Mitochondrial KATP channel-mediated autophagy contributes to angiotensin II-induced vascular dysfunction in mice.

BACKGROUND AND AIM: The present study aimed to investigate whether the mitochondrial KATP channel contributes to angiotensin II (Ang II)-induced vascular dysfunction, the development of hypertension, and atherosclerosis. METHODS AND RESULTS: ApoE (-/-) mice fed a high-fat diet were chronically infused with Ang II for eight weeks and concomitantly treated with losartan (ARB), apocynin, or 5-hydroxy decanoate (5-HD), or 3-methyladenine (3-MA). Systolic blood pressure was measured, and pathological changes of aortic or liver tissue were observed. Nitric oxide (NO), superoxide dismutase 2 (SOD2) levels and vasorelaxation rate were measured, and protein and mRNA expressions were examined by western blot and RT-PCR. Ang II-induced development of hypertension was suppressed not only by ARB, and apocynin but also by 5-HD or 3-MA. Ang II infusion decreased aortic NO production and relaxation, as well as SOD2 activity in liver, which were improved by all treatments. In addition, Ang II-induced activation of autophagy was suppressed by 5-HD in aortic tissue, furthermore, Ang II increases the atherosclerotic index in plasma and exacerbates the development of atherosclerosis by increases of fat deposition in the aorta and liver. Lipid metabolism-related mRNA expressions (LXR-α, LDLR, SRBI, Acca, and FASN) were changed by Ang II. Similarly, not only ARB, and apocynin, but also 5-HD and 3-MA suppressed Ang II-induced these changes. CONCLUSIONS: Our present findings evidence that mitochondrial KATP channel-mediated autophagy contributes to Ang II-induced vascular dysfunction, development of hypertension, and atherosclerosis.

[Expression and significance of matriptase in ovarian cancer cells with diverse metastatic potential].

OBJECTIVE: To study the expression and significance of matriptase in different metastatic potential of human ovarian cancer cells. METHODS: High-metastatic human ovarian cancer cell HO8910PM and ovarian cancer cell HO8910 were collected.The ability of metastatic of the former was stronger than that of the latter. Compared the ability of invasion and migration in HO8910PM and HO8910 by scratch assay and by millicell chamber artificial reconstituted basement membrane invasion assay. Detected the matriptase mRNA and protein expression levels in HO8910PM and HO8910 through reverse transcription(RT)-PCR and immunocytochemistry methods. RESULTS: The 24 hours' migration distance (347 ± 8) µm of HO8910PM cells were significantly higher than that in HO8910 group (154 ± 10) µm (P < 0.01);The number of HO8910PM cells that penetrated the matrigel after 24 hours' incubation were significantly higher than that in HO8910 group (90.7 ± 2.1 vs 63.3 ± 1.5,P < 0.01). The expression of matriptase mRNA in HO8910PM cells was higher than that in HO8910 group (0.72 ± 0.03 vs 0.38 ± 0.04,P < 0.01). The migration was positively correlated with the matriptase mRNA expression levels (r = 0.992, P < 0.01); and the invasiveness was also positively correlated with the matriptase mRNA expression levels (r = 0.973, P < 0.01). As far protein level,the expression of matriptase protein in HO8910PM cells was higher than that in HO8910 group (15.6 ± 0.8 vs 7.6 ± 1.3,P < 0.01). The migration was positively correlated with matriptase protein expression levels (r = 0.971, P < 0.01); And the invasiveness was also positively correlated with the matriptase protein expression levels (r = 0.958, P < 0.01). CONCLUSIONS: The relationship between the expression levels of matriptase and the metastatic of ovarian cancer cells may be correlative. The function of matriptase in ovarian cancer cells metastatic mechanism still need to be confirmed.

[Significance of urodynamic analysis in the patients with recent voiding dysfunction after radical hysterectomy].

OBJECTIVE: To study the urodynamic changes in patients with recent non-infective voiding dysfunction following radical hysterectomy and assess its significance. METHODS: Ninety-six patients with cervical cancer, who were not found any abnormal representation of urodynamics before the operation, were selected into this study group. Eighty-three patients in the study group without urinary infection were detected by urodynamic examination following radical hysterectomy, in order to analyze the urodynamic reasons for the non-infective voiding dysfunction following the surgery. RESULTS: Forty-two patients were found with non-infective voiding dysfunction after the operation. Low compliance bladder, bladder destrusor dysfunction and destrusor overactivity were the three leading types of postoperative bladder dysfunction. Moreover, the incidences of low compliance bladder (50.0% vs. 17.1%), bladder destrusor dysfunction (58.4% vs. 14.6%) and destrusor overactivity (31.0% vs. 4.9%) in the group with voiding dysfunction were significantly higher than the corresponding values in the group without voiding dysfunction (P < 0.01). Secondarily, forty-two patients with recent non-infective voiding dysfunction were divided into simple irritation sign group, simple obstruction sign group and mixed sign group according to their main symptoms. The incidence of bladder destrusor dysfunction in the simple obstruction sign group was significant higher than that in the simple irritation sign group, and the incidence of detrusor overactivity in the simple irritation sign group was significant higher than that in the other two groups (P < 0.05). CONCLUSIONS: There were many different types of urodynamic disorder in the patients with recent non-infective voiding dysfunction after radical hysterectomy. Low compliance bladder, bladder destrusor dysfunction and detrusor overactivity caused by the damage of the pelvic autonomic nerve during the operation may be the main reasons for the recent non-infective voiding dusfunction after radical hysterectomy. Moreover, bladder destrusor dysfunction and detrusor overactivity may be the key points for the symptoms of bladder irritation and bladder obstruction. Urodynamic study is important for the etiology analysis and clinical treatment of recent non-infective voiding dysfunction postoperation.

[Influence of urodynamic factors on urinary retention in patients with cervical carcinoma after radical hysterectomy].

OBJECTIVE: To study the effect of urodynamic factors on the urinary retention of the patients with cervical cancer received radical hysterectomy. METHODS: Seventy-two patients with cervical cancer International Federation of Gynecology and Obstetrics (FIGO) stage Ib1 to IIa hospitalized in Fujian Provincial Maternity and Child Health Hospital between June 2006 and August 2009, who were not found any abnormal representation of urodynamics before the operation, were divided into the group with urinary retention and the group without urinary retention based on whether urinary retention after the operation. All patients were detected by urodynamic examination following radical hysterectomy. Data obtained from urodynamic examination were analysed by logistic regression to evaluate the influence of urodynamic factors on the urinary retention postoperation. RESULTS: Twenty-one patients out of all were found with urinary retention after the operation, the incidence rate of urinary retention was 29%. The first sensation after operation in both groups were increased significantly than those before operation [(171 ± 61) ml vs. (126 ± 28) ml, (134 ± 39) ml vs. (119 ± 17) ml, all P < 0.05], while the maximum volume [(337 ± 66) and (300 ± 66) ml, respectively], the compliance [(31 ± 25) and (29 ± 18) ml/cm H2O (1 cm H2O = 0.098 kPa), respectively], the maximum flow rate [(10 ± 4) and (12 ± 5) ml/s, respectively] and the pressure at the maximum flow rate [(27 ± 9) and (32 ± 8) cm H2O, respectively] were decreased obviously after radical hysterectomy in both the group with urinary retention and the group without urinary retention (all P < 0.05), compared with the corresponding value before the operation. The urodynamic changes in urinary retention group was much more severe than those in group without urinary retention (P < 0.05). The single factor analysis results showed that bladder destusor dysfunction (OR = 8.20, 95%CI: 2.62-25.66, P < 0.01) and lack of sensation (OR = 6.90, 95%CI: 1.95-24.43, P < 0.01) were relevant to the urinary retention post-operation. While there were not relationship was found between low compliance bladder (OR = 1.99, 95%CI: 0.70-5.63, P = 0.195), detrusor overactivity (OR = 2.51, 95%CI: 0.73-8.67, P = 0.144), bladder outlet obstruction (OR = 3.77, 95%CI: 0.76-18.57, P = 0.104) or dyssynergia of urethral external sphincter (OR = 2.67, 95%CI: 0.49-14.45, P = 0.255) and urinary retention following the operation. There were an antagonistic effects (OR = 7.60, 95%CI: 1.43-40.39, P = 0.017) of detrusor overactivity and bladder destrusor dysfunction on urinary retention. The multiple factors analysis results revealed that bladder destusor dysfunction (OR = 7.01, P < 0.01) and lack of sensation (OR = 5.45, P = 0.018)were the independent risk factors influencing on the urinary retention post-operation. CONCLUSIONS: There are obvious urodynamic change in cervical cancer patients following radical hysterectomy. Bladder destrusor dysfunction and lack of sensation are the independent urodynamic risk factors influencing on urinary retention following radical hysterectomy, while detrusor over activity may be a protective effect on bladder destrusor dysfunction post-operation in some degree. Urodynamic test is important for analysis and treatment of urinary retention following radical hysterectomy.

[Randomized study of thalidomide combined with vinorelbine and cisplatin chemotherapy for the treatment of advanced non-small cell lung cancer].

OBJECTIVE: To evaluate the efficacy, median time to progression (TTP), quality of life and toxicity in the patients with advanced non-small cell lung cancer (NSCLC), treated with thalidomide plus vinorelbine and cisplatin (NP) or NP alone. METHODS: Sixty six patients with advanced NSCLC were divided randomly into two groups, the trial and control groups. The trial group was treated with vinorelbine 25 approximately 30 mg/m(2) i.v. on D1 and D8, cisplatin 70 approximately 80 mg/m(2) i.v. on D1 (NP regimen), and thalidomide 200 mg orally and daily from D1. The control group received vinorelbine and cisplatin as above described. RESULTS: Of 66 assessable patients, the overall response rate was 51.5% in the trial group and 36.4% in the control group (P = 0.22). The median TTP was 6.0 months for the trial group, and 3.6 months for the control group (P < 0.001). The score of quality of life in trial group was higher than that in the control group, but no significant difference was observed between the two groups (P > 0.05). There were no significant differences in toxicities between the two groups (P > 0.05). CONCLUSION: NP regimen combined with thalidomide can significantly prolong the median time to tumor progression in patients with advanced NSCLC. Thalidomide may have a synergic activity with NP regimen without increased toxicities.

[Analysis different transcriptional factors in different phenotype endometrial cancer cells].

OBJECTIVE: To analysis the activity of transcriptional factors in endometrial cancer cell lines with different estrogen receptor subtypes. METHODS: The mRNA levels of estrogen receptor (ER) was detected by quantitative RT-PCR, and the activity of transcriptional factors was also analysed by 345-channel protein/DNA array in RL-952 (the expression status of ERalpha and ERbeta both positive), HEC-1A [ERalpha (+/-), while ERbeta negative] and HEC-1B (ERalpha and ERbeta both negative). The transcription factors of NFkappaBp65 and p38MAPK with different activity were tested by enzyme-linked immunosorbent assay (ELISA) to confirm the results of protein/DNA array. RESULTS: The mRNA levels of ERalpha in RL-952, HEC-1A and HEC-1B were (6780+/-282), (684+/-84) and (168+/-38) copy/ng, respectively. Among 345 candidate transcriptional factors, there were 28 factors associated with ER status. Compared with RL-952 cells, 13 transcriptional activity factors were concomitantly up-regulation, while 15 concomitantly down-regulation in HEC-1A and HEC-1B cells. Transcriptional activities of TTF (1)-1, NRF-1, TCE were significantly correlated with the high-expression status of ERalpha mRNA (r=0.523, P=0.037), while RFX123 and Ikaros were significantly correlated with the low-expression status of ERalpha mRNA (r=-0.312, P=0.041). CONCLUSION: Transcriptional factors of TTF (1)-1, NRF-1, TCE may be associated with ER-mediated signal pathway, while RFX123 and Ikaros may be associated with non ER-mediated signal pathway in endometrial cancer.