Codelivery of Genistein and miRNA-29b to A549 Cells Using Aptamer-Hybrid Nanoparticle Bioconjugates.

This study aimed to evaluate the anti-cancer effect of a combination therapy of miRNA-29b and genistein loaded in mucin-1 (MUC 1)-aptamer functionalized hybrid nanoparticles in non-small cell lung cancer (NSCLC) A549 cell line. Genistein-miRNA-29b-loaded hybrid nanoparticles (GMLHN) was prepared and characterized. Particle size and zeta potential were measured using photon correlation spectroscopy (PCS). Encapsulation efficiency and loading efficiency were determined using HPLC. Preferential internalization of MUC 1-aptamer functionalized GMLHN by A549 cells was evaluated and compared to normal MRC-5 cells. The ability of GMLHN to downregulate targeted oncoproteins Phosphorylated protein kinase, strain AK, Thymoma (Phosphorylated protein kinase B) (pAKT), Phosphorylated phosphoinositide 3-kinase (p-PI3K), DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) and Myeloid Cell Leukemia Sequence 1 (MCL 1) was evaluated using western blot, while antiproliferative effect and ability to initiate apoptosis was also assessed in A549 cells. MUC 1-aptamer functionalized GMLHN nanoparticles were prepared. These nanoparticles were preferentially internalized by A549 cells but less so, in MRC-5 cells. pAKT, p-PI3K, DNMT3B and MCL 1 were efficiently downregulated by these nanoparticles without affecting the levels of AKT and PI3K in A549 cells. GMLHN demonstrated a superior antiproliferative effect compared to individual genistein and miRNA-29b-loaded nanoparticles. Results generated were able to demonstrate that genistein-miRNA-29b-loaded hybrid nanoparticles (GMLHN) could be a potential treatment modality for NSCLC because of the ability of the payloads to attack multiple targets

Pathogen genetic diversity a challenge for vaccine development: Looking for the pathogen’s Achilles’ heel

Creation of variant forms has serious consequences in diagnostic, treatment strategies and the future vaccine development. Thus, the actual and future roles of the altered or emergent pathogens in the global pandemic of AIDS, Malaria, Flu and Ebola must be monitored in new molecular epidemiological studies. During the last 5 years, we studied the genetic structure of several pathogens such as 1] malaria parasite showing that gene deletion, recombination can occur and lead to false RDT negative and to the creation of new antigens (hybrid parasites); 2] in HIV, our findings indicate a shift in the virus population circulating over time in Mali. Those observations are suggesting that a vaccine development against those pathogens such Plasmodium falciparum parasite and HIV will be a challenge. Our approach that is to target pieces of antigens within a genome which must be well conserved across the specie and immunogenic enough in boosting the immune response. Four steps were identified in that approach which are: 1] Genome mining using computational and experimental tools to identify genes that encode proteins with promising vaccine antigens properties, 2] use of the Immunoinformatics tools to map protein sequences for short, linear putative T-cell epitopes CTL/ T helper, 3] then candidates are synthesized as peptides and evaluated for HLA binding and antigenicity (in vitro evaluation) and then 4] Prototype epitope-based vaccines are evaluated for immunogenicity in human Host (in vivo evaluation). Our laboratory has partnered with the GAIA foundation to test this approach in Mali

Evaluation of Cercospora oryzae Miyake under natural pressure conditions.

Objective: This study is a contribution to the knowledge of Cercospora oryzae Miyake, in order to increase yields. It will consist in: i) evaluating the resistance of five varieties of rice, ii) evaluating the effect of Cercospora oryzae Miyake on the leaf and panicle stages and iii) evaluating the yield.Methodology and results: The study will combine phenotypic and agromorphological tools. On the ninety first (91th) day after sowing, a high incidence of leaf Cercosporiosis was recorded on the varieties TS2 (29.74%), FKR34 (27%) and a very low incidence on the variety ORYLUX6 (5, 78%). From tillering to panicle initiation, the rate of progression of the epidemic r2 = 0.879 is significant in TS2. The ORYLUX6 variety is the most capable of slowing the progression of the epidemic. At the panicular level, from the pasty grain stage to the milky grain stage, the incidence has increased for most of the varieties. The ORYLUX6 recorded the highest yield with 4.38 t/ ha.Conclusion and application potential of the results: Cercospora oryzae Miyake causes a drop in yield by reducing the leaf area of thr leaves. Cercospora oryzae Miyake is an important disease of rice in Sud-Benin. These results constiyute a stage of an in-depth research work on the characterization (agronomic and genetic) of Cercospora oryzae Miyake in order to propose methods of control. Objectifs : L’étude a été une contribution à la connaissance de Cercospora oryzae Miyake afin d’accroitre les rendements. Elle a consistée a : i) évaluer la résistance de cinq variétés de riz, ii) évaluer l’effet de Cercospora oryzae Miyake sur les stades foliaires et paniculaires et iii) évaluer le rendement.Méthodologie et résultats : L’étude a combinée des outils phénotypiques et agromorphologiques. Au quatre-vingt onzième jour après semis on a enregistré une forte incidence de la cercosporiose foliaire sur les variétés TS2 (29,74%), FKR34 (27%) et une très faible incidence sur la variété ORYLUX6 (5,78%). Du stade tallage à l’initiation paniculaire le taux de progression de l’épidémie r2=0,879 a été important chez TS2. La variété ORYLUX6 a été la plus apte à freiner la progression de l’épidémie. Du stade grain pâteux au stade grain laiteux l’incidence à augmentée pour la plus part des variétés. ORYLUX6 a enregistré le rendement le plus élève (4,38 t/ha).Conclusion et application potentielle des résultats: Cercospora oryzae Miyake entraine une baisse de rendement en réduisant les surfaces foliaires des feuilles. La cercosporiose est une affection importante du riz au Sud-Bénin. Ces résultats constituent une étape d’un travail de recherche approfondi sur la caractérisation (agronomique et génétique) de Cercospora oryzae Miyake afin de proposer des méthodes de luttes

Les aspects parasitologiques de l'épidémiologie du paludisme dans le Sahara malien

Dans le cadre de l'évaluation épidémiologique de la Transsaharienne, une enquête transversale paludométrique a été réalisée d'Août 1988 à Septembre 1988 le long du tronçon malien. Neuf localités ont été visitées : Douentza, Gossi, Bourem, Almoustarat, Anefis, Aguel-Hoc, Tarlit, Tessalit, Kidal, Bouressa. 2185 unités ont été prélevées pour les études cliniques, parasitologiques et immunologiques. L'indice plasmodique global est de 5,3 % avec une grande variation du Sud (44,6 %) au Nord (0 %). L'indice gamétocytique et l'indice splénique sont très faibles. #P. falciparum est l'espèce dominante. #P. malariae a été décrit une fois en association avec #P. falciparum. #P. ovale n'a jamais été observé. Par contre un cas de #P. vivax a été décrit chez une jeune fille leucoderme de 8 ans à Kidal. #A. gambiae s.s. (forme Mopti) et #A. arabiensis sont les principaux vecteurs au Nord du Mali. Une hypothèse de circulation de #P. vivax dans le Sahara malien est émise. (Résumé d'auteur

Cross-conservation of T-cell epitopes: Now even more relevant to (H7N9) influenza vaccine design

A novel avian-origin H7N9 influenza strain emerged in China in April 2013. Since its re-emergence in October–November 2013, the number of reported cases has accelerated; more than 220 laboratory-confirmed cases and 112 deaths (case fatality rate of 20–30%) have been reported. The resurgence of H7N9 has re-emphasized the importance of making faster and more effective influenza vaccines than those that are currently available. Recombinant H7 hemagglutinin (H7-HA) vaccines have been produced, addressing the first problem. Unfortunately, these recombinant subunit vaccine products appear to have failed to address the second problem, influenza vaccine efficacy. Reported unadjuvanted H7N9 vaccine seroconversion rates were between 6% and 16%, nearly 10-fold lower than rates for unadjuvanted vaccine seroconversion to standard H1N1 monovalent (recombinant) vaccine (89% to pandemic H1N1). Could this state of affairs have been predicted? As it turns out, yes, and it was. In that previous analysis of available H7-HA sequences, we found fewer T-cell epitopes per protein than expected, and predicted that H7-HA-based vaccines would be much less antigenic than recent seasonal vaccines. Novel approaches to developing a more immunogenic HA were offered for consideration at the time, and now, as the low immunogenicity of H7N9 vaccines appears to indicate, they appear to be even more relevant. More effective H7N9 influenza vaccines can be produced, provided that the role of T-cell epitopes is carefully considered, and accumulated knowledge about the importance of cross-conserved epitopes between viral subtypes is applied to the design of those vaccines

ADÉNOPATHIES CERVICO-FACIALES EN ODONTO STOMATOLOGIE: ÉTUDE DE 82 OBSERVATIONS.

Objectif : étudier les adénopathies cervico-faciales en rapport avec la tuberculose dans notre pratique Odonto-stomatologique. Matériels et Méthodes : Nous avons réalisé une étude rétrospective sur une période de quatre ans (janvier 2007 à décembre 2010), au Centre Hospitalier Universitaire d’Odontostomatologie (CHU OS) de Bamako, sur des cas successifs d’adénopathies cervico-faciales. L’IDRT et l’anatomopathologie de la pièce biopsique ont servi pour le diagnostic étiologique de la tuberculose. Les données ont été recueillies à partir des dossiers médicaux et saisies puis analysées avec le logiciel Epiinfo.fr 6.0. Résultats : Les lésions ont concerné 82 patients dont 37 hommes (45,1%) avec un sex ratio de 0,82. La tranche d’âge la plus représentée a été celle de 20 et 29 ans (28%). Le siège anatomique privilégié était la région cervicale avec 34,14%.Nos patients ont bénéficié d’une radiographie thoracique dans 90,20% des cas. L’IDRT a été effectuée chez 72% des patients et l’adénite tuberculeuse caséo- folliculaire a été retrouvée dans 8,50% des cas. Conclusion : Notre étude a révélé une prévalence de 0,31% d‘adénopathies cervico-faciales dont 80,50% était d’origine tuberculeuse. Devant toute adénopathie cervico-faciale dans une zone d’endémie tuberculeuse, une IDRT et un examen anatomopathologique de la biopsie ganglionnaire devrait être systématique pour la prise en charge précoce de la tuberculose

The usefulness of rapid diagnostic tests in the new context of low malaria transmission in zanzibar.

BACKGROUND\ud \ud We assessed if histidine-rich-protein-2 (HRP2) based rapid diagnostic test (RDT) remains an efficient tool for Plasmodium falciparum case detection among fever patients in Zanzibar and if primary health care workers continue to adhere to RDT results in the new epidemiological context of low malaria transmission. Further, we evaluated the performance of RDT within the newly adopted integrated management of childhood illness (IMCI) algorithm in Zanzibar.\ud \ud METHODS AND FINDINGS\ud \ud We enrolled 3890 patients aged ≥2 months with uncomplicated febrile illness in this health facility based observational study conducted in 12 primary health care facilities in Zanzibar, between May-July 2010. One patient had an inconclusive RDT result. Overall 121/3889 (3.1%) patients were RDT positive. The highest RDT positivity rate, 32/528 (6.1%), was found in children aged 5-14 years. RDT sensitivity and specificity against PCR was 76.5% (95% CI 69.0-83.9%) and 99.9% (95% CI 99.7-100%), and against blood smear microscopy 78.6% (95% CI 70.8-85.1%) and 99.7% (95% CI 99.6-99.9%), respectively. All RDT positive, but only 3/3768 RDT negative patients received anti-malarial treatment. Adherence to RDT results was thus 3887/3889 (99.9%). RDT performed well in the IMCI algorithm with equally high adherence among children <5 years as compared with other age groups.\ud \ud CONCLUSIONS\ud \ud The sensitivity of HRP-2 based RDT in the hands of health care workers compared with both PCR and microscopy for P. falciparum case detection was relatively low, whereas adherence to test results with anti-malarial treatment was excellent. Moreover, the results provide evidence that RDT can be reliably integrated in IMCI as a tool for improved childhood fever management. However, the relatively low RDT sensitivity highlights the need for improved quality control of RDT use in primary health care facilities, but also for more sensitive point-of-care malaria diagnostic tools in the new epidemiological context of low malaria transmission in Zanzibar.\ud \ud TRIAL REGISTRATION\ud \ud ClinicalTrials.gov NCT01002066

Genetic Diversity of a Parasitic Weed, Striga hermonthica, on Sorghum and Pearl Millet in Mali

Eleven populations of witchweed, Striga hermonthica, were collected in four regions of Mali and investigated with 12 microsatellite markers. Extensive genetic diversity was observed, with most plants heterozygous for most markers. Allelic diversity was broadly distributed across populations with little genetic differentiation and large amounts of gene flow. Nearby fields of pearl millet and sorghum were found to have indistinguishable witchweed populations. Some population structure was apparent, but did not correlate with the local environment or host genotype, suggesting that seed transportation or other human-driven variables act to differentiate central Malian S. hermonthica populations from southern Malian populations