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Chronic alcohol consumption causes liver steatosis, cell death, and inflammation. Melatonin (MLT) is reported to alleviate alcoholic liver disease (ALD)-induced injury. However, its direct regulating targets in hepatocytes are not fully understood. In the current study, a cell-based screening model and a chronic ethanol-fed mice ALD model were used to test the protective mechanisms of MLT. MLT ameliorated ethanol-induced hepatocyte injury in both cell and animal models (optimal doses of 10 μmol/L and 5 mg/kg, respectively), including lowered liver steatosis, cell death, and inflammation. RNA-seq analysis and loss-of-function studies in AML-12 cells revealed that telomerase reverse transcriptase (TERT) was a key downstream effector of MLT. Biophysical assay found that epidermal growth factor receptor (EGFR) on the hepatocyte surface was a direct binding and regulating target of MLT. Liver specific knock-down of Tert or Egfr in the ALD mice model impaired MLT-mediated liver protection, partly through the regulation of nuclear brahma-related gene-1 (BRG1). Long-term administration (90 days) of MLT in healthy mice did not cause evident adverse effect. In conclusion, MLT is an efficacious and safe agent for ALD alleviation. Its direct regulating target in hepatocytes is EGFR and downstream BRG1-TERT axis. MLT might be used as a complimentary agent for alcoholics.
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[Objective]To compare the differences of neuromyelitis optica spectrum disorder(NMOSD)and multiple sclerosis (MS) on pregnancy ,and analyze the mutual impact of pregnancy on the diseases.[Methods]Prospectively collected clinical information of 235 NMOSD patients and 125 MS patients ,including the annualized relapse rate (ARR),the Expanded Disability Status Scale(EDSS)and pregnancy outcomes. 70 NMOSD patients and 30 MS patients were screened out as information patients. The ARR and EDSS score in two groups were compared during the year before pregnancy,during pregnancy and after 1 year postpartum, respectively. 50 cases of normal pregnant women for the same period as the control group ,then to compared the difference of three groups on pregnancy outcomes.[Results]Attacks occurring during pregnancy or one year after childbirth/abortion in NMOSD and MS were 53.25%(41/77)and 20.00%(7/35)(P=0.001);The ARR during the first 3 months postpartum periods of NMOSD and MS group(2.65,2.51)was significantly higher than during the year before pregnancy(0.27,0.49,P < 0.001)and during pregnancy (0.32,0.2,P<0.001);The EDSS score of two groups increased after 1 year postpartum(3.06 ± 2.16,2.19 ± 1.28)than that during the year before pregnancy(1.58 ± 0.48,1.92 ± 1.29,P < 0.001)and during pregnancy(1.92 ± 1.35,1.67 ± 0.70,P < 0.001). There was no difference on ARR and EDSS score between NMOSD and MS group. NMOSD ,MS and normal control group had no dif?ference on pregnancy outcomes and neonatal weight.[Conclusions]Compared with MS,the attack of NMOSD had more closer relation?ship with pregnancy;both NMOSD and MS would increase the risk of disease relapsing and disability after pregnancy;the diseases had no effect on pregnancy outcomes.
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Objective To investigate the change of serum nitric oxide ( NO ) in premature rupture of membrane (PROM) and its clinical significance, so as to assess the role of NO in the mechanism of PROM . Method The serum NO in 40 advanced stage pregnant women,28 premature delivery PROM,40 unknown reason term pregnancy PROM ,40 term pregnancy ,40 term labor were detected and compared. Results The serum NO was higher in unknown reason term pregnancy PROM [(95.364±3.562) (u)ol/L] than that in term pregnancy [(75.020±3.416)(u)ol/L] and term labor [(31.457±3.859)(u)ol/L](P<0.01). The serum NO was higher in premature delivery PROM [(101.256±3.124)(u)ol/L] than that in advanced stage pregnant women [(80.363±5.112)(u)ol/L] (P<0.0l),but similar with unknown reason term pregnancy PROM (P = 0.086). Conclusions The serum NO in PROM of term pregnancy significantly is higher than that of advanced stage and term labor women,indicates PROM relating to the increase of NO level. Because the increase of NO links to infection,it suggests that PROM relate closely to the amniotic infection.
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Objective To analyze the clinical presentation and maternal-neonatal outcome of HELLP syndrome.Methods 32 cases with HELLP syndrome from January 2003 to January 2009 were analyzed retrospectively.Results The incidence of HELLP syndrome in preeclampsia was 3.7%.Complete HELLP were 17 cases,partial HELLP were 15 cases.Two pregnant women died(one case of intracranial hemorrhage,one case of acute left cardiac failure),the mortality was 6.3%.Five newborns died,the mortality was 15.6%.The main materal complications were DIC(8 cases),placental abruption(2 cases),intracranial hemorrhage(2 cases).The main perinatal complications were preterm labor(20 cases),newborn asphysia(17 cases),SGA(15 cases).Conclusion HELLP syndrome is one of the most serious obstetric complications,early diagnosis,early therapy,controlling hypertension and termination of pregnancy in time are most important for treatment.
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Objective To explore the clinical characteristics,causes,diagnosis and treatment of pelvic mass in adolescents caused by gynecologic diseases. Methods One hundred and twenty-six adolescents with gynecologic diseases presented as pelvic mass were retrospectively reviewed. Results The average age of all patients was 17. 6 years,ranging from 10. 0 to 19. 0 years. Ectopic pregnancy was found in 38 patients(30. 2%) ,the average age of the patients was 18.6 ±0.5 years, ranging from 17.0 to 19.0 years. Ovarian neoplasm was found in 35 patients (27. 8%) ,the average age of the patients was 17. 1 ± 2. 1 years, ranging from 10. 0 to 19. 0 years. Twenty cases (57. l%)had germ cell tumor, eighteen with mature teratomas, one with endodermal sinus tumor and one with immature teratoma. Thirteen cases(37. 2%)had epithelial ovarian tumors;eight with serous cystadenomas,three with mucinous cystadenoma, one with mucinous cystadenoma complicated with serous cystadenoma and one with borderline mucinous cystadenoma. Two cases had simple cyst of the ovary (5. 7%) . Congenital abnormality of reproductive tract was found in 14 patients (11. 1%), the average age was 14. 7 ±2. 2 years, ranging from 13.0 to 19. 0 years. Seven had imperforate hymens, two had rudimentary horn of uterus,four had atresia of vagina,one had atresia of vagina complicated with rudimentary horn of uterus,and one had oblique septum of vagina. Corpus luteum rupture was found in 11 patients (8. 7%) , the average age was 18. 1 ± 1. 9 years, ranging from 13. 0 to 19. 0 years. 116 patients underwent operative treatment and 10 patients underwent conservative therapy. Conclusions According to the stage of adolescents, main causes of pelvic mass in adolescents are different Main causes of pelvic mass in early adolescents are tumorous disease. Congenital abnormalities of reproductive tract are usually in middle adolescents. The gonads develop closely mature in late adolescent period; main causes of pelvic mass are ectopic pregnancy, ovarian neoplasm and physiologic ovarian cyst Surgery is the main therapy of pelvic mass in adolescents.
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Objective To investigate the apoptotic and proliferation effects of signal transduction inhibitors on human endometrial carcinoma cells with different PTEN gene expression. Methods FTEN antisense oligonucleotide and pcDNA3.1/PTEN vector contained PTEN gene were transfected into endometrial carcinoma cells (HEC-1A and Ishikawa). The expression of PTEN protein was detected by confocal spectral microscopy. The endometrial carcinoma cells (HEC-1A, HEC-1A-PTEN-null, Ishikawa, Ishikawa-PTEN) were treated with signal transduction inhibitors, RG-14620, SB203580 (SB) and rapamycin, respectively. Cell apoptosis morphology, cell apoptosis and cell cycle were detected by Hoechst 33258 staining and flow cytometry. Cell viability was determined by methyl thiazolyl tetrazolium assay. Results The PTEN protein expression in two endometrial carcinoma cells (Ishikawa, HEC-1A) was exchanged by PTEN antisense oligonucleotide blocked and pcDNA3. 1/PTEN stable transfected. After treated with RG-14620, SB and rapamycin, marked morphological changes of apoptosis were observed in HEC-1A-PTEN-null and Ishikawa cells. The cell apoptosis of HEC-1A-PTEN-null and Ishikawa cells exposed to SB were significantly increase [(31.6±0.8)% and (37.8±0.8)%, respectively], the G1 phase cells were increased to (84.1±3.2)% and (87.5±1.9)%. While cell viability was significantly decreased in HEC-1A-PTEN-null and Ishikawa cells, the cell viability of HEC-1A-PTEN-null and Ishikawa cells exposed to SB were (54.0±2.1) % and (49.0±1.7) %. Conclusion Loss of PTEN in endometrial carcinoma cells may improve the G_1 phase cells and apoptotic effects, inhibit the cell proliferation, which due to the sensitivity of cells to related signal transduction inhibitors.