Hepatocarcinoma is one of the malignant cancers with significant morbidity and mortality.Immunotherapy has emerged in clinical treatment,owing to the limitation and severe side effects of chemotherapy.In the immune sy...Hepatocarcinoma is one of the malignant cancers with significant morbidity and mortality.Immunotherapy has emerged in clinical treatment,owing to the limitation and severe side effects of chemotherapy.In the immune system,natural killer（NK）cells are important effectors required to eliminate malignant tumor cells without the limitation of major histocompatibility complex（MHC）molecule issues.Hence,treatment which could stimulate NK cells is of great interest.Here,we investigated the efficacy of the combined therapy of TT-1（a mutant of melittin）and interferon-α（IFN-α）on NK cells and human liver cancer HepG-2/Huh7 cells in vitro and in vivo,as well as the mechanism involved.The combination therapy significantly inhibited the growth of HepG-2/Huh7 cells in vivo,but this effect was impaired after depleting NK cells.TT-1 not only up-regulated MHC class I-related chain molecules A（MICA）expression,but also prevented the secretion of soluble MICA（sM ICA）.Both the mR NA and protein of a disintegrin and metallopeptidase 10（ADAM 10）in HepG-2/Huh7 cells were decreased after TT-1 treatment.The combined therapy of TT-1 and IFN-αcould suppress the growth of HepG-2/Huh7 xenografted tumor effectively via promoting the interaction of NK group 2,member D（NKG2D）and MICA,indicating that TT-1＋IFN-αwould be a potential approach in treating liver cancer.展开更多
The T-tubule (TT) system forms the structural basis for excitation-contraction coupling in heart and muscle cells. The morphogenesis of the TT system is a key step in the maturation of heart cells because it does not ...The T-tubule (TT) system forms the structural basis for excitation-contraction coupling in heart and muscle cells. The morphogenesis of the TT system is a key step in the maturation of heart cells because it does not exist in neonatal cardiomyocytes. In the present study, we quantified the morphological changes in TTs during heart cell maturation and investigated the role of junctophilin-2 (JP2), a protein known to anchor the sarcoplasmic reticulum (SR) to TT, in changes to TT morphological parameters. Analysis of confocal images showed that the transverse elements of TTs increased, while longitudinal elements decreased during the maturation of TTs. Fourier transform analysis showed that the power of ~2 m spatial components increased with cardiomyocytes maturation. These changes were preceded by increased expression of JP2, and were reversed by JP2 knockdown. These findings indicate that JP2 is required for the morphogenesis of TTs during heart development.展开更多
基金supported by the Outstanding Young Talent Foundation Project of Science and Technology Department in Jilin Province(No.20170520018JH),China
文摘Hepatocarcinoma is one of the malignant cancers with significant morbidity and mortality.Immunotherapy has emerged in clinical treatment,owing to the limitation and severe side effects of chemotherapy.In the immune system,natural killer（NK）cells are important effectors required to eliminate malignant tumor cells without the limitation of major histocompatibility complex（MHC）molecule issues.Hence,treatment which could stimulate NK cells is of great interest.Here,we investigated the efficacy of the combined therapy of TT-1（a mutant of melittin）and interferon-α（IFN-α）on NK cells and human liver cancer HepG-2/Huh7 cells in vitro and in vivo,as well as the mechanism involved.The combination therapy significantly inhibited the growth of HepG-2/Huh7 cells in vivo,but this effect was impaired after depleting NK cells.TT-1 not only up-regulated MHC class I-related chain molecules A（MICA）expression,but also prevented the secretion of soluble MICA（sM ICA）.Both the mR NA and protein of a disintegrin and metallopeptidase 10（ADAM 10）in HepG-2/Huh7 cells were decreased after TT-1 treatment.The combined therapy of TT-1 and IFN-αcould suppress the growth of HepG-2/Huh7 xenografted tumor effectively via promoting the interaction of NK group 2,member D（NKG2D）and MICA,indicating that TT-1＋IFN-αwould be a potential approach in treating liver cancer.
基金supported by the National Basic Research Program of China (2011CB809101)the National Natural Science Foundation of China (30730013)
文摘The T-tubule (TT) system forms the structural basis for excitation-contraction coupling in heart and muscle cells. The morphogenesis of the TT system is a key step in the maturation of heart cells because it does not exist in neonatal cardiomyocytes. In the present study, we quantified the morphological changes in TTs during heart cell maturation and investigated the role of junctophilin-2 (JP2), a protein known to anchor the sarcoplasmic reticulum (SR) to TT, in changes to TT morphological parameters. Analysis of confocal images showed that the transverse elements of TTs increased, while longitudinal elements decreased during the maturation of TTs. Fourier transform analysis showed that the power of ~2 m spatial components increased with cardiomyocytes maturation. These changes were preceded by increased expression of JP2, and were reversed by JP2 knockdown. These findings indicate that JP2 is required for the morphogenesis of TTs during heart development.
