Inactivated Sendai Virus Strain Tianjin Induces Apoptosis in Human Breast Cancer MDA-MB-231 Cells

Sendai virus strain Tianjin is a novel genotype. Here, we investigate the antitumor and proapoptotic effects of ultraviolet-inactivated Sendai virus strain Tianjin (UV-Tianjin) on human breast cancer MDA-MB-231 cells in vitro, as well as the involvement of the apoptotic pathway in the mechanism of UV-Tianjin-induced antitumor effects. MTT assays showed that treatment with UV-Tianjin dose-dependently inhibited the proliferation of MDAMB-231 cells but not normal MCF 10A breast epithelium cells. Hoechst staining and flow cytometric analysis revealed that UV-Tianjin induced apoptosis of MDA-MB-231 cells in a dose-dependent manner. Moreover, UV-Tianjin treatment resulted in reduction in the mitochondria membrane potential (MMP) and release of cytochrome complex (cyt c) via regulation of Bax and Bcl-2, as well as activation of caspase-9, caspase-3, Fas, FasL and caspase-8 in MDA-MB-231 cells. In summary, our study suggests that UV-Tianjin exhibits anticancer activity in human breast cancer MDA-MB-231 cells through inducing apoptosis, which may involve both the endogenous mitochondrial and exogenous death receptor pathways.     

Sendai virus defective-interfering genomes and the activation of interferon-beta

The ability of some Sendai virus stocks to strongly activate IFNbeta has long been known to be associated with defective-interfering (DI) genomes. We have compared SeV stocks containing various copyback and internal deletion DI genomes (and those containing only nondefective (ND) genomes) for their ability to activate reporter genes driven by the IFNbeta promoter. We found that this property was primarily due to the presence of copyback DI genomes and correlated with their ability to self-anneal and form dsRNA. The level of IFNbeta activation was found to be proportional to that of DI genome replication and to the ratio of DI to ND genomes during infection. Over-expression of the viral V and C proteins was as effective in blocking the copyback DI-induced activation of the IFNbeta promoter as it was in reducing poly-I/C-induced activation, providing evidence that these DI infections activate IFNbeta via dsRNA. Infection with an SeV stock that is highly contaminated with copyback DI genomes is thus a very particular way of potently activating IFNbeta, presumably by providing plentiful dsRNA under conditions of reduced expression of viral products which block the host antiviral response.     

副粘病毒Tianjin株F基因克隆及序列分析

目的探索副粘病毒Tianjin株的来源和种系进化地位。方法以副粘病毒Tianjin株基因组RNA为模板，通过RT-PCR方法获得包括F基因全长的两个质粒克隆，分别进行序列测定。将拼接得到的F基因核苷酸序列及推导出的氨基酸序列与GenBank中公布的15株仙台病毒相应序列进行同源性比较，并构建系统进化树。结果副粘病毒Tianjin株与15株仙台病毒F基因核苷酸及氨基酸序列同源性分别在85．3％～94．5％和90．4％～95．4％之间。进化树分析表明，Tianjin株与仙台病毒BB1株亲缘关系较近，但仍有一定差距，与其他仙台病毒株关系较远。结论副粘病毒Tianjin株很可能不属于仙台病毒现有的Ohita株、Z株及BB1株所代表的3个进化分支，而是独立于这3个分支之外。     

Respiratory viral infections and atopic development: From possible mechanisms to advances in treatment

Atopic sensitization and allergic diseases are increasing in modernized countries. These diseases affect millions of individuals, but the mechanisms behind their development are not fully understood. One hypothesis relates to early life respiratory viral infections driving the development of atopic disease including asthma. This review presents the current state of the field, focusing on epidemiologic data supporting a role for early life respiratory viruses in the development of specific IgE, both against aeroallergens and the respiratory virus. Our own work using the Sendai mouse model is then summarized to provide a potential mechanistic explanation for how a respiratory viral infection could drive development of atopic sensitization and disease. We then discuss the components of this mechanistic pathway that have and have not been validated in humans. Finally, we discuss areas ripe for research, as well as potential and current therapeutics that might disrupt the link between respiratory viral infections in early life and atopic sensitization/disease.     

Quantitative analysis of postoperative changes in the pulmonary vasculature of patients with complete transposition of the great arteries and pulmonary hypertension.

Postoperative changes in the medial thickness of the small pulmonary arteries and the degree of pulmonary vascular disease were estimated histometrically and histopathologically in three cases of late death after total correction of complete transposition of the great arteries with large ventricular septal defect and pulmonary hypertension. In the postoperative course of two of the three cases extreme medial hypertrophy of the small pulmonary arteries as well as severe pulmonary vascular disease were found. In the third case, the thickening of the media was mild and pulmonary vascular disease had not progressed owing to a residual ventricular septal defect. Examination of three additional cases of late death and 15 autopsy cases of complete transposition of the great arteries revealed that hypertrophy of pulmonary arterial media after radical surgery for complete transposition of the great arteries is a common phenomenon. In cases of complete transposition of the great arteries with severe pulmonary hypertension, the deveopment of marked hypertrophy of the media accompanied by pulmonary vascular disease after total correction is usually seen and seems to be the most likely cause of death in the postoperative period.     

Novel Mucosal Insulin Delivery Systems Based on Fusogenic Liposomes

Purpose Fusogenic liposomes (FLs) are unique delivery vehicles capable of introducing their contents directly into the cytoplasm with the aid of envelope glycoproteins of Sendai virus (SeV). The objective of this study was to evaluate the potential of FL to improve the mucosal absorption of insulin from rat intestinal membranes. Method The FLs containing insulin were prepared by fusing insulin-loaded liposomes with inactivated SeV particles and were administered directly into the ileal, the colonic, and the rectal loops (10 IU/kg). Results The FL successfully enhanced the insulin absorption and induced a significant hypoglycemic effect following the colonic and the rectal administration without detectable mucosal damage. This enhancing effect of insulin absorption was further improved by increasing the amount of insulin loaded in the FL and by coencapsulating insulin-degrading enzyme inhibitor. In contrast, the insulin absorption was not increased by the ileal administration of FL because the mucous/glycocalyx layers overlaid on the ileal epithelium impede the fusion of FL to the intestinal mucosa. Conclusion Our results indicated that FL is a useful carrier for improving the absorption of poorly absorbable drugs, such as insulin, via the intestinal tract.