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Signal Transduct Target Ther ; 6(1): 165, 2021 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-33895786


The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires an urgent need to find effective therapeutics for the treatment of coronavirus disease 2019 (COVID-19). In this study, we developed an integrative drug repositioning framework, which fully takes advantage of machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor, CVL218, currently in Phase I clinical trial, may be repurposed to treat COVID-19. Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect. In addition, we showed that CVL218 can interact with the nucleocapsid (N) protein of SARS-CoV-2 and is able to suppress the LPS-induced production of several inflammatory cytokines that are highly relevant to the prevention of immunopathology induced by SARS-CoV-2 infection.

Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/metabolismo , Simulação por Computador , Reposicionamento de Medicamentos , Modelos Biológicos , SARS-CoV-2/metabolismo , Humanos
Exp Ther Med ; 20(6): 258, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33199984


The aim of the present study was to evaluate macular vascular density (MVD) variation after uneventful cataract surgery using optical coherence tomography angiography (OCTA) in patients with high myopia. Patients with cataracts scheduled for cataract surgery were divided into a high-myopia group [spherical equivalent (SE)≤-6.0 diopter (D) and axial length (AL)≥25 mm] and a low-myopia group (SE>-6.0 D and AL<25 mm). All patients were examined for MVD and retinal thickness (RT) with OCTA pre-operatively and post-operatively (1 day, 1 week, and 1 and 3 months after surgery). A total of 55 eyes from 44 patients were included. MVD and RT both changed after cataract surgery. The mean change in superficial vascular density (SVD) in patients with high myopia was significantly lower than that in the low-myopia group at the four post-operative time-points (all P<0.05). In addition, the RT of eyes with high myopia exhibited a different variation compared with that of the low-myopia group. Significant correlations were identified between AL, RT, intraocular pressure and SVD after surgery. In conclusion, superficial retinal perfusion in patients with high myopia was significantly lower than that in low myopia patients, which may lead to complications caused by poor perfusion.

J Coll Physicians Surg Pak ; 29(10): 1009-1011, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31564281


The aim of this study was to compare curative effects of valsartan alone or combined with alpha-lipoic acid (ALA) on inflammatory cytokine indices including hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α) and renal function indices including urinary albumin excretion rate (UAER), ß2-microglobulin (ß2-MG) and cystatin C (Cys C) of patients with early-stage diabetic kidney disease (DKD). One hundred and two patients with early-stage DKD were randomly divided into group A and group B, with 51 patients in each group. Group A was administered with valsartan alone, while group B was administered with valsartan combined with ALA. Research showed that 14 days after treatment, group B had significantly lowered hs-CRP, TNF-α, UAER, ß2-MG and Cys C when compared with group A (all p<0.001). Compared to valsartan alone, valsartan combined with ALA can reduce level of inflammatory cytokines in serum and improve renal function.

Anti-Hipertensivos/uso terapêutico , Citocinas/sangue , Citocinas/efeitos dos fármacos , Nefropatias Diabéticas/tratamento farmacológico , Ácido Tióctico/uso terapêutico , Valsartana/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , China , Quimioterapia Combinada , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade
Clin Lab ; 60(4): 587-97, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24779292


BACKGROUND: Primary hepatic carcinoma (PHC) is currently one of the most common worldwide causes of cancer death. Golgi protein 73 (GP73) has been proposed as potential diagnostic marker. However, it is controversial because of inconsistent diagnostic accuracy in different studies. The aim of this study was to assess the diagnostic accuracy of GP73 for PHC. METHODS: All the studies relating to the diagnostic accuracy of GP73 for patients with PHC from 1978 to January 2013 were collected. Methodological quality was assessed by Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). The overall diagnostic sensitivity, specificity, and area under the receiver operating characteristic curve were used to evaluate the diagnostic accuracy of GP73 using Meta-DiSc statistical software. RESULTS: Altogether 5,637 subjects were included in the 25 selected studies. The sensitivity and specificity (95% confidence interval) of GP73 was 0.75 (0.73-0.76) and 0.84 (0.83 - 0.86), respectively. The area under the summary receiver operating characteristic curve (AUC) and Q* index of GP73 was 0.8616 and 0.8021. CONCLUSIONS: Serum GP73 has a relatively high diagnostic accuracy in primary hepatic carcinoma with better sensitivity and high specificity than AFP.

Biomarcadores Tumorais/sangue , Carcinoma/sangue , Neoplasias Hepáticas/sangue , Proteínas de Membrana/sangue , Ensaio de Imunoadsorção Enzimática , Humanos , Curva ROC , alfa-Fetoproteínas/metabolismo