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1.
J Enzyme Inhib Med Chem ; 37(1): 2063-2077, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35875937

RESUMO

In this study, a set of novel benzoxazole derivatives were designed, synthesised, and biologically evaluated as potential VEGFR-2 inhibitors. Five compounds (12d, 12f, 12i, 12l, and 13a) displayed high growth inhibitory activities against HepG2 and MCF-7 cell lines and were further investigated for their VEGFR-2 inhibitory activities. The most potent anti-proliferative member 12 l (IC50 = 10.50 µM and 15.21 µM against HepG2 and MCF-7, respectively) had the most promising VEGFR-2 inhibitory activity (IC50 = 97.38 nM). A further biological evaluation revealed that compound 12l could arrest the HepG2 cell growth mainly at the Pre-G1 and G1 phases. Furthermore, compound 12l could induce apoptosis in HepG2 cells by 35.13%. likely, compound 12l exhibited a significant elevation in caspase-3 level (2.98-fold) and BAX (3.40-fold), and a significant reduction in Bcl-2 level (2.12-fold). Finally, docking studies indicated that 12l exhibited interactions with the key amino acids in a similar way to sorafenib.


Assuntos
Antineoplásicos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Antineoplásicos/química , Apoptose , Benzoxazóis , Relação Dose-Resposta a Droga , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases , Relação Estrutura-Atividade
2.
Biomark Med ; 16(8): 589-597, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35350852

RESUMO

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.


Assuntos
COVID-19 , Biomarcadores , COVID-19/diagnóstico , Glicopeptídeos , Humanos , Prognóstico , Índice de Gravidade de Doença
3.
Saudi J Biol Sci ; 28(11): 6465-6470, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34305426

RESUMO

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.

4.
BMC Res Notes ; 14(1): 36, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33499929

RESUMO

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).


Assuntos
Lectinas/genética , Febre Reumática , Cardiopatia Reumática , Adolescente , Egito , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Cardiopatia Reumática/genética
5.
Clin Rheumatol ; 40(7): 2927-2937, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33459954

RESUMO

OBJECTIVE: Rheumatoid arthritis (RA) is an inflammatory autoimmune disorder, which can cause progressive and functional disability. Previous data suggests that some inflammatory cytokines are dysregulated in patients with RA. Polymorphisms in the NFKB1 gene were studied in different populations with RA. Specific studies showed that the NFKB1 promoter -94ins/delATTG (rs28362491) polymorphism appears to be correlated with alterations in the IL-6 expression and may lead to disease development. We aimed to evaluate the association between the NFKB1 -94ins/delATTG polymorphism and biochemical, and clinical markers for severity of RA in Egyptian patients. METHODS: Study subjects included 196 RA patients from the Egyptian population. NFKB1 -94ins/delATTG polymorphism was genotyped by real-time PCR using the TaqMan assay. Concentrations of plasma IL-6 were assessed using the ELISA method. RESULTS: The frequencies of (del/del + ins/del) genotype in cases with erosive arthritis were significantly increased as compared to cases with non-erosive arthritis (63.0% vs. 47.7%, OR = 1.86, 95% CI: 1.05-3.30, p: 0.043). Carriers of del allele had high activity and severity markers compared with those of ins/ins genotype. The del allele was significantly associated with higher IL-6 levels in a dose-dependent manner. Plasma levels of IL-6 were significantly higher in the del/del (41.4 ± 16.2 pg/ml) and ins/del (19.1 ± 12.4 pg/ml) genotype when compared with the ins/ins genotype (11.4 ± 4.21 pg/ml). In a multivariate analysis of variance, including confounding factors associated with higher IL-6 levels (RF, disease duration, and DAS28), the NFKB1 -94ins/delATTG polymorphism retained its role. Logistic regression analyses revealed that high IL-6 plasma levels independently associated with an increased risk of presenting erosive RA, while -94ins/delATTG polymorphism has no direct association with the progression of erosive arthritis. CONCLUSION: Our data indicate that the NFKB1 -94ins/delATTG polymorphism contributes to the severity and progression of RA through IL-6 levels modulation in Egyptian patients. Key Points • Carriers of del allele had high activity and severity markers compared with those of ins/ins genotype. • In RA patients, the del allele was significantly associated with higher IL-6 levels in a dose-dependent manner. • IL-6 plasma levels are independently associated with an increased risk of presenting erosive arthritis. • The NFKB1 -94ins/delATTG polymorphism contributes to the severity and progression of RA through IL-6 levels modulation in Egyptian patients.


Assuntos
Artrite Reumatoide , Interleucina-6/sangue , Subunidade p50 de NF-kappa B/genética , Artrite Reumatoide/genética , Estudos de Casos e Controles , Progressão da Doença , Egito , Predisposição Genética para Doença , Genótipo , Humanos
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