RESUMO
Background: The emergence of the COVID-19 pandemic has created an environment in which numerous determinants of poor mental health are intensified. Lockdown, re-lockdown, and media coverage of the spread of the virus, have the potential to contribute to increased levels of anxiety and depression. Mindfulness may act as a buffer against COVID-19-related depressive and anxiety disorders. Methods: We conducted a systematic review and meta-analysis by searching PubMed, PsycINFO, Web of Science, and Google Scholar for any study published between January 2020 and March 2022. In this study, Comprehensive Meta-Analysis Version 3.3 software was applied to evaluate the effect size by random effect model. In addition, the heterogeneity analysis was evaluated using indicators Q and I2 indicators. Three methods were used to test for publication bias: funnel plot, Classic Fail-safe N, and Egger's linear regression. According to the features of the included articles, subgroup analysis was utilized for the moderator analysis of this study. Results: The analysis finally included 12 articles (16 samples, N = 10,940) and obtained 26 independent effect sizes. In accordance with the meta-analysis, in the random effect model, the correlation between mindfulness and anxiety was -0.330 (p < 0.001), and the correlation between mindfulness and depression was -0.353 (p < 0.001), which supported the effect of mindfulness on anxiety and depression. In the meta-analysis of the correlation between mindfulness and anxiety, study region had an essential moderating effect (p < 0.001). The Sample type did not produce a significant moderating effect (p = 0.190). The mode of action of mindfulness was a significant moderator (p = 0.038). In the meta-analysis of the linkage between mindfulness and depression, regional differences had a significant moderating effect (p < 0.001). The sample type had no discernible moderating impact (p = 0.213). The mode of action of mindfulness was a significant moderator (p = 0.003). Conclusion: Our meta-analysis indicated that there was an essential correlation between public mindfulness and mental health. Our systematic review added evidence supporting the beneficial nature of mindfulness. A cascading development of beneficial traits that improve mental health may start with mindfulness.
RESUMO
A novel series of N-(3-((7H-purin-6-yl)thio)-4-hydroxynaphthalen-1-yl)-sulfonamides were designed and synthesized. Biological characterization revealed that several compounds exerted enhanced anti-proliferative activity against human umbilical vein endothelial cells (HUVECs) and several cancer cell lines and high specific protein kinase and angiogenesis inhibitory activities. Compared with our previously synthesized compounds, the substitution of sulfonamide structure for amide fragment played an essential role for the advance of inhibitory activities. In addition, the replacement of 1H-1,2,4-triazole ring by 7H-purine did not result in obvious decrease of inhibition efficacy, indicating that the sulfonamide structure contributes even more to the inhibition efficacy than the 1H-1,2,4-triazole ring. Among these compounds, compound 9n demonstrated comparable in vitro antiangiogenic activities to pazopanib in both HUVEC tube formation assay and the rat thoracic aorta rings (TARs) test. Meanwhile, compound 9n was identified to inhibit Akt1 (IC50=1.73 µM) and Abl tyrosine kinase (IC50=1.53 µM) effectively.
Assuntos
Inibidores da Angiogênese/síntese química , Inibidores de Proteínas Quinases/síntese química , Proteínas Quinases/química , Purinas/síntese química , Sulfonamidas/química , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Células HCT116 , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases/metabolismo , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas c-abl/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-abl/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Purinas/química , Purinas/farmacologia , Ratos , Ratos Sprague-Dawley , Sulfonamidas/síntese química , Sulfonamidas/farmacologiaRESUMO
A virtual screening approach was performed to develop novel and potent vascular endothelial growth factor receptor 2 inhibitors. The Specs database was filtered by 'rule of five', a pharmacophore model, and docking filter. Sixteen molecules were selected for tube formation assay, a naphthalenol group containing molecule, 12, showed good performance in the study. In the following aortic ring assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 12 was discovered to efficiently inhibit angiogenesis and tumor cell growth. It is the first time to discover naphthalenol scaffold as potent vascular endothelial growth factor receptor 2 inhibitors. Thus, a molecular dynamic simulation process was applied to discover key features of 12 in binding to vascular endothelial growth factor receptor 2. Hydrophobic interactions were discovered to play significant role in the ligand-receptor binding.