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OBJECTIVES: Long non-coding RNAs (LncRNAs) act as an indispensable role in the Preeclampsia (PE)-related trophoblast function, while its relationship with Small Nucleolar RNA Host Gene 22 (SNHG22) remains unknown. Hence, this study aimed to investigate the roles of lncRNA SNHG22 in the Preeclampsia (PE)-related trophoblasts function and the underlying mechanism. METHOD: Normal placentas and placentas from PE patients were collected to detect the expression of lncRNA SNHG22. Then, trophoblasts HTR-8/Svneo and JEG-3 were purchased, cultured, and treated to investigate the roles of lncRNA SNHG22 on cell migration and invasion as well as its underlying regulatory mechanism. RESULTS: The SNHG22 was downregulated in PE patients, and it was found that SNHG22 overexpression could drive migration and invasion of trophoblasts, while SNHG22 depletion exerted a suppressive effect. Mechanistically, SNHG22 was validated to regulate microRNA-128-3p (miR-128-3p), and Protocadherin 11 X-Linked (PCDH11X) was identified as the target gene of miR-128-3p. Furthermore, it was found that SNHG22 acted as a promoter in the migration and invasion of trophoblast cells in a miR-128-3p/PCDH11X dependent manner, and SNHG22 silencing weakened the activation of PCDH11X-mediated PI3K/Akt signaling pathways through inhibiting miR-128-3p, thereby preventing migration and invasion of trophoblasts. CONCLUSION: SNHG22 acted as a driver in the migration and invasion of trophoblasts and may be considered a candidate for the amelioration of PE.
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MicroARNs , Preeclampsia , ARN Largo no Codificante/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Femenino , Humanos , MicroARNs/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Placenta , Preeclampsia/genética , Embarazo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Protocadherinas/metabolismo , ARN Largo no Codificante/metabolismo , Transducción de Señal/fisiología , TrofoblastosRESUMEN
Abstract Objectives Long non-coding RNAs (LncRNAs) act as an indispensable role in the Preeclampsia (PE)-related trophoblast function, while its relationship with Small Nucleolar RNA Host Gene 22 (SNHG22) remains unknown. Hence, this study aimed to investigate the roles of lncRNA SNHG22 in the Preeclampsia (PE)-related trophoblasts function and the underlying mechanism. Methods Normal placentas and placentas from PE patients were collected to detect the expression of lncRNA SNHG22. Then, trophoblasts HTR-8/Svneo and JEG-3 were purchased, cultured, and treated to investigate the roles of lncRNA SNHG22 on cell migration and invasion as well as its underlying regulatory mechanism. Results The SNHG22 was downregulated in PE patients, and it was found that SNHG22 overexpression could drive migration and invasion of trophoblasts, while SNHG22 depletion exerted a suppressive effect. Mechanistically, SNHG22 was validated to regulate microRNA-128-3p (miR-128-3p), and Protocadherin 11 X-Linked (PCDH11X) was identified as the target gene of miR-128-3p. Furthermore, it was found that SNHG22 acted as a promoter in the migration and invasion of trophoblast cells in a miR-128-3p/PCDH11X dependent manner, and SNHG22 silencing weakened the activation of PCDH11X-mediated PI3K/Akt signaling pathways through inhibiting miR-128-3p, thereby preventing migration and invasion of trophoblasts. Conclusion SNHG22 acted as a driver in the migration and invasion of trophoblasts and may be considered a candidate for the amelioration of PE.
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BACKGROUND: Interventions in patients with a left ventricular assist device (LVAD) in the intensive care unit (ICU) are typically performed based on the results of conventional monitoring, such as vital signs and Swan-Ganz catheter (SGC) and LVAD parameters. These variables might not always accurately reflect a patient's cardiac function, volume status, and interventricular septal configuration, however. To assess the accuracy of standard monitoring, we performed routine continuous hemodynamic transesophageal echocardiography (hTEE) to evaluate cardiac function, volume status, and septal position. METHODS: Between 2011 and 2015, 93 HeartMate II LVADs were implanted. The study group comprised 30 patients with an SGC in place who were monitored routinely by hTEE in the ICU every 1 to 3 hours until extubation. A total of 147 hTEE studies were analyzed retrospectively to observe differences between conventional monitoring and hTEE. RESULTS: Among the 30 patients studied, 26 (87%) had at least 1 disagreement between conventional monitoring and hTEE findings. In 22 patients (73%), at least 1 of the hTEE studies was abnormal whereas conventional parameters were normal. Abnormal hTEE findings included a shift in the interventricular septum in 19 patients (63%), abnormal ventricular volume status in 22 patients (73%), and right ventricular failure in 9 patients (30%). Based on conventional monitoring, none of the patients required an LVAD speed change, whereas hTEE showed that 14 patients (47%) needed an LVAD speed adjustment. CONCLUSIONS: Conventional monitoring in the ICU might not provide an accurate representation of cardiac function, ventricular volume status, or septal position in patients with LVAD. Continuous monitoring with hTEE in patients with an LVAD may help guide optimal intervention in the ICU setting during the early postoperative period.
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Cateterismo de Swan-Ganz , Ecocardiografía Transesofágica , Insuficiencia Cardíaca/terapia , Corazón Auxiliar , Hemodinámica , Monitoreo Ambulatorio/métodos , Función Ventricular Izquierda , Adulto , Anciano , Femenino , Estado de Salud , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Diseño de Prótesis , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Tabique Interventricular/diagnóstico por imagen , Tabique Interventricular/fisiopatología , Adulto JovenRESUMEN
BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA ECMO) has been used for profound cardiogenic shock to bridge to decision, ventricular assist device(s) (VADs), or transplant. To assess ventricular function and volume status along with hemodynamics during ECMO weaning, we developed a standardized weaning protocol, guided by a miniaturized transesophageal echocardiography probe designed for continuous hemodynamic monitoring (hemodynamic transesophageal echocardiography [hTEE]). We reviewed our experience with this weaning protocol with hTEE guidance to assess if we could predict patient outcomes. METHODS: During the academic year of 2011, hTEE-guided ECMO weaning was performed in 21 patients on VA ECMO. Left and right ventricular function and volume status were assessed by continuous hTEE, while attempting to wean ECMO after a standardized protocol. The clinical outcomes, management, and positive predictive value of the device were investigated and analyzed for this cohort of patients. RESULTS: Of the 21 patients, 6 (29%) had left and right ventricular recovery and underwent optimal medical therapy or revascularization for underlying coronary artery disease; 7 (33%) had nonrecoverable left and right ventricular function; and 8 (38%) had right ventricular recovery without improvement of the left ventricular function. These 8 patients underwent left VAD placement; none subsequently developed profound right ventricular failure. The positive predictive value for ventricular recovery by hTEE was 100% using our standardized ECMO weaning protocol (95% confidence interval, 73%-100%). CONCLUSIONS: The hTEE-guided ECMO weaning protocol accurately predicted the ability to wean ECMO to decision. This protocol can be applied by cardiac intensivists as a part of standard bedside intensive care unit assessment.