Yi He

The protective effects of Zhen-Wu-Tang against cisplatin-induced acute kidney injury in rats

Acute kidney injury (AKI) is a common clinical condition that confers a risk of progression of chronic kidney disease and a high risk of death. The purpose of the current study is to investigate the anti-apoptotic and anti-fibrotic effects of Zhen-Wu-Tang (ZWT) on cisplatin (CIS)-induced renal injury and elucidate the involvement of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), the PI3K/Akt signaling pathway, transforming growth factor (TGF)-β and the Wnt/β-catenin signaling pathway in the positive effects of Zhen-Wu-Tang on the kidneys. Wistar rats were randomly assigned into six groups of 6 rats each as follows: normal control 1; normal control 2; CIS 1 and CIS 2, which received single intraperitoneal injections of CIS (6 mg/kg); CIS+ZWT 4 and CIS+ZWT 10, which received ZWT (1 ml/100 g/day, ig) starting days after the CIS injection for 4 and 10 days, respectively. Hematoxylin-eosin (H&E) staining was performed to identify the amelioration of histopathological changes in the kidneys and apoptosis of the renal proximal tubular cells. Picrosirius red staining was used to evaluate renal fibrosis after ZWT treatment. The relationship between ZWT and the upregulation of Nrf2, phosphorylation of Akt, and the downregulation of TGF-β and WNT/β-catenin were determined by Western blotting. At the end of the experiment, serum was isolated from the orbital blood of rats, and blood urea nitrogen (BUN) and creatinine (Cr) levels were measured. The results showed that ZWT restored the histological alterations, aberrant collagen deposition in the kidneys and the BUN and Cr levels that were increased by CIS. Treatment with ZWT reduced the expression levels of TGF-β and Wnt and increased the expression levels of Nrf2, PI3K and Akt in the CIS-exposed kidney tissues. Furthermore, ZWT downregulated apoptosis and fibrosis by modulating the expression levels of caspase-3, Bax and alpha-smooth muscle actin (α-SMA). In conclusion, this study provides evidence for the anti-fibrotic and anti-apoptotic roles of ZWT in CIS-induced experimental kidney injury.

Dexmedetomidine promotes liver regeneration in mice after 70% partial hepatectomy by suppressing NLRP3 inflammasome not TLR4/NFκB

ABSTRACT Inflammasome activation is mediated by NOD‐like receptors (NLRs) that play important role in cellular proliferation. NLRP3 senses the widest array of stimuli. But its role in the liver regeneration after partial hepatectomy (PHx) is still unknown. Dexmedetomidine (Dex) has been documented to protect the liver against ischemia‐reperfusion injury via the suppression of the TLR4/NF‐&kgr;B pathway, which is important for NLRP3 inflammasome activation and liver regeneration. We tested whether Dex contributes to liver regeneration, and investigated its consequent effect on inflammasome activation. In vitro, L02 human liver cells were treated with Dex at different concentrations. The 70% PHx was performed in C57 BL/6 mice as PHx group, and sham‐operated animals as Sham group, Dex‐treated animals were assigned into two groups: Dex + PHx, which received single intraperitoneal injections of Dex (25 &mgr;g/kg) before PHx 30 mins; Dex + PHx + Dex, which received additional Dex (25 &mgr;g/kg) after PHx for 3 days. Dex significantly inhibited the proliferation of Lo2 cells in vitro and decreased the expression of TLR4/NF&kgr;B. In vivo, Dex + PHx exhibited promoted effect on liver regeneration and liver function recovery via inhibiting NLRP3 inflammasome activation. Dex + PH + Dex inhibited the liver regeneration, which may be associated with suppressed expression levels of TLR4/NF&kgr;B pathway. Though Dex pretreatment contributed to liver regeneration and function recovery via inflammation suppression, excessive inflammation suppression accompanied with TLR4 suppression could be related to the diminished liver regeneration, suggesting that TLR4/NF&kgr;B played important role in liver regeneration and Dex + PHx might be a useful therapeutic strategy to promote liver regeneration in clinical. HighlightsNLRP3 inflammasome activation was involved in liver regeneration after PHx.TLR4/NF‐&kgr;B pathway played important role in liver regeneration.Over‐suppression of inflammation, accompanied with TLR4 suppression, may be related to diminished liver regeneration induced by Dex+PHx+Dex.

Resveratrol improves urinary dysfunction in rats with chronic prostatitis and suppresses the activity of the stem cell factor/c-Kit signaling pathway

Chronic prostatitis (CP) is a common urological disorder, with bladder voiding dysfunction being the primary clinical manifestation. Resveratrol is polyphenolic compound isolated from numerous plants, with widely‑reported anti-inflammatory properties. The present study aimed to investigate whether resveratrol may improve overactive bladder in rats with CP and to investigate the underlying molecular mechanisms. Furthermore, the potential pharmacological synergy between resveratrol and solifenacin was also investigated as a potential treatment for CP. Following the successful establishment of a rat model of CP by subcutaneously injecting DPT vaccine, rats were treated with resveratrol or a combination of resveratrolxa0+xa0solifenacin. Bladder pressure and volume tests were performed to investigate the effect of resveratrol and solifenacin on urinary dysfunction in rats with chronic prostatitis. Western blot analysis and immunohistochemical staining were used to examine the expression of c‑Kit receptor, stem cell factor (SCF), AKT and phosphorylated‑AKT (p‑AKT) in the bladder tissue. The results of the bladder pressure and volume test indicated that the maximum capacity of the bladder, residual urine volume and maximum voiding pressure in the control group were 0.57xa0ml, 0.17xa0ml and 29.62xa0cmxa0H2O, respectively. These values were increased by 71, 27 and 206% in rats in the CP group compared with the control group. Following treatment with resveratrol, the results in the resveratrol group were reduced by 25.77, 44.23 and 13.32% compared with the CP group. The results of western blot analysis, immunohistochemical staining and immunofluorescence labeling demonstrate that the protein expression of SCF, c‑Kit and p‑AKT in the bladder of rats in the CP group was 4.32, 6.13 and 6.31xa0times higher compared with the control group, respectively. Following treatment with resveratrol, protein expression was significantly reduced. However, no significant differences were observed between the protein expression of the SCF, c‑Kit and p‑AKT in the bladder between the resveratrol and combination groups. In conclusion, resveratrol may improve overactive bladder by downregulating the protein expression of SCF, c‑Kit and p‑AKT in the bladder of rats with CP. Furthermore, a combination of resveratrol and solifenacin may have potential pharmacological synergy as a treatment for patients with CP.

Resveratrol improves prostate fibrosis during progression of urinary dysfunction in chronic prostatitis

AIMnWe investigated whether prostate fibrosis was associated with urinary dysfunction in chronic prostatitis (CP) and whether resveratrol improved urinary dysfunction and the underlying molecular mechanism.nnnMETHODSnRat model of CP was established via subcutaneous injections of DPT vaccine and subsequently treated with resveratrol. Bladder pressure and volume tests investigated the effect of resveratrol on urinary dysfunction in CP rats. Western blotting and immunohistochemical staining examined the expression level of C-kit/SCF and TGF-β/Wnt/β-catenin.nnnRESULTSnCompared to the control group, the maximum capacity of the bladder, residual urine volume and maximum voiding pressure, the activity of C-kit/SCF and TGF-β/Wnt/β-catenin pathways were increased significantly in the CP group. Resveratrol treatment significantly improved these factors.nnnCONCLUSIONnCP induced significantly prostate fibrosis, which exhibits a close relationship with urinary dysfunction. Resveratrol improved fibrosis, which may be associated with the suppression of C-kit/SCF and TGF-β/Wnt/β-catenin pathway.

Resveratrol improves smooth muscle carcinogenesis in the progression of chronic prostatitis via the downregulation of c-kit/SCF by activating Sirt1

PURPOSEnBladder smooth muscle cell death accompanied by hyperplasia and hypertrophy, as induced by inflammation, is the primary cause for poor bladder function. There are emerging evidences on the role of chronic inflammation as a factor involved in carcinogenesis and progression. We aim to determine the bladder smooth muscle pathological changes and dysfunction in chronic prostatitis (CP), to investigate whether resveratrol can improve the urinary dysfunction and the role of c-kit/SCF pathway, that has been associated with the smooth muscle carcinogenesis.nnnMETHODnRat model of CP was established via subcutaneous injections of DPT vaccine and subsequently treated with resveratrol. H&E staining was performed to identify the histopathological changes in prostates and bladders. Western blotting and immunohistochemical staining examined the expression level of C-kit, stem cell factor (SCF), Sirt1, apoptosis associated proteins.nnnRESULTSnthe model group exhibited severe diffuse chronic inflammation, characterized by leukocyte infiltration and papillary frond protrusion into the gland cavities, and a notable increase in prostatic epithelial height. Meanwhile, bladder muscle arranged in disorder with fracture, and cells appeared atypia. The activity of C-kit/SCF was up-regulated, the carcinogenesis associated proteins are dysregulated significantly in CP rats. Resveratrol treatment significantly improved these factors by Sirt1 activation.nnnCONCLUSIONSnactivated c-kit/SCF and bladder muscle carcinogenesis were involved in the pathological processes of CP, which was improved after resveratrol treatment via the downregulation of c-kit/SCF by activating Sirt1.

FTO mRNA expression in the lower quartile is associated with bad prognosis in clear cell renal cell carcinoma based on TCGA data mining

Fat mass and obesity associated (FTO) is a protein-coding gene, also known as the obesity gene. It has been reported previously to be associated with a variety of malignant cancers, such as breast, thyroid and acute myeloid leukemia. The aim of the present study was to investigate the FTO mRNA expression in human clear cell renal cell carcinoma and its clinical value. FTO mRNA expression and its prognostic value were investigated by bioinformatic analysis of the data from The Cancer Genome Atlas (TCGA, https://cancergenome.nih.gov/). The Kaplan-Meier analysis showed that FTO mRNA expression in the lower quartile is significantly associated with poor survival in clear cell renal cell carcinoma patients (Pu202f<u202f0.0001). This study indicated that higher FTO mRNA expression may have a protective role and it may be a vital molecular marker in the prognosis of clear cell renal cell carcinoma patients.

Resveratrol improves prostate fibrosis during progression of urinary dysfunction in chronic prostatitis by mast cell suppression

Voiding dysfunction is the primary clinical manifestation of chronic prostatitis (CP), which is a common urological disease. The present study investigated whether prostate fibrosis was associated with urinary dysfunction in CP and if resveratrol improved urinary dysfunction, and the underlying molecular mechanism. A rat model of CP was established via subcutaneous injections of the pertussis-diphtheria-tetanus vaccine, which was followed by treatment with resveratrol. Bladder pressure and volume tests were performed to investigate the effect of resveratrol on urinary dysfunction in CP rats. Western blotting and immunohistochemical staining examined the expression levels of tryptase, chymase, transforming growth factor (TGF)-β, Wnt and α-smooth muscle actin (α-SMA). The results demonstrated that the maximum capacity of the bladder, residual urine volume and maximum voiding pressure were increased significantly in the CP group compared with the control group. Mast cell (MC) activation, the activity of TGF-β/Wnt/β-catenin pathways, and the expression levels of tryptase and α-SMA in the CP group were increased significantly compared with the control group. Resveratrol treatment significantly reversed these factors. Therefore, the results indicate that MC infiltration may induce prostate fibrosis, which exhibits a close association with urinary dysfunction in CP. Resveratrol may improve fibrosis via the suppression of MC activation and TGF-β/Wnt/β-catenin pathway activities.

The Effects and Possible Mechanisms of Puerarin to Treat Uterine Fibrosis Induced by Ischemia-Reperfusion Injury in Rats

Background Tissues fibrosis is caused by ischemia-reperfusion injury (IRI) and results in organ dysfunction. In this study, we aimed to investigate whether fibrosis occurs after uterine ischemia-reperfusion injury, and to investigate the effects of puerarin (Pur) on the fibrosis process in rats. Material/Methods Twenty-four female Wistar rats were randomly divided into three groups (8 in each group): the control group rats only received operation without uterine ischemic, the IRI group and the IRI + Pur group rats received 30-minutes ischemia and 2-weeks of reperfusion. Pur was orally administered at the onset of reperfusion. Picrosirius red staining was used to assess uterine fibrosis. Immunohistochemistry was used to detect the expression levels of transforming growth factor (TGF)-β and α-smooth muscle actin (α-SMA). Western blotting was used to evaluate the expression of chymase, TGF-β, α-SMA, and the activity of the Wnt/β-catenin pathway. Results Uterine fibrosis in the IRI+Pur group was significantly decreased compared with the IRI group. In addition, immunohistochemistry reveals that TGF-β and α-SMA were decreased in the IRI+Pur group compared with the IRI group. Western blotting results showed that Pur significantly suppresses the increase in chymase, α-SMA, TGF-β, and β-catenin expression levels induced by IRI. Conclusions The results indicated that IRI could induce uterine fibrosis and that Pur had an improvement effect on IRI-induced uterine fibrosis by downregulating the activity of mast cell chymase, TGF-β, α-SMA, and the Wnt/β-catenin pathway.

Resveratrol Improved the Progression of Chronic Prostatitis via the Downregulation of c-kit/SCF by Activating Sirt1

The regulation mechanism of inflammation inducing prostate carcinogenesis remains largely unknown. Therefore, we investigated the role of the c-kit/SCF pathway, which has been associated with the control of prostate carcinogenesis, in chronic prostatitis (CP) rats and evaluated the anti-prostatitis effect of resveratrol. We performed hemolysin and eosin staining to evaluate the histopathological changes in prostates. Multiple approaches evaluated the expression levels of c-kit, stem cell factor (SCF), Sirt1, and carcinogenesis-associated proteins. The CP group exhibited severe diffuse chronic inflammation. Meanwhile, the prostate cells appeared atypia; the activity of c-kit/SCF was upregulated, and carcinogenesis-associated proteins are dysregulated significantly in CP rats. Resveratrol treatment significantly improved these factors by Sirt1 activation. In summary, CP could further cause prostate carcinogenesis, which may be associated with activated c-kit/SCF signaling. Resveratrol treatment could improve the progression of CP via the downregulation of c-kit/SCF by activating Sirt1.

Resveratrol improved detrusor fibrosis induced by mast cells during progression of chronic prostatitis in rats.

Abstract To investigate the detrusor fibrosis and urinary dysfunction in chronic prostatitis (CP), and to investigate whether resveratrol can improve the urinary dysfunction and the underlying molecular mechanism. After rat model of CP is established by subcutaneously injecting DPT vaccine, rats are treated with resveratrol. Experiments of bladder pressure and volume test in rats are used to investigate the effect of resveratrol on urinary dysfunction in CP rats. To assess tissue fibrosis, picrosirius red staining is performed. H&E staining is performed to identify the histopathological changes. Western blot and immunohistochemical staining are used to examine the expression of c‐kit, SCF, tryptase, TGF‐&bgr;, Wnt and &agr;‐SMA. The results of bladder pressure and volume test show that the maximum capacity of the bladder, residual urine volume and maximum voiding are increased significantly in CP rats. CP rats show significantly increased collagen deposition in the detrusor. H&E staining show that detrusor muscle arranged in disorder with fracture from CP rats. The results of western blot and immunohistochemical staining demonstrate that the activity of c‐kit/SCF and TGF‐&bgr;/Wnt/&bgr;‐catenin pathway, expression levels of tryptase and &agr;‐SMA in bladder detrusor of CP group are significantly increased compared with the control group. However, resveratrol treatment significantly improved these factors. mast cell activation induced by the increased expression of c‐kit/SCF in CP rats, may promote detrusor fibrosis which have a close relationship with urinary dysfunction. Resveratrol can improve the dysfunction by downregulating the mast cell activation and the activity of TGF‐&bgr;/Wnt/&bgr;‐catenin pathway.