The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is a viral oncogene and it is essential for the transformation of resting B cells by the virus. The protein acts as a ligand-less membrane receptor and triggers numerous cellular signaling pathways. Cellular transformation frequently has been associated with genomic instability. To investigate whether EBV LMP1 induces chromosomal aberrations, micronucleus (MN) formation was examined in LMP1-expressing epithelial cells. The expression of wild-type LMP1 enhanced both spontaneous and bleomycin-induced MN formation. MN formation may be induced by inactivation of DNA repair and, therefore, we investigated the effect of LMP1 on DNA repair, using a host cell reactivation (HCR) assay. In the HCR assay, LMP1 reduced the capacity for DNA repair of both NPC-TW01 (p53-wild-type) and H1299 (p53-deficient) cells. As reduction of DNA repair by LMP1 occurs in p53-wild-type and p53-deficient cells, it seems that LMP1 can repress DNA repair in a p53-independent manner. Inactivation of DNA repair may render cells sensitive to DNA-damaging agents. In this study, H1299 cells harboring LMP1 were shown to be more sensitive to UV and bleomycin than those with a vector control. Using various deletion mutants of EBV LMP1 to determine the regions of LMP1 required to enhance MN formation, inhibit DNA repair and sensitize cells to DNA-damaging agents, we found that the region a. a. 189-222 (located within the CTAR1 domain) was responsible for sensitizing cells to UV and bleomycin, as well as for enhancing MN formation and repressing DNA repair. Based on these results, we suggest that disruption of DNA repair by LMP-1 results in an accumulation of unrepaired DNA and consequent genomic instability, which may contribute to the oncogenesis of LMP1 in human epithelial cells.

Objectives: To investigate the effect of a social robot intervention on depression, loneliness, and quality of life of older adults in long-term care (LTC) and to explore participants’ experiences and perceptions after the intervention. Design: A mixed-methods approach consisting of a single group, before and after quasi-experimental design, and individual interview. Participants: Twenty older adults with depression from four LTC facilities in Taiwan were recruited. Intervention: Each participant participated in 8 weeks of observation and 8 weeks of intervention. In the observation stage, participants received usual care or activities without any research intervention. In the intervention stage, each participant was given a Paro (Personal Assistive RobOt) to keep for 24 hours, 7 days a week. Measurements: The Geriatric Depression Scale, the UCLA Loneliness Scale Version 3, and the World Health Organization Quality of Life Questionnaire for older adults were administered at four time points. Individual qualitative interviews with thematic analysis followed. Results: A repeated multivariate analysis of variance and Friedmanʼs test showed no significant changes during the observation stage between T1 and T2 for depression and quality of life (p >.5). For the intervention stage, statistically significant changes in decreasing depression and loneliness and improving quality of life over time were identified. Three themes emerged from the interviews: (i) humanizing Paro through referring to personal experiences and engagement; (ii) increased social interaction with other people; and (iii) companionship resulting in improved mental well-being. Conclusions: There were significant improvements in mental well-being in using Paro. Further research may help us to understand the advantages of using a Paro intervention as depression therapy.

Compared with 12-month interval, US surveillance at 4-month interval detected more patients with HCC ≤ 2 cm who were in BCLC very-early stage and were fit for curative treatments. Up to 4-year follow-up, however, the overall survival was not different.

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Cancer metastasis is a multiple-step process that involves the regulated interaction of diverse cellular proteins. We recently reported that the expression of tumor-associated antigen L6 (TAL6) promoted the invasiveness of lung cancer cells and was inversely correlated with disease-free survival of squamous lung carcinoma patients. We now report that CD13 (aminopeptidase N) can associate with TAL6 and can enhance cancer cell migration. CD13 was shown by coimmunoprecipitation to associate in vitro with TAL6 on several cancer cell lines and to associate in vivo by antibody-mediated copatching immunofluorescence. CD13 was selectively expressed on highly invasive CL1-5 lung cancer cells as compared to poorly invasive CL1-0 lung cancer cells. The role of CD13 aminopeptidase activity in regulating cell motility was investigated with chemical inhibitors, specific antibodies and a catalytically inactive CD13 protein. Inhibition of CD13 aminopeptidase activity by nontoxic concentrations of leuhistin modestly decreased the migration of CL1-5 cells. In contrast, binding of CD13 by specific antibodies significantly reduced both the migration and the invasion of CL1-5 cells. Poorly invasive CL1-0 cells that stably expressed CD13 displayed significantly (p < or = 0.0005) enhanced cell migration (300% of control). Expression of an enzymatically inactive CD13 mutant on CL1-0 cells also significantly (p < or = 0.0005) enhanced cell migration (200% of control). Our results show that TAL6 and CD13 can form a complex on lung cancer cells, that these molecules can modulate cell migration and invasion and that the influence of CD13 on cell motility did not strictly depend on its aminopeptidase activity.

This large scale community-based study demonstrated that subjects with seropositivity for Hepatitis C not only had lower prevalence of hypercholesterolemia and hypertriglyceridemia but subjects with seropositivity for Hepatitis B had the same trend.

Social robots are being used with increasing frequency to potentially provide personal support to older adults living in long-term care facilities. Social robots can be used to help alleviate depressive symptoms when used in group activities.

The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV), a viral oncogene, is essential for transformation of resting B cells by the virus. We previously demonstrated that LMP1 could repress DNA repair in p53-wild-type and p53-deficient human epithelial cells. In this study, using a host cell reactivation (HCR) assay, we demonstrated that p53-enhanced DNA repair was repressed by LMP1 in p53-deficient cells. Moreover, we found that LMP1 was able to repress p53-dependent transcriptional activity. Regarding the mechanisms of p53 repression by LMP1, we found that LMP1 did not inhibit p53 function through direct interaction, by promoting protein degradation or reducing its DNA-binding ability. Using chimeric proteins in the reporter assay, we demonstrated that LMP1 inhibited p53 transactivation by influencing the N-terminal transactivation domain of p53. Subsequent experiments using various LMP1 deletion mutants indicated that a C-terminus-activating region of LMP1, CTAR1 or CTAR2, is responsible for the repression of p53-mediated DNA repair and p53-dependent transcription, which is correlated with the region responsible for NF-jB activation. Furthermore, blockage of NF-jB signalling by IjB-DN was shown to abolish the repression of p53 by LMP1, suggesting that LMP1 likely repressed p53 function through the NF-jB pathway. Based on these results, we propose that inhibition of p53-dependent transcriptional activity and DNA repair by LMP1 results in the loss of p53 activity for maintaining genomic stability, which may contribute to the oncogenesis of LMP1 in human epithelial cells.