ABSTRACT
OBJECTIVE@#To explore the role of small nuclear noncoding RNA 7SK in embryonic stem cell (ESCs) proliferation and the value of 7SK as a target for early diagnosis and treatment for primordial dwarfism (PD).@*METHODS@#ESC line R1 was transfected with the CRISPR/Cas9 system, and sequencing of the PCR product and glycerol gradient analysis were performed to identify novel 7SK deletion mutations. A lentivirus system was used to knock down cyclin-dependent kinase 9 (CDK9) in clones with 7SK deletion mutations, and the effect of CDK9 knockdown on the protein level of cell division cycle 6 (CDC6) was analyzed with Western blotting.@*RESULTS@#We identified a novel deletion mutation of 7SK at 128-179 nt in the ESCs, which resulted in deficiency of cell proliferation. 7SK truncation at 128-179 nt significantly reduced the protein expressions of La-related protein 7 (LARP7) and CDC6.@*CONCLUSIONS@#7SK truncation at 128-179 nt can significantly impair proliferation of ESCs by downregulating CDC6. 7SK is a key regulator of proliferation and mediates the growth of ESCs through a mechanism dependent on CDK9 activity, suggesting the value of 7SK truncation at 128-179 nt as a potential target for early diagnosis and treatment of PD.
Subject(s)
Humans , Cell Cycle Proteins , Cell Proliferation , Embryonic Stem Cells/metabolism , HeLa Cells , Nuclear Proteins , Positive Transcriptional Elongation Factor B/metabolism , RNA, Long Noncoding/genetics , RNA-Binding Proteins , Ribonucleoproteins , Transcription FactorsABSTRACT
Heart failure is a complex clinical syndrome,and impaired filling or ejection disorders result from any ventricular structure or dysfunction can cause heart failure.The prevalence of heart failure in adult populations in developed countries has reached 1% to 2%,while the prevalence in elderly people over 70 years of age has increased to ≥ 10%. With the population aging and the prevalence of coronary heart disease increased, the prevalence of heart failure has increased,becoming a disable and fatal disease.The changes of the central nervous system hormones such as renin-angiotensin system (RAS),inflammatory cytokines (proinflammatory cytokines,PIC),and reactive oxygen species (ROS)may be closely related to increased central activity in heart failure,which can significantly alter the activities of peripheral sympathetic nerves. Constant sympathetic nervous activity is an important cause of development of heart failure,so reducing the sympathetic excitability of heart failure is regarded as one of the focuses of treatment and research.This paper focuses on the influence of central neurohormone on heart failure and possible central mechanism.
ABSTRACT
ABSTRACT:Hypertension,the first risk factor for stroke and coronary heart disease in the Chinese population, seriously endangers people’s health.At present,China has more than 270 million people with hypertension and an annual increase rate of 1 0 million people.Then how to improve prevention and treatment of hypertension has become an urgent need to solve major medical and social problems.In the past,research on hypertension mainly focused on the peripheral area,while recent research has shown that the central regulation plays an important role in the development of hypertension. Hypothalamic paraventricular nucleus (PVN ), which plays a key role in maintaining cardiovascular activity, can directly control the sympathetic preganglionic neurons and regulate peripheral sympathetic nerve activity,thus being closely related to the development of hypertension.Research in recent years shows that the comprehensive effects of proinflammatory cytokines (PIC ),reactive oxygen species (ROS),renin-angiotensin system (RAS),neurotransmitter (NT)and nuclear factorκB (NF-κB)are involved in the pathogenesis of hypertension.However,it is unclear how these neurohormones in PVN are activated,how they interact with each other and what role they play in the regulatory mechanism of hypertension.Therefore,the key focus of this research is to explore the impact of activated neurohormones in PVN on hypertension.This study will provide new content for the study on hypertension.