Analysis of prostate transcriptome landscape characteristics in benign prostate hyperplasia patients taking finasteride / 现代泌尿外科杂志

【Objective】 To explore the effects of finasteride on the gene expression in patients with benign prostatic hyperplasia (BPH) through transcriptome analysis. 【Methods】 Postoperative prostate tissues from patients who underwent prostatectomy at Peking University Third Hospital during Oct.2020 and Oct.2021 were collected.The patients were divided into medication group and non-medication group based on whether they had taken finasteride for a long time before surgery, with 8 patients in either groups.Transcriptome sequencing analysis was performed and the results were validated with qPCR and immunohistochemistry analysis. 【Results】 Compared with the non-medication group, 857 up-regulated and 806 down-regulated genes were screened in the medication group.Pathway enrichment analysis showed that finasteride induced down-regulation of vascular endothelial growth factor D (VEGFD) expression in the focal adhesion pathway.Inter group network analysis suggested that the calcium signaling pathway was key in the entire process.GSEA enrichment analysis further revealed the up regulation of CD38 gene expression in the calcium signaling pathway.The qPCR and immunohistochemistry analysis supported the transcriptome results mentioned above, and found that androgen receptor (AR) expression was also increased. 【Conclusion】 Finasteride reduces prostate microvascular formation by downregulating the expression of VEGFD in the focal adhesion pathway, thereby reducing the risk of bleeding during prostate hyperplasia surgery. Long-term use of finasteride leads to the up regulation of CD38 expression in the calcium signaling pathway, which may lead to the development of finasteride resistance.

Role of pregnane X receptor (PXR) in endobiotic metabolism / 生理学报

As a member of the nuclear receptor superfamily, the pregnane X receptor (PXR) is a ligand-activated transcription factor. PXR is highly expressed in liver and intestinal tissues, and also found in other tissues and organs, such as stomach and kidney. After heterodimerization with retinoid X receptor (RXR), PXR recruits numerous co-activating factors, and binds to specific DNA response elements to perform transcriptional regulation of the downstream target genes. As an acknowledged receptor for xenobiotics, PXR was initially considered as a nuclear receptor regulating drug metabolizing enzymes and transporters. However, nowadays, PXR has also been recognized as an important endobiotic receptor. Recent studies have shown that PXR activation can regulate glucose metabolism, lipid metabolism, steroid endocrine homeostasis, detoxification of cholic acid and bilirubin, bone mineral balance, and immune inflammation in vivo. This review focuses on the role of PXR in metabolism of endogenous substances.

Effects of chloroquine on autophagy and collagen metabolism in activated hepatic stellate cells in vitro / 中国病理生理杂志

AIM:To explore the effects of chloroquine (CQ) on collagen Ⅰ and collagen Ⅲ expression in activated rat hepatic stellate cell line HSC-T6 and the possible mechanism.METHODS:Transforming growth factor-β1 (TGF-β1) was used to activate HSC-T6 cells and 3 doses of CQ was administered for 24 h.The cells were divided into 5 groups as follows:control group,TGF-β1 group,TGF-β1 + CQ (15 μmol/L) group,TGF-β1 + CQ (30 μ mol/L) group and TGF-β1 + CQ (60 μmol/L) group.Western blot was used to determine the expression of LC3-Ⅱ/LC3-Ⅰ,P62 and o-SMA in activated HSC-T6 cells.The expression of collagen Ⅰ and collagen Ⅲ was detected by immunocytochemical staining,Western blot and RT-qPCR.Western blot and RT-qPCR were also used to detect the expression of matrix metalloproteinase-13 (MMP-13),tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 at mRNA and protein levels.RESULTS:The ratio of LC3-Ⅱ / LC3-Ⅰ and P62 expression were increased after CQ intervention.Moreover,they were significantly higher in the TGF-β1 + CQ groups than those in TGF-β1 group (P ＜ 0.01).The expression of collagen Ⅰ and collagen Ⅲ at mRNA and protein levels was significantly increased in all TGF-β1 + CQ groups as compared with TGF-β1 group (P ＜0.01),and it was markedly increased among TGF-β1 + CQ groups in a dose-dependent manner.The expression of MMP-13 at mRNA and protein levels was significantly lowered and that of TIMP-1 and TIMP-2 was significantly increased in TGF-β1 + CQ groups as compared with TGF-β1 group (P ＜0.05).CONCLUSION:Inhibition of autophagy by CQ in activated HSC-T6 cells up-regulates the expression of collagen Ⅰ and collagen Ⅲ in a dose-dependent way,probably due to reduction of MMP-13 and enhancement of TIMP-1 and TIMP-2 expression.

Effects of chloroquine on autophagy and collagen metabolism in activated hepatic stellate cells in vitro / 中国病理生理杂志

AIM:To explore the effects of chloroquine (CQ) on collagen Ⅰ and collagen Ⅲ expression in activated rat hepatic stellate cell line HSC-T6 and the possible mechanism.METHODS:Transforming growth factor-β1 (TGF-β1) was used to activate HSC-T6 cells and 3 doses of CQ was administered for 24 h.The cells were divided into 5 groups as follows:control group,TGF-β1 group,TGF-β1 + CQ (15 μmol/L) group,TGF-β1 + CQ (30 μ mol/L) group and TGF-β1 + CQ (60 μmol/L) group.Western blot was used to determine the expression of LC3-Ⅱ/LC3-Ⅰ,P62 and o-SMA in activated HSC-T6 cells.The expression of collagen Ⅰ and collagen Ⅲ was detected by immunocytochemical staining,Western blot and RT-qPCR.Western blot and RT-qPCR were also used to detect the expression of matrix metalloproteinase-13 (MMP-13),tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 at mRNA and protein levels.RESULTS:The ratio of LC3-Ⅱ / LC3-Ⅰ and P62 expression were increased after CQ intervention.Moreover,they were significantly higher in the TGF-β1 + CQ groups than those in TGF-β1 group (P ＜ 0.01).The expression of collagen Ⅰ and collagen Ⅲ at mRNA and protein levels was significantly increased in all TGF-β1 + CQ groups as compared with TGF-β1 group (P ＜0.01),and it was markedly increased among TGF-β1 + CQ groups in a dose-dependent manner.The expression of MMP-13 at mRNA and protein levels was significantly lowered and that of TIMP-1 and TIMP-2 was significantly increased in TGF-β1 + CQ groups as compared with TGF-β1 group (P ＜0.05).CONCLUSION:Inhibition of autophagy by CQ in activated HSC-T6 cells up-regulates the expression of collagen Ⅰ and collagen Ⅲ in a dose-dependent way,probably due to reduction of MMP-13 and enhancement of TIMP-1 and TIMP-2 expression.

Application of home care mobile app in discharged patients with permanent enterostomy in Jiangsu Province / 中华护理杂志

Objective To explore effects of application of home care mobile app for management of discharged patients with permanent enterostomy.Methods The home care mobile app was designed and developed.Totally 100 patients with permanent enterostomy from 15 tertiary hospitals in Jiangsu Province were provided with mobile home care intervention,and effects of the app were evaluated.Results Six months after discharge,the DET score of patients who used the app was 0.47±1.55 and was lower than those who did not use the app 1.16±3.01.Meanwhile 83％ of the patients could complete stoma self-care through the platform without going to the hospital,and 98.0％ of the patients were satisfied with the home care service platform.Conclusion The home care mobile app can improve skin problem around the stoma,and ensure the continuity of nursing after discharge.

Role of extracellular signal-regulated kinase 1/2 in pathogenesis of stree-induced gastric ulcer / 第二军医大学学报

Objective: To investigate the role of extracellular signal-regulated kinase 1/2 (ERK1/2) signal pathway in the pathogenesis of stress-induced gastric ulcer. Methods: Animal model of stress-induced gastric ulcer was established in rats with water-immersion restraint (WIR) stress. The mucosal activation of ERK1/2 was observed before and 5, 15 and 30 min, and 1, 2 and 3.5 h after WIR stress. Some animals were also treated with an intravenous injection of PD98059 (1 mg/kg), a specific ERK1/2 inhibitor, 1 h prior to WIR stress. Expression of total ERK1/2 and caspase-3 were detected by Western blot analysis; ERK1/2 activity was measured by kinase activity assay using myelin basic protein as a specific substrate. DNA-binding activities of the transcription factors activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) were determined by electrophoretic mobility shift assays (EMSA). Mucosal TNF-α and IL-1β mRNA expression was analyzed by Northern blot analysis. The degrees of the gastric mucosal lesions were expressed as ulcer index (UI) and pathological evaluation. Apoptosis in the gastric mucosa was examined by an in situ TdT-mediated dUTP nick-end labeling (TUNEL) method. Results: Activated ERK1/2 was very weakly expressed in the gastric mucosa of normal rats. ERK1/2 was rapidly activated in the gastric mucosa of rats 15 min after WIR stress and the activity reached the maximal after 3.5 h. Pretreatment with PD98059 significantly inhibited ERK1/2 activation, decreased AP-1 and NF-κB activities and TNF-α and IL-β mRNA expression, and obviously relieved gastric mucosal lesions, accompanied by caspase-3 activation and increased apoptosis. Conclusion: The present results indicate that ERK1/2 activation plays an important role in the development of stress-induced gastric ulcer.