Oncogenic comparison of human papillomavirus type 58 E7 variants.

Human papillomavirus 58 (HPV58) ranks the second or third in East Asian cervical cancers. Current studies on HPV58 are scarce and focus on the prototype. Previously, we identified the three most common circulating HPV58 E7 strains contained amino acid alterations: G41R/G63D (51%), T20I/G63S (22%) and T74A/D76E (14%) respectively. Among them, the T20I/G63S variant (V1) had a stronger epidemiological association with cervical cancer. We therefore suggested that V1 possessed stronger oncogenicity than the other two variants. Here, we performed phenotypic assays to characterize and compare their oncogenicities with HPV58 E7 prototype. Our results showed that overexpression of V1 conferred a higher colony-forming ability to primary murine epithelial cells than prototype (P < 0.05) and other variants, implicating its higher immortalising potential. Further experiments showed that both V1 and prototype enhanced the anchorage-independent growth of NIH/3T3 cells (P < 0.001), implicating their stronger transforming power than the two other variants. Moreover, they possessed an increased ability to degrade pRb (P < 0.001), which is a major effector pathway of E7-driven oncogenesis. Our work represents the first study to compare the oncogenicities of HPV58 E7 prototype and variants. These findings deepened our understanding of HPV58 and might inform clinical screening and follow-up strategy.

Prevalence and factors associated with healthcare service use among Chinese elderly with disabilities.

BACKGROUND: Demand for healthcare services among older population is expected to rise, especially among those living with disabilities. This study aims to estimate the prevalence rate and identify the factors associated with healthcare service use among Chinese elderly with disabilities. METHODS: This study employed a nationally representative survey and defined healthcare service utilization as use of curative care, auxiliary aids or rehabilitation services for elderly with disabilities (aged ≥60 years) in China. Population-weighted numbers, proportions and prevalence rates were calculated. Multivariate logistic regression was used to calculate the adjusted odd ratios and 95% confidence interval (CI). RESULTS: A weighted total of 45 005 026 Chinese elderly with disabilities were reported. The weighted prevalence rate of healthcare service use was 36.6% (95% CI: 35.6-37.5). Significantly less use of healthcare services was observed among those who were older, males, less educated, singles, rural dwellers, non-eastern residents, with lower annual family income, without medical insurance coverage, without a disability certificate, with a single disability and with less severe disabilities. CONCLUSIONS: Low use of healthcare services indicates an unmet need among Chinese elderly with disabilities especially for the old-old. More effort should be warranted to enhance healthcare service use among the elderly with disabilities.

p53 regulates autophagic activity in senescent rat mesenchymal stromal cells.

The tumor suppressor protein p53 is an important player in the regulation of cell senescence, its functions are largely carried out by modulating its downstream genes. Emerging evidence has suggested that senescence and autophagy appear to be regulated by overlapping signaling pathways. Furthermore, autophagy markers have been observed in senescent cells. In this study, we sought to explore the effects of the expression pattern and function of p53 on the activity of autophagy and replicative senescence in bone marrow derived mesenchymal stromal cells (BMSCs). We found that more than 85% of BMSCs stained positive for SA-ß-gal at passage 6 (senescent BMSCs) with increased expressions of senescence related genes (p16(ink4a) and p21(waf1)). These results were accompanied by the up-regulation of p53, down-regulation of mammalian target of rapamycin (mTOR) and phosphorylation of Rb. Senescent BMSCs displayed an increased monodansylcadaverine (MDC) staining and autophagy related genes (LC3 and atg12) level compared with BMSCs at passage 2. Knockdown of p53 alleviated the senescent state and reduced autophagic activity during the progression of BMSC senescence, which was accompanied by significantly up-regulated levels of mTOR and phosphorylation of Rb. These results demonstrate that autophagy increases when BMSCs enter the replicative senescence state, and p53 contributes a crucial role in the up-regulation of autophagy in this state.