BackgroundRenal fibrosis is characterized by infiltration of interstitial inflammatory cells and release of inflammatory mediators, activation and proliferation of fibroblasts, and deposition of excessive extracellular matrix (ECM). The aim of this study was to evaluate the effect of human umbilical cord-derived mesenchymal stem cell (hucMSC) conditioned medium (CM) on renal tubulointerstitial inflammation and fibrosis.MethodsRenal interstitial fibrosis was prepared in vivo using the unilateral ureteral obstruction (UUO). Rats were divided randomly into Sham group, Sham group with CM, UUO group, and UUO group with CM. The effect of hucMSC-CM on kidney injury induced by UUO was assessed by detecting kidney histopathology, serum creatinine (SCr), and blood urea nitrogen (BUN). The levels of TNF-α, IL-6, and IL-1β in serum and kidney tissues were detected by ELISA. The expression of proteins associated with fibrosis and renal inflammation was investigated using immunohistochemical staining and western blotting. The effects of hucMSC-CM on the TGF-β1-induced epithelial–mesenchymal transition (EMT) process and on inflammation in NRK-52E cells were investigated by immunofluorescent staining, ELISA, and western blotting.ResultshucMSC-CM reduced extracellular matrix deposition and inflammatory cell infiltration as well as release of inflammatory factors in UUO-induced renal fibrosis. Furthermore, hucMSC-CM markedly attenuated the EMT process and proinflammatory cytokines in rats with UUO and TGF-β1-induced NRK-52E cells. hucMSC-CM also inhibited the TLR4/NF-κB signaling pathway in vivo and in vitro.ConclusionsOur results suggest that hucMSC-CM has protective effects against UUO-induced renal fibrosis and that hucMSC-CM exhibits its anti-inflammatory effects through inhibiting TLR4/NF-κB signaling pathway activation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0760-6) contains supplementary material, which is available to authorized users.

This study shows that CM protects UUO-induced kidney damage and therefore could be a potential tool to prevent CKD progression.

BackgroundTyrosine kinase inhibitors (TKIs) have been developed during the last decade that target the vascular endothelial growth factor receptor (VEGFR) are currently being evaluated as treatments for malignant tumors. The increased application of VEGFR-TKIs means that the probability of hypertension is a serious concern. However, the reported incidence varies markedly between clinical trials. Here, we undertook an up-to-date, comprehensive meta-analysis on clinical works to build the incidence of hypertension along with VEGFR-TKIs. The goal was to understand better of the overall venture of cancer patients’ hypertension treated with these drugs.MethodsDatabases (EMBASE, PubMed, and Cochrane library) and the abstracts of the American Society of Clinical Oncology annual meeting and European Society of Medical Oncology were searched to identify related studies. 95% confidence intervals (CIs), summary incidences, and relative risk (RR) were calculated utilizing either fixed-effects models on the basis of the heterogeneity of the included studies or random-effects.ResultsSeventy-two randomized controlled trials (including 30013 patients) were involved. The total incidence of high-grade and all-grade hypertensive events along with VEGFR-TKIs was 23.0% (95% CI, 20.1–26.0%) and 4.4% (95% CI, 3.7–5.0%), respectively. The use of VEGFR-TKIs remarkably enhanced the venture of developing high-grade (RR, 4.60; 95% CI, 3.92–5.40; P < 0.001) and all-grade (RR, 3.85; 95% CI, 3.37–4.40; P < 0.001) hypertensive events. Subgroup analyses revealed that the risk of a hypertensive event varied significantly in accordance with tumor type, VEGFR-TKI, trial phase, VEGFR-TKIs-based regimen, control therapy, and chemotherapy regimen.ConclusionsPatients with cancer that receive VEGFR-TKIs are at a remarkable venture of developing hypertension. Therefore, suitable treatment and monitoring should be introduced to avoid cardiovascular complications.

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The reported incidence of arterial and venous thromboembolic events varies markedly between VEGFR-TKI-related clinical trials. Here, we performed a meta-analysis to determine the incidence and the relative risk (RR) of venous thromboembolism events (VTEs) and arterial thromboembolic events (ATEs) associated with these agents. Databases (PubMed, Web of Science) were searched for relevant studies. Statistical analyses were conducted to calculate the summary incidences, RRs and 95% confidence intervals (CIs) using either random-effects or fixed-effects models according to the heterogeneity of the included studies. A total of 24,855 patients from 48 studies were included. The overall incidence of all-grade and high-grade VTEs associated with VEGFR-TKIs was 3.6% (95% CI 2.3-5.2%) and 1.6% (95% CI 1.0-2.4%), respectively. The use of VEGFR-TKIs did not significantly increase the risk of developing all-grade (RR 0.91; 95% CI 0.68-1.22; P = 0.558) and high-grade (RR 1.05; 95% CI 0.84-1.31; P = 0.769) VTEs. The overall incidence of all-grade and high-grade ATEs associated with VEGFR-TKIs was 2.7% (95% CI 1.7-3.6%) and 0.6% (95% CI 0.2-1.2%), respectively. The use of VEGFR-TKIs significantly increase the risk of developing all-grade (RR 3.09; 95% CI 1.41-6.76; P = 0.033) ATEs, and a tendency to increase the risk of high-grade (RR 1.49; 95% CI 0.99-2.24; P = 0.101) ATEs was also detected. Patients with cancer that receive VEGFR-TKIs are at high risk of developing ATEs. Physicians should be aware of these adverse effects and should monitor cancer patients receiving VEGFR-TKIs.

• Depletion of Brg1 improves the integrity of airway epithelium in asthma by regulating E-cadherin expression in lung epithelial cells. • Knockdown of Brg1 increased the cell proliferation and migration by human bronchial epithelial 16HBE cells. • Brg1 might bLLe a novel therapeutic target in asthma.

In conclusion, these observations demonstrated that P. aeruginosa-derived exosomes could induce protection against allergic sensitization in asthma mice, and our study provided a new insight to prevent allergic diseases.

The novel pyrazoline derivative, BHX, has recently been shown to exhibit potent anti-tumour activity by blocking the Wnt/β-catenin signalling pathway. However, its effect on breast cancer growth and invasion are unknown. Our results show that BHX suppresses MDA-MB-231 cell viability and colony formation in a dose-dependent manner, and induces apoptosis and G0/G1 phase arrest. BHX-treated breast cancer cells showed morphological characteristics of cells undergoing apoptosis. Furthermore, BHX inhibited cell migration and invasion, which was associated with increased E-cadherin mRNA and protein expression, and down-regulation of SNAIL and vimentin. In addition, BHX induced the generation of intracellular ROS and decreased β-catenin protein and mRNA expression. We used a mouse xenograft model to investigate the effects of BHX in vivo, where the growth of MDA-MB-231 xenografted tumours was suppressed in nude mice treated continuously with BHX for 21 days. Finally, the rat plasma concentration of BHX was measured by ultra-performance liquid-chromatography tandem mass spectrometry and the pharmacokinetic parameters of BHX were processed by non-compartmental analysis. In conclusion, BHX merits further study as a novel therapeutic small molecule for the treatment of breast cancer.