Expression of ZEB1 in the prepuce of hypospadias children and its implication / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the expression of zinc finger E-box binding homebox 1 (ZEB1) in the prepuce of hypospadias children and its relationship to the incidence of hypospadias.</p><p><b>METHODS</b>Prepuce tissues were collected from 37 children aged 6-15 months undergoing hypospadias repair and 11 age-matched controls receiving circumcision. Based on the position of the urethral meatus, the hypospadias cases were classified as severe (n = 13) and mild-moderate (n = 24). The mRNA and protein expressions of ZEB1 were determined by immunohistochemistry and RT-PCR.</p><p><b>RESULTS</b>The expression of the ZEB1 protein was remarkably higher in the severe (100% [13/13]) and mild-moderate hypospadias patients (75.0% [18/24]) than in the controls (9.1% [1/11]), with statistically significant differences between any two groups (P < 0.05). RT-PCR showed the integrated density value (IDV) of the ZEB1 mRNA expression to be (0.67 ± 0.21), (0.81 ± 0.24), and (1.55 ± 0.29) in the control, mild-moderate, and severe hypospadias patients, respectively, significantly higher in the severe hypospadias than in the control and mild-moderate hypospadias groups (P < 0.05), but with no significant difference between the latter two (P = 0.64).</p><p><b>CONCLUSION</b>The expression of ZEB1 is significantly increased in hypospadias patients, and its upregulation is positively correlated with the severity of hypospadias, which suggests that the overexpression of ZEB1 may contribute to the development of hypospadias.</p>

Protection of human islets from induction of apoptosis and improved islet function with HO-1 gene transduction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Islet transplantation represents an ideal therapeutic approach for treatment of type 1 diabetes but islet function and regeneration may be influenced by necrosis or apoptosis induced by oxidative stress and other insults. Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in the catabolism of heme into biliverdin, releasing free iron and carbon monoxide. It has also been reported to be an antioxidant enzyme which can improve the function of grafted islets by cytoprotection via free radical scavenging and apoptosis prevention. In the present study, we investigated whether transduction of HO-1 genes into human islets with an adenovirus vector has cytoprotective action on islets cultured in vitro and discuss this method of gene therapy for clinical islet transplantation.</p><p><b>METHODS</b>Cadaveric pancreatic islets were isolated and purified in vitro. Transduction efficiency of islets was determined by infecting islets with adenovirus vector containing the enhanced green fluorescent protein gene (Ad-EGFP) at multiplicities of infection (MOI) of 2, 5, 10, or 20. Newly isolated islets were divided into three groups: EGFP group, islets transduced with Ad-EGFP using MOI = 20; HO-1 group, transduced with adenovirus vectors containing the human HO-1 gene using MOI = 20; and control group, mock transduced islets. Insulin release after glucose stimulation of the cell lines was determined by a radioimmunoassay kit and the stimulation index was calculated. Flow cytometry was used to detect apoptotic cells in the HO-1 group and in the control group after induction by recombinant human tumor necrosis factor-alpha (rTNFalpha) and cycloheximide (CHX) for 48 hours.</p><p><b>RESULTS</b>Adenovirus vectors have a high efficiency of gene transduction into adult islet cells. Transduction of islets with the Ad-EGFP was most successful at MOI 20, at which MOI fluorescence was very intense on day 7 after transduction and EGFP was expressed in cultured islet cells for more than four weeks in vitro. The insulin release in the control group was (182.36 +/- 58.96) mIU/L after stimulation by high glucose media (16.7 mmol/L), while insulin release from the HO-1 group and the EGFP group were (270.09 +/- 89.37) mIU/L and (175.95 +/- 75.05) mIU/L respectively. Compared to the control group and the EGFP group, insulin release in the HO-1 group increased significantly (P < 0.05). After treatment with rTNFalpha and CHX the apoptotic ratio of islet cells was (63.09 +/- 10.86)% in the HO-1 group, significantly lower than (90.86 +/- 11.25)% in the control group (P < 0.05).</p><p><b>CONCLUSIONS</b>Transduction of human islets with Ad-HO-1 can protect against TNF-alpha and CHX mediated cytotoxicity. The HO-1 gene also appears to facilitate insulin release from human islets. Transduction of donor islets with the adenovirus vector containing an HO-1 gene might have potential value in clinical islet transplantation.</p>

Juxtaglomerular cell tumor of the kidney: a clinicopathologic analysis of five cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the morphologic characteristics and immunophenotype of juxtaglomerular cell tumor of the kidney (JGCT), with discussion on its diagnostic clues and possible histogenesis.</p><p><b>METHODS</b>The clinical, pathologic and immunohistochemical features of 5 cases of JGCT were evaluated. In addition, 5 cases of hemangiopericytoma and 5 cases of cutaneous glomus tumor were selected for comparative immunohistochemical analysis.</p><p><b>RESULTS</b>The JGCT cases came from 4 females and 1 male (mean age at diagnosis = 32 years). All of them manifested symptoms of systemic hypertension. Four of the patients received partial nephrectomy and the remaining patient was treated by radial nephrectomy. All of them were followed up for a period of 4 to 66 months (average = 27 months). There was no evidence of local recurrence or distant metastases. On gross examination, these JGCTs were well-circumscribed and situated in the renal cortex and measured 4.4 cm in greatest dimension on average. Histologically, the tumor was characterized by the following three features: (1) solid sheets of relatively uniform polygonal to round cells with lightly eosinophilic cytoplasm, sometimes containing PAS-positive intracytoplasmic granules; (2) absence of or very scanty mitotic figures; (3) interstitium rich in thin-walled capillaries, associated with focal hyaline change and hemangiopericytoma-like architectural pattern. Under electron microscopy, characteristic rhomboid-shaped renin granules were found in the cytoplasm. All JGCTs were immunoreactive for renin, CD34, actin, and calponin. In contrast, all glomus tumors were negative for renin and all hemangiopericytomas were negative for actin.</p><p><b>CONCLUSIONS</b>JGCT is a rare benign renal neoplasm typically found in young adults and manifests as systemic hypertension. The tumor cells may be originated from modified vascular smooth muscle cells. The identification of renin granules by electron microscopy and demonstration of the characteristic immunophenotype is the key to correct pathologic diagnosis.</p>