Wu L.,Huazhong University of Science and Technology |
Tao Q.,Peking University |
Chen W.,Huazhong University of Science and Technology |
Wang Z.,Huazhong University of Science and Technology |
And 4 more authors.
Investigative Ophthalmology and Visual Science | Year: 2013
PURPOSE. We assessed the association between complement pathway genes and age-related macular degeneration (AMD) in a Chinese population. METHODS. In a case-control study, 165 AMD patients and 216 unrelated controls were recruited from two hospitals in central China. We selected and genotyped six single nucleotide polymorphisms (SNPs) of four complement pathway genes, including rs800292 and rs1410996 of complement H (CFH), rs9332739 of complement 2 (C2), rs4151667 of complement factor B (CFB), and rs2241394 and rs2230199 of complement 3 (C3). The associations between SNPs and AMD, adjusted by age and sex, were assessed by using logistic regression models and haplotype association analysis. RESULTS. In our study, two SNPs of CFH and their haplotypes were associated significantly with AMD, and the adjusted odd ratios (ORs) were 2.45 (95% confidence interval [CI] 1.25- 4.79) for rs800292 (genotype GG versus AA), 2.49 (95% CI 1.24-5.00) for rs1410996 (genotype TT versus CC), and 4.45 (95% CI 2.32-8.55) for haplotype block of rs800292- rs1410996 (haplotype G-C versus A-C), respectively. The haplotype of C2/CFB also was associated significantly with AMD, and the adjusted OR was 8.86 (95% CI 1.88-41.69) for the haplotype block of rs9332739-rs4151667 (haplotype G-A versus G-T), though no relationship was found in genotype association analysis of the two SNPs of C2/CFB. With the sample size of our study, no relationship was found for AMD and the two SNPs of C3. CONCLUSIONS. Gene variants in CFH and C2/CFB contribute to AMD in the Chinese population. © 2013 The Association for Research in Vision and Ophthalmology, Inc.
PubMed | Tongren Hospital, Xi'an Jiaotong University, Xiamen University, Peking University and 5 more.
Type: | Journal: Scientific reports | Year: 2015
Several single-center studies have investigated whether narrow-band imaging (NBI) cystoscopy is more effective in detecting primary and recurrent non-muscle invasive bladder cancer (NMIBC) compared with white-light imaging (WLI) cystoscopy. In this study, we further evaluated the diagnostic value of NBI cystoscopy compared with WLI cystoscopy for primary NMIBC in a multi-center study. Suspected bladder cancer patients from 8 research centers received both NBI and WLI. Two experienced doctors in each center were responsible for the NBI and WLI assessments, respectively. The number of tumors and position of each tumor were recorded, and suspicious tissues were clamped and histologically examined. The sensitivity, specificity, and false-positive rate of NBI and WLI were evaluated. Of the 384 patients, 78 had a confirmed urothelial carcinoma (UC). The sensitivities of NBI and WLI were 97.70%, and 66.67%, respectively (P<0.0001); the specificities were 50% and 25%, respectively; and the false positive rates were 50% and 75%, respectively. Based on 300 valid biopsy specimens, the NBI and WLI sensitivities were 98.80% and 75.45%, respectively (P<0.0001). These results suggest that NBI has a high sensitivity and has superior early bladder tumor and carcinoma in situ (CIS) detection rates compared with WLI cystoscopy.
Pan T.,Wuhan General Hospital of Guangzhou Military Region |
Gao L.,Wuhan General Hospital of Guangzhou Military Region |
Wu G.,PLA Fourth Military Medical University |
Shen G.,Wuhan General Hospital of Guangzhou Military Region |
And 6 more authors.
Biochemical and Biophysical Research Communications | Year: 2015
Cancer cells reprogram their metabolism towards aerobic glycolysis and elevated glutaminolysis, which contributes to the aggressive phenotype. Understanding how these metabolic pathways are regulated may provide critical targets for therapeutic intervention. Glutaminase (GLS1) is a key enzyme that converts glutamine to glutamate. In this study, we show the loss of GLS1 function by RNA interference or inhibitor diminished the rates of glucose utilization, growth and invasiveness of prostate cancer cells. We propose that GLS1 positively regulates glucose uptake in addition to glutaminolysis. Further, GLS1 involves the transcriptional repression of thioredoxin interacting protein (TXNIP), which is a potent negative regulator of glucose uptake and aerobic glycolysis. Most importantly, we provided direct evidence that elevated GLS1 expression was highly correlated with the tumor stage and progression in prostate cancer patients. Together, we defined a key role for GLS1 in coupling glutaminolysis of the TCA cycle with elevated glucose uptake and consequently the growth of prostate cancer cells. These data extends the role of GLS1 in regulating cell metabolism and the clinical utility of GLS1 inhibitors in the restriction of essential nutrients. © 2014 Elsevier Inc. All rights reserved.
Gao L.,Wuhan General Hospital of Guangzhou Military Region
Zhonghua nan ke xue = National journal of andrology | Year: 2011
To investigate the effects of staurosporine (ST) on the proliferation and apoptosis of prostate cancer PC-3 cells. Prostate cancer PC-3 cells were treated in vitro with ST at 10(-8) mol/L. The expressions of cyclin A and cyclin D1 proteins in the cells were detected by Western blot, the effect of ST on the proliferation of the cells determined by MTT assay and plate colony formation, the apoptosis of the cells examined by flow cytometry, and their morphological changes observed under the light microscope. ST treatment markedly decreased the expressions of cyclin A and cyclin D1 in the PC-3 cells, and significantly inhibited the growth of the PC-3 cells (19.35%) at 48 h. (F = 31.06, P < 0.01). The colony formation rate of the PC-3 cells was (37.10 +/- 3.43) % in the ST group, significantly lower than (64.80 +/- 4.34) % in the control (chi2 = 14.59, P < 0.05) and (62.80 +/- 4.36) % in the DMSO group (chi2 = 12.50, P < 0.05), while the apoptosis rate of the cells was remarkably higher in the ST group ([19.6 +/- 2.20] %) than in the control ([5.33 +/- 1.40] %) and the DMSO group ([5.50 +/- 0.96] %) (F = 104.36, P < 0.01). Under the light microscope, the ST-treated cells were round with indistinct margins as compared with those of the other two groups. ST could significantly inhibit the proliferation and induce the apoptosis of PC-3 cells.
Dong C.,Central South University |
Li H.-J.,Central South University |
Li H.-J.,Wuhan General Hospital of Guangzhou Military Region |
Chang S.,Central South University |
And 4 more authors.
Gut and Liver | Year: 2013
Background/Aims: We aimed to investigate the correlation between a disintegrin and metalloprotease with thrombospondin motif 2 (ADAMTS-2) and transforming growth factor-?1 (TGF-?1) in clinical human cirrhotic tissues. Methods: The liver tissues of 24 patients (16 cases with cirrhotic portal hypertension as the cirrhosis group and eight cases with healthy livers as the normal group) were collected. Immunohistochemistry and Western blots were performed to evaluate the protein expression levels of ADAMTS-2 and TGF-?1. Western blots for other key mediators of cirrhotic progression, including SMAD2, SMAD3, TGF-? receptor II (TGF?RII), matrix metalloproteinases 2 (MMP2), and tissue inhibitor of matrix metalloproteinases 2 (TIMP2), were also performed. Results: Cirrhotic tissues showed higher percentages of collagen. The protein expression levels of ADAMTS-2 and TGF-?1 were significantly higher in the cirrhotic group as compared to the matched normal group (p<0.05), and there was a positive correlation between these two proteins (r=0.862, p<0.01). The protein expressions of MMP2, TIMP2, and TGF?RII, as well as the phosphorylated forms of SMAD2 and SMAD3, were significant higher in the cirrhotic group (p<0.01 or p<0.05). Conclusions: These findings suggested that ADAMTS-2 and TGF-?1 may play important roles in the pathogenesis of human cirrhosis; specifically, TGF-?1 may induce the expression of ADAMTS-2 through the TGF?/SMAD pathway.
Tao X.,Chongqing Medical University |
Liu J.,Chongqing Medical University |
Chen L.,Wuhan General Hospital of Guangzhou Military Region |
Zhou Y.,Chongqing Medical University |
Tang K.,Chongqing Medical University
Cellular Physiology and Biochemistry | Year: 2015
Background/Aims: The rate of healing failure after surgical repair of chronic rotator cuff tears is considerably high. The aim of this study was to investigate the function of the zinc finger transcription factor early growth response 1 (EGR1) in the differentiation of tendon stem cells (TSCs) and in tendon formation, healing, and tendon tear repair using an animal model of rotator cuff repair. Methods: Tenocyte, adipocyte, osteocyte, and chondrocyte differentiation as well as the expression of related genes were determined in EGR1-overexpressing TSCs (EGR1-TSCs) using tissue-specific staining, immunofluorescence staining, quantitative PCR, and western blotting. A rabbit rotator cuff repair model was established, and TSCs and EGR1-TSCs in a fibrin glue carrier were applied onto repair sites. The rabbits were sacrificed 8 weeks after repair operation, and tissues were histologically evaluated and tenocyte-related gene expression was determined. Results: EGR1 induced tenogenic differentiation of TSCs and inhibited non-tenocyte differentiation of TSCs. Furthermore, EGR1 promoted tendon repair in a rabbit model of rotator cuff injury. The BMP12/Smad1/5/8 signaling pathway was involved in EGR1-induced tenogenic differentiation and rotator cuff tendon repair. Conclusion: EGR1 plays a key role in tendon formation, healing, and repair through BMP12/Smad1/5/8 pathway. EGR1-TSCs is a promising treatment for rotator cuff tendon repair surgeries. © 2015 S. Karger AG, Basel.
Xu Y.P.,Wuhan General Hospital of Guangzhou Military Region
Zhonghua nan ke xue = National journal of andrology | Year: 2010
To investigate the effects of intraprostatic injection of botulinum toxin A (BTX-A) on benign prostate hyperplasia (BPH) in rats. Models of BPH were established in adult male Sprague-Dawley rats by injection of testosterone propionate, and then divided into three BTX-A groups, injected with BTX-A into the ventral prostate at the doses of 5 U, 10 U and 20 U, a negative control group, injected with saline only, and a sham operation group, with 12 in each. The prostates of the animals were harvested at 2 or 4 weeks after the injection, their volumes and weights measured, histological changes examined by HE staining, and glandular and interstitial areas semi-quantified by the image analysis system. Two rats died in the 20 U group within 3 days after BTX-A injection. Compared with the saline group, the 5 U, 10 U and 20 U BTX-A groups showed significant decreases in prostatic volume (P < 0.01, 0.01 and 0.05), weight, and glandular and interstitial areas as well as atrophic epithelia in the glandular tube at 2 weeks. These changes were lessened at 4 weeks, especially in the 5 U group. Intraprostatic injection of BTX-A induces obvious atrophy and histological changes of the prostate, but meanwhile may potentially result in death at a large dose.
Chen L.,Wuhan General Hospital of Guangzhou Military Region |
Liu J.-P.,Chongqing Medical University |
Tang K.-L.,Chongqing Medical University |
Wang Q.,Wuhan General Hospital of Guangzhou Military Region |
And 3 more authors.
Cellular Physiology and Biochemistry | Year: 2014
Background/Aims: Tendon injuries are common, difficult to cure and usually healed with fibrosis and scar tissue. The aim of this study was to evaluate tendon derived stem cells (TDSCs) and platelet rich plasma (PRP) in the treatment of collagenase induced Achilles tendinopathy in rat. Methods: Four and 8 weeks (n=18) after TDSCs, PRP, PRP with TDSC or PBS (control) injection into collagenase or saline (sham) injected rat Achilles tendon, tendon tissue was harvested and tendon quality was evaluated by histology and biomechanical testing. TDSCs were cultured and treated by 10% PRP, and the FAK/ERK1/2 signaling pathway and tenocyte-related genes were detected by western blot analysis. Results: Compared to the control, PRP treatment resulted in better healing of injured tendons with improved histological outcomes and biomechanical functions. The addition of TDSCs to PRP treatment significantly enhanced the effects of PRP treatment alone. TDSC injection alone had little effect on tendon healing. PRP and PRP with TDSC treatments of collagenase induced tendon injuries also increased the mRNA and protein expression of tenocyte-related genes (type I collagen, SCX, Tenascin C) and activated the focal adhesion kinase (FAK) and extracellular-regulated kinase (ERK) 1/2 signaling pathways. Treatment of TDSCs in vitro with 10% PRP significantly increased the phosphorylation levels of FAK and ERK1/2 and the protein levels of tenocyte-related genes (Col I, SCX and Tenascin C). Inhibition of the FAK and ERK1/2 signaling pathways abolished the effect of PRP. Conclusion: This study concludes that PRP combined with TDSCs is potentially effective for the treatment of tendinopathy. The PRP induced, FAK and ERK1/2 dependent activation of tenocyte related genes in TDSCs in vitro suggests that the beneficial healing effect of the PRP with TDSC combination might occur by means of an improved TDSC differentiation toward the tenocyte lineage. Thus, a PRP with TDSC combination therapy may be clinically useful. © 2015 S. Karger AG, Basel.
Zhang X.M.,Wuhan General Hospital of Guangzhou Military Region
Zhonghua nan ke xue = National journal of andrology | Year: 2010
To screen serum biomarker candidates in prostate cancer with bone metastasis by two-dimensional gel electrophoresis (2-DGE) and mass spectrometry. Serum samples were obtained from 5 prostate cancer patients with bone metastasis, and another 5 without it. After depletion of the most abundant protein albumin from the serum, the samples were separated by 2-DGE and analyzed with the ImageMaster 2D Platinum software. The differentially expressed protein spots in the serum of those with bone metastases were identified by peptide-fingerprinting with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Compared with the serum samples from those without bone metastasis, 10 protein spot-features were found to be significantly increased and 5 significantly decreased, and the 3 identified proteins, Zn-alpha2-glycoprotein (ZAG), haptoglobin and apolipoprotein C-III, were all increased in the bone-metastasis group. The combination of 2-DGE and mass spectrometry is an ideal platform and an effective means for the differential proteomic analysis of human sera. The identified proteins involved in the formation and progression of prostate cancer bone metastasis might be applied as biomarkers for bone metastasis from prostate cancer.
PubMed | Wuhan General Hospital of Guangzhou Military Region
Type: Journal Article | Journal: Gene | Year: 2015
Invasive progression is the major lethal cause of prostate cancer. In this study, we aimed to investigate the role of kindlin-2, an integrin-binding focal adhesion protein, in the regulation of invasiveness of prostate cancer. We found that downregulation of kindlin-2 using small interfering RNA (siRNA) technology significantly inhibited the invasion of PC-3 and DU-145 prostate cancer cells in a Matrigel Transwell assay. Conversely, overexpression of kindlin-2 promoted the invasiveness of prostate cancer cells. Kindlin-2 overexpression was found to activate nuclear factor (NF)-B-dependent signaling and upregulate the expression of matrix metalloproteinase-9 (MMP-9) and MMP-2, whereas kindlin-2 silencing led to opposing effects on the expression of NF-B and MMPs. Most importantly, kindlin-2-induced invasiveness was almost completely abolished by pretreatment with pyrrolidine dithiocarbamate (an inhibitor of NF-B signaling) or co-transfection with MMP-9 or MMP-2 siRNA. Taken together, our data indicate that kindlin-2 promotes the invasiveness of prostate cancer cells largely through NF-B-dependent upregulation of MMP-9 and MMP-2. Further studies are warranted to evaluate the significance of kindlin-2 as a therapeutic target for metastatic prostate cancer.