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1.
J Clin Lab Anal ; 36(1): e24185, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34919739

RESUMO

BACKGROUND: Tuberculosis poses a severe threat to human health. At present, compared with the traditional diagnostic methods for tuberculosis pleural effusion, such as Löwenstein-Jensen culture, pleural biopsy, and Ziehl-Neelsen smear microscopy, Xpert MTB/RIF was regarded as an emerging technology for its efficiency. The Xpert MTB/RIF accuracy for tuberculous pleural effusion diagnosis was evaluated in this systematic study. MATERIALS AND METHODS: We searched the relevant literature published before January 2021 in PubMed, Cochrane, EMBASE, and Web of Science databases. Utilizing Review Manager 5.3 software, the quality of the included literature was evaluated based on the Quality Assessment of Diagnostic Accuracy Studies criteria. Sensitivity, specificity, and the summary receiver operating characteristic curves were plotted and analyzed with Metadisc 1.40 software. We used Stata 12.0 software to evaluate the publication bias of this study. RESULTS: Eighteen articles were identified in total. The sensitivity of Xpert MTB/RIF in the pleural effusion was 0.24, and specificity was 1.00, respectively. The area under the summary receiver operating characteristic curve was 0.9737, which indicated that the overall accuracy of the Xpert MTB/RIF was high. In addition, based on the Deeks funnel plot, no publication bias of the study was found. CONCLUSION: Xpert MTB/RIF is a rapid method with high specificity but relatively low sensitivity for detecting Mycobacterium tuberculosis in pleural effusion. Its less sensitivity made it difficult to be used clinically, but the high specificity suggests that it can be used as a specific diagnostic method for tuberculous pleural effusion.


Assuntos
Mycobacterium tuberculosis/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico , Derrame Pleural/microbiologia , Tuberculose/diagnóstico , Humanos , Curva ROC , Padrões de Referência , Sensibilidade e Especificidade
2.
Eur J Med Chem ; 205: 112661, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32827851

RESUMO

Based on the structural modification of molecular-targeted agent sorafenib, a series of quinazolinyl-arylurea derivatives were synthesized and evaluated for their anti-proliferative activities against six human cancer cell lines. Compared with other cell lines tested, T24 was more sensitive to most compounds. Compound 7j exhibited the best profile with lower IC50 value and favorable selectivity. In this study, we focused on 7j-induced death forms of T24 cells and tried to elucidate the reason for its potent proliferative inhibitory activity. Compound 7j treatment could trigger three different cell death forms including apoptosis, ferroptosis, and autophagy; which form would occur depended on the concentrations and incubation time of 7j: (1) Lower concentrations within the initial 8 h of 7j treatment led to apoptosis-dependent death. (2) Ferroptosis and autophagy occurred in the case of higher concentrations combining with extended incubation time through effectively regulating the Sxc-/GPx4/ROS and PI3K/Akt/mTOR/ULK1 pathways, respectively. (3) The above death forms were closely associated with intracellular ROS generation and decreased mitochondrial membrane potential induced by 7j. In molecular docking and structure-activity relationship analyses, 7j could bind well to the active site of the corresponding receptor glutathione peroxidase 4 (GPx4). Compound 7j could be a promising lead for molecular-targeted anti-bladder cancer agents' discovery.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Quinazolinas/química , Ureia/síntese química , Ureia/farmacologia , Neoplasias da Bexiga Urinária/patologia , Antineoplásicos/química , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Técnicas de Química Sintética , Glutationa Peroxidase/química , Glutationa Peroxidase/metabolismo , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Simulação de Acoplamento Molecular , Conformação Proteica , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Ureia/química , Ureia/metabolismo
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