Early growth response factor 1 upregulates pro-fibrotic genes through activation of TGF-ß1/Smad pathway via transcriptional regulation of PAR1 in high-glucose treated HK-2 cells.

Tubulointerstitial fibrosis (TIF) makes a key role in diabetic kidney disease (DKD). In this study, we revealed that the expressions of Egr1 and protease-activated receptor 1 (PAR1) were increased in renal tissues of DKD rats. In vitro experiments demonstrated that both Egr1 overexpression and high glucose (HG) condition could promote the expressions of PAR1, fibronectin (FN) and collagen I (COL I). Furthermore, HG stimulation enhanced the binding capacity of Egr1 to PAR1 promoter. Both HG condition and Egr1 upregulation could increase, and thrombin inhibitor did not affect activity of TGF-ß1/Smad pathway via PAR1. Collectively, Egr1 is involved in TIF of DKD partly through activating TGF-ß1/Smad pathway via transcriptional regulation of PAR1 in HG treated HK-2 cells.

The Amomum tsao-ko Essential Oils Inhibited Inflammation and Apoptosis through p38/JNK MAPK Signaling Pathway and Alleviated Gentamicin-Induced Acute Kidney Injury.

The clinical application of gentamicin may lead to acute kidney injury (AKI), and the nephrotoxicity of gentamicin is related to the pathological mechanism of several oxidative and inflammatory cytokines. Plant-derived essential oils have good anti-inflammatory and antioxidant properties. This study aimed to clarify the protective effect of Amomum tsao-ko essential oils (AOs) on gentamicin-induced AKI in rats and its possible mechanism. The rat AKI model was induced by intraperitoneal injection of gentamicin. After 14 days of oral AO treatment, the renal function and pathological changes of the kidney tissues were evaluated, and the level of kidney tissue oxidative stress was detected. The content of inflammatory cytokines was measured by ELISA. The expression of ERK1/2, JNK1/2, p38, NF-κB, caspase-3, and Bax/Bcl-2 proteins were estimated by Western blot analysis. The results showed that taking AO reduced the contents of serum urea and creatinine in AKI rats and improve the pathological changes and oxidative stress of the kidney tissue in rats. At the same time, AO reduced inflammation and apoptosis during AKI by regulating the MAPK pathway. The data show that AO has a protective effect on the kidneys and may be a potential drug for treating kidney injury.

Longitudinal Multi-omics and Microbiome Meta-analysis Identify an Asymptomatic Gingival State That Links Gingivitis, Periodontitis, and Aging.

Most adults experience episodes of gingivitis, which can progress to the irreversible, chronic state of periodontitis, yet roles of plaque in gingivitis onset and progression to periodontitis remain elusive. Here, we longitudinally profiled the plaque metagenome, the plaque metabolome, and salivary cytokines in 40 adults who transited from naturally occurring gingivitis (NG) to healthy gingivae (baseline) and then to experimental gingivitis (EG). During EG, rapid and consistent alterations in plaque microbiota, metabolites, and salivary cytokines emerged as early as 24 to 72 h after oral-hygiene pause, defining an asymptomatic suboptimal health (SoH) stage of the gingivae. SoH features a swift, full activation of 11 salivary cytokines but a steep synergetic decrease of plaque-derived betaine and Rothia spp., suggesting an anti-gum inflammation mechanism by health-promoting symbionts. Global, cross-cohort meta-analysis revealed, at SoH, a greatly elevated microbiome-based periodontitis index driven by its convergence of both taxonomical and functional profiles toward the periodontitis microbiome. Finally, post-SoH gingivitis development accelerates oral microbiota aging by over 1 year within 28 days, with Rothia spp. depletion and Porphyromonas gingivalis elevation as hallmarks. Thus, the microbiome-defined, transient gum SoH stage is a crucial link among gingivitis, periodontitis, and aging.IMPORTANCE A significant portion of world population still fails to brush teeth daily. As a result, the majority of the global adult population is afflicted with chronic gingivitis, and if it is left untreated, some of them will eventually suffer from periodontitis. Here, we identified periodontitis-like microbiome dysbiosis in an asymptomatic SoH stage as early as 24 to 72 h after oral-hygiene pause. SoH features a swift, full activation of multiple salivary cytokines but a steep synergetic decrease of plaque-derived betaine and Rothia spp. The microbial ecology during early gingivitis is highly similar to that in periodontitis under both taxonomical and functional contexts. Unexpectedly, exposures to gingivitis can accelerate over 10-fold the normal rate of oral microbiota aging. Our findings underscore the importance of intervening at the SoH stage of gingivitis via proper oral-hygiene practices on a daily basis, so as to maintain a periodontitis-preventive plaque and ensure the healthy aging of the oral ecosystem.

Immunosuppressive therapy for steroid-resistant nephrotic syndrome: a Bayesian network meta-analysis of randomized controlled studies.

BACKGROUND: The purpose of this study was to conduct a meta-analysis examining the efficacy of cyclophosphamide, cyclosporin, and tacrolimus in treating steroid resistant nephrotic syndrome. METHODS: Medline, Cochrane, EMBASE, and Google Scholar were searched until May 02, 2017 using the keywords: immunosuppressive therapy, steroid-resistant nephrotic syndrome, cyclophosphamide, cyclosporine A, and tacrolimus. Inclusion criteria were randomized controlled trials (RCTs) including patients with SRNS treated with an immunosuppressive therapy or placebo. RESULTS: Seven RCTs were included, and the number of patients ranged from 30 to 131. Conventional pair-wise meta-analysis indicated a higher odds of complete or partial remission with tacrolimus as compared to cyclophosphamide [odds ratio (OR) 4.908, 95% confidence interval (CI) 2.278-10.576, P < 0.001], and cyclophosphamide (OR 0.143, 95% CI 0.028-0.721, P = 0.019) and placebo (OR 0.043, 95% CI 0.012-0.157, P < 0.001) were associated with a lower likelihood of complete or partial remission than cyclosporine. Bayesian analysis indicated that tacrolimus and cyclosporine were the best and the second-best agents for inducing a complete or partial remission (rank probability = 0.53 for tacrolimus and 0.46 for cyclosporine). CONCLUSION: As compared to cyclophosphamide and cyclosporin, tacrolimus is more effective at inducing remission in patients with SRNS.

Sleep quality, daytime sleepiness and health-related quality-of-life in maintenance haemodialysis patients.

OBJECTIVES: To assess the relationship between sleep quality, daytime sleepiness and health-related quality-of-life (HRQoL) in Chinese patients undergoing maintenance haemodialysis (MHD). METHODS: This cross-sectional study enrolled patients undergoing MHD. Self-reported sleep quality (Pittsburgh Sleep Quality Index [PSQI]), daytime sleepiness (Epworth Sleepiness Scale [ESS]) and HRQoL (36-item Short Form [SF-36]) were recorded for all patients. RESULTS: Sixty eight patients (mean ± SD age = 61.75 ± 16.56 years; 43 male/25 female) who regularly received MHD were included. The prevalence of poor sleepers was 69.1% (47/68) and daytime sleepiness was 11.8% (eight of 68). Poor sleepers had a significantly lower Physical Component Scale (PCS) score, Mental Component Scale (MCS) score and total SF-36 score than good sleepers. The PSQI score correlated inversely with both the PCS and MCS scores and correlated positively with age. Independent variables associated with total SF-36 score were duration of MHD, ESS score and PSQI score. CONCLUSIONS: Poor sleep quality is a common and severe issue for MHD patients in east China. Both sleep quality and daytime sleepiness were associated with lower HRQoL scores.