Cytotoxic effect of hemin in colonic epithelial cell line: Involvement of 18kDa translocator protein (TSPO).

Aims The aim of this study is to investigate the effect of hemin in colonic epithelial cells (Caco-2) cell proliferation and if this effect was due to a direct modulation of 18-kDa translocator protein (TSPO) and/or heme oxygenase type 1 (HO-1). Main methods The main methods are as follow: cell proliferation and cell cytotoxic assays on Caco-2 cell lines treated with hemin in the presence or not of 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK 11195) and Sn-protoporphyrin IX (Sn-PPIX), and immunoblotting for TSPO and HO-1 protein analysis, siRNA directed against TSPO. Key findings Hemin was shown to be toxic for the Caco-2 cell line in a concentration and time dependent manner. Although hemin was able to induce HO-1 in a dose dependent manner, a specific HO-1 inhibitor, Sn-PPIX, was unable to interfere with the effect of hemin on Caco-2 cells. Instead, PK 11195, a specific TSPO ligand, was able to counteract the effect of hemin, suggesting an important role of TSPO in the hemin activity. Cell viability assay further confirms the high cytotoxic effects exerted by hemin on Caco-2 cells expressing TSPO compared to the siRNA-TSPO targeted cells. In addition, hemin was able to decrease significantly the TSPO protein density in a dose dependent manner after 24 h of incubation. Significance The interaction and the consecutive down regulation of TSPO by hemin played an important role in the control of Caco-2 cell viability. The presented data suggest that TSPO might contribute to protect cells from potential toxic compounds such as free tetrapyrroles, candidating this receptor as a survival receptor protein

Development of vegetable farming: a cause of the emergence of insecticide resistance in populations of Anopheles gambiae in urban areas of Benin

<p>Abstract</p> <p>Background</p> <p>A fast development of urban agriculture has recently taken place in many areas in the Republic of Benin. This study aims to assess the rapid expansion of urban agriculture especially, its contribution to the emergence of insecticide resistance in populations of <it>Anopheles gambiae</it>.</p> <p>Methods</p> <p>The protocol was based on the collection of sociological data by interviewing vegetable farmers regarding various agricultural practices and the types of pesticides used. Bioassay tests were performed to assess the susceptibility of malaria vectors to various agricultural insecticides and biochemical analysis were done to characterize molecular status of population of <it>An. gambiae</it>.</p> <p>Results</p> <p>This research showed that:</p> <p>(1) The rapid development of urban agriculture is related to unemployment observed in cities, rural exodus and the search for a balanced diet by urban populations;</p> <p>(2) Urban agriculture increases the farmers' household income and their living standard;</p> <p>(3) At a molecular level, PCR revealed the presence of three sub-species of <it>An. gambiae </it>(<it>An. gambiae s.s., Anopheles melas and Anopheles arabiensis</it>) and two molecular forms (M and S). The <it>kdr </it>west mutation recorded in samples from the three sites and more specifically on the M forms seems to be one of the major resistance mechanisms found in <it>An. gambiae </it>from agricultural areas. Insecticide susceptibility tests conducted during this research revealed a clear pattern of resistance to permethrin (76% mortality rate at Parakou; 23.5% at Porto-Novo and 17% at Cotonou).</p> <p>Conclusion</p> <p>This study confirmed an increase activity of the vegetable farming in urban areas of Benin. This has led to the use of insecticide in an improper manner to control vegetable pests, thus exerting a huge selection pressure on mosquito larval population, which resulted to the emergence of insecticide resistance in malaria vectors.</p

In vitro Anticancer Screening of 24 Locally Used Nigerian Medicinal Plants

Background: Plants that are used as traditional medicine represent a relevant pool for selecting plant candidates that may have anticancer properties. In this study, the ethnomedicinal approach was used to select several medicinal plants native to Nigeria, on the basis of their local or traditional uses. The collected plants were then evaluated for cytoxicity. Methods: The antitumor activity of methanolic extracts obtained from 24 of the selected plants, were evaluated in vitro on five human cancer cell lines. Results: Results obtained from the plants screened indicate that 18 plant extracts of folk medicine exhibited promising cytotoxic activity against human carcinoma cell lines. Erythrophleum suaveolens (Guill. & Perr.) Brenan was found to demonstrate potent anti-cancer activity in this study exhibiting IC50 = 0.2-1.3 $\mu$g/ml. Conclusions: Based on the significantly potent activity of some plants extracts reported here, further studies aimed at mechanism elucidation and bio-guided isolation of active anticancer compounds is currently underway.Chemistry and Chemical Biolog

Comparison of immature and mature bone marrow-derived dendritic cells by atomic force microscopy

A comparative study of immature and mature bone marrow-derived dendritic cells (BMDCs) was first performed through an atomic force microscope (AFM) to clarify differences of their nanostructure and adhesion force. AFM images revealed that the immature BMDCs treated by granulocyte macrophage-colony stimulating factor plus IL-4 mainly appeared round with smooth surface, whereas the mature BMDCs induced by lipopolysaccharide displayed an irregular shape with numerous pseudopodia or lamellapodia and ruffles on the cell membrane besides becoming larger, flatter, and longer. AFM quantitative analysis further showed that the surface roughness of the mature BMDCs greatly increased and that the adhesion force of them was fourfold more than that of the immature BMDCs. The nano-features of the mature BMDCs were supported by a high level of IL-12 produced from the mature BMDCs and high expression of MHC-II on the surface of them. These findings provide a new insight into the nanostructure of the immature and mature BMDCs

The Macroeconomic Consequences of Renouncing to Universal Access to Antiretroviral Treatment for HIV in Africa: A Micro-Simulation Model

AIM: Previous economic literature on the cost-effectiveness of antiretroviral treatment (ART) programs has been mainly focused on the microeconomic consequences of alternative use of resources devoted to the fight against the HIV pandemic. We rather aim at forecasting the consequences of alternative scenarios for the macroeconomic performance of countries. METHODS: We used a micro-simulation model based on individuals aged 15-49 selected from nationally representative surveys (DHS for Cameroon, Tanzania and Swaziland) to compare alternative scenarios : 1-freezing of ART programs to current levels of access, 2- universal access (scaling up to 100% coverage by 2015, with two variants defining ART eligibility according to previous or current WHO guidelines). We introduced an "artificial" ageing process by programming methods. Individuals could evolve through different health states: HIV negative, HIV positive (with different stages of the syndrome). Scenarios of ART procurement determine this dynamics. The macroeconomic impact is obtained using sample weights that take into account the resulting age-structure of the population in each scenario and modeling of the consequences on total growth of the economy. RESULTS: Increased levels of ART coverage result in decreasing HIV incidence and related mortality. Universal access to ART has a positive impact on workers' productivity; the evaluations performed for Swaziland and Cameroon show that universal access would imply net cost-savings at the scale of the society, when the full macroeconomic consequences are introduced in the calculations. In Tanzania, ART access programs imply a net cost for the economy, but 70% of costs are covered by GDP gains at the 2034 horizon, even in the extended coverage option promoted by WHO guidelines initiating ART at levels of 350 cc/mm(3) CD4 cell counts. CONCLUSION: Universal Access ART scaling-up strategies, which are more costly in the short term, remain the best economic choice in the long term. Renouncing or significantly delaying the achievement of this goal, due to "legitimate" short term budgetary constraints would be a misguided choice

The Disease Burden of Taenia solium Cysticercosis in Cameroon

Taenia solium cysticercosis is a zoonotic disease occurring in many developing countries. A relatively high prevalence in humans and pigs has been reported in several parts of the world, but insufficient data are available on the disease burden. Disease impact assessment needs detailed information on well-defined epidemiological and economic parameters. Our work conducted in West Cameroon over several years allowed us to collect the necessary information to estimate the impact of the parasite on the human and animal populations in this area using both cost and Disability Adjusted Life Year (DALY) estimations. This study identified the professional inactivity caused by the disease as the major loss factor in comparison to the cost of health care and losses due to infected pigs. These findings should allow a simpler estimation of the global disease burden based on information on salary levels and human cysticercosis prevalence in endemic areas of the world. In addition, the number of DALYs lost was higher than estimates already available for some other neglected tropical diseases in sub-Saharan Africa

Track E Implementation Science, Health Systems and Economics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd

LiDAR-based reference aboveground biomass maps for tropical forests of South Asia and Central Africa

Accurate mapping and monitoring of tropical forests aboveground biomass (AGB) is crucial to design effective carbon emission reduction strategies and improving our understanding of Earth’s carbon cycle. However, existing large-scale maps of tropical forest AGB generated through combinations of Earth Observation (EO) and forest inventory data show markedly divergent estimates, even after accounting for reported uncertainties. To address this, a network of high-quality reference data is needed to calibrate and validate mapping algorithms. This study aims to generate reference AGB datasets using field inventory plots and airborne LiDAR data for eight sites in Central Africa and five sites in South Asia, two regions largely underrepresented in global reference AGB datasets. The study provides access to these reference AGB maps, including uncertainty maps, at 100 m and 40 m spatial resolutions covering a total LiDAR footprint of 1,11,650 ha [ranging from 150 to 40,000 ha at site level]. These maps serve as calibration/validation datasets to improve the accuracy and reliability of AGB mapping for current and upcoming EO missions (viz., GEDI, BIOMASS, and NISAR)