RESUMO
ADAM10 is part of the ADAM superfamily containing cell surface proteins with special structures and potential adhesion and protease domains. This paper provides a review of the specific effects of ADAM10 in kidney development as well as its relations with renal diseases. ADAM10 plays an important role in developing tissues and organs and the pathogenesis of multiple diseases. The catalytic mechanism of ADAM10 on kidney-related molecules, including Notch, epidermal growth factor receptors, tumor necrosis factor-α, CXCL16, E-cadherin, cell adhesion molecule 1, meprin and klotho. ADAM10 is also closely associated with the progress of glomerular diseases, acute kidney injury and renal fibrosis. It probably is a good therapeutic target for renal diseases.
Assuntos
Secretases da Proteína Precursora do Amiloide , Proteínas de Membrana , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Proteína ADAM10/genética , Proteína ADAM10/metabolismo , Proteínas ADAM/metabolismo , Rim/metabolismoRESUMO
Cholangiocarcinoma (CCA) is a complex and refractor type of cancer with global prevalence. Several barriers remain in CCA diagnosis, treatment, and prognosis. Therefore, exploring more biomarkers and therapeutic drugs for CCA management is necessary. CCA gene expression data was downloaded from the TCGA and GEO databases. KEGG enrichment, GO analysis, and protein-protein interaction network were used for hub gene identification. miRNA were predicted using Targetscan and validated according to several GEO databases. The relative RNA and miRNA expression levels and prognostic information were obtained from the GEPIA. The candidate drug was screened using pharmacophore-based virtual screening and validated by molecular modeling and through several in vitro studies. 301 differentially expressed genes (DEGs) were screened out. Complement and coagulation cascades-related genes (including AHSG, F2, TTR, and KNG1), and cell cycle-related genes (including CDK1, CCNB1, and KIAA0101) were considered as the hub genes in CCA progression. AHSG, F2, TTR, and KNG1 were found to be significantly decreased and the eight predicted miRNA targeting AHSG, F2, and TTR were increased in CCA patients. CDK1, CCNB1, and KIAA0101 were found to be significantly abundant in CCA patients. In addition, Molport-003-703-800, which is a compound that is derived from pharmacophores-based virtual screening, could directly bind to CDK1 and exhibited anti-tumor activity in cholangiocarcinoma cells. AHSG, F2, TTR, and KNG1 could be novel biomarkers for CCA. Molport-003-703-800 targets CDK1 and work as potential cell cycle inhibitors, thereby having potential for consideration for new chemotherapeutics for CCA.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , MicroRNAs , Humanos , Biologia Computacional , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , MicroRNAs/genética , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/metabolismo , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologiaRESUMO
BACKGROUND: Lower respiratory tract infection (LRTI) is one of the leading cause of death in children under 5 years old around the world between 1980 and 2016. Distinguishing between viral and bacterial infection is challenging when children suffered from LRTI in the absence of pathogen detection. The aim of our study is to analyze the difference of serum ß2-microglobulin (ß2-MG) between viral LRTI and bacterial LRTI in children. METHODS: This retrospective study included children with LRTI caused by a single pathogen from Yancheng Third People's Hospital, Yancheng, China, between January 1, 2016 and December 31, 2019. Participants were divided into the younger group (1 year old ≤ age < 3 years old) and the older group (3 years old ≤ age < 5 years old) for subgroup analysis. RESULTS: A total of 475 children with LRTI caused by common respiratory pathogens were identified. In the younger group as well as the older group, the serum level of ß2-MG in respiratory syncytial virus, influenza A virus and influenza B virus groups were significantly increased compared to that in the Mycoplasma pneumoniae group. Compared with Streptococcus pneumoniae infection group, the serum ß2-MG level of respiratory syncytial virus, influenza A virus and influenza B virus groups were significantly higher in children between 1 and 3 years old. CONCLUSIONS: The serum ß2-MG may distinguish viral infection from bacterial infection in children with LRTI.