病理性周期性张应力诱导人牙周膜细胞凋亡的机制研究

目的:阐明病理性周期性张应力诱导人牙周膜细胞凋亡的分子机制。方法:人牙周膜细胞取自健康前磨牙,经过3?5代传代,细胞受到20%牵张力,时间为6 h或24 h,通过用膜联蛋白异硫氰酸荧光素(V-FITC)和碘化丙啶(PI)结合流式细胞仪检测细胞凋亡,用Western Blot法研究caspase-3,cleaved caspase-3,116 kDa PARP-1和85 k Da PARP-1蛋白的表达变化。结果:人PDL细胞受到病理性周期性张应力时存在凋亡,并以一种时间依赖的方式增加。受到病理性周期性张应力后裂解的caspase-3和PARP蛋白随着时间增加,然而抑制caspase-3的活性却可以抑制细胞的凋亡,但并不能抑制由其他通路导致的凋亡。结论:病理性周期性张应力通过caspase-3/PARP途径诱导人牙周膜细胞的凋亡。

Large Papular Syphilid:A Case Report

SYPHILIS 1S CHARACTERIZED by several clinical stages: primary, secondary, latent and tertiary. Due to the variety of lesions that may present during the second stage, syphilis has its reputation of being the "great impostor." Therefore, delays in its diagnosis and treatment are commonly reported.

Effects and mechanisms of silibinin on human hepatoma cell lines

AIM： To investigate in vitro effects and mechanisms of silibinin on hepatocellular carcinoma （HCC） cell growth, METHODS： Human HCC cell lines were treated with different doses of silibinin. The effects of silibinin on HCC cell growth and proliferation, apoptosis, cell cycle progression, histone acetylation, and other related signal transductions were systematically examined. RESULTS： We demonstrated that silibinin significantly reduced the growth of HUH7, HepG2, Hep3B, and PLC/PRF/5 human hepatoma cells. Silibinin-reduced HuH7 cell growth was associated with significantly up- regulated p21/CDK4 and p27/CDK4 complexes, down- regulated Rb-phosphorylation and E2F1/DP1 complex. Silibinin promoted apoptosis of HuH7 cells that was associated with down-regulated survivin and upregulated activated caspase-3 and -9. Silibinin＇s antiangiogenic effects were indicated by down-regulated metalloproteinase-2 （MMP2） and CD34. We found that silibinin-reduced growth of HuH7 cells was associated with increased activity of phosphatase and tensin homolog deleted on chromosome ten （PTEN） and decreased p-Akt production, indicating the role of PTEN/ PI3K/Akt pathway in silibinin-mediated anti-HCC effects. We also demonstrated that silibinin increased acetylation of histone H3 and H4 （AC-H3 and AC-H4）, indicating a possible role of altered histone acetylation in silibininreduced HCC cell proliferation. CONCLUSION： Our results defined silibinin＇s in vitro anti-HCC effects and possible mechanisms, and provided a rationale to further test silibinin for HCC chemoprevention.

Endothelial adhesion of synchronized gastric tumor cells changes during cell cycle transit and correlates with the expression level of CD44 splice variants

AIM To study adhesion capacity and CD44 expression of human gastric adenocarcinoma MKN45 cells at different stages of a first cell cycle. METHODS MKN45 cells were synchronized by aphidicolin and assayed for adhesion to an endothelial cell （HUVEC） monolayer. Surface expression of CD44 and CD44 splice variants on MKN45 cells was evaluated by flow cytometry. Functional relevance of CD44 adhesion receptors was investigated by blocldng studies using anti CD44 monodonal antibodies or by hyaluronan digestion. RESULTS： Adhesion of MKN45 to HUVEC was increased during G2/M transit, after which adhesion returned to baseline levels with cell cycle completion. In parallel, CD44 splice vadants CD44v4, CD44v5, and CD44v7 were all upregulated on MKN45 during cell cycle progression with a maximum effect in G2/M. The function of CD44 surface receptors was assessed with specific receptor blocking monoclonal antibodies or removal of hyaluronan by digestion with hyaluronidase. Both strategies inhibited tumor cell adhesion to HUVEC by nearly 50%, which indicates that MKN45-HUVEC-interaction is CD44 dependent. CONCLUSION CD44 expression level is linked to the cell cycle in gastrointestinal tumor cells, which in turn leads to cell cycle dependent alterations of their adhesion behaviour to endothelium.

p21 and p27 immunoexpression in gastric well differentiated endocrine tumors(ECL-cell carcinoids)

AIM： To investigate the expression of cyclin-dependent kinase inhibitors p21 and p27 in gastric well differentiated endocrine tumors （GWDET） （ECLocell carcinoids）.METHODS： The expressions of p21 and p27 were examined immunhistochemically in endoscopic biopsy specimens from 16 patients matching the diagnostic criteria of GWDET. Percentage of positive nuclear staining either weak or strong was noted. The association of immunoexpressions with age, gender, tumor localization, multifocality and accompanying chronic atrophic gastritis, neuroendocrine cell hyperplasia （NEH）, neuroendocrine dysplasia （NED）, intestinal metaplasia （IM）, Ki-67 proliferation index and clinical outcome were also evaluated.RESULTS： All cases expressed p27 with a mean expression score of 43.6%, while 31.3% of the cases showed any p21 expression, p21 and p27 immunoexpressions were significantly correlated with each other （P 〈 0.01）, and the p21-expressing group had higher p27 expression scores （68% vs 22%）. p21 and p27 expressions were lower in women, in non-atrophic mucosa and cases whose tumors were located somewhere other than fundus without submucosal extension. On contrary, p21 and p27 expressions were higher in males and the patients with submucosal extension and atrophic gastritis. Cases presenting lower p27 scores had solitary tumors showing neither NEH-NED nor IM. Despite, cases with lower p21 expression presented multifocal tumors accompanied by NEH-NED. However, no correlation of p21 and p27 expressions was found with age and Ki-67 expression.CONCLUSION： p27 is widely expressed in GWDETs, while p21 expression is sparse and observed in two thirds of the cases. Loss of p21 and p27 expressions may be correlated with different carcinoid tumor subtypes; however,more studies are needed to assess the role of these prospective markers in gastrointestinal endocrine tumors.

Effects of allitridi on cell cycle arrest of human gastric cancer cells

AIM： To determine the effect of allitridi on cell cycle of human gastric cancer （HGC） cell lines MGC803 and SGC7901 and its possible mechanism. METHODS： Trypan blue dye exclusion was used to evaluate the proliferation, inhibition of cells and damages of these ceils were detected with electron microscope, Flow cytometry and cell mitotic index were used to analyze the change of cell cycle, immunohistochemistry, and RT- PCR was used to examine expression of the p21^WAF1 gene, RESULTS： MGC803 cell growth was inhibited by allitridi with 24 h ICso being 6.4μg/mL, SGC7901 cell growth was also inhibited by allitridi with 24 h IC50 being 7.3μg/mL, After being treated with allitridi at the concentration of 12μg/mL for 24 h, cells were found to have direct cytotoxic effects, including broken cellular membrane, swollen and vesiculated mitochondria and rough endoplasmic reticula, and mass lipid droplet, When cells were treated with allitridi at the concentration of 3, 6, and 9μg/mL for 24 h, the percentage of Go/G1 phase cells was decreased and that of G2/M phase cells was significantly increased （P = 0.002） compared with those in the group, When cells were treated with allitridi at the concentration of 6μg/mL, cell mitotic index was much higher （P = 0.003） than that of control group, indicating that allitridi could cause gastric cancer cell arrest in M phase, Besides, the expression levels of p21^WAF1 gene of MGC803 cells and p21^WAF1 gene of SGC7901 cells were remarkably upregulated after treatment, CONCLUSION： Allitridi can cause gastric cancer cell arrest in M phase, and this may be one of the mechanisms for inhibiting cell proliferation, Effect of allitridi on cells in M phase may be associated with the upregulation of p21^WAF1 genes. This study provides experimental data for clinical use of allitridi in the treatment of gastric carcinoma.

Targeting host factors:A novel rationale for the management of hepatitis C virus

Hepatitis C is recognized as a major threat to global public health. The current treatment of patients with chronic hepatitis C is the addition of ribavirin to interferon-based therapy which has limited efficacy, poor tolerability, and significant expense. New treatment options that are more potent and less toxic are much needed. Moreover, more effective treatment is an urgent priority for those who relapse or do not respond to current regimens. A major obstacle in combating hepatitis C virus （HCV） infection is that the fidelity of the viral replication machinery is notoriously low, thus enabling the virus to quickly develop mutations that resist compounds targeting viral enzymes. Therefore, an approach targeting the host cofactors, which are indispensable for the propagation of viruses, may be an ideal target for the development of antiviral agents because they have a lower rate of mutation than that of the viral genome, as long as they have no side effects to patients. Drugs targeting, for example, receptors of viral entry, host metabolism or nuclear receptors, which are factors required to complete the HCV life cycle, may be more effective in combating the viral infection. Targeting host cofactors of the HCV life cycle is an attractive concept because it imposes a higher genetic barrier for resistance than direct antiviral compounds. However the principle drawback of this strategy is the greater potential for cellular toxicity.

Clinicopathologic features of 112 cases with mantle cell lymphoma

Objective： This study aims to explore the clinicopathologic features of 112 patients with mantle cell lymphoma （MCL）. Methods： Data from 112 MCL cases were collected, and immunohistochemical assay was conducted. Fluorescence in situ hybridization （FISH） detected a break in the CCND 1 gene. The t-test was used in the statistical analysis. Results： All tumor cells in the 112 cases expressed B cell-related antigen, including 1 blastoid subtype and 1 polymorphic subtype. Among all cases, 106 expressed CD5 and 104 expressed cyclin D1. A break in the CCND1 gene was not found in 3 cases with CDS-MCL. IgH/CCND 1 polyploid was observed in 2 classic cases. Conclusion： MCL is a type of special immunophenotypic B-cell lymphoma, The prognoses ofblastoid and polymorphic subtypes are poor. Special subtypes should be classified during diagnosis.

Evaluation of the best follow-up period and curative effect for acoustic neuroma treated with a gamma knife

Objective: To determine the best follow-up period with regard to curative effect for acoustic neuroma treated with a gamma knife. Methods: Sixty cases of acoustic neuroma were treated with a gamma knife. The follow-up period was from 3 to 102 months. Changes in the lesions and peripheral tissues and clinical symptoms were compared and the curative effectiveness of gamma knife treatment was evaluated. Results: The highest total effective rate (92.3%) was in the third period. There was a significant difference in the tumor size postoperatively. There was no edema in the peripheral tissues surrounding the tumor. It was not obvious that clinical symptoms changed. Conclusion: In this report, the best follow-up period was 24-36 months. Gamma knife treatment was still effective after 60 months post-operation.