AIM: To investigate whether non-canonical autophagy transport receptor cell cycle progression 1(CCPG1) is involved in the corneal antifungal immune response.METHODS: Human corneal epithelial cells(HCECs) and human mye...AIM: To investigate whether non-canonical autophagy transport receptor cell cycle progression 1(CCPG1) is involved in the corneal antifungal immune response.METHODS: Human corneal epithelial cells(HCECs) and human myeloid leukemia mononuclear cells(THP-1) macrophages stimulated by Aspergil us fumigatus(A. fumigatus) were used as cell models. The expression of CCPG1 m RNA was detected by q RT-PCR. Western blot was used to determine the protein expression of CCPG1 and interleukin-1β(IL-1β). The dectin-1 neutralizing antibody was used to detect the association between dectin-1 and CCPG1. Immunofluorescence was used to observe the colocalization of CCPG1 and C-type lectin-like receptor-1(CLEC-1) in THP-1 macrophages.RESULTS: The expression of CCPG1 started to increase at 4 h after infection and increased in a time-dependent manner in HCECs and THP-1 macrophages. With dectin-1 neutralizing antibody pretreatment, the expression of IL-1β was down-regulated. CCPG1 up-regulation in response to A. fumigatus infection was independent of dectin-1. Immunofluorescence showed the colocalization of CCPG1 and CLEC-1 in THP-1 macrophages.CONCLUSION: As a specific autophagy protein of noncanonical autophagy pathway, CCPG1 is involved in corneal infection with A. fumigatus.展开更多
Cyclin Dependent Kinases (CDKs) are closely connected to the regulation of cell cycle progression, having been first identified asthe kinases able to drive cell division. In reality, the human genome contains 20 diffe...Cyclin Dependent Kinases (CDKs) are closely connected to the regulation of cell cycle progression, having been first identified asthe kinases able to drive cell division. In reality, the human genome contains 20 different CDKs, which can be divided in at leastthree different sub-family with different functions, mechanisms of regulation, expression patterns and subcellular localization. Mostof these kinases play fundamental roles the normal physiology of eucaryotic cells;therefore, their deregulation is associated withthe onset and/or progression of multiple human disease including but not limited to neoplastic and neurodegenerative conditions.Here, we describe the functions of CDKs, categorized into the three main functional groups in which they are classified, highlightingthe most relevant pathways that drive their expression and functions. We then discuss the potential roles and deregulation of CDKsin human pathologies, with a particular focus on cancer, the human disease in which CDKs have been most extensively studied andexplored as therapeutic targets. Finally, we discuss how CDKs inhibitors have become standard therapies in selected human cancersand propose novel ways of investigation to export their targeting from cancer to other relevant chronic diseases. We hope that theeffort we made in collecting all available information on both the prominent and lesser-known CDK family members will help inidentify and develop novel areas of research to improve the lives of patients affected by debilitating chronic diseases.展开更多
基金Supported by the National Natural Science Foundation of China(No.82171019)the Natural Science Foundation of Shandong Province(No.ZR2021MH368)+1 种基金Traditional Chinese Medicine Research Project of Qingdao(No.2020-zyy055)Shandong Qingdao Outstanding Health Professional Development Fund。
文摘AIM: To investigate whether non-canonical autophagy transport receptor cell cycle progression 1(CCPG1) is involved in the corneal antifungal immune response.METHODS: Human corneal epithelial cells(HCECs) and human myeloid leukemia mononuclear cells(THP-1) macrophages stimulated by Aspergil us fumigatus(A. fumigatus) were used as cell models. The expression of CCPG1 m RNA was detected by q RT-PCR. Western blot was used to determine the protein expression of CCPG1 and interleukin-1β(IL-1β). The dectin-1 neutralizing antibody was used to detect the association between dectin-1 and CCPG1. Immunofluorescence was used to observe the colocalization of CCPG1 and C-type lectin-like receptor-1(CLEC-1) in THP-1 macrophages.RESULTS: The expression of CCPG1 started to increase at 4 h after infection and increased in a time-dependent manner in HCECs and THP-1 macrophages. With dectin-1 neutralizing antibody pretreatment, the expression of IL-1β was down-regulated. CCPG1 up-regulation in response to A. fumigatus infection was independent of dectin-1. Immunofluorescence showed the colocalization of CCPG1 and CLEC-1 in THP-1 macrophages.CONCLUSION: As a specific autophagy protein of noncanonical autophagy pathway, CCPG1 is involved in corneal infection with A. fumigatus.
基金supported by the Ministero della Salute:Ricerca Corrente CRO Aviano core grant(linea 1),CO-2018-1236705 and PNRR-MAD-2022-12375663 to GBand RF-2021-12371961 to BB and GR-2021-12373937 to IS.Ministero dell’UniversitàARS01_00568 to GB+2 种基金Associazione Italiana Ricerca sul Cancro(AIRC)IG 26253 to GB,IG 20061 to BB,MFAG 28993 to IPCRO Aviano 5‰intramural grants to GB and BB.
文摘Cyclin Dependent Kinases (CDKs) are closely connected to the regulation of cell cycle progression, having been first identified asthe kinases able to drive cell division. In reality, the human genome contains 20 different CDKs, which can be divided in at leastthree different sub-family with different functions, mechanisms of regulation, expression patterns and subcellular localization. Mostof these kinases play fundamental roles the normal physiology of eucaryotic cells;therefore, their deregulation is associated withthe onset and/or progression of multiple human disease including but not limited to neoplastic and neurodegenerative conditions.Here, we describe the functions of CDKs, categorized into the three main functional groups in which they are classified, highlightingthe most relevant pathways that drive their expression and functions. We then discuss the potential roles and deregulation of CDKsin human pathologies, with a particular focus on cancer, the human disease in which CDKs have been most extensively studied andexplored as therapeutic targets. Finally, we discuss how CDKs inhibitors have become standard therapies in selected human cancersand propose novel ways of investigation to export their targeting from cancer to other relevant chronic diseases. We hope that theeffort we made in collecting all available information on both the prominent and lesser-known CDK family members will help inidentify and develop novel areas of research to improve the lives of patients affected by debilitating chronic diseases.
