Eplerenone protects contralateral kidney tissue from obstruction in pregnant rats with chronic kidney disease / 中国药理学通报

Aim To study the protective effect of eplerenone on the contralateral kidney in pregnant rats with chronic kidney disease (CKD) and its mechanism. Methods Female Wistar rats were randomly divided into sham-operation group, sham-operation pregnancy group, model group and eplerenone group. The rats in the model group and eplenone group had ligation unilateral ureter, and the rats in the eplenone group were treated with 100 mg • kg

Transcriptomic analysis reveals key lncRNAs associated with ribosomal biogenesis and epidermis differentiation in head and neck squamous cell carcinoma / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVE@#In this study, we aimed to expand current knowledge of head and neck squamous cell carcinoma (HNSCC)-associated long noncoding RNAs (lncRNAs), and to discover potential lncRNA prognostic biomarkers for HNSCC based on next-generation RNA-seq.@*METHODS@#RNA-seq data of 546 samples from patients with HNSCC were downloaded from The Cancer Genome Atlas (TCGA), including 43 paired samples of tumor tissue and adjacent normal tissue. An integrated analysis incorporating differential expression, weighted gene co-expression networks, functional enrichment, clinical parameters, and survival analysis was conducted to discover HNSCC-associated lncRNAs. The function of CYTOR was verified by cell-based experiments. To further identify lncRNAs with prognostic significance, a multivariate Cox proportional hazard regression analysis was performed. The identified lncRNAs were validated with an independent cohort using clinical feature relevance analysis and multivariate Cox regression analysis.@*RESULTS@#We identified nine HNSCC-relevant lncRNAs likely to play pivotal roles in HNSCC onset and development. By functional enrichment analysis, we revealed that CYTOR might participate in the multistep pathological processes of cancer, such as ribosome biogenesis and maintenance of genomic stability. CYTOR was identified to be positively correlated with lymph node metastasis, and significantly negatively correlated with overall survival (OS) and disease free survival (DFS) of HNSCC patients. Moreover, CYTOR inhibited cell apoptosis following treatment with the chemotherapeutic drug diamminedichloroplatinum (DDP). HCG22, the most dramatically down-regulated lncRNA in tumor tissue, may function in epidermis differentiation. It was also significantly associated with several clinical features of patients with HNSCC, and positively correlated with patient survival. CYTOR and HCG22 maintained their prognostic values independent of several clinical features in multivariate Cox hazards analysis. Notably, validation either based on an independent HNSCC cohort or by laboratory experiments confirmed these findings.@*CONCLUSIONS@#Our transcriptomic analysis suggested that dysregulation of these HNSCC-associated lncRNAs might be involved in HNSCC oncogenesis and progression. Moreover, CYTOR and HCG22 were confirmed as two independent prognostic factors for HNSCC patient survival, providing new insights into the roles of these lncRNAs in HNSCC as well as clinical applications.

Protective effects of chailing decoction on cyclosporine A induced chronic renal injury and its mechanisms / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effects of Chailing Decoction (CD) on transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF), renal cell apoptosis and proliferation in rats with chronic cyclosporine A nephropathy (CCN), and to explore its possible mechanism for inhibiting renal fibrosis.</p><p><b>METHODS</b>The CCN rat model was prepared using oral administration of cyclosporine A (CsA, 30 mg x kg(-1) x d(-1)). Meanwhile, they were treated with CD (3 g x kg(-1) x d(-1)) by gastrogavage. The serum blood urea nitrogen (BUN), serum creatinine (SCr), and creatinine clearance rate (CCr) were measured by the end of the fourth week of the experiment. The kidneys were taken out on the next day. The degree of renal fibrosis was detected using Masson staining. The protein and gene expressions of TGF-beta1, and CTGF were observed using immunohistochemical assay and RT-PCR. The renal cell apoptosis rate and the proliferation index were detected by flow cytometry.</p><p><b>RESULTS</b>Compared with the control group (BUN: 6.123 +/- 0.588 mmol/L; SCr: 75.654 +/- 8.196 micromol/L; CCr: 0.539 +/- 0.169 mL/min), the renal function of the model group (BUN: 11.600 +/- 1.437 mmol/L; SCr: 101.985 +/- 10.809 micromol/L; CCr: 0.272 +/- 0.060 mL/min) obviously declined (P < 0.01). The collagen deposition in the renal interstitial area significantly increased. The protein and mRNA expressions of TGF-beta1, and CTGF in the tubular epithelial cells and the mesenchymal cells were significantly enhanced (P < 0.01). The cell proliferation index and the apoptosis rate both increased, but the ratio of apoptosis to proliferation (0.317 +/- 0.059) decreased more than that in the control group (0.680 +/- 0.150, P < 0.01). After treatment by CD, the renal function (BUN: 7.340 +/- 0.857; SCr: 84.923 +/- 10.627; CCr: 0.405 +/- 0.081) was significantly enhanced (P < 0.05, P < 0.01), the collagen deposition decreased, the high protein and mRNA expressions of TGF-beta1 and CTGF were down-regulated (P < 0.01), the ratio of apoptosis to proliferation increased (0.650 +/- 0.092, P<0. 01).</p><p><b>CONCLUSION</b>CD could improve the renal function of CCN model rats, inhibit the expressions of TGF-beta1 and CTGF, and recover the balance between the renal cell apoptosis and proliferation by inducing cell apoptosis and inhibiting cell proliferation, thus delaying the renal fibrosis process.</p>

Inhibitory effect of chailing decoction on renal tubular epithelial phenotype transformation in rats with cyclosporine A-induced nephropathy / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Chailing Decoction (CLD) on alpha-smooth muscular actin (alpha-SMA, a marker of renal tubular epithelial phenotype transformation) in rats with cyclosporine A (CsA)-induced nephropathy for investigate its mechanism of action in inhibiting tubulo-interstitial fibrosis.</p><p><b>METHODS</b>Forty Sprague-Dawley rats were equally randomized into four groups: the normal group, the model group, the positive control group and the Chinese medicine (CM) group. Excepting those in the normal group received gastrogavage with olive oil, rats in the other three groups were made into nephropathy model by oral infusion of CsA 30 mg/ (kg x d) for 28 days. At the same time of modeling, rats in the positive control and CM groups were treated respectively with Valsartan 10 mg/(kg x d) and CLD 3 g/(kg x d). The mRNA and protein expressions of alpha-SMA in rats' kidney were detected by RT-PCR, Western blot, immunohistochemical and flow cytometry, and the mRNA expressions of transforming growth factor-beta1 (TGF-beta1) and collagen type III (Col III) were determined by RT-PCR.</p><p><b>RESULTS</b>Levels of (alpha-SMA, TGF-beta1, and Col III were significantly higher in the model group than those in the normal group respectively (P < 0.01 or P < 0.05), and the high levels were down-regulated in the positive control and CM groups after treatment (P < 0.01 or P < 0.05).</p><p><b>CONCLUSION</b>CLD could retard the progress of renal interstitial fibrosis by way of inhibiting renal tubular epithelial phenotype transformation.</p>

Effect of Ang II on PDGF receptor expression in vascular smooth muscle cell / 中国应用生理学杂志

<p><b>AIM</b>To study the effect of angiotensin II (Ang II) on platelet-derived growth factor(PDGF) receptor expression in vascular smooth muscle cell(VSMC).</p><p><b>METHODS</b>Restenosis model was established by balloon injury in rat aorta. The morphologic change and level of Ang II were measured at 14th day after operation. The expression of PDGF-beta receptor was detected by Western blot. The cultured VSMC pretreated with or without losartan were treated with Ang II.</p><p><b>RESULTS</b>Compared with sham group, the sections of injured aorta showed marked intimal thickening with large numbers of VSMCs proliferation throughout intima and media, the level of Ang II obviously increased by 78.8% (P < 0.05), the expression of PDGF-beta receptor significantly increased by 83.9% (P < 0.05) at 14th day after operation. The expression of PDGF-beta receptor in cultured VSMC treated with Ang II was higher than that of control group (P < 0.01). The effect of Ang II was inhibited remarkably by pretreatment with losartan.</p><p><b>CONCLUSION</b>Ang II can stimulate PDGF receptor expression in VSMC, it may be an important mechanism of Ang II-induced VSMC proliferation.</p>