The combination of EGCG with warfarin reduces deep vein thrombosis in rabbits through modulating HIF-1α and VEGF via the PI3K/AKT and ERK1/2 signaling pathways.

Deep venous thrombosis (DVT) poses a major challenge to public health worldwide. Endothelial cell injury evokes inflammatory and oxidative responses that contribute to thrombus formation. Tea polyphenol (TP) in the form of epigallocatechin-3-gallate (EGCG) has anti-inflammatory and oxidative effect that may ameliorate DVT. However, the precise mechanism remains incompletely understood. The current study was designed to investigate the anti-DVT mechanism of EGCG in combination with warfarin (an oral anticoagulant). Rabbits were randomly divided into five groups. A DVT model of rats was established through ligation of the inferior vena cava (IVC) and left common iliac vein, and the animals were orally administered with EGCG, warfarin, or vehicle for seven days. In vitro studies included pretreatment of human umbilical vein endothelial cells (HUVECs) with different concentrations of EGCG for 2 h before exposure to hydrogen peroxide. Thrombus weight and length were examined. Histopathological changes were observed by hematoxylin-eosin staining. Blood samples were collected for detecting coagulation function, including thrombin and prothrombin times, activated partial thromboplastin time, and fibrinogen levels. Protein expression in thrombosed IVCs and HUVECs was evaluated by Western blot, immunohistochemical analysis, and/or immunofluorescence staining. RT-qPCR was used to determine the levels of AGTR-1 and VEGF mRNA in IVCs and HUVECs. The viability of HUVECs was examined by CCK-8 assay. Flow cytometry was performed to detect cell apoptosis and ROS generation was assessed by 2',7'-dichlorofluorescein diacetate reagent. In vitro and invivo studies showed that EGCG combined with warfarin significantly reduced thrombus weight and length, and apoptosis in HUVECs. Our findings indicated that the combination of EGCG and warfarin protects HUVECs from oxidative stress and prevents apoptosis. However, HIF-1α silencing weakened these effects, which indicated that HIF-1α may participate in DVT. Furthermore, HIF-1α silencing significantly up-regulated cell apoptosis and ROS generation, and enhanced VEGF expression and the activation of the PI3K/AKT and ERK1/2 signaling pathways. In conclusion, our results indicate that EGCG combined with warfarin modifies HIF-1α and VEGF to prevent DVT in rabbits through anti-inflammation via the PI3K/AKT and ERK1/2 signaling pathways.

[Calculus formation in the prostatic cavity after transurethral resection of the prostate: causes, treatment and prevention].

OBJECTIVE: To study the causes, clinical manifestations, treatment and prevention of calculus that develops in the prostatic cavity after transurethral resection of the prostate. METHODS: We reported 11 cases of calculus that developed in the prostatic cavity after transurethral resection or transurethral plasmakinetic resection of prostate. The patients complained of repeated symptoms of frequent micturition, urgent micturition and urodynia after operation, accompanied with urinary tract infection and some with urinary obstruction, which failed to respond to anti-infective therapies. Cystoscopy revealed calculi in the prostatic cavity, with eschar, sphacelus, uneven wound surface and small diverticula in some cases. After diagnosis, 1 case was treated by holmium laser lithotripsy and a second transurethral resection of the prostate, while the other 10 had the calculi removed under the cystoscope, followed by 1 -2 weeks of anti-infective therapy. RESULTS: After treatment, all the 11 cases showed normal results of routine urinalysis, and no more symptoms of frequent micturition, urgent micturition and urodynia. Three- to six-month follow-up found no bladder irritation symptoms and urinary tract infection. CONCLUSION: Repeated symptoms of frequent micturition, urgent micturition, urodynia and urinary tract infection after transurethral resection of the prostate should be considered as the indicators of calculus in the prostatic cavity, which can be confirmed by cystoscopy. It can be treated by lithotripsy or removal of the calculus under the cystoscope, or even a second transurethral resection of the prostate. For its prevention, excessive electric coagulation and uneven wound surface should be avoided and anti-infection treatment is needed.

[Effects of hyperbaric oxygen on tumor growth in the mouse model of LNCaP prostate cancer cell line].

OBJECTIVE: To assess the safety of hyperbaric oxygen in the treatment of radiation-induced hemorrhagic cystitis in patients with prostate cancer, and to investigate its effect on the growth of indolent prostate cancer in vivo. METHODS: Thirty severe combined-immunodeficient mice received subcutaneous injection of human prostate cancer LNCaP cells. Then they were randomized to an experimental and a control group and exposed to 20 sessions of hyperbaric oxygen and normobaric air, respectively, followed by a 4-week observation on the growth of the transplanted tumors and analyses of their histopathological features at 28 days, including the volume, microvessel density (CD34), apoptosis markers (p53 and p27 proteins) and the proliferation index (Ki-67) of the LNCaP tumors. RESULTS: On the 28th day after tumor vaccination, the tumor volume was (120 +/- 7.9) mm3 in the HBO and (122 +/- 8.2) mm3 in the control group; the microvessel density and the expressions of Ki-67, p53 and p27 were 39.3 +/- 5.2, (78.1 +/- 7.6)%, (40.4 +/- 6.2)% and (63.7 +/- 5.1)% in the former, and 36.2 +/- 4.9, (75.3 +/- 8.4)%, (44.2 +/- 5.7)% and (61.5 +/- 5.5)% in the latter. There were no significant differences in all the indexes above between the two groups (P > 0.05). CONCLUSION: Hyperbaric oxygen did not promote the growth of indolent prostate cancer in the murine model, nor did it have any significant effect on the new vessels.

[Grape seed extract inhibits the growth of prostate cancer PC-3 cells].

OBJECTIVE: To investigate the inhibitory effect of grape seed extract (GSE) on the growth of prostate cancer PC-3 cells. METHODS: PC-3 cells were treated with GSE at the concentration of 100, 200 and 300 microg/ml for 24, 48 and 72 hours, respectively. The the inhibitory effect of GSE on the growth of the PC-3 cells and the kidney cells of SD rats was determined by MTT reduction assay, with primarily cultured kidney cells of 1-3 days old SD rats as the normal control. RESULTS: GSE significantly inhibited the growth of PC-3 cells in a concentration- and time-dependent manner, but had only a mild inhibitory effect on the kidney cells. CONCLUSION: GSE inhibits the growth of prostate cancer PC-3 cells and can be used as a new drug for the treatment of prostate cancer.

[Grape seed extract induces morphological changes of prostate cancer PC-3 cells].

OBJECTIVE: To observe the morphological changes of prostate cancer PC-3 cells induced by grape seed extract (GSE). METHODS: PC-3 cells were incubated with different concentrations of GSE (100, 200 and 300 microg/ml) for 24, 48 and 72 hours, and then observed for morphological changes by invert microscopy, HE staining and transmission electron microscopy. RESULTS: The incubated PC-3 cells appeared round, small, wrinkled and broken under the invert microscope and exhibited the classical morphological characteristics of cell death under the electron microscope, including cell atrophy, increased vacuoles, crumpled nuclear membrane, and chromosome aggregation. CONCLUSION: GSE can cause morphological changes and induce necrosis and apoptosis of PC-3 cells.

[Value of preoperative urodynamics to the prognosis of transurethral prostate resection for benign prostatic hyperplasia].

OBJECTIVE: To establish the value of preoperative urodynamics to the outcome prediction of transurethral prostate resection (TURP) for benign prostatic hyperplasia (BPH). METHODS: One hundred and sixty patients with BPH underwent urodynamic tests. Preoperative IPSS (International Prostate Symptom Score) and QOL (Quality of Life) were compared with those 8 to approximately 11 months after operation. RESULTS: The parameters of urodynamic tests (max. free flow, detrusor pressure at max. flow, Schafer grade, Abrams-Griffiths No, urethral resistance factor, cystometric capacity, effective capacity). IPSS and QOL were improved after operation (P < 0.001). And all the relative coefficients of linear dependence analysis, IPSS, QOL and max. free flow, detrusor pressure at max. flow, Schafer grade, Abrams-Griffiths value, urethral resistance factor, cystometric capacity, and effective capacity conducted postoperatively, were statistically significant. CONCLUSION: Preoperative urodynamics of transurethral prostate resection for benign prostatic hyperplasia may provide indication for operation and predict postoperative improvement of symptoms. Preoperative urodynamics should be considered as a routine examination.