Surveillance for variants of SARS-CoV-2 to inform risk assessments.

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged, some leading to large increases in infections, hospitalizations and deaths globally. The virus's impact on public health depends on many factors, including the emergence of new viral variants and their global spread. Consequently, the early detection and surveillance of variants and characterization of their clinical effects are vital for assessing their health risk. The unprecedented capacity for viral genomic sequencing and data sharing built globally during the pandemic has enabled new variants to be rapidly detected and assessed. This article describes the main variants circulating globally between January 2020 and June 2023, the genetic features driving variant evolution, and the epidemiological impact of these variants across countries and regions. Second, we report how integrating genetic variant surveillance with epidemiological data and event-based surveillance, through a network of World Health Organization partners, supported risk assessment and helped provide guidance on pandemic responses. In addition, given the evolutionary characteristics of circulating variants and the immune status of populations, we propose future directions for the sustainable genomic surveillance of SARS-CoV-2 variants, both nationally and internationally: (i) optimizing variant surveillance by including environmental monitoring; (ii) coordinating laboratory assessment of variant evolution and phenotype; (iii) linking data on circulating variants with clinical data; and (iv) expanding genomic surveillance to additional pathogens. Experience during the COVID-19 pandemic has shown that genomic surveillance of pathogens can provide essential, timely and evidence-based information for public health decision-making.

Depuis le début de la pandémie de coronavirus survenue en 2019 (COVID-19), de nombreux variants du coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2) sont apparus, certains entraînant une forte augmentation du nombre d'infections, d'hospitalisations et de décès dans le monde. L'impact du virus sur la santé publique dépend de nombreux facteurs, notamment l'émergence de nouveaux variants viraux et leur propagation à l'échelle mondiale. Par conséquent, la détection précoce et la surveillance des variants ainsi que la caractérisation de leurs effets cliniques sont essentielles pour évaluer leur risque pour la santé. La capacité sans précédent de séquençage du génome viral et de partage des données, capacité mise en place à l'échelle mondiale pendant la pandémie, a permis de détecter et d'évaluer rapidement de nouveaux variants. Le présent article décrit les principaux variants circulant dans le monde entre janvier 2020 et juin 2023, les caractéristiques génétiques à l'origine de leur évolution et leur impact épidémiologique dans les différents pays et régions. Ensuite, nous expliquerons comment l'intégration de la surveillance des variants génétiques aux données épidémiologiques et à la surveillance fondée sur les événements, par l'intermédiaire d'un réseau de partenaires de l'Organisation mondiale de la santé, a permis de faciliter l'évaluation des risques et de fournir des orientations sur les mesures à prendre en période de pandémie. En outre, compte tenu des caractéristiques évolutives des variants en circulation et de l'état immunitaire des populations, nous proposons des orientations futures pour une surveillance génomique durable des variants du SARS-CoV-2, au niveau tant national qu'international: (i) optimiser la surveillance des variants en incluant le suivi environnemental; (ii) coordonner l'évaluation en laboratoire de l'évolution des variants et du phénotype; (iii) établir un lien entre les données sur les variants en circulation et les données cliniques; et (iv) étendre la surveillance génomique à d'autres agents pathogènes. L'expérience de la pandémie de COVID-19 a mis en évidence que la surveillance génomique des agents pathogènes peut fournir en temps utile des informations essentielles fondées sur des preuves en vue de la prise de décisions en matière de santé publique.

Desde el inicio de la pandemia de la enfermedad por coronavirus de 2019 (COVID-19), han aparecido numerosas variantes del coronavirus de tipo 2 causante del síndrome respiratorio agudo severo (SRAS-CoV-2), algunas de las que han provocado un gran aumento de las infecciones, hospitalizaciones y muertes en todo el mundo. El impacto del virus en la salud pública depende de muchos factores, entre ellos la aparición de nuevas variantes víricas y su propagación mundial. En consecuencia, la detección y vigilancia tempranas de las variantes y la caracterización de sus efectos clínicos son vitales para evaluar su riesgo sanitario. La capacidad sin precedentes de secuenciación genómica viral y de intercambio de datos creada a nivel mundial durante la pandemia ha permitido detectar y evaluar rápidamente variantes nuevas. En este artículo se describen las principales variantes que circulan a nivel mundial entre enero de 2020 y junio de 2023, la característica genética que impulsa la evolución de las variantes y el impacto epidemiológico de estas variantes en los diferentes países y regiones. En segundo lugar, se informa de cómo la integración de la vigilancia de variantes genéticas con los datos epidemiológicos y la vigilancia basada en eventos, a través de una red de asociados de la Organización Mundial de la Salud, apoyó la evaluación de riesgos y ayudó a proporcionar orientación sobre las respuestas a la pandemia. Además, dadas las características evolutivas de las variantes circulantes y el estado inmunitario de las poblaciones, se proponen orientaciones futuras para la vigilancia genómica sostenible de las variantes del SRAS-CoV-2, tanto a nivel nacional como internacional: (i) optimizar la vigilancia de las variantes mediante la inclusión de la monitorización ambiental; (ii) coordinar la evaluación de laboratorio de la evolución y el fenotipo de las variantes; (iii) vincular los datos sobre las variantes circulantes con los datos clínicos; y (iv) ampliar la vigilancia genómica a patógenos adicionales. La experiencia durante la pandemia de la COVID-19 ha demostrado que la vigilancia genómica de patógenos puede proporcionar información esencial, oportuna y basada en evidencias para la toma de decisiones en materia de salud pública.

Effect of Ce-doped bioactive glass/collagen/chitosan nanocomposite scaffolds on the cell morphology and proliferation of rabbit's bone marrow mesenchymal stem cells-derived osteogenic cells.

BACKGROUND: Cerium-containing materials have wide applications in the biomedical field, because of the mimetic catalytic activities of cerium. The study aims to deeply estimate the biocompatibility of different scaffolds based on Ce-doped nanobioactive glass, collagen, and chitosan using the first passage of rabbit bone marrow mesenchymal stem cells (BM-MSCs) directed to osteogenic lineage by direct and indirect approach. One percentage of glass filler was used (30 wt. %) in the scaffold, while the percentage of CeO2 in the glass was ranged from 0 to 10 mol. %. Cytotoxicity was evaluated by monitoring of cell morphological changes and reduction in cell proliferation activity of BMMSCs maintained under osteogenic condition using proliferation assays, MTT assay for the direct contact of cells/scaffolds twice in a week, trypan blue and hemocytometer cell counting for indirect contact of cells/scaffolds extracts at day 7. Cell behaviors growth, morphology characteristics were monitored daily under a microscope and cell counting were conducted after 1 week of the incubation of the cells with the extracts of the four composite scaffolds in the osteogenic medium at the end of the week. RESULTS: Showed that at 24 h after direct contact with composite scaffold, all scaffolds showed proliferation of cells > 50% and increased in cell density on day 7. The scaffold of the highest percentage of CeO2 in bioactive glass nanoparticles (sample CL/CH/C10) showed the lowest inhibition of cell proliferation (< 25%) at day 7. Moreover, the indirect cell viability test showed that all extracts from the four composite scaffolds did not demonstrate a toxic effect on the cells (inhibition value < 25%). CONCLUSION: The addition of CeO2 to the glass composition improved the biocompatibility of the composite scaffold for the proliferation of rabbit bone marrow mesenchymal stem cells directed to osteogenic lineage.

In-silico screening of naturally derived phytochemicals against SARS-CoV Main protease.

Coronavirus disease 2019 (COVID-19) is a rapidly growing pandemic that requires urgent therapeutic intervention. Finding potential anti COVID-19 drugs aside from approved vaccines is progressively going on. The chemically diverse natural products represent valuable sources for drug leads. In this study, we aimed to find out safe and effective COVID-19 protease inhibitors from a library of natural products which share the main nucleus/skeleton of FDA-approved drugs that were employed in COVID-19 treatment guidelines or repurposed by previous studies. Our library was subjected to virtual screening against SARS-CoV Main protease (Mpro) using Molecular Operating Environment (MOE) software. Twenty-two out of those natural candidates showed higher binding scores compared to their analogues. We repurpose these natural products including alkaloids, glucosinolates, and phenolics as potential platforms for the development of anti-SARS-CoV-2 therapeutics. This study paves the way towards discovering a lead used in the treatment of COVID-19 from natural sources and introduces phytomedicines with dual therapeutic effects against COVID-19 besides their original pharmacological effects. We recommend further in vitro evaluation of their anti-COVID-19 activity and future clinical studies.

PPAR agonists as effective adjuvants for COVID-19 vaccines, by modifying immunogenetics: a review of literature.

BACKGROUND: Several coronavirus vaccine have been fast-tracked to halt the pandemic, the usage of immune adjuvants that can boost immunological memory has come up to the surface. This is particularly of importance in view of the rates of failure of seroconversion and re-infection after COVID-19 infection, which could make the vaccine role and response debatable. Peroxisome proliferator-activated receptors (PPARs) have an established immune-modulatory role, but their effects as adjuvants to vaccination have not been explored to date. It is increasingly recognized that PPAR agonists can upregulate the levels of anti-apoptotic factors such as MCL-1. Such effect can improve the results of vaccination by enhancing the longevity of long-lived plasma cells (LLPCs). The interaction between PPAR agonists and the immune system does not halt here, as T cell memory is also stimulated through enhanced T regulatory cells, antagonizing PD-L1 and switching the metabolism of T cells to fatty acid oxidation, which has a remarkable effect on the persistence of T memory cells. What is even of a more significant value is the effect of PPAR gamma on ensuring a profound secretion of antibodies upon re-exposure to the offending antigen through upregulating lipoxin B4, therefore potentially assisting the vaccine response and deterring re-infection. SHORT CONCLUSION: In view of the above, we suggest the use of PPAR as adjuvants to vaccines in general especially the emerging COVID-19 vaccine due to their role in enhancing immunologic memory through DNA-dependent mechanisms.

Synthesis of imidazolidine-2,4-dione and 2-thioxoimidazolidin-4-one derivatives as inhibitors of virulence factors production in Pseudomonas aeruginosa.

In an attempt to counteract bacterial pathogenicity, a set of novel imidazolidine-2,4-dione and 2-thioxoimidazolidin-4-one derivatives was synthesized and evaluated as inhibitors of bacterial virulence. The new compounds were characterized and screened for their effects on the expression of virulence factors of Pseudomonas aeruginosa, including protease, hemolysin, and pyocyanin. Imidazolidine-2,4-diones 4c, 4j, and 12a showed complete inhibition of the protease enzyme, and they almost completely inhibited the production of hemolysin at 1/4 MIC (1/4 minimum inhibitory concentration; 1, 0.5, and 0.5 mg/ml, respectively). 2-Thioxoimidazolidin-4-one derivative 7a exhibited the best inhibitory activity (96.4%) against pyocyanin production at 1 mg/ml (1/4 MIC). A docking study was preformed to explore the potential binding interactions with quorum-sensing receptors (LasR and RhlR), which are responsible for the expression of virulence genes.

Impact of breast cancer and combination chemotherapy on oxidative stress, hepatic and cardiac markers.

PURPOSE: Carcinoma of the breast is the most prevalent cancer among Egyptian women and constitutes 29% of National Cancer Institute cases. The aim of this study was to determine the effect of breast cancer on oxidative stress, cardiac markers and liver function tests, moreover the role of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) in the treatment of breast cancer and its mechanism through changing the measured markers. METHODS: Forty female breast cancer patients who were admitted to the Department of Oncology of the Beni-Suef University Hospital were enrolled in the study. This study included three arms: a control group of healthy age-matched females (n=20), breast cancer patients who weren't receiving treatment (n=20), and patients undergoing treatment with anticancer combination drugs FAC (n=20). Blood samples collected from the control subjects and patients were analysed to determine levels of catalase, reduced glutathione (GSH), uric acid, nitric oxide (NO), malondialdehyde, creatine kinase (CK), lactate dehydrogenase (LDH), liver enzymes (alanine aminotransferase and aspartate aminotransferase), and creatinine. RESULTS: The levels of catalase and GSH were significantly reduced (p<0.05) in breast carcinoma and FAC treated breast cancer patients. The lipid peroxidation and NO levels were significantly enhanced in both untreated and FAC treated breast cancer patients. The CK and LDH were significantly enhanced (p<0.05) in the FAC group. CONCLUSION: The results from the present study show that oxidative stress is implicated in breast carcinoma and chemotherapy aggravates this oxidative stress which causes damage to many cellular targets and has the main side effect of cardiotoxicity.