Prevalence and spatiotemporal distribution of rotavirus diarrhea among children younger than five years old in Lagos, Nigeria.

Data on spatiotemporal distribution of rotavirus diarrhea are limited in many endemic settings. This study determined the prevalence and seasonal distribution of rotavirus among Nigerian children with diarrhea. Here, a total of 406 fecal samples were collected from patients attending six health facilities in Lagos between January - December 2019. Socio-demographic data of each enrolled child were collected. Rotavirus VP6 antigen was detected by enzyme-linked immunoassay (ELISA) and confirmation by VP7 gene detection by reverse transcription polymerase-chain reaction. The overall rotavirus diarrhea prevalence was 16.3% by ELISA with children above 2 years having 29.2% of this prevalence and higher occurrence in females (59.1%) than males (40.9%) (P < .05). Rotavirus diarrhea diagnosis using RT-PCR showed 100% concordance with ELISA. Cases of rotavirus diarrhea were detected from March to July and from September to November with the highest number of cases detected in May and June (22.7% each), followed by July (21.2%). The prevalence of rotavirus diarrhea remains high in Lagos with an emerging higher disease activity in children above 2. A different rotavirus transmission dynamics compared to previous studies from Nigeria and other African countries was found. VP6 ELISA may reliably be used for continuous rotavirus surveillance in Nigeria.

Promising disruptors of p53-MDM2 dimerization from some medicinal plant phytochemicals: a molecular modeling study.

Cancer is a major global health issue that has a high mortality rate. p53, which functions as a tumor suppressor, is critical in preventing tumor development by regulating the cell cycle and inducing apoptosis in damaged cells. However, the tumor suppressor function of p53 is effectively inhibited by its direct interaction with the hydrophobic cleft of MDM2 protein via multiple mechanisms As a result, restoring p53 activity by blocking the p53-MDM2 protein-protein interaction has been proposed as a compelling therapeutic strategy for cancer treatment. The use of molecular docking and phytochemical screening procedures are appraised to inhibit MDM2's hydrophobic cleft and disrupt the p53-MDM2 interaction. For this purpose, a library of 51 bioactive compounds from 10 medicinal plants was compiled and subjected to structure-based virtual screening. Out of these, only 3 compounds (Atalantoflavone, Cudraxanthone 1, and Ursolic acid) emerged as promising inhibitors of MDM2-p53 based on their binding affinities (-9.1 kcal/mol, -8.8 kcal/mol, and -8.8 kcal/mol respectively) when compared to the standard (-8.8 kcal/mol). Moreover, these compounds showed better pharmacokinetic and drug-like profiling than the standard inhibitor (Chromonotriazolopyrimidine 1). Finally, the 100 ns MD simulation analysis confirmed no significant perturbation in the conformational dynamics of the simulated binary complexes when compared to the standard. In particular, Ursolic acid was found to satisfy the molecular enumeration the most compared to the other inhibitors. Our overall molecular modeling finding shows why these compounds may emerge as potent arsenals for cancer therapeutics. Nonetheless, extensive experimental and clinical research is needed to augment their use in clinics.Communicated by Ramaswamy H. Sarma.

Enzyme Responsive Vaginal Microbicide Gels Containing Maraviroc and Tenofovir Microspheres Designed for Acid Phosphatase-Triggered Release for Pre-Exposure Prophylaxis of HIV-1: A Comparative Analysis of a Bigel and Thermosensitive Gel.

The challenges encountered with conventional microbicide gels has necessitated the quest for alternative options. This study aimed to formulate and evaluate a bigel and thermosensitive gel, designed to combat the challenges of leakage and short-residence time in the vagina. Ionic-gelation technique was used to formulate maraviroc and tenofovir microspheres. The microspheres were incorporated into a thermosensitive gel and bigel, then evaluated. Enzyme degradation assay was used to assess the effect of the acid phosphatase enzyme on the release profile of maraviroc and tenofovir microspheres. HIV efficacy and cytotoxicity of the microspheres were assessed using HIV-1-BaL virus strain and HeLa cell lines, respectively. Maraviroc and tenofovir release kinetics followed zero-order and Higuchi model kinetics. However, under the influence of the enzyme, maraviroc release was governed by first-order model, while tenofovir followed a super case II transport-mechanism. The altered mode of release and drug transport mechanism suggests a triggered release. The assay of the microspheres suspension on the HeLa cells did not show signs of cytotoxicity. The thermosensitive gel and bigel elicited a progressive decline in HIV infectivity, until at concentrations of 1 µg/mL and 0.1 µg/mL, respectively. The candidate vaginal gels have the potential for a triggered release by the acid phosphatase enzyme present in the seminal fluid, thus, serving as a strategic point to prevent HIV transmission.