Verapamil inhibits ureteral scar formation by regulating CaMK II-mediated Smad pathway.

Verapamil is reported to prevent scar formation. However, whether verapamil is involved in the ureteral stricture scar and the underlying mechanism need further investigation. Fibroblasts were isolated from ureteral scar tissues. TGF-ß1 stimulation was used to induce fibrosis of fibroblasts. Inhibition of CaMK II was achieved by shRNA transfection. CCK-8 was performed to evaluate cell viability. qRT-PCR was applied to determine the level of mRNA while western blotting was used to determine the level of proteins. Immunofluorescence was used to detect the level of vimentin, collagen I and collagen III. Primary fibroblasts was successfully isolated from ureteral scar tissues. TGF-ß1 stimulation was capable to induce collagen production and fibrosis in primary fibroblasts while inhibition of CaMK II attenuate collagen production. Overexpression of wild type CaMK II lead to further increase of collagen production upon TGF-ß1 stimulation while the mutated CaMK II did not exert this promotion. Treatment of verapamil inhibits TGF-ß1 induced collagen production via inhibiting CaMK II. In present study, we revealed a vital role of Verapamil and CaMK II in the formation of ureteral scar. Verapamil inhibited TGF-ß1 induced collagen fiber formation by regulating CaMK II. Our finding might provide new insight into mechanism of prevention and treatment of ureteral scar.

Study on chemical constituents of an edible mushroom Volvariella volvacea and their antitumor activity in vitro.

Phytochemical investigation of the fruiting body of Volvariella volvacea led to the isolation of a new furanone, 2(5H)-furanone-4-propionic acid named volvafuranone A (1), together with twelve known compounds (2-13). Compounds 2-7, 9-11 were isolated from this mushroom for the first time. The isolated compounds were assessed for their cytotoxicity against four human tumour lines (SGC-7901, PC-3M, MCF-7, HepG-2), and the results showed that compound 2, 3, 12, 13 have significant cytotoxicity with IC50 values of 5.90 µM (HepG-2), 20.72 µM (HepG-2), 27.98 µM (PC-3M) and 23.15 µM (PC-3M), respectively.

MiR-93 functions as a tumor promoter in prostate cancer by targeting disabled homolog 2 (DAB2) and an antitumor polysaccharide from green tea (Camellia sinensis) on their expression.

Our previous work has demonstrated that the role of miR-93 in prostate cancer (PC) progression. The aim of this study was to determine the downstream gene regulated by miR-93 and the molecular mechanisms underlying its roles in PC. Bioinformatics analysis and luciferase reporter assays predicted disabled homolog 2 (DAB2) as a direct target gene of miR-93. Real time quantitative polymerase chain reaction (qRT-PCR) and Western blot analysis revealed that DAB2 was tumor repressor in PC cells, and its mRNA expression was negatively correlated with miR-93 in PC tissues. Gain and loss of function experiments also indicated DAB2 overexpression significantly suppressed PC cells proliferation, invasion and migration, while knockdown of its expression came to the opposite effect. Furthermore, a rescue experiment indicated miR-93 directly regulated PC cell growth and migration, as well as AKT and ERK activation by targeting DAB2. Additionally, antitumor effect of a Green tea polysaccharide (GTP) on PC-3 cells could be achieved by increasing DAB2 protein expression and inactivating AKT and ERK1/2 signaling. Our study suggests that miR-93 promoted PC progression and metastasis by repressing DAB2 to activate Akt/ERK1/2 pathway, and elevation of DAB2 and inactivation of Akt/ERK1/2 might be a potential therapeutic target for PC by GTP.

Long-term Clinical Efficacy and Safety Profile of Transurethral Resection of Prostate Versus Plasmakinetic Resection of the Prostate for Benign Prostatic Hyperplasia.

OBJECTIVE: To investigate the differences on clinical efficacy, complications, and safety profile between transurethral resection of the prostate (TURP) and bipolar plasmakinetic resection of the prostate (PKRP) for benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Six hundred ninety patients of BPH were recruited from May 2008 to May 2011 and divided into TURP group and PKRP group. The International Prostate Symptom Score (IPSS), quality of life score (QoL), postvoid residual urine (PVR), maximum flow rate (Qmax), complications, International Index of Erectile Function-5 (IIEF-5) questionnaire, and retrograde ejaculation were used for evaluation of clinical efficacy and safety and sexual function between the 2 groups. RESULTS: The intraoperative irrigation volume, postoperative irrigation volume, postoperative irrigation time, decrease in sodium, intraoperative blood loss, and duration of catheterization of the PKRP group were significantly lower than those of the TURP group (P <.05). For comparison of complications, the incidence rates of massive hemorrhage, blood transfusion, capsular perforation, prolonged hematuria, micturition frequency, micturition urgency, and micturition pain of the PKRP group were significantly less than those of the TURP group (P <.05). During the 5-year follow-up, the PKRP group showed better effect on IPSS, QoL, PVR, and Qmax compared with the TURP group (P <.05), but there were no significant differences on IIEF-5 and retrograde ejaculation (P > .05). CONCLUSION: PKRP is just as efficacious as TURP and is associated with a lower rate of certain morbidities. Its lower complications and better safety profile make PKRP an attractive alternative for treatment of BPH.

TIPE2 Overexpression Suppresses the Proliferation, Migration, and Invasion in Prostate Cancer Cells by Inhibiting PI3K/Akt Signaling Pathway.

Tumor necrosis factor-α (TNF-α)-induced protein 8-like 2 (TNFAIP8L2, TIPE2) is involved in the invasion and metastasis of human tumors. However, the functional role of TIPE2 in prostate cancer remains unclear. In the present study, we explored the role of TIPE2 in prostate cancer and cancer progression including the molecular mechanism that drives TIPE2-mediated oncogenesis. Our results showed that TIPE2 was lowly expressed in human prostate cancer tissues and cell lines. In addition, restored TIPE2 obviously inhibits proliferation in prostate cancer cells. TIPE2 overexpression also suppresses the epithelial-mesenchymal transition (EMT) process and migration/invasion in prostate cancer cells. Mechanistically, TIPE2 overexpression obviously inhibits the phosphorylation levels of phosphatidylinositol 3-kinase (PI3K) and Akt in prostate cancer cells. In conclusion, for the first time we demonstrated that TIPE2 overexpression may suppress proliferation, migration, and invasion in prostate cancer cells by inhibiting the PI3K/Akt signaling pathway. Therefore, TIPE2 might serve as a potential therapeutic target for human prostate cancer.

Anticancer effect of deoxypodophyllotoxin induces apoptosis of human prostate cancer cells.

Deoxypodophyllotoxin (DPPT) is extracted and separated from citrus-related plants, including Podophyllum (P.) peltatum, P. pleianthum, P. emodi (also called P. hexandrum) and Diphylleia grayi. DPPT has significant antitumor and antiviral activity. However, due to its strong toxicity and side effects, its use is limited in practical applications. The in vitro antitumor efficacy of DPPT on human prostate cancer (PCa) cells remains to be determined. The present study investigated the anticancer effect of DPPT on human PCa cells and its potential mechanism. The data revealed that DPPT markedly reduced cell proliferation and activated the caspase-3 expression level by an increase in apoptotic cell death in DU-145 cells. In addition, treatment with DPPT markedly downregulated the levels of phosphorylated Akt and activated the p53/B-cell lymphoma 2 associated X protein (Bax)/phosphatase and tensin homolog (PTEN) signaling pathway in DU-145 cells, suggesting that caspase-mediated pathways were involved in DPPT-induced apoptosis. The present study suggested the role of DPPT as a novel chemotherapeutic drug for human PCa, which may function through the Akt/p53/Bax/PTEN signaling pathway.

Investigation of carbon dioxide emission in China by primary component analysis.

Principal component analysis (PCA) is employed to investigate the relationship between CO2 emissions (COEs) stemming from fossil fuel burning and cement manufacturing and their affecting factors. Eight affecting factors, namely, Population (P), Urban Population (UP); the Output Values of Primary Industry (PIOV), Secondary Industry (SIOV), and Tertiary Industry (TIOV); and the Proportions of Primary Industry's Output Value (PPIOV), Secondary Industry's Output Value (PSIOV), and Tertiary Industry's Output Value (PTIOV), are chosen. PCA is employed to eliminate the multicollinearity of the affecting factors. Two principal components, which can explain 92.86% of the variance of the eight affecting factors, are chosen as variables in the regression analysis. Ordinary least square regression is used to estimate multiple linear regression models, in which COEs and the principal components serve as dependent and independent variables, respectively. The results are given in the following. (1) Theoretically, the carbon intensities of PIOV, SIOV, and TIOV are 2573.4693, 552.7036, and 606.0791 kt per one billion $, respectively. The incomplete statistical data, the different statistical standards, and the ideology of self sufficiency and peasantry appear to show that the carbon intensity of PIOV is higher than those of SIOV and TIOV in China. (2) PPIOV, PSIOV, and PTIOV influence the fluctuations of COE. The parameters of PPIOV, PSIOV, and PTIOV are -2706946.7564, 2557300.5450, and 3924767.9807 kt, respectively. As the economic structure of China is strongly tied to technology level, the period when PIOV plays the leading position is characterized by lagging technology and economic developing. Thus, the influence of PPIOV has a negative value. As the increase of PSIOV and PTIOV is always followed by technological innovation and economic development, PSIOV and PTIOV have the opposite influence. (3) The carbon intensities of P and UP are 1.1029 and 1.7862 kt per thousand people, respectively. The carbon intensity of the rural population can be inferred to be lower than 1.1029 kt per thousand people. The characteristics of poverty and the use of bio-energy in rural areas result in a carbon intensity of the rural population that is lower than that of P.

[Environmental impacts of sewage treatment system based on emergy analysis].

"Integrated sewage treatment system" (ISTS) consists of sewage treatment plant system and their products (treated water and dewatered sludge) disposal facilities, which gives a holistic view of the whole sewage treatment process. During its construction and operation, ISTS has two main impacts on the environment, i.e., the consumption of resources and the damage of discharged pollutants on the environment, while the latter was usually ignored by the previous researchers when they assessed the impacts of wastewater treatment system. In order to more comprehensively understanding the impacts of sewage treatment on the environment, an analysis was made on the ISTS based on the theories of emergy analysis, and, in combining with ecological footprint theory, the sustainability of the ISTS was also analyzed. The results showed that the emergy of the impacts of water pollutants on the environment was far larger than that of the impacts of air pollutants, and NH3-N was the main responsible cause. The emergy consumption of ISTS mainly came from the emergy of wastewater and of local renewable resources. The "sewage treatment plant system + landfill system" had the highest emergy utilization efficiency, while the "sewage treatment plant system + reclaimed water reuse system + incineration system" had the lowest one. From the aspect of environmental sustainability, the "sewage treatment plant system + reclaimed water reuse system + landfill system" was the best ISTS, while the "sewage treatment plant system + incineration system" was the worst one.

Certain antioxidant enzymes and lipid peroxidation of radish (Raphanus sativus L.) as early warning biomarkers of soil copper exposure.

Copper (Cu) is a major heavy metal contaminant with various anthropogenic and natural sources. Recently, using biomarkers to monitor the effects of pollutants has attracted increased interest. Pot culture experiments using radish (Raphanus sativus L.) was performed to investigate Cu phytotoxic effects on antioxidant enzymes and other early warning biomarkers of soil Cu exposure. Under low dose Cu stress (lower than the EC10, Cu concentration reducing root length by 10%), activity and isozyme expression of superoxide dismutase (SOD), catalase (CAT), and peroxidases (POD) increased significantly; no significant variations in chlorophyll, carotenoid, and malondialdehyde (MDA) content in leaves and toxic symptoms were observed. Under a slightly higher Cu stress (close to the EC10), activity and isozyme expression of SOD and MDA content were enhanced significantly; those of CAT and POD decreased due to an inverted U-shape dose response. Chlorophyll content remained unchanged. Thus, antioxidant enzymes and MDA content are more sensitive to Cu stress, showing significant variations ahead of chlorophyll and toxic symptoms under Cu stress (lower than about 200 mg kg(-1) soil). Thus, the joint monitoring of antioxidant enzymes and MDA content of R. sativus can be used as biomarkers of soil Cu contamination.

A uniform source-and-sink scheme for calculating thermal conductivity by nonequilibrium molecular dynamics.

A uniform source-and-sink (USS) scheme, which combines features of the reverse [F. Müller-Plathe, J. Chem. Phys. 106, 6082 (1997)] and improved relaxation [B. Y. Cao, J. Chem. Phys. 129, 074106 (2008)] methods, is developed to calculate the thermal conductivity by nonequilibrium molecular dynamics (NEMD). The uniform internal heat source and sink are realized by exchanging the velocity vectors of individual atoms in the right half and left half systems, and produce a periodically quadratic temperature profile throughout the system. The thermal conductivity can be easily extracted from the mean temperatures of the right and left half systems rather than by fitting the temperature profiles. In particular, this scheme greatly increases the relaxation of the exited localized phonon modes which often worsen the calculation accuracy and efficiency in most other NEMD methods. The calculation of the thermal conductivities of solid argon shows that the simple USS scheme gives accurate results with fast convergence.