No abstract

Acute gastroenteritis (AGE) is the highest cause of mortality worldwide in children under the age of 5 years, with the highest mortalities occurring in low-to-middle income countries. Treatment can involve use of unregulated herbal medication and antibiotics. A cross sectional study was carried out to investigate the use of antibiotics and traditional herbal medications in the management of AGE among Yòrùbá-speaking communities in Kwara State, Nigeria. Our findings suggest habitual use of antibiotics (54.6%) and herbal medication (42.5%) in the management of AGE with high levels of self-prescription of antibiotics (21.7%) and herbal medications (36.2%) within the community. Ethanolic extracts of selected herbal plants reported (i.e. Aristolochia ringens, Azadirachta indica, Chromolaena odorata, Etanda Africana, Ficus capensis, Ficus vogelii, Mangifera indica, Momordica charantia, Ocimum gratisimum, Senna alata, Sorghum bicolor and Vernonia amygdalina) were investigated for antibacterial properties, using bacteria known to be causative agents of AGE. Our findings showed that, with exception of Ficus vogelii, which enhanced bacterial growth, the plant extracts reported all showed some antibacterial activity. We further discuss our findings within a regulatory context, with the aim to guide the use of traditional and herbal medication in low-to medium income countries (LMICs) and reduce the potential risks associated with the development of antimicrobial resistance.

The COVID-19 global pandemic is being driven by evolving SARS-CoV-2 variants with consequential implications on virus transmissibility, host immunity, and disease severity. Continuous molecular and genomic surveillance of the SARS-CoV-2 variants is therefore necessary for public health interventions toward the management of the pandemic. This study is a retrospective analysis of COVID-19 cases reported in a Nigerian tertiary institution from July to December 2021. In total, 705 suspected COVID-19 cases that comprised 547 students and 158 non-students were investigated by real time PCR (RT-PCR); of which 372 (~52.8%) tested positive for COVID-19. Using a set of selection criteria, 74 (~19.9%) COVID-19 positive samples were selected for next generation sequencing. Data showed that there were two outbreaks of COVID-19 within the university community over the study period, during which more females (56.8%) tested positive than males (47.8%) (p<0.05). Clinical data together with phylogenetic analysis suggested community transmission of SARS-CoV-2 through mostly asymptomatic and/or pre-symptomatic individuals. Confirmed COVID-19 cases were mostly mild, however, SARS-CoV-2 delta (77%) and omicron (4.1%) variants were implicated as major drivers of respective waves of infections during the study period. This study highlights the importance of integrated surveillance of communicable disease during outbreaks.

The safety and efficacy of mitoquinol mesylate (MitoQ) in attenuating the progression of hepatocellular carcinoma (HCC) in Wistar rats has been reported. However, the binding modes for MitoQ as well as its molecular mechanisms in cirrhosis and liver cancer have not been fully investigated. This study sought to understand the structural and molecular mechanisms of MitoQ in modulating the expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) and mitochondrial succinate dehydrogenase (SDH) in cirrhotic‐HCC rats. The research indicates that the upregulated Nrf2 expression in cirrhotic‐HCC rats was significantly (p < 0.05) reduced by MitoQ while the activity of SDH was significantly (p < 0.05) increased. Analysis of binding modes revealed MitoQ interacts with amino acid residues in the active pocket of tramtrack and bric‐a‐brac (BTB) and KELCH domains of KEAP1 with average binding affinities of −66.46 and −74.74 kcal/mol, respectively. Also, MitoQ interacted with the key amino acid residues at the active site of mitochondrial complex II with a higher average binding affinity of −75.76 kcal/mol compared to co‐crystallized ligand of complex II (−62.31 kcal/mol). Molecular dynamics simulations data showed the binding of MitoQ to be stable with low eigenvalues while the quantum mechanics calculations suggest MitoQ to be very reactive with its mechanism of chemical reactivity to be via electrophilic reactions. Thus, MitoQ modulates expression of Nrf2 and enhances activity of mitochondrial SDH in cirrhotic‐HCC rats via its interaction with key amino acid residues in the active pocket of BTB and KELCH domains of KEAP1 as well as amino residues at the active site of SDH. These findings are significant in demonstrating the potential of Nrf2 and SDH as possible biomarkers for the diagnosis and/or prognosis of hepatocellular carcinoma in patients. This study also supports repurposing of mitoQ for the treatment/management of liver cirrhosis and HCC.

Exportin-1, the ubiquitous nuclear protein transporter, is widely confirmed as an active chemotherapeutic target in non-small cell lung cancer condition while Juglans mandshurica is a well-studied anticancer plant in some lung cancer cell lines. We intend to find novel exportin-1 inhibitor from Juglans mandshurica with better potential tolerability and pharmaco-dynamo-kinetic properties than the current selective inhibitors of nuclear export in non-small cell lung cancer treatment. Osiris property explorer DataWarrior, Glide standard precision docking, quantum mechanics polarized ligand docking, MMGBSA binding free energy calculations, Jaguar density functional theory analysis, and the online web-based SwissADME were employed respectively in this study to filter the retrieved compounds based on tolerability, toxicity, and Lipinsky&rsquo;s rule of five violation potential, determine their druggability, establish relative stability of the lead compound in water solvation model, and evaluates druglikeness, lead-likeness, as well as synthetic accessibility of the lead compound. This study reveals eriodictyol as having higher binding free energy (-40 kcal/mol) than that of standard (-39.56 kcal/mol) in exportin-1 active site, better synthetic accessibility score (3.15 versus 3.29), high GI absorption, non-blood brain barrier permeant, lacks Brenk and PAINS alert, obeying Lipinski&rsquo;s, Ghose&rsquo;s, Veber&rsquo;s, Egan&rsquo;s, and Muegge&rsquo;s rule of druglikeness and lead-likeness as well as non-cytotoxic to HepG2 cells. We therefore found eriodictyol as a lead-like, non-toxic exportin-1 inhibitor with good predictive stability and pharmacokinetic potential and thus provided data for further validation of eriodictyol as a candidate exportin-1 inhibitor in both preclinical and clinical studies involving lung cancer therapy.