Abstract Background Ischemia-reperfusion (IR) induces increased release of extracellular vesicles in the heart and exacerbates myocardial IR injury. We have previously shown that propofol attenuates hypoxia/reoxygenation (HR)-induced injury in human umbilical vein endothelial cells (HUVECs) and that microvesicles derived from propofol-treated HUVECs inhibit oxidative stress in endothelial cells. However, the role of microvesicles derived from propofol post-treated HUVECs ((HR + P)-EMVs) in IR-injured cardiomyocytes is unclear. In this study, we aimed to investigate the role of (HR + P)-EMVs in cardiac IR injury compared to microvesicles derived from hypoxic/reoxygenated HUVECs (HR-EMVs) and to elucidate the underlying mechanisms. Methods Hypoxia/reoxygenation (HR) models of HUVECs and AC16 cells and a mouse cardiac IR model were established. Microvesicles from HR-injured HUVECs, DMSO post-treated HUVECs and propofol post-treated HUVECs were extracted by ultra-high speed centrifugation, respectively. The above EMVs were co-cultured with HR-injured AC16 cells or injected intracardially into IR mice. Flow cytometry and immunofluorescence were used to determine the levels of oxidative stress and apoptosis in cardiomyocytes. Apoptosis related proteins were detected by Western blot. Echocardiography for cardiac function and Evans blue-TTC staining for myocardial infarct size. Expression of lncCCT4-2 in EMVs and AC16 cells was analysed by whole transcriptome sequencing of EMVs and RT-qPCR. The molecular mechanism of inhibition of myocardial injury by (HR + P)-EMVs was elucidated by lentiviral knockdown of lncCCT4-2, plasmid overexpression or knockdown of CCT4, and actinomycin D assay. Results In vitro and in vivo experiments confirmed that HR-EMVs exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes, leading to increased infarct size and worsened cardiac function. Notably, (HR + P)-EMVs induced significantly less oxidative stress and apoptosis in IR-injured cardiomyocytes compared to HR-EMVs. Mechanistically, RNA sequencing of EMVs and RT-qPCR showed that lncCCT4-2 was significantly upregulated in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs. Reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. Furthermore, the anti-apoptotic activity of lncCCT4-2 from (HR + P)-EMVs was achieved by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in cardiomyocytes. Conclusions Our study showed that (HR + P)-EMVs uptake by IR-injured cardiomyocytes upregulated lncCCT4-2 in cardiomyocytes and promoted CCT4 expression, thereby inhibiting HR-EMVs induced oxidative stress and apoptosis. Highlights Microvesicles from hypoxic/reoxygenated HUVECs (HR-EMVs) exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes. Microvesicles from propofol post-treated HUVECs ((HR + P)-EMVs) induced diminished oxidative stress and apoptosis in IR-injured cardiomyocytes compared with microvesicles from hypoxic/reoxygenated HUVECs (HR-EMVs). lncCCT4-2 was significantly highly expressed in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs, and reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. lncCCT4-2 inhibited HR-EMVs induced oxidative stress and apoptosis in HR-injured AC16 cells by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in AC16 cells.

RESUMO Introdução: A dificuldade em adormecer está ligada ao mau funcionamento do mecanismo do ciclo sono-vigília no corpo humano e é causada por diversos motivos. Existe uma serie de reações adversas que resultam da má qualidade – ou qualidade anormal - do sono, especificamente durante o sono. Esses sintomas afetam seriamente a condição física e a saúde mental das pessoas. Objetivo: Explorar o efeito de exercícios físicos em pacientes com dificuldade em adormecer. Métodos: Estatísticas matemáticas foram usadas para analisar 60 pacientes com dificuldade em adormecer. Dividimos os pacientes em um grupo de esportes e outro de controle. Os pacientes no grupo de esportes tiveram treinamento esportivo, enquanto o grupo de controle não. Após duas semanas de intervenção e comparação, usamos estatísticas matemáticas para avaliar a função cognitiva dos grupos. Resultados: Após o exercício físico, houve melhora na qualidade de sono dos pacientes e os transtornos do sono diminuíram. Conclusão: A atividade física é uma forma simples e popular de se exercitar. É eficaz na melhora da função cognitiva de pacientes com dificuldade de adormecer. Nível de evidência II; Estudos terapêuticos – investigação de resultados de tratamento.

ABSTRACT Introduction: Difficulty falling asleep is connected to the malfunctioning of the sleep and wakefulness mechanism of the human body caused by various reasons. There are a series of adverse reactions resulting from abnormal or poor quality of sleep during sleep per se. This symptom severely affects an individual's physical condition and mental health. Objective: To explore the effect of physical exercise on patients with difficulty falling asleep. Methods: Mathematical statistics were used to analyze 60 patients with difficulty falling asleep. We divided the patients into a sports group and a control group. The patients in the sports group took sports training, while the control group did not. After two weeks of intervention and comparison, we used mathematical statistics to evaluate the groups’ cognitive function. Results: After physical exercise, the patient's sleep quality was higher and sleep disorders were reduced. Conclusion: Physical activity is a simple and popular way of exercising. It is effective in improving the cognitive function of patients with difficulty falling asleep. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMEN Introducción: La dificultad en dormirse se relaciona al mal funcionamiento del mecanismo del ciclo sueño-vigilia en el cuerpo humano y es causada por diversos motivos. Existe una serie de reacciones adversas que resultan de la mala calidad o calidad anormal del sueño, durante el sueño en sí. Esos síntomas afectan seriamente la condición física y la salud mental de las personas. Objetivo: Explorar el efecto de ejercicios físicos en pacientes con dificultad en dormirse. Métodos: Dividimos los pacientes en un grupo de deportes y otro de control. Los pacientes en el grupo de deportes tuvieron entrenamiento deportivo, mientras el grupo de control no. Tras dos semanas de intervención y comparación, usamos estadísticas matemáticas para evaluar la función cognitiva de los grupos. Resultados: Tras el ejercicio físico, hubo mejoría en la calidad del sueño de los pacientes y los trastornos del sueño disminuyeron. Conclusión: La actividad física es una forma simple y popular de ejercitarse. Es eficaz en la mejoría de la función cognitiva de pacientes con dificultad de dormirse. Nivel de evidencia II; Estudios terapéuticos – investigación de resultados de tratamiento.

ABSTRACT Objectives: To compare the sealing ability and biocompatibility of Biodentine with mineral trioxide aggregate (MTA) when used as root-end filling materials. Methodology: The Cell Counting Kit-8 (CCK-8) assay was used to compare the cytotoxicity of MTA and Biodentine. Twenty-one extracted teeth with a single canal were immersed in an acidic silver nitrate solution after root-end filling. Then, the volume and depth of silver nitrate that infiltrated the apical portion of the teeth were analyzed using micro-computed tomography (micro-CT). Seventy-two roots from 3 female beagle dogs were randomly distributed into 3 groups and apical surgery was performed. After six months, the volume of the bone defect surrounding these roots was analyzed using micro-CT. Results: Based on the results of the CCK-8 assay, MTA and Biodentine did not show statistically significant differences in cytotoxicity (P>0.05). The volume and the depth of the infiltrated nitrate solution were greater in the MTA group than in the Biodentine group (P<0.05). The volume of the bone defect was larger in the MTA group than in the Biodentine group. However, the difference was not significant (P>0.05). The volumes of the bone defects in the MTA and Biodentine groups were smaller than the group without any filling materials (P<0.05). Conclusions: MTA and Biodentine exhibited comparable cellular biocompatibility. Biodentine showed a superior sealing ability to MTA in root-end filling. Both Biodentine and MTA promoted periradicular bone healing in beagle dog periradicular surgery models.