HYPOLIPIDEMIC AND ANTI-FATTY LIVER EFFECTS EXERTED BY STANDARDIZED PUNICA GRANATUM L. PEEL EXTRACT IN HEPG2 CELL-LINE AND HIGH-FAT DIET-INDUCED MICE

Objective: Pomegranate, (Punica granatum L., Lythraceae) peel has concentrated amounts of lipid-lowering elements that demonstrated, in various hoary and recent studies, their effects against obesity and hyperlipidemia, which involves elevated rates of lipid and lipoprotein levels in blood and increases risks of cardiovascular diseases.We aim to study expression modulation of genes involved in lipid metabolism by the impact of standardized pomegranate peel extract (PPE) in a comprehensive research on human liver cells and experimental mice.Methods: Using reverse-transcription real-time PCR, an in vitro study harnessing HepG2 cell line was conducted to determine the hyperlipidemia-related gene expression profiles and cytotoxic effects upon treatment with PPE. In another complementary in vivo study, male C57BL/6J mice were fed a high-fat diet (HFD) or an HFD supplemented with PPE for 14 d to define the expression of lipid metabolism related genes that control obesity. Fatty liver proportions were also estimated after treatment.Results: Higher mRNA expression of LDL receptor (LDL-R) and down-regulation of sterol regulatory element-binding protein (SREBF-2), (SRBEP-1c), Fatty acid synthase (FAS) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) upon PPE treatment in HepG2 cell line were significantly recorded. In vivo study indicated significant weight reduction of body and liver, besides amelioration of fatty liver state detected by histological analysis. Moreover, the reverse-transcription real-time PCR assay demonstrated suppression (FAS) expression and up regulation of hormone sensitive lipase (HSL) in mice isolated liver and white adipose tissues.Conclusion: Our study manages to affirm the hypolipidemic and anti-fatty liver influence of Punica granatum L. peel extract, reflected by molecular evaluation above and beyond other physiological assays.Keywords: Pomegranate, Peel extract, Hyperlipidemia, LDLR, SREBP, FAS, HMGCR, HS

Synthesis, physicochemical characterization, toxicity and efficacy of a PEG conjugate and a hybrid PEG conjugate nanoparticle formulation of the antibiotic moxifloxacin

Antibiotic resistance is increasing at such an alarming rate that it is now one of the greatest global health challenges. Undesirable toxic side-effects of the drugs lead to high rates of non-completion of treatment regimens which in turn leads to the development of drug resistance. We report on the development of delivery systems that enable antibiotics to be toxic against bacterial cells while sparing human cells. The broad-spectrum fluoroquinolone antibiotic moxifloxacin (Mox) was successfully conjugated to poly(ethylene glycol) (PEG) which was further encapsulated into the hydrophobic poly(3- caprolactone) (PCL) nanoparticles (NPs) with high efficiency, average particle size of 241.8 4 nm and negative zeta potential. Toxicity against erythrocytes and MDBK cell lines and drug release in human plasma were evaluated. Hemocompatibility and reduced cytotoxicity of the PEG–Mox and PCL(PEG– Mox) NPs were demonstrated in comparison to free Mox. Antimicrobial activity was assessed against drug sensitive and resistant: Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae. The antibacterial activity of Mox was largely maintained after conjugation. Our data shows that the toxicity of Mox can be effectively attenuated while, in the case of PEG–Mox, retaining significant antibacterial activity. At the conditions employed in this study for antimicrobial activity the encapsulated conjugate (PCL(PEG–Mox) NPs) did not demonstrate, conclusively, significant antibacterial activity. These systems do, however, hold promise if further developed for improved treatment of bacterial infections.The National Research Foundation of South Africa and the Ministry of Higher Education and Scientific Research, Egypt.http://pubs.rsc.org/en/journals/journalissues/raam2021Chemistr

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Bioinformatics prediction of B and T cell epitopes within the spike and nucleocapsid proteins of SARS-CoV2

BACKGROUND: The striking difference in severity of SARS CoV2 infection among global population is partly attributed to viral factors. With the spike (S) and nucleocapsid (N) are the most immunogenic subunits, genetic diversity and antigenicity of S and N are key players in virulence and in vaccine development. AIM: This paper aims at identifying immunogenic targets for better vaccine development and/or immunotherapy of COVID 19 pandemic. METHODS: 18 complete genomes of SARS CoV2 (n = 14), SARS CoV (n = 2) and MERS CoV (n = 2) were examined. Bioinformatics of viral genetics and protein folding allowed functional tuning of NH2 Terminal Domain (NTD) of S protein and development of epitope maps for B and T cell responses. CONCLUSION: A deletion of amino acid residues Y144 and G107 were discovered in NTD of S protein derived from Indian and French isolates resulting in altered pocket structure exclusively located in NTD and reduced affinity of NTD binding to endogenous nAbs and disrupted NTD mediated cell entry. We therefore, proposed a set of B and T cell epitopes based on Immune Epitope Database, homologous epitopes for nAbs in convalescent plasma post SARS CoV infection and functional domains of S (NTD, Receptor Binding domain and the unique polybasic Furin cleavage site at S1/S2 junction). Nevertheless, laboratory data are required to develop vaccine and immunotherapeutics