ABSTRACT
In order to solve the difficulties and challenges in the implementation of the original blood distribution and collection regulations caused by the expansion of hospital area, the extension of blood transfer time, the changeability of blood transfer environment, and the strain of personnel due to the increase of workload, as well as to ensure the accuracy of the information throughout blood remote verification and distribution and the safety of clinical blood transfusion, , Shanghai experts related to clinical transfusion and blood management had made a systematic study on the applicable scope and management rules of remote verification of blood distribution and collection, and formulated this Expert Consensus combined with the development status of digital, intelligent and remote communication technologies, so as to provide corresponding guidance for clinical medical institutions in line with the changes in reality.
ABSTRACT
Williams syndrome transcription factor (WSTF) is a transcription factor and tyrosine kinase. WSTF overexpression promotes migration and proliferation of various cancers, and Ser158 (WSTFS158) phosphorylation plays an important role in this process. However, the role of the other posttranslational modifications of WSTF is unknown. Here, we report that lysine (K) 426 on WSTF is acetylated by MOF and deacetylated by SIRT1. Mechanistically, male-specific lethal (MSL) 1v1 interaction with WSTF facilitates its interaction with MOF for WSTF acetylation, which in turn promotes WSTFS158 phosphorylation. The kinase and transcriptional regulatory activity of WSTF were enhanced by acetylation. WSTFK426ac levels positively and significantly correlated with tumor size, histological grade, and age. Moreover, we demonstrated that acetylated WSTF promotes cancer cell proliferation, migration, invasion, and tumor formation. In conclusion, we identified the enzymes regulating WSTF K426 acetylation, and demonstrated an acetylation-dependent mechanism that modulates the activities of WSTF and contributes to tumorigenesis. Our findings provide new clues to study WSTF-mediated normal development and disease.
Subject(s)
Carcinogenesis/pathology , Histone Acetyltransferases/metabolism , Neoplasms/pathology , Transcription Factors/metabolism , Acetylation , Animals , Carcinogenesis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Female , Gene Expression Regulation , HEK293 Cells , Histone Acetyltransferases/genetics , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness/genetics , Neoplasm Transplantation , Phosphorylation , Protein Processing, Post-Translational , RNA Interference , RNA, Small Interfering/genetics , Sirtuin 1/genetics , Sirtuin 1/metabolism , Transplantation, HeterologousABSTRACT
Overexpression of Jumonji domain-containing 6 (JMJD6) has been reported to be associated with more aggressive breast cancer characteristics. However, the precise role of JMJD6 in breast cancer development remains unclear. Here, we demonstrate that JMJD6 has intrinsic tyrosine kinase activity and can utilize ATP and GTP as phosphate donors to phosphorylate Y39 of histone H2A.X (H2A.XY39ph). High JMJD6 levels promoted autophagy in triple negative breast cancer (TNBC) cells by regulating the expression of autophagy-related genes. The JMJD6-H2A.XY39ph axis promoted TNBC cell growth via the autophagy pathway. We show that combined inhibition of JMJD6 kinase activity and autophagy efficiently decreases TNBC growth. Together, these findings suggest an effective strategy for TNBC treatment.
Subject(s)
Autophagy , Histones/metabolism , Jumonji Domain-Containing Histone Demethylases/metabolism , Neoplasm Proteins/metabolism , Triple Negative Breast Neoplasms/metabolism , Animals , Female , Histones/genetics , Humans , Jumonji Domain-Containing Histone Demethylases/genetics , Mice , Mice, Inbred BALB C , Neoplasm Proteins/genetics , Phosphorylation , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathologyABSTRACT
Objective To evaluate the efficacy and safety of tranexamic acid in blood protection in liver transplantation.Methods We searched the Cochrane library,MEDLINE,CNKI,VIP,CBM (from inception to May 2017),to collect all the randomized controlled trials of tranexamic acid for liver transplantation.the quality of the included studies was evaluated,and meta-analyses were performed with Cochrane Collaboration's RevMan 5.3 software.Results 1) A total of 8 studies involving 1107 patients were included.the results of meta-analyses showed:Compared with placebo,tranexamic acid was effective in reducing postoperative blood loss [SMD =-1.95,95％ CI (-3.21,-0.69)],P＜0.05],there were statistical heterogeneity between the studies (I2=94％,P＜0.05),2)Tranexamic acid was effective in reducing postoperative transfusion rates of RBC during the operation [SMD=-0.43,95％ CI (-0.74,-0.11)],P＜0.05];however,less effective than the placebo in terms of reducing postoperative FFP and PLT transfusion.Compared with placebo and other antifibrinolitic drugs the bleeding,renal insufficiency,thrombosis,infection,death and the incidence of other adverse events were not increased in tranexamic acid group after surgery.Conclusion Tranexamic acid was a safe and effective antifibrinolitic drug in liver transplantation,for it can reduce the amount of bleeding and red blood cell transfusion,However,due to the limited quality of the included studies,further verification with more high quality trials was needed.
