RESUMEN
Glioma is the most common and aggressive primary brain tumor in adults. Long-non coding RNAs (lncRNAs) have been recently shown to play important roles in regulating numerous biological processes both in physiologic and pathologic condition. However, the role of lncRNAs in glioma remains largely unknown. In this study, we firstly found that lncRNA CCND2-AS2 is significantly up regulated in malignant glioma tissues and cell lines. Both loss- and gain-functions assays show that CCND2-AS1 promotes glioma cells proliferation and growth. In addition, we also revealed that highly expressed CCND2-AS1 could enhance Wnt/ß-catenin signaling in glioma. Taken together, our findings revealed a novel lncRNA CCND2-AS1 promotes glioma cell proliferation through Wnt/ß-catenin signaling and CCND2-AS1 might function as a potential novel therapeutic target for the treatment of glioma.
Asunto(s)
Neoplasias Encefálicas/metabolismo , Ciclina D2/metabolismo , Glioma/metabolismo , ARN Largo no Codificante/genética , Vía de Señalización Wnt , Astrocitos/metabolismo , Ciclo Celular , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Pronóstico , Transfección , Regulación hacia ArribaRESUMEN
There is an urgent need for new therapeutic avenues to improve the outcome of patients with glioblastoma multiforme (GBM). Current studies have suggested that cucurbitacin I, a natural selective inhibitor of JAK2/STAT3, has a potent anticancer effect on a variety of cancer cell types. This study showed that autophagy and apoptosis were induced by cucurbitacin I. Exposure of GBM cells to cucurbitacin I resulted in pronounced apoptotic cell death through activating bcl-2 family proteins. Cells treatment with cucurbitacin I up-regulated Beclin 1 and triggered autophagosome formation and accumulation as well as conversion of LC3I to LC3II. Activation of the AMP-activated protein kinase/mammalian target of rapamycin/p70S6K pathway, but not the PI3K/AKT pathway, occurred in autophagy induced by cucurbitacin I, which was accompanied by decreased hypoxia-inducible factor 1α. Stable overexpression of hypoxia-inducible factor 1α induced by FG-4497 prevented cucurbitacin I-induced autophagy and down-regulation of bcl-2. Knockdown of beclin 1 or treatment with the autophagy inhibitor 3-methyladenine also inhibited autophagy induced by cucurbitacin I. A coimmunoprecipitation assay showed that the interaction of Bcl-2 and Beclin 1/hVps34 decreased markedly in cells treated with cucurbitacin I. Furthermore, knockdown of beclin 1 or treatment with the lysosome inhibitor chloroquine sensitized cancer cells to cucurbitacin I-induced apoptosis. Finally, a xenograft model provided additional evidence for the occurrence of cucurbitacin I-induced apoptosis and autophagy in vitro. Our findings provide new insights into the molecular mechanisms underlying cucurbitacin I-mediated GBM cell death and may provide an efficacious therapy for patients harboring GBM.
Asunto(s)
Autofagia/efectos de los fármacos , Glioblastoma/tratamiento farmacológico , Extractos Vegetales/farmacología , Triterpenos/farmacología , Animales , Apoptosis , Proteínas Reguladoras de la Apoptosis/metabolismo , Beclina-1 , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cloroquina/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Glioblastoma/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , ARN Interferente Pequeño/metabolismo , Transducción de Señal , Transfección , Triterpenos/uso terapéuticoRESUMEN
OBJECTIVE: To investigate the relationship of verumontanum hypertrophy with chronic prostatitis. METHODS: Fifty-two patients with chronic prostatitis underwent cystourethroscopy for comparing the size of the verumontanum before and after treatment. RESULTS: Before treatment, all the patients showed different degrees verumontanum hypertrophy, of whom 50 were treated by conventional drug therapy, and the other 2 with voiding dysfunction by drug therapy combined with transurethral resection. Cystourethroscopy revealed significantly decreased size of the verumontanum in 44 of the patients after treatment (P < 0.05). CONCLUSION: Patients with chronic prostatitis often have verumontanum hypertrophy, which could be an indicator of the effect of treatment.
Asunto(s)
Genitales Masculinos/patología , Prostatitis/patología , Adulto , Enfermedad Crónica , Humanos , Hipertrofia , Masculino , Persona de Mediana Edad , Prostatitis/etiología , Adulto JovenRESUMEN
OBJECTIVE: To explore the clinical effects of posterior short-segment pedicle screw internal fixation combined with vertebroplasty for the treatment of Kümmell disease with kyphosis. METHODS: Twenty-four patients with Kümmell disease complicated with kyphosis treated by posterior short-segment pedicle screw internal fixation combined with vertebroplasty from January 2016 to December 2018 were retrospectively analyzed, including 6 males and 18 females, aged 63 to 85 (73.1±6.5) years old. The clinical effect was evaluate by visual analogue scale (VAS), Oswestry Disability Index (ODI), the anterior height of injured vertebral body, and the sagittal Cobb angle of the affected segment beforeoperation, at 3 days and final follow up after operation. And the surgical complications were observed. RESULTS: All 24 patients were followed up from 12 to 24 months with an average of (15.5±3.2) months. The VAS score was decreased from 5.21±1.06 preoperatively to 2.38±0.58 at 3 days postoperatively and 1.71±0.75 at final follow-up;ODI was decreased from (50.4±13.5)% preoperatively to (20.9±8.0)% at 3 days postoperatively and (16.7±9.6)% at final follow-up;the anterior height of injured vertebral body was restored from (8.0±4.2) mm before surgery to (18.1±5.0) mm at 3 days after surgery and (16.8±5.1) mm at final follow up;the sagittal Cobb angle of affected segment was decreased from (19.5±6.3)° preoperatively to (7.6±2.1)° at 3 days after surgery and(8.4±1.7)° at final follow-up. VAS, ODI, anterior height of injured vertebral body, and sagittal Cobb angle of affected segment were significantly improved at 3 days after operation and at final follow-up (P<0.05). Two patients had complications, including asymptomaticcement leakage in 1 patient and superficial wound infection in 1 patient. CONCLUSION: Posterior short-segment pedicle screw internal fixation combined with vertebroplasty for the treatment of Kümmell disease with kyphosis has relatively small surgical trauma, excellent clinical results, good vertebral height recovery, satisfactory correction of kyphotic angle, and fewer complications, etc. It is a safe and effective surgical method to treat Kümmell disease with kyphosis.
Asunto(s)
Cifosis , Tornillos Pediculares , Fracturas de la Columna Vertebral , Vertebroplastia , Femenino , Humanos , Cifosis/cirugía , Vértebras Lumbares/lesiones , Masculino , Estudios Retrospectivos , Vértebras Torácicas/lesiones , Vértebras Torácicas/cirugíaRESUMEN
Studies have shown that men and women exhibit significant differences regarding iron status. However, the effects of sex on iron accumulation and distribution are not well established. In this study, female and male Sprague-Dawley rats were killed at 4 months of age. Blood samples were analyzed to determine the red blood cell (RBC) count, hemoglobin (Hb) concentration, hematocrit (Hct), and mean red blood cell volume (MCV). The serum samples were analyzed to determine the concentrations of serum iron (SI), transferrin saturation (TS), ferritin, soluble transferrin receptor (sTfR), and erythropoietin (EPO). The tissue nonheme iron concentrations were measured in the liver, spleen, bone marrow, kidney, heart, gastrocnemius, duodenal epithelium, lung, pallium, cerebellum, hippocampus, and striatum. Hepatic hepcidin expression was detected by real-time PCR analysis. The synthesis of ferroportin 1 (FPN1) in the liver, spleen, kidney, and bone marrow was determined by Western blot analysis. The synthesis of duodenal cytochrome B561 (DcytB), divalent metal transporter 1 (DMT1), FPN1, hephaestin (HP) in the duodenal epithelium was also measured by Western blot analysis. The results showed that the RBC, Hb, and Hct in male rats were higher than those in female rats. The SI and plasma TS levels were lower in male rats than in female rats. The levels of serum ferritin and sTfR were higher in male rats than in female rats. The EPO levels in male rats were lower than that in female rats. The nonheme iron contents in the liver, spleen, bone marrow, and kidney in male rats were also lower (56.7, 73.2, 60.6, and 61.4 % of female rats, respectively). Nonheme iron concentrations in the heart, gastrocnemius, duodenal epithelium, lung, and brain were similar in rats of both sexes. A moderate decrease in hepatic hepcidin mRNA content was also observed in male rats (to 56.0 % of female rats). The levels of FPN1 protein in the liver, spleen, and kidney were higher in male rats than in female rats. There was no significant change in FPN1 expression in bone marrow. Significant difference was also not found in DcytB, DMT1, FPN1, and HP protein levels in the duodenal epithelium between male and female rats. These data suggest that iron is distributed differently in male and female rats. This difference in iron distribution may be associated with the difference in the hepcidin level.