Transforming Growth Factor-β1 Induces Apoptosis through Down-Regulation of c-mycGene and Overexpression of p27Protein in Cervical Carcinoma

Transforming growth factor-β1 (TGF-β1) is known to be a potent growth inhibitor for many cell types, including most epithelial cells. In skin keratinocytes, TGF-β1 has been shown to inhibit growth and to rapidly reduce c-mycexpression. However, the molecular mechanism of TGF-β1 action on cell growth of cervical carcinoma has not yet been elucidated. We thus assessed the effect of TGF-β1 on the growth of cervical carcinoma cell lines. Two cervical squamous carcinoma cell lines, CUMC-3 and CUMC-6, were incubated with varying concentrations of TGF-β1, and growth inhibition was evaluated with tetrazolium-based colorimetric assay. After culture in TGF-β1 for 24 h, inhibition of growth was detected in a dose-dependent manner at concentrations of 0.1–10 ng/ml in both cell lines. This effect of TGF-β1 on cultured carcinoma cells was associated with apoptotic process including oligonucleosomal ladder DNA and apoptotic body formations. Northern blot analysis revealed c-mycmRNA expression was suppressed by 10 ng/ml of TGF-β1 following 3 h of treatment in both cell lines. Western blot analysis showed that the level of p27^Kip1protein was increased after TGF-β1 treatment in both cell lines. These results suggest that the mechanisms by which TGF-β1 inhibits the growth of cervical carcinoma are complex and may include effects on down-regulation of c-mycgene, and overexpression of p27^Kip1protein.     

Sociotropy and Autonomy as Vulnerabilities to Specific Life Events: Issues in Life Event Categorization

This study examined the relations betweensociotropy, autonomy, and stress severity ratings forhypothetical life events that were objectivelycategorized as interpersonal or achievement-related infocus. The hypothesis that sociotropy and autonomyserve as vulnerability factors to dysphoria in thepresence of life stress that matches the theme of thevulnerability was also examined in 6-week and 12-week follow-up evaluations. Results provided onlypartial support for the predicted relations amongsociotropy, autonomy, and perceived stress severityratings of interpersonal and achievement-related events. Longitudinal results failed to support thehypothesis that sociotropy and autonomy serve asvulnerability factors for matching interpersonal andachievement-related stress. It was concluded thatobjectively categorizing life events as interpersonal orachievement-related is problematic given that themeaning of life events can vary across individuals, andthat these meanings are likely to vary partly as a function of sociotropy and autonomy.     

小叶锦鸡儿的抗炎作用

小叶锦鸡儿可明显对抗角叉菜胶、热烫及巴豆油所致的炎症,抑制小鼠毛细血管通透性、单核巨噬细胞系统的吞噬功能、肉芽组织增生及大鼠炎症部位PGE₂的合成和释放。     

原发性肝癌患者肝切除术前、后免疫细胞表型分析

目的研究原发性肝癌(PrimaryLiverCarcinoma,PLC)患者肝切除术前、后免疫细胞表型的变化。方法采用直接免疫荧光标记,流量血细胞计数法(FlowCytometry,FCM)检测方法,动态观察120例PLC患者肝切除术前后外周血T淋巴细胞亚群、NK细胞和HLA鄄DR含量变化。结果肝切除术前肝功能Child鄄PughB级、OGTTL型和术前施行肝动脉栓塞化疗患者外周血CD8+T细胞含量明显低于正常人组,CD4+/CD8+比值则较高(P<0郾05)。全部肝癌患者肝切除术前、后CD3+CD4+T细胞和NK细胞(CD3-CD16+CD56+)含量无明显差异。术后第1天、第3天、第7天和第2周外周血淋巴细胞CD3+CD8+含量明显低于肝切除术前和术后第3周(P<0.01);而CD4+/CD8+比值则显著高于肝切除术前和术后第3周(P<0郾01)。结论PLC合并肝硬变肝储备功能不足、术前肝动脉栓塞化疗和肝切除术可导致机体细胞免疫功能低下,PLC患者肝切除术前行肝动脉栓塞化疗的价值有待深入研究。     

The effects of chymase on matrix metalloproteinase-2 activation in neointimal hyperplasia after balloon injury in dogs.

Chymase is known to generate angiotensin II in the vascular wall. In this study we investigated a novel role for chymase other than angiotensin II production in vascular proliferation after balloon injury. Chymase promoted the migration of vascular smooth muscle cells in the matrix-coated invasion chambers and activated promatrix metalloproteinase-2 obtained from the culture medium of vascular smooth muscle cells. Two weeks after balloon injury, significant neointimal formation was found in dog carotid arteries. After injury, active matrix metalloproteinase-2 was increased in parallel with the augmentation of chymase activity that was seen in the proliferating region of the vascular wall. The oral administration of NK3201 (1 mg/kg per day), a chymase inhibitor, prevented neointimal formation and significantly suppressed both active matrix metalloproteinase-2 and chymase activities 2 weeks after injury. These results suggest that chymase inhibitors can prevent the development of intimal hyperplasia via the inhibition of matrix metalloproteinase-2 activation in balloon-injured arteries.     

Fidgetin-like 1 gene inhibited by basic fibroblast growth factor regulates the proliferation and differentiation of osteoblasts.

The FIGNL1 gene was proven to be a new subfamily member of ATPases associated with diverse cellular activities (AAA proteins). In this in vitro study, the AAA proteins inhibited osteoblast proliferation and stimulated osteoblast differentiation. We showed that FIGNL1 may play some regulatory role in osteoblastogenesis. INTRODUCTION: The fidgetin-like 1 (FIGNL1) gene encodes a new subfamily member of ATPases associated with diverse cellular activities (AAA proteins). Although the FIGNL1 protein localizes to both the nucleus and cytoplasm, the function of FIGNL1 remains unknown. In a previous study, we identified several genes that mediate the anabolic effects of basic fibroblast growth factor (bFGF) on bone by using microarray data. FIGNL1 was one of the genes that downregulated >2-fold in MC3T3-E1 cells after treatment with bFGF. Therefore, this study was aimed to identify and confirm the function of FIGNL1 on osteoblastogenesis. MATERIALS AND METHODS: We examined the effect of the FIGNL1 gene on proliferation, differentiation, and apoptosis in mouse osteoblast cells (MC3T3-E1 and mouse primary calvarial cells) using flow cytometry, RT-PCR, cell proliferation assay, and cell death assay. MC3T3-E1 cells and mouse calvarial cells were transfected with small interfering RNA (siRNA) directed against the FIGNL1 or nontargeting control siRNA and examined by cell proliferation and cell death assays. Also, FIGNL1 was fused to enhance green fluorescent protein (EGFP), and the EGFP-fused protein was transiently expressed in MC3T3-E1 cells. RESULTS: Reduced expression of FIGNL1 by bFGF and TGF-beta1 treatment was verified by RT-PCR analysis. Overexpression of FIGNL1 reduced the proliferation of MC3T3-E1 and calvarial cells, more than the mock transfected control cells did. In contrast, siFIGNL1 transfection significantly increased the proliferation of osteoblasts, whereas overexpression of FIGNL1 did not seem to alter apoptosis in osteoblasts. Meanwhile, overexpression of FIGNL1 enhanced the mRNA expression of alkaline phosphatase (ALP) and osteocalcin (OCN) in osteoblasts. In contrast, siFIGNL1 decreased the expression of ALP and OCN. A pEGFP-FIGNL1 transfected into MCT3-E1 cells had an initially ubiquitous distribution and rapidly translocated to the nucleus 1 h after bFGF treatment. CONCLUSIONS: From these results, we proposed that FIGNL1, a subfamily member of the AAA family of proteins, might play some regulatory role in osteoblast proliferation and differentiation. Further analyses of FIGNL1 will be needed to better delineate the mechanisms contributing to the inhibition of proliferation and stimulation of osteoblast differentiation.     

Association of the GNAS1 gene variant with hypertension is dependent on alcohol consumption.

The beta-adrenoceptor (beta-AR)-stimulatory guanine nucleotide-binding (Gs) protein system has been shown to play important roles in the cardiovascular system. The gene encoding the alpha-subunit of Gs proteins (GNAS1) is a candidate genetic determinant for hypertension. Because alcohol consumption is known to affect blood pressure partly through the beta-AR-Gs protein system, we examined the possible interaction between GNAS1 T393C polymorphism and drinking status in the association with hypertension in the present study. As a result, a non-significant but reasonable trend supporting the presence of an interaction was shown (p = 0.076). In line with this trend, the T393C polymorphism significantly interacted with drinking status in the association with systolic blood pressure (p = 0.028). Moreover, supporting the presence of an interaction, T allele carriers consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than CC homozygotes in non-drinkers and light drinkers. In contrast, CC homozygotes consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than T allele carriers in moderate to heavy drinkers. The present study also showed a significant interaction between the T393C polymorphism and drinking status in the association with pulse pressure (p = 0.026), reflected by a significant association between the T393C polymorphism and pulse pressure in moderate to heavy drinkers (p = 0.026). These findings may be helpful in conducting further molecular and biological studies on the relationship among the effects of alcohol, the beta-AR-Gs protein system, and hypertension.     

Serial CT findings of Paragonimus infested dogs and the Micro-CT findings of the worm cysts.

OBJECTIVE: To investigate the serial CT findings of Paragonimus westermani infected dogs and the microscopic structures of the worm cysts using Micro-CT. MATERIALS AND METHODS: This study was approved by the committee on animal research at our institution. Fifteen dogs infected with P. westermani underwent serial contrast-enhanced CT scans at pre-infection, after 10 days of infection, and monthly thereafter until six months for determining the radiologic-pathologic correlation. Three dogs (one dog each time) were sacrificed at 1, 3 and 6 months, respectively. After fixation of the lungs, both multi-detector CT and Micro-CT were performed for examining the worm cysts. RESULTS: The initial findings were pleural effusion and/or subpleural ground-glass opacities or linear opacities at day 10. At day 30, subpleural and peribronchial nodules appeared with hydropneumothorax and abdominal or chest wall air bubbles. Cavitary change and bronchial dilatation began to be seen on CT scan at day 30 and this was mostly seen together with mediastinal lymphadenopathy at day 60. Thereafter, subpleural ground-glass opacities and nodules with or without cavitary changes were persistently observed until day 180. After cavitary change of the nodules, the migratory features of the subpleural or peribronchial nodules were seen on all the serial CT scans. Micro-CT showed that the cyst wall contained dilated interconnected tubular structures, which had communications with the cavity and the adjacent distal bronchus. CONCLUSION: The CT findings of paragonimiasis depend on the migratory stage of the worms. The worm cyst can have numerous interconnected tubular channels within its own wall and these channels have connections with the cavity and the adjacent distal bronchus.     

中西医联合治疗单纯疱疹性角膜炎的疗效观察

目的 :探讨单纯疱疹性角膜炎是中西医联合用药的治疗方法。方法 :本组 10 0例 ( 10 6只眼 )单纯疱疹性角膜炎患者应用抗病毒药物联合清热解毒中药的疗效观察。结果 :本组病例治疗后总有效率 82 .0 8%。结论 :中西医联合治疗措施是我们对单纯疱疹性角膜炎治疗的一项新的探讨。