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Biomed Pharmacother ; 157: 113977, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36370519


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.

Biomark Med ; 16(8): 589-597, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35350852


Aim: To investigate the change in a serum level of copeptin, a neuroendocrine biomarker, in differentiating grades of COVID-19 severity on admission time and to find its diagnostic potential. Materials & Methods: 160 COVID-19 patients were classified according to disease severity into 80 mild to moderate and 80 severe patients. Serum copeptin level was assessed by ELISA on their admission time. Besides, serum CRP, ferritin and D-dimer were estimated. Results: Severe COVID-19 patients showed higher serum copeptin level in comparison to mild to moderate cases, with diagnostic potential to distinguish disease severity with 93.33% sensitivity and 100% specificity at cutoff value >18.5 Pmol/l. Conclusion: Serum copeptin was remarkably increased with COVID-19 severity with reasonable differentiation potential for recently admitted patients.

We conducted a biochemical study on the role of copeptin ­ a biomarker of acute stress due to COVID-19 infection ­ in classification of COVID-19 severity on admission over 160 adult patients. Copeptin was highly elevated in severe cases more than the mild to moderate ones. So, it may be an early marker in admission departments to ease early clinical decisions and medical intervention.

COVID-19 , Biomarcadores , COVID-19/diagnóstico , Glicopeptídeos , Humanos , Prognóstico , Índice de Gravidade de Doença
J Enzyme Inhib Med Chem ; 37(1): 380-396, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34923885


In the current work, some 1,3,4-oxadiazole-naphthalene hybrids were designed and synthesised as VEGFR-2 inhibitors. The synthesised compounds were evaluated in vitro for their antiproliferative activity against two human cancer cell lines namely, HepG-2 and MCF-7. Compounds that exhibited promising cytotoxicity (5, 8, 15, 16, 17, and 18) were further evaluated for their VEGFR-2 inhibitory activities. Compound 5 showed good antiproliferative activity against both cell lines and inhibitory effect on VEGFR-2. Besides, it induced apoptosis by 22.86% compared to 0.51% in the control (HepG2) cells. This apoptotic effect was supported by a 5.61-fold increase in the level of caspase-3 compared to the control cells. Moreover, it arrested the HepG2 cell growth mostly at the Pre-G1 phase. Several in silico studies were performed including docking, ADMET, and toxicity studies to predict binding mode against VEGFR-2 and to anticipate pharmacokinetic, drug-likeness, and toxicity of the synthesised compounds.

Antineoplásicos/farmacologia , Desenho de Fármacos , Naftalenos/farmacologia , Oxidiazóis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Naftalenos/síntese química , Naftalenos/química , Oxidiazóis/síntese química , Oxidiazóis/química , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
Saudi J Biol Sci ; 28(11): 6465-6470, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34305426


The use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in coronavirus disease 2019 (COVID-19) patients has been claimed as associated with the risk of COVID-19 infection and its subsequent morbidities and mortalities. These claims were resulting from the possibility of upregulating the expression of angiotensin-converting enzyme 2 (ACE2), facilitation of SARS-CoV-2 entry, and increasing the susceptibility of infection in such treated cardiovascular patients. ACE2 and renin-angiotensin-aldosterone system (RAAS) products have a critical function in controlling the severity of lung injury, fibrosis, and failure following the initiation of the disease. This review is to clarify the mechanisms beyond the possible deleterious effects of angiotensin II (Ang II), and the potential protective role of angiotensin 1-7 (Ang 1-7) against pulmonary fibrosis, with a subsequent discussion of the latest updates on ACEIs/ARBs use and COVID-19 susceptibility in the light of these mechanisms and biochemical explanation.

BMC Res Notes ; 14(1): 36, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33499929


OBJECTIVE: Ficolin-3 is one of the innate immunity molecules that was thought to play a pivotal role in Streptococcus pyogenes autoimmunity and its complications; rheumatic fever (RF) and rheumatic heart disease (RHD). We aimed to disclose if there is an association between ficolin-3 (FCN3) gene polymorphisms (rs4494157 and rs10794501) and RF with or without RHD for the first time in Egyptian adolescents. RESULTS: Serum ficolin-3 level was significantly elevated in patients suffering from RF with and without RHD in comparison with control. Regarding FCN3 gene (rs4494157) polymorphism, a significant correlation was found between the A allele and the susceptibility to RF with or without RHD (OR = 2.93, P = 0.0002 and OR = 2.23, P = 0.008 respectively). Besides, AA homozygous genotype showed a significant association with RHD risk (OR = 3.47, P = 0.026). Patients carrying the A allele (CA + AA) had significantly higher serum ficolin-3 than those carrying the CC genotype (P ˂ 0.0001). While the frequency of (rs10794501) polymorphism revealed no significant differences between the controls and RF patients with or without RHD (OR = 1.43, P = 0.261 and OR = 1.48, P = 0.208 respectively).

Lectinas/genética , Febre Reumática , Cardiopatia Reumática , Adolescente , Egito , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Cardiopatia Reumática/genética
Diabetes Metab Syndr ; 14(6): 2057-2062, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33113473


BACKGROUND AND AIMS: Salusin-ß is a newly defined biomarker that plays a role in atherogenesis and in homeostasis. The study aimed to assess serum salusin-ß level in relation to atherosclerosis and ventricular dysfunction in type 2 diabetes mellitus (T2DM) patients. METHODS: Sixty T2DM patients and twenty-five age-matched healthy controls were included. Serum salusin-ß was determined by ELISA. Echocardiography and carotid ultrasonography were carried out for all individuals. RESULTS: Serum salusin-ß level was significantly elevated in patients with T2DM than in controls (P < 0.001). It was positively correlated with obesity parameters, insulin resistance index (r = 0.280,P < 0.001), atherogenic dyslipidemia and with carotid intima media thickness (CIMT) (r = 0.411, P < 0.001). Echocardiographic findings showed a positive correlation between salusin-ß and left ventricular hypertrophy (LVH) parameters and a negative correlation with left ventricular (LV) diastolic and systolic functions. Regression analysis showed that serum salusin-ß level was a significant predictor of diastolic dysfunction. CONCLUSION: Serum salusin-ß may be associated with atherosclerosis and LV dysfunction in T2DM.

Aterosclerose/diagnóstico , Biomarcadores/sangue , Espessura Intima-Media Carotídea , Diabetes Mellitus Tipo 2/complicações , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Disfunção Ventricular Esquerda/diagnóstico , Aterosclerose/sangue , Aterosclerose/etiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Prognóstico , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/etiologia
Environ Sci Pollut Res Int ; 27(14): 16189-16202, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32112355


Polycyclic aromatic hydrocarbons (PAHs)/aryl hydrocarbon receptor (AhR) regulate the expression of target genes, including drug transporter genes which harbor xenobiotic response element (XRE) in their promoter regions. Thus, PAHs/AhR could alter the toxicokinetic profile of many nephrotoxic drugs, including aminoglycosides. In the current study, we investigated the expression and localization of AhR and megalin in rat kidney. Furthermore, we investigated whether AhR and its ligands could modulate the expression of megalin and consequently the gentamicin-induced nephrotoxicity (GN) in rats. Both megalin and AhR receptors are expressed in the proximal tubules of the rat kidney. Treatment with AhR agonist benzo(a)pyrene aggravated GN as indicated by a significant increase in serum creatinine, BUN, KIM1, NAGL, CD-86, and urinary albumin/creatinine ratio. On the other hand, treatment with AhR antagonist resveratrol ameliorated GN as manifested by a pronounced decrease in the aforementioned parameters. The effects of AhR ligands on GN were associated with altered expression of megalin receptor.

Hidrocarbonetos Policíclicos Aromáticos , Receptores de Hidrocarboneto Arílico , Animais , Benzo(a)pireno , Gentamicinas , Ligantes , Ratos
Gene ; 626: 26-31, 2017 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-28479383


Diabetes mellitus is a fast-growing health problem in Egypt affecting morbidity, mortality and health care resources. Irisin, a new exercise-induced myokine inducing browning of white adipose tissues, has gained a great interest as a potential new target for combating type 2 diabetes mellitus (T2DM) and its complications. In this study, we assessed serum irisin levels in T2DM and diabetic nephropathy to elucidate possible relationships between irisin and metabolic parameters and renal functions. We also investigated, for the first time in Egypt, the association of FNDC5 rs16835198 G>T polymorphism with T2DM, diabetic nephropathy and irisin levels. One hundred type 2 diabetic patients (40 normoalbuminuric and 60 with nephropathy) as well as fifty control subjects were enrolled in this study. Serum irisin and insulin were evaluated by ELISA. Genomic DNA was genotyped for FNDC5 rs16835198 polymorphism using TaqMan genotyping assay. Serum irisin levels were lower in diabetic patients compared to controls and this decrease was more pronounced in diabetic nephropathy. Irisin correlates with metabolic parameters and renal functions. Frequencies of T allele and TT genotype were significantly lower among T2DM and diabetic nephropathy patients compared to controls. Moreover, G allele was associated with elevated insulin resistance and dyslipidemia without effect on circulating irisin levels. IN CONCLUSION: T2DM and diabetic nephropathy are associated with decreased levels of irisin. FNDC5 rs16835198 TT genotype associates with decreased risk of T2DM in Egyptians with no effect on renal complications. Also, G allele has insulin desensitizing action with no association with circulating irisin levels.

Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/genética , Dislipidemias/genética , Fibronectinas/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/sangue , Dislipidemias/etiologia , Egito , Fibronectinas/sangue , Humanos , Resistência à Insulina/genética , Masculino , Projetos Piloto