FH535 Suppresses Osteosarcoma Growth In Vitro and Inhibits Wnt Signaling through Tankyrases

Osteosarcoma (OS) is an aggressive primary bone tumor which exhibits aberrantly activated Wnt signaling. The canonical Wnt signaling cascade has been shown to drive cancer progression and metastasis through the activation of β-catenin. Hence, small molecule inhibitors of Wnt targets are being explored as primary or adjuvant chemotherapy. In this study, we have investigated the ability of FH535, an antagonist of Wnt signaling, to inhibit the growth of OS cells. We found that FH535 was cytotoxic in all OS cell lines which were tested (143b, U2OS, SaOS-2, HOS, K7M2) but well tolerated by normal human osteoblast cells. Additionally, we have developed an in vitro model of doxorubicin-resistant OS and found that these cells were highly responsive to FH535 treatment. Our analysis provided evidence that FH535 strongly inhibited markers of canonical Wnt signaling. In addition, our findings demonstrate a reduction in PAR-modification of Axin2 indicating inhibition of the tankyrase 1/2 enzymes. Moreover, we observed inhibition of auto-modification of PARP1 in the presence of FH535, indicating inhibition of PARP1 enzymatic activity. These data provide evidence that FH535 acts through the tankyrase 1/2 enzymes to suppress Wnt signaling and could be explored as a potent chemotherapeutic agent for the control of OS

Emerging nanotechnology approaches for HIV/AIDS treatment and prevention

Currently, there is no cure and no preventive vaccine for HIV/AIDS. Combination antiretroviral therapy has dramatically improved treatment, but it has to be taken for a lifetime, has major side effects and is ineffective in patients in whom the virus develops resistance. Nanotechnology is an emerging multidisciplinary field that is revolutionizing medicine in the 21st century. It has a vast potential to radically advance the treatment and prevention of HIV/AIDS. In this review, we discuss the challenges with the current treatment of the disease and shed light on the remarkable potential of nanotechnology to provide more effective treatment and prevention for HIV/AIDS by advancing antiretroviral therapy, gene therapy, immunotherapy, vaccinology and microbicides

Emerging nanotechnology approaches for HIV/AIDS treatment and prevention

Currently, there is no cure and no preventive vaccine for HIV/AIDS. Combination antiretroviral therapy has dramatically improved treatment, but it has to be taken for a lifetime, has major side effects and is ineffective in patients in whom the virus develops resistance. Nanotechnology is an emerging multidisciplinary field that is revolutionizing medicine in the 21st century. It has a vast potential to radically advance the treatment and prevention of HIV/AIDS. In this review, we discuss the challenges with the current treatment of the disease and shed light on the remarkable potential of nanotechnology to provide more effective treatment and prevention for HIV/AIDS by advancing antiretroviral therapy, gene therapy, immunotherapy, vaccinology and microbicides. © 2010 Future Medicine Ltd

Multilevel analysis of quality of antenatal care and associated factors among pregnant women in Ethiopia: a community based cross-sectional study

Objective To determine the magnitude of quality of antenatal care and associated factors among pregnant women in Ethiopia.Design A community-based cross-sectional study.Setting Ethiopia.Participants A total of 4757 weighted sample of pregnant women from 18 January 2016 to 27 June 2016, were included for this analysis.Outcome Quality of antenatal care (ANC).Methods Our analysis was based on secondary data using the 2016 Ethiopian Demographic and Health Survey. The quality of ANC was measured when all six essential components, such as blood pressure measurements, blood tests, urine tests, nutrition counselling, birth preparation advice during pregnancy and information on potential complications, were provided. Stata V.14 software was used for analysis. A multilevel mixed-effect logistic regression analysis was fitted. Adjusted OR (AOR) with 95% CIs was used to show the strength and direction of the association. Statistical significance was declared at a p value less than 0.05.Results The magnitude of quality of ANC in Ethiopia was 22.48% (95% CI: 21.31% to 23.69%). Educational status; primary (AOR=1.34; 95% CI: 1.06 to 1.68) and secondary (AOR=2.46; 95% CI: 1.76 to 3.45), middle (AOR=1.31; 95% CI: 1.01 to 1.72) and rich (AOR=2.08; 95% CI: 1.59 to 2.72) wealth status, being married (AOR=2.34; 95% CI: 1.08 to 5.10) and four or more ANC (AOR=2.01; 95% CI: 1.67 to 2.40) were statistically significant associated factors of quality ANC in Ethiopia.Conclusions This study found that nearly only one in five pregnant women received quality ANC during pregnancy. To improve the quality of ANC in Ethiopia, Ministry of Health and health facilities are needed to increase financial support strategies that enable pregnant women from poor households to use health services and enhance pregnant women’s understanding of the significance of quality of ANC through health education. Additionally, Community health workers should also be placed on supporting unmarried pregnant women to have quality ANC

Multilevel analysis of factors associated with untreated diarrhea among under five children in Ethiopia using Ethiopian demographic and health survey

Abstract Diarrhea refers to the abrupt onset of three or more loose or liquid stools per day. It is the second leading cause of death in infants worldwide. It is an endemic disease and continues to be a serious threat to children in Ethiopia. Despite being a condition that may be prevented, diarrhea can have a negative impact on a child's health. Also, studies have not been able to explore the role of socio-economic characteristics in hindering the treatment. Therefore, this study aimed to explore socio-economic factors that influence treatment of childhood diarrhea. Secondary data analysis was conducted based on the demographic and health surveys data conducted in Ethiopia. A total weighted sample of 1227 under-five children was included for this study. Mixed-effect binary logistic regression analysis was done to identify associated factors of untreated diarrhea. Adjusted Odds Ratio with 95% CI was used to declare the strength and significance of the association. Prevalence of untreated diarrhea among under five children in Ethiopia was 57.32% (95% CI 54.52–60.06%). In the mixed-effect analysis; Children aged 6–11, 12–23, and 24–35 (AOR 0.384, 95% CI 0.187–0.789), 71% (AOR 0.29, 95% CI 0.149–0.596), and 51% (AOR 0.49, 95% CI 0.238–0.995). Children from family number six and above (AOR 1.635, 95% CI 1.102–2.426). Children from middle wealth of family (AOR 1.886, 95% CI 1.170–3.3040). Children from a community with high level of uneducated (AOR 2.78, 95% CI 1.065–3.442) were significantly associated with untreated diarrhea. The prevalence of untreated diarrhea among under-five children in Ethiopia is high. Age of child, family number, household wealth, and community-level educational status were significantly associated with untreated diarrhea among under-five children in Ethiopia. Hence, increasing community educational status, boosting the economic status of the community, and family planning for the community should get due attention

Individual and community level predictors of women’s autonomy in health care decision-making among youth in East African countries: a multilevel analysis

Objective The autonomy of young women in healthcare decision-making has been reported to be lower, particularly in low-income and middle-income countries. This study was conducted to estimate the magnitude and the factors associated with autonomy in healthcare decision-making among youth in East African countries.Design and setting A population-based, cross-sectional study was conducted with data from the most recent Demographic and Health Surveys conducted in 11 East African countries (Burundi, Ethiopia, Kenya, Comoros, Malawi, Mozambique, Rwanda, Tanzania, Uganda, Zambia, Zimbabwe) conducted from 2011 to 2019.Participants Weighted sample of 24 135 women aged 15–24 years.Primary outcomes Healthcare decision-making autonomy.Methods A multi-level logistic regression model was used to identify factors associated with women’s autonomy in making decisions about their healthcare. Statistical significance was determined using an adjusted OR with 95% CI at a p value less than 0.05.Results Healthcare decision-making autonomy among youth in East Africa was 68.37% (95% CI 68%, 70%). In a multivariable analysis older aged youths (20–24 years) (adjusted OR (AOR)=1.27; 95% CI 1.19, 1.36), youths having an occupation (AOR=1.34; 95% CI 1.25, 1.53), having employed husband (AOR=1.12 95% CI 1.00, 1.26), exposure to media (AOR=1.18 95% CI 1.08, 1.29), rich wealth index 1.18 (AOR=1.18 95% CI 1.08, 1.29), female household head, youths having secondary and higher education, youths whose husband had secondary and higher education, and country were significant predictors of healthcare decision making autonomy.Conclusion Almost one-third of young women have no autonomy in healthcare decision-making. Older youth, being educated, having an educated husband, having an occupation, having an employed husband, exposure to media, female household head, rich wealth index and country are significant predictors for being autonomous in healthcare decision-making. Public health interventions should target uneducated and unemployed youth, poor families and those without media exposure to increase autonomy in health decisions

Inhibiting DNA-PKCS radiosensitizes human osteosarcoma cells

© 2017 Elsevier Inc. Osteosarcoma survival rate has not improved over the past three decades, and the debilitating side effects of the surgical treatment suggest the need for alternative local control approaches. Radiotherapy is largely ineffective in osteosarcoma, indicating a potential role for radiosensitizers. Blocking DNA repair, particularly by inhibiting the catalytic subunit of DNA-dependent protein kinase (DNA-PKCS), is an attractive option for the radiosensitization of osteosarcoma. In this study, the expression of DNA-PKCS in osteosarcoma tissue specimens and cell lines was examined. Moreover, the small molecule DNA-PKCS inhibitor, KU60648, was investigated as a radiosensitizing strategy for osteosarcoma cells in vitro. DNA-PKCS was consistently expressed in the osteosarcoma tissue specimens and cell lines studied. Additionally, KU60648 effectively sensitized two of those osteosarcoma cell lines (143B cells by 1.5-fold and U2OS cells by 2.5-fold). KU60648 co-treatment also