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1.
FASEB J ; 33(10): 10973-10985, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31318608

RESUMO

RNA-binding motif protein 5 (RBM5) acts as a tumor suppressor in various human cancers and presents with several important characteristics, such as the potentiation of apoptosis, inhibition of the cell cycle, and alternative splicing of Fas and caspase-2 precursor mRNA. However, its role in bladder urothelial carcinoma (BUC) remains unknown. In this study, we found that RBM5 expression was significantly down-regulated in BUC tissues when compared with the adjacent nontumor tissues. The down-regulation of RBM5 activates ß-catenin, which binds to the T-cell factor/lymphocyte enhancer factor element of the miR-432-5p promoter and elevates the expression of miR-432-5p in bladder cancer cells. The up-regulated miR-432-5p directly targets 3'-UTR and depresses RBM5 expression. Thus, RBM5-miR-432-5p-ß-catenin forms a feedback loop in regulating bladder cancer cell apoptosis. Our findings provide evidence that the regulatory feedback loop among RBM5, miR-432-5p, and Wnt-ß-catenin is responsible for the progress of bladder cancer cells.-Zhang, Y.-P., Liu, K.-L., Wang, Y.-X., Yang, Z., Han, Z.-W., Lu, B.-S., Qi, J.-C., Yin, Y.-W., Teng, Z.-H., Chang, X.-L., Li, J.-D., Xin, H., Li, W. Down-regulated RBM5 inhibits bladder cancer cell apoptosis by initiating an miR-432-5p/ß-catenin feedback loop.


Assuntos
Apoptose , Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Retroalimentação Fisiológica , MicroRNAs/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas Supressoras de Tumor/genética , Neoplasias da Bexiga Urinária/metabolismo , beta Catenina/metabolismo , Animais , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/metabolismo , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Neoplasias da Bexiga Urinária/genética , Urotélio/metabolismo , beta Catenina/genética
2.
Zhonghua Nan Ke Xue ; 23(10): 899-902, 2017 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-29727539

RESUMO

OBJECTIVE: To investigate the effect of alpha-lipoic acid (α-LA) combined with tamoxifen citrate (TC) in the treatment of oligoasthenospermia. METHODS: From June to November 2016, we treated 60 patients with oligoasthenospermia in our Department of Andrology, 30 (the trial group) with oral α-LA (0.6 g, qd) + TC (20 mg, qd) and the other 30 (the control group) with oral L-carnitine (1g, bid) + TC (20 mg, qd). Before and after 3 months of medication, we examined the semen parameters of the patients and the levels of their seminal oxidative stress biomarkers, including methylenedioxyamphetamine (MDA) and total antioxidant capacity (TAC) in the seminal plasma. We also compared the pregnancy rate and adverse reactions between the two groups. RESULTS: Totally, 57 of the patients completed the treatment, 28 in the trial group and 29 in the control. Compared with the baseline, the patients of the trial group showed significant improvement after 3 months of medication in the semen volume (ï¼»2.50 ± 0.71ï¼½ vs ï¼»3.37 ± 0.70ï¼½ ml, P <0.05), sperm concentration (ï¼»12.00 ± 1.65ï¼½ vs ï¼»19.34 ± 2.04ï¼½ ×106/ml, P <0.05), percentage of progressively motile sperm (PMS) (ï¼»18.01 ± 3.01ï¼½% vs ï¼»35.41 ± 6.49ï¼½%, P<0.05), MDA level (ï¼»14.96 ± 2.76ï¼½ vs ï¼»10.04 ± 1.04ï¼½ nmol/ml, P <0.05), and TAC in the seminal plasma (ï¼»9.83 ± 1.02ï¼½ vs ï¼»12.25 ± 1.11ï¼½ U/ml, P <0.05), and so did the controls in the semen volume (ï¼»2.76 ± 0.67ï¼½ vs ï¼»3.36 ± 0.93ï¼½ ml, P <0.05), sperm concentration (ï¼»11.47 ± 1.10ï¼½ vs ï¼»17.77 ± 3.56ï¼½ ×106/ml, P <0.05), percentage of PMS (ï¼»19.22 ± 1.41ï¼½ vs ï¼»36.01 ± 5.22ï¼½ %, P <0.05), MDA level (ï¼»14.66 ± 2.75ï¼½ vs ï¼»10.14 ± 1.01ï¼½ nmol/ml, P <0.05), and TAC in the seminal plasma (ï¼»9.84 ± 0.90ï¼½ vs ï¼»11.14 ± 0.84ï¼½ U/ml, P <0.05). There were no statistically significant differences in the above post-medication parameters between the trial and control groups (P >0.05) except in TAC, which was markedly more improved in the former than in the latter (P <0.05), nor in the percentage of morphologically normal sperm before and after treatment in either of the two groups (P >0.05). After 3 months of treatment, 3 pregnancies were achieved in the trial group and 1 in the control (10.7% vs 3.45%, P >0.05). No obvious adverse events occurred during the treatment. CONCLUSIONS: Alpha-lipoic acid combined with tamoxifen citrate can evidently improve semen parameters in oligoasthenospermia patients by relieving oxidative stress injury.


Assuntos
Astenozoospermia/tratamento farmacológico , Oligospermia/tratamento farmacológico , Tamoxifeno/uso terapêutico , Ácido Tióctico/uso terapêutico , Antioxidantes , Biomarcadores/análise , Carnitina/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Estresse Oxidativo , Gravidez , Taxa de Gravidez , Análise do Sêmen , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Espermatozoides/efeitos dos fármacos
3.
Zhonghua Nan Ke Xue ; 16(5): 420-2, 2010 May.
Artigo em Chinês | MEDLINE | ID: mdl-20684322

RESUMO

OBJECTIVE: One of the important reasons for male infertility is asthenozoospermia, for which there is no specific cure for the time being. The authors explored the clinical effect of L-carnitine for infertile males with asthenozoospermia. METHODS: A total of 135 patients with asthenozoospermia were randomly divided into Groups A (n = 68) and B (n = 67), the former treated with L-carnitine (2 g/d) and vitamin E, while the latter with vitamin E only, both for 3 months. All the patients received semen analyses before and after the treatment, and were observed for adverse effects. The pregnancy rates of their wives were recorded. RESULTS: Group A showed a significantly increased percentage of forward motile sperm after the treatment (45.4% +/- 11.1%) as compared with pretreatment (28.6% +/- 9.2%) (P < 0.01), but no statistically significant differences were found in sperm density and the percentage of the sperm of normal morphology (P > 0.05). The rate of pregnancy was significantly higher in Group A (31.1%) than in B (3.8%) after the treatment (P < 0.01). No adverse events were found during the treatment. CONCLUSION: L-carnitine, capable of significantly improving sperm motility and raising the rate of pregnancy, is a safe and effective therapeutic option for asthenozoospermia.


Assuntos
Astenozoospermia/tratamento farmacológico , Carnitina/uso terapêutico , Vitamina E/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Gravidez , Taxa de Gravidez , Motilidade dos Espermatozoides/efeitos dos fármacos , Resultado do Tratamento , Adulto Jovem
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