RESUMO
Exploring the mechanism of self-renewal and pluripotency maintenance of human embryonic stem cells (hESCs) is of great significance in basic research and clinical applications, but it has not been fully elucidated. Long non-coding RNAs (lncRNAs) have been shown to play a key role in the self-renewal and pluripotency maintenance of hESCs. We previously reported that the lncRNA ESRG, which is highly expressed in undifferentiated hESCs, can maintain the self-renewal and pluripotency of hPSCs. RNA pull-down mass spectrometry showed that ESRG could bind to other proteins, among which heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) attracted our attention. In this study, we showed that HNRNPA1 can maintain self-renewal and pluripotency of hESCs. ESRG bound to and stabilized HNRNPA1 protein through the ubiquitin-proteasome pathway. In addition, knockdown of ESRG or HNRNPA1 resulted in alternative splicing of TCF3, which originally and primarily encoded E12, to mainly encode E47 and inhibit CDH1 expression. HNRNPA1 could rescue the biological function changes of hESCs caused by ESRG knockdown or overexpression. Our results suggest that ESRG regulates the alternative splicing of TCF3 to affect CDH1 expression and maintain hESCs self-renewal and pluripotency by binding and stabilizing HNRNPA1 protein. This study lays a good foundation for exploring the new molecular regulatory mechanism by which ESRG maintains hESCs self-renewal and pluripotency.
Assuntos
Processamento Alternativo , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Autorrenovação Celular , Células-Tronco Embrionárias Humanas , Células-Tronco Pluripotentes , Humanos , Processamento Alternativo/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Diferenciação Celular/genética , Autorrenovação Celular/genética , Ribonucleoproteína Nuclear Heterogênea A1/metabolismo , Ribonucleoproteína Nuclear Heterogênea A1/genética , Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Embrionárias Humanas/citologia , Células-Tronco Pluripotentes/metabolismo , Células-Tronco Pluripotentes/citologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
OBJECTIVES: Acute type A aortic dissection frequently induces aortic root disease; however, the optimal surgical strategy for aortic root dissection remains a challenge. The objective of this study was to introduce a novel technique for reconstruction of type A dissection to improve patient prognosis. METHODS: We performed a retrospective review of 791 consecutive patients with acute type A aortic dissection between January 2003 and July 2015. Among these patients, 151 were selected (72% men, age 51.7 ± 9.8 years) to have the modified sandwich repair of aortic root dissection. RESULTS: The in-hospital mortality rate of the 151 patients was 6.6% (10/151). During a mean follow-up period of 52.7 ± 28.6 months, the survival rate was 100, 89.1 and 69.7% at 1, 5 and 10 years, respectively. Echocardiography and computed tomographic angiography were performed every year to monitor the pathological change in the aortic root. Freedom from severe aortic regurgitation at 5 years was 100%. No patients required reintervention due to dissection or pseudoaneurysm of the proximal aortic root. CONCLUSIONS: Aortic valve resuspension and repair of the sinus of Valsalva with the modified sandwich technique using Teflon felt strips for acute type A dissection could be reliable and effective.
Assuntos
Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular/métodos , Procedimentos de Cirurgia Plástica/métodos , Complicações Pós-Operatórias/epidemiologia , Doença Aguda , Adulto , Idoso , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/mortalidade , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/mortalidade , China/epidemiologia , Angiografia por Tomografia Computadorizada , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de TempoRESUMO
BACKGROUND: The optimal surgical strategy for the left subclavian artery (LSA) during total arch replacement combined with stented elephant trunk implantation for acute type A aortic dissection remains a challenge. The objective of the study is to report a novel surgical technique aiming to simplify the revascularization procedure of total aortic arch replacement combined with stented elephant trunk implantation. METHODS: We retrospectively reviewed the result of 167 patients who underwent total aortic arch replacement combined with stented elephant trunk implantation between January 2000 and December 2012. Of the 167 patients, 51 were selected to undergo the simplified revascularization, which is to fenestrate a stent graft of the descending aorta instead of performing reconstruction of the LSA. Before performing the new LSA revascularization, we had performed the elephant trunk procedure whereby the tubular material completely covered the LSA. The ensuing revascularization was modified by removing a patch of the polyester fabric of the elephant trunk that was located at the origin of the LSA. Both perioperative variables and postoperative outcome of the surgery were assessed. RESULTS: The indication for adopting the LSA fenestration was under the circumstance of absence of dissection at the origin of the LSA. The nosocomial mortality of the 51 patients was 7.8% (multiorgan failure 2, renal failure 1, infection 1). During a mean follow-up period of 51.3 ± 27.6 months, the survival rate of the 47 patients was 100%, 90.8%, and 70.2% at 1, 5, and 10 years, respectively. No stroke and left limb ischemia were observed. No patients required reintervention because of anastomotic leak between the LSA and the descending aorta during follow-up. CONCLUSIONS: The LSA fenestration technique during total arch replacement combined with stented elephant trunk implantation for acute type A aortic dissection is reliable and effective for patients who have no dissection at the LSA. Furthermore, because the simplified surgical procedure largely shortens the time of operation, it effectively improves the patient's prognosis.
Assuntos
Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular/métodos , Guias de Prática Clínica como Assunto , Stents , Artéria Subclávia/cirurgia , Doença Aguda , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
The occurrence of aortic regurgitation (AR) attributable to Behçet's disease is rare, but it brings extraordinary complexity to surgical intervention due to the high risk of postoperative morbidity as the result of valve dehiscence or pseudoaneurysms caused by fragile aortic structures and inflamed tissue. The high rate of prosthetic valve detachment after aortic valve replacement is one of the most serious consequences of aortic regurgitation in Behçet's disease, which results in severe aortic annular destruction, presenting a big challenge to cardiac surgeons. Under this condition, a conventional surgical technique is necessary to be modified for improving postoperative prognosis of patients. In this paper, we described the surgical treatment of 5 patients with Behçet's aortitis and report their long-term outcomes.