhancer binding protein) is a transcription factor that promotes cellular accumulation of organic osmolytes in the hypertonic renal medulla by stimulating expression its target genes. Genetically modified animals with deficient activity kidney suffer from severe medullary atrophy association cell death, demonstrating essential for survival cells. Using both knockout cells and RNA interference TonEBP, we found promoted adaptation to stress. Microarray analyses...

<b><i>Background:</i></b> We recently reported that long-term cyclosporine (CsA)-induced oxidative stress is associated with decreased expression of <i>klotho</i>, an anti-aging gene. This study evaluated whether the antioxidant effect statin might upregulate klotho in CsA-induced renal injury. <b><i>Methods:</i></b> Two separate experiments were performed. First, dose-dependent on was normal mouse kidneys. Second, experimental...

<b><i>Background:</i></b> This study was performed to investigate whether ginseng extract has a protective effect in an experimental mouse model of chronic cyclosporine (CsA) nephropathy. <b><i>Methods:</i></b> Mice were treated with CsA (30 mg/kg/day, subcutaneously) or without Korean red (KRG) (0.2, 0.4 g/kg/day, orally) on 0.01% salt diet for 4 weeks. The KRG CsA-induced renal injury evaluated by assessing function and pathology, mediators...

Abstract We previously reported that oxidative stress induced by long-term tacrolimus treatment impairs mitochondrial function in pancreatic beta cells. In this study, we aimed to investigate the therapeutic potential of coenzyme Q 10 , which is known be a powerful antioxidant, dysfunction tacrolimus-induced diabetic rats. rat model diabetes mellitus, improved cell function. The administration insulin immunoreactivity within islets, was accompanied reductions and apoptosis. Assessment...

Tonicity-responsive enhancer binding protein (TonEBP or NFAT5) is a regulator of cellular adaptation to hypertonicity, macrophage activation and T-cell development. Here we report that TonEBP an epigenetic thermogenesis obesity. In mouse subcutaneous adipocytes, expression increases > 50-fold in response high-fat diet (HFD) feeding. Mice with haplo-deficiency adipocyte-specific deficiency are resistant HFD-induced obesity metabolic defects (hyperglycemia, hyperlipidemia, hyperinsulinemia)....

Abstract In this study, a novel polyhistidine‐incorporated lipid nanoparticle (pHis/LNP) is developed for the delivery of therapeutic globotriaosylceramide (Gb3) synthase siRNAs using microfluidic device with pHis as biocompatible method endosome escape. To inhibit expression Gb3 synthase, six against are designed and an optimal siRNA sequence selected. Selected incorporated into pHis/LNP to prepare spherical size 62.5 ± 1.9 nm surface charge −13.3 4.2 mV. The successfully protects from...

Celiac disease (CeD) is an autoimmune disorder triggered by gluten, primarily affecting the small intestine but potentially impacting other systems, including nervous system through gut-brain axis. This study employed Mendelian randomization (MR) to explore causal relationships between CeD and several neurological disorders, with a particular focus on multiple sclerosis (MS). Utilizing genetic data from OpenGWAS Finngen databases, we applied various MR methods, Inverse Variance Weighted...

Accumulating evidence suggests that Th17 cells play a role in the development of chronic allograft injury transplantation various organs. However, influence current immunosuppressants on Th17-associated immune responses has not been fully investigated. We prospectively investigated changes peripheral blood mononuclear (PBMCs) collected before and 1 3 months after KT 26 patients we suppressive effect tacrolimus vitro. In early posttransplant period, percentage proportion IL-17-producing...

Background The study was performed to investigate the influence of cyclosporine A (CsA)–induced renal injury on autophagy in an experimental model chronic CsA nephropathy. Methods Three dosages (7.5, 15, and 30 mg/kg/day) were administered mice for 4 weeks. formation autophagosomes measured with microtubule-associated protein 1 light chain 3 phospholipid-conjugated form (LC3-II) beclin-1, ability autophagic clearance examined sequestosome-1 (p62). Autophagic vacuoles visualized counted using...

<b><i>Background:</i></b> Klotho is highly expressed in the kidney, present circulation and urine, has protective effects against various renal injuries. We examined whether reduced expression affects tacrolimus (Tac)-induced injury an experimental model of chronic Tac nephropathy. <b><i>Methods:</i></b> First, we evaluated association between dose by giving different doses (0.25, 0.5, 1 mg/kg) to wild-type (WT) mice for 4 weeks. Second,...

Diabetic nephropathy (DN) has become the single leading cause of ESRD in developed nations. Bearing mind paucity effective treatment for DN and progressive CKD, novel targets are sorely needed. We previously reported that increased activity tonicity-responsive enhancer-binding protein (TonEBP) monocytes was associated with early humans. now extend these findings by testing hypotheses TonEBP macrophages promotes hyperglycemia-mediated proinflammatory activation chronic renal inflammation to...

Recently, we showed that tacrolimus-induced renal injury was closely associated with impairment of autophagy clearance, and Klotho deficiency aggravated injury. In this study, evaluated the effect treatment on clearance in We an experimental mouse model vitro by tacrolimus and/or recombinant Klotho. vivo studies impaired lysosomal acidification decreased cathepsin B activity, expression lysosome-associated membrane protein 2, transcription factor EB (TFEB), a master regulator for biogenesis....

It is not clear whether ginseng affects cyclosporine A (CsA)-induced desirable immunosuppressive action. In this study, we evaluated the immunological influence of combined treatment with CsA.Using CD4+ T cells from mouse spleens stimulated cell receptor (TCR) or allogeneic antigen-presenting (APCs), examined differentiation naïve into helper 1 (Th1), Th2, Th17, and regulatory (Tregs), their cytokine production during by Korean Red Ginseng extract (KRGE) and/or CsA. The KRGE on response was...