Upstream and downstream regulators of Klotho expression in chronic kidney disease.

Klotho is a critical protein that protects the kidney. Klotho is severely downregulated in chronic kidney disease (CKD), and its deficiency is implicated in the pathogenesis and progression of CKD. Conversely, an increase in Klotho levels results in improved kidney function and delays CKD progression, supporting the notion that modulating Klotho levels could represent a possible therapeutic strategy for CKD treatment.

The controversy of klotho as a potential biomarker in chronic kidney disease.

Klotho is an identified longevity gene with beneficial pleiotropic effects on the kidney. Evidence shows that a decline in serum Klotho level occurs in early chronic kidney disease (CKD) and continues as CKD progresses. Klotho deficiency is associated with poor clinical outcomes and CKD mineral bone disorders (CKD-MBD).

CCL5 Suppresses Klotho Expression p-STAT3/DNA Methyltransferase1-Mediated Promoter Hypermethylation.

Background: Enhanced inflammation and reduced Klotho are common features in chronic kidney disease (CKD). Inflammation induces DNA hypermethylation. This study assessed the performance of inflammatory marker C-C motif chemokine 5 (CCL5) in epigenetic regulation of Klotho expression.

Abnormally decreased renal Klotho is linked to endoplasmic reticulum-associated degradation in mice.

: Endoplasmic reticulum-associated degradation (ERAD), which involves degradation of improperly folded proteins retained in the ER, is implicated in various diseases including chronic kidney disease. This study is aimed to determine the role of ERAD in Klotho deficiency of mice and human kidney tubular epithelial cells (HK-2) with renal interstitial fibrosis (RIF). : Following establishment of a mouse RIF model by unilateral ureteral obstruction (UUO), a specific ERAD inhibitor, Eeyarestatin I (EerI), was administered to experimental animals by intraperitoneal injection.

Correlation Between Soluble Klotho and Vascular Calcification in Chronic Kidney Disease: A Meta-Analysis and Systematic Review.

The correlation between soluble Klotho (sKlotho) level and vascular calcification (VC) in patients with chronic kidney disease (CKD) remains controversial. Using meta-analysis, we aimed to address this controversy and assess the feasibility of applying sKlotho as a biomarker for VC. Medical electronic databases were thoroughly searched for eligible publications on the association between sKlotho level and VC in CKD patients.

Meta-analysis of the association between sclerostin level and adverse clinical outcomes in patients undergoing maintenance haemodialysis.

Background: Studies regarding the relationship of sclerostin (Scl) with clinical outcomes in patients undergoing maintenance haemodialysis have yielded controversial findings. This meta-analysis was performed to investigate the predictive role of Scl in this patient population.

Methods: Several electronic medical databases (e.

Association of Soluble Klotho Level with Adverse Outcomes in Patients on Maintenance Hemodialysis.

Background: The predictive value of soluble Klotho (sKlotho) for adverse outcomes in patients on maintenance hemodialysis (MHD) is controversial. In this study, we aimed to clarify the potential association of sKlotho levels with adverse outcomes in this patient population.

Materials: A total of 211 patients on MHD were identified and stratified according to the median sKlotho level.

The prognostic value of soluble Klotho in patients with haemodialysis: a systematic review and meta-analysis.

Aim: The correlation between soluble Klotho (sKlotho) levels and clinical outcomes remains inconclusive for patients undergoing maintenance haemodialysis (MHD). We aimed to evaluate the potential predictive significance of sKlotho in this population by conducting a meta-analysis.

Methods: PubMed, Embase, Web of Science and Cochrane Library were comprehensively searched for studies concerning the association between sKlotho level and clinical outcomes including cardiovascular (CV) events and all-cause mortality.

The Prognostic Role of Klotho in Patients with Chronic Kidney Disease: A Systematic Review and Meta-analysis.

Objective: The prognostic role of Klotho in patients with chronic kidney disease is still controversial. Therefore, we performed this meta-analysis to assess the relationship between the low sKlotho level and the risk of adverse kidney outcomes.

Materials And Methods: We systematically searched medical databases, such as PubMed, Embase, and the Cochrane Library, for eligible publications regarding the relationship between the low sKlotho level and risk of adverse kidney outcomes.

Ginsenoside-Rg1 Protects against Renal Fibrosis by Regulating the Klotho/TGF-β1/Smad Signaling Pathway in Rats with Obstructive Nephropathy.

Ginsenoside-Rg1 (G-Rg1) is an agent isolated from Panax ginseng that exerts anti-fibrotic effects; however, the mechanism is still unclear. Herein, we investigated whether G-Rg1 administration can mitigate or reverse unilateral ureteral obstruction (UUO)-induced renal fibrosis by regulating the Klotho/transforming growth factor (TGF)-β1/Smad signaling pathway in rats. Sprague-Dawley male rats were subjected to UUO, and rats in the treatment group were administered G-Rg1 or G-Rg1 plus Klotho short hairpin RNA interference (shRNA), while rats in the control and model groups were administered vehicle for 14 d.

Quinoline's influence on nitrogen removal performance and microbial community composition of the anammox process.

This study aimed to evaluate the effects of quinoline on nitrogen removal performance and microbial community of an anaerobic biofilm reactor with anammox activity. Results showed that 20 mg L quinoline addition leading the ammonia and nitrite removal efficiency of the ABR reduced from about 90% to 40%. Illumina MiSeq sequencing study indicated that microbial community structure and composition varied with the additive of quinoline.

Plasma s-Klotho is related to kidney function and predicts adverse renal outcomes in patients with advanced chronic kidney disease.

To investigate whether the soluble Klotho (s-Klotho) level in patients with chronic kidney disease (CKD) is related to kidney function and whether a low s-Klotho level can predict adverse renal outcomes or CKD progression in patients with advanced CKD. 112 patients with CKD stages 3-5 and 30 healthy volunteers were enrolled. Blood samples were collected to measure serum creatinine, calcium, phosphorus, intact parathyroid hormone, and hemoglobin.

Klotho mitigates cyclosporine A (CsA)-induced epithelial-mesenchymal transition (EMT) and renal fibrosis in rats.

Purpose: Klotho deficiency is implicated in various kidney diseases, including renal fibrosis. The aim of this study was to investigate the effect of Klotho administration on epithelial-mesenchymal transition (EMT) and renal fibrosis induced by cyclosporine A (CsA) in rats.

Methods: CsA-induced renal fibrosis was established by oral administration of CsA (30 mg/kg) to rats on a low-salt diet for 28 days.

Apelin-13 upregulates Egr-1 expression in rat vascular smooth muscle cells through the PI3K/Akt and PKC signaling pathways.

Previous studies have shown that Apelin-13 upregulates early growth response factor-1 (Egr-1) via the extracellular signal-regulated protein kinase (ERK) signaling pathway. Apelin-13 induces proliferation and migration of vascular smooth muscle cells (VSMCs) as well as the upregulation of osteopontin (OPN) via the upregulation of Egr-1. This study was designed to further explore the activity of Apelin-13 in VSMCs by investigating members of the mitogen-activated protein kinase (MAPK) family, in particular Jun kinase (JNK) and p38 mitogen-activated protein kinase (P38).

Ameliorating effect of Klotho on endoplasmic reticulum stress and renal fibrosis induced by unilateral ureteral obstruction.

Introduction: Expression of Klotho is decreased and endoplasmic reticulum (ER) stress is activated in patients with chronic kidney disease. This study aimed to investigate the effect of Klotho protein on ER stress-related apoptosis and renal fibrosis in rates with unilateral ureteral obstruction (UUO).

Materials And Methods: Twenty-four rats were divided into the sham, UUO, and Klotho treatment groups.

Ginsenoside-Rg1 inhibits endoplasmic reticulum stress-induced apoptosis after unilateral ureteral obstruction in rats.

Aim: Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are implicated in many fibrotic diseases, including renal fibrosis. Whether Ginsenoside-Rg1 (G-Rg1) could attenuate renal fibrosis via suppression of ER stress and UPR has not been reported. The aim of this study was to explore the effect of G-Rg1 on ER stress and UPR-induced apoptosis in kidneys with unilateral ureteral obstruction (UUO) rat model.

'Cool and quiet' therapy for malignant hyperthermia following severe traumatic brain injury: A preliminary clinical approach.

Malignant hyperthermia increases mortality and disability in patients with brain trauma. A clinical treatment for malignant hyperthermia following severe traumatic brain injury, termed 'cool and quiet' therapy by the authors of the current study, was investigated. Between June 2003 and June 2013, 110 consecutive patients with malignant hyperthermia following severe traumatic brain injury were treated using mild hypothermia (35-36°C) associated with small doses of sedative and muscle relaxant.

Tranilast attenuates TGF-β1-induced epithelial-mesenchymal transition in the NRK-52E cells.

We previously reported that tranilast can halt the pathogenesis of chronic cyclosporine nephrotoxicity in rats via the transforming growth factor-β (TGF-β) /Smad pathway, an important signaling system involved in epithelial-mesenchymal transition (EMT), but the exact underlying cellular mechanisms are not yet clear. Thus, by selecting TGF-β1-induced normal rat kidney proximal tubular epithelial cells (NRK-52E) as a model, we demonstrated potential modifying effect of tranilast on EMT-induced by TGF-β1 in vitro. NRK-52E cells were incubated with the blank vehicle (Dulbecco's modified Eagle's medium and F-12 (DMEM/F12) added with 10% fetal bovine serum (FBS)), 10 ng/ml TGF-β1 alone or together with 100, 200 or 400μM tranilast for 48 h after incubation in medium containing 1% FBS for 24 h.

Apelin-13-induced proliferation and migration induced of rat vascular smooth muscle cells is mediated by the upregulation of Egr-1.

Apelin-13 plays an important role in the migration and proliferation of vascular smooth muscle cells (VSMCs); however, the underlying mechanisms are still unclear. Egr-1 is a nuclear transcription factor, which is considered to be the critical initiating factor of the processes of VSMC proliferation and migration. Egr-1 is known to regulate the expression of osteopontin (OPN), which is a marker of the phenotypic modulation that is a necessary condition of VSMC proliferation and migration.

[Clinicopathologic characteristics and prognosis in young Chinese women with breast cancer].

Objective: To analyze the clinicopathologic characteristics and evaluate the prognosis in young Chinese women with breast cancer.

Methods: A total of 1538 female patients with operable primary breast cancer (stage I-III) treated at our hospital from December 1994 to December 2003 were analyzed retrospectively. Among them, 1075 patients (≤ 60 yrs) with the complete follow-up data were divided into two groups according to age: young breast cancer group (≤ 40 yrs, n = 208) and control group (41 - 60 yrs, n = 867) to analyze the differences in their clinicopathologic characteristics and evaluate the prognosis of both groups.

Positive regulation of the Egr-1/osteopontin positive feedback loop in rat vascular smooth muscle cells by TGF-beta, ERK, JNK, and p38 MAPK signaling.

Previous studies identified a positive feedback loop in rat vascular smooth muscle cells (VSMCs) in which early growth response factor-1 (Egr-1) binds to the osteopontin (OPN) promoter and upregulates OPN expression, and OPN upregulates Egr-1 expression via the extracellular signal-regulated protein kinase (ERK) signaling pathway. The current study examined whether transforming growth factor-beta (TGF-beta) activity contributes to Egr-1 binding to the OPN promoter, and whether other signaling pathways act downstream of OPN to regulate Egr-1 expression. ChIP assays using an anti-Egr-1 antibody showed that amplification of the OPN promoter sequence decreased in TGF-beta DNA enzyme-transfected VSMCs relative to control VSMCs.

Egr-1 upregulates OPN through direct binding to its promoter and OPN upregulates Egr-1 via the ERK pathway.

Early growth response factor-1 (Egr-1) and osteopontin (OPN) play important roles in the migration and proliferation of vascular smooth muscle cells (VSMC), but little is known about their relationship. Therefore, we transfected VSMCs with either Egr-1 cDNA, Opn cDNA, a DNA enzyme designed to target Egr-1 (ED5), or antisense Opn oligodeoxynucleotides and examined changes in Egr-1 and OPN expression at the mRNA and protein levels. OPN expression levels were increased in cells that were stably transfected with Egr-1 cDNA.

[Experimental study in renal protective effect of tranilast on rats with adriamycin nephropathy].

Objective: To investigate the effect and mechanism of tranilast on the adriamycin-induced nephrotic syndrome of rats.

Methods: Twenty four rats were randomly divided into 4 groups: normal control group, model group, irbesartan treatment group and tranilast treatment group. The rats in normal control group were injected with normal saline via the tail vein.