Ahmed I. Abulsoud

COVID-19 is a worldwide pandemic caused by SARS-coronavirus-2 (SARS-CoV-2). Less than a year after the emergence of the Covid-19 pandemic, many vaccines have arrived on the market with innovative technologies in the field of vaccinology. Based on the use of messenger RNA (mRNA) encoding the Spike SARS-Cov-2 protein or on the use of recombinant adenovirus vectors enabling the gene encoding the Spike protein to be introduced into our cells, these strategies make it possible to envisage the vaccination in a new light with tools that are more scalable than the vaccine strategies used so far. Faced with the appearance of new variants, which will gradually take precedence over the strain at the origin of the pandemic, these new strategies will allow a much faster update of vaccines to fight against these new variants, some of which may escape neutralization by vaccine antibodies. However, only a vaccination policy based on rapid and massive vaccination of the population but requiring a supply of sufficient doses could make it possible to combat the emergence of these variants. Indeed, the greater the number of infected individuals, the faster the virus multiplies, with an increased risk of the emergence of variants in these RNA viruses. This review will discuss SARS-CoV-2 pathophysiology and evolution approaches in altered transmission platforms and emphasize the different mutations and how they influence the virus characteristics. Also, this article summarizes the common vaccines and the implication of the mutations and genetic variety of SARS-CoV-2 on the COVID-19 biomedical arbitrations.

AIMS: The first-line treatment for advanced hepatocellular carcinoma (HCC) is the multikinase inhibitor sorafenib (SOR). Sofafenib resistance is linked to protein kinase B/ mammalian target of rapamycin (AKT/mTOR) and nuclear factor kappa B (NF-κB) activation, apoptosis inhibition and oxidative stress. This study investigated selenium nanoparticles (SeNps) to overcome SOR resistance in thioacetamide (TAA) induced HCC in rats. MATERIALS AND METHODS: TAA (200 mg/kg/twice weekly, i.p.) was administered for 16 weeks to induce HCC.s. Rats were treated with oral SOR (10 mg/Kg daily), selenium, and SeNps (5 mg/kg three times/week) alone or in combination, for two weeks. Apoptosis, proliferation, angiogenesis, metastasis and drug resistance were assessed. Cleaved caspase 3 (C. CASP3), mTOR, and NF-κB were determined by western blotting. Expression of p53 gene and long-noncoding RNA-AF085935 was determined by qRT-PCR. Expression of B- Cell Leukemia/Lymphoma 2 (Bcl2), Bcl associated X protein (Bax)and glypican 3 (GPC3) was determined by enzyme-linked immunosorbent assay. Liver functions, antioxidant capacity, histopathology and CD34 immunohistochemistry were performed. KEY FINDINGS: SOR/SeNps reversed TAA-induced HCC in rats, through reduction of oxidative stress, activation of p53, Bax and CASP3, and inhibition of Bcl2. SOR/SeNps ameliorated the HCC-induced effect on cell proliferation and drug resistance by targeting mTOR and NF-κB pathways. SOR/SeNps decreased CD34 immunostaining indicating a decrease in angiogenesis and metastasis. SOR/SeNps regulated HCC epigenetically through the lncRNA-AF085935/GPC3 axis. SIGNIFICANCE: SOR/SeNps are a promising combination for tumor suppression and overcoming sorafenib resistance in HCC by modulating apoptosis, AKT/mTOR and NF-κB pathways, as well as CD34 and lncRNA-AF085935/GPC3 axis.

Objective: This study aims to evaluate the expression pattern of circulating microRNAs (miR)-486-5p, miR-497, miR-509-5p, and miR-605 in the serum of metabolic syndrome (MetS) Egyptian male patients. Methods: In this study, the circulating miR-486-5p, miR-497, miR509-5p, and miR-605 were amplified and quantitatively detected by quantitative real-time polymerase chain reaction in sera of 55 MetS male patients in comparison to 20 male controls. The level of fasting plasma glucose and triacylglycerol (TAG) were measured using calorimetric assay. Blood pressure was measured using mercuric sphygmomanometer. Anthropometric measurements were done to each individual. Furthermore, MetS patients were defined according to the criteria proposed by the American Heart Association and divided into three groups according to MetS index. Results: The study was performed on three groups and a control group defined as follows: group 1: 15 MetS patients who fulfilled all diagnostic criteria of MetS; group 2: 20 MetS patients with normal blood pressure; group 3: 20 MetS patients with normal TAG levels.The levels of miRs are expressed as [median (IQR)]. miR-486-5-p and miR-497 expression were elevated in group 1 [31.9(49), p˂ 0.0001; 73.1(42.5), p˂ 0.0001], group 2 [36.4(15.7), p˂ 0.0001; 68.3(54.8), p˂ 0.0001], and group (3) [10.8(18.9), p= 0.0014; 27.5(39.7), p= 0.0012]. MiR-509-5p was elevated in groups 1 and 2 [501(468), p= 0.0001], [309(436), p= 0.0006], respectively, while normally expressed in group 3 [0.93(0.077), p= 0.0001]. miR-605 was elevated in groups 1 and 3 [25.4(20.0), p= 0.0018], [54.8(65.8), p˂ 0.0001], while normally expressed in group 2 [0.84(0.67), p˂ 0.0001]. Conclusion: miRs (486-5p, 497, 509-5p, and 605) serum levels were higher in MetS patients than in healthy control subjects; therefore, these serum miRs can serve as early biomarkers and can be used to follow-up the prognosis of MetS. Keywords: metabolic syndrome (MetS), miR-486-5p, miR-497, miR509-5p, miR-605, metabolic syndrome index (MSI)