Enhanced external counterpulsation improves sleep quality in chronic insomnia: A pilot randomized controlled study.

PURPOSE: To investigate the short-term efficacy of enhanced external counterpulsation (EECP) on chronic insomnia. METHODS: This is a pilot randomized, participant-blind, and sham-controlled study. Forty-six participants with chronic insomnia were randomly assigned in a 1:1 ratio to receive EECP or sham EECP intervention (total of 35 sessions with 45 min each). The primary outcome was Pittsburgh Sleep Quality Index (PSQI). The secondary outcomes included sleep diary, Hospital Anxiety and Depression Scale (HADS), Short-Form Health Survey (SF12), flow mediated dilation (FMD), serum biomarkers of melatonin, cortisol, interleukin-6, and high sensitivity C-reactive protein. Outcomes were assessed after treatment and at 3-month follow-up. RESULTS: The PSQI was significantly decreased in both EECP and sham groups after 35-session intervention (13.74 to 6.96 in EECP and 13.04 to 9.48 in sham), and EECP decreased PSQI more than sham EECP (p = 0.009). PSQI in two groups kept improved at 3-month follow-up. After treatment, the total sleep time, sleep efficiency, FMD value and SF12 mental component of EECP group were significantly improved, and group differences were found for these outcomes. At follow-up, total sleep time, sleep efficiency and SF12 mental component of EECP group remained improved, and group difference for SF12 mental component was found. Post-treatment and follow-up HADS-A significantly decreased in both groups, with no differences between groups. Post-treatment serum biomarkers showed no differences within and between groups. LIMITATION: Lack of objective sleep measurement. CONCLUSION: EECP could improve sleep quality and mental quality of life in chronic insomnia and the therapeutic effect maintained for 3 months.

Mast cell-derived exosomal miR-181a-5p modulated trophoblast cell viability, migration, and invasion via YY1/MMP-9 axis.

BACKGROUND: Mast cells regulate the process of preeclampsia (PE). Since we previously identified mast cells specifically expressing miR-181a-5p in the placenta of PE patients, it is plausible to examine the effect and mechanism of mast cell-derived exosomal miR-181a-5p on trophoblast cells. METHODS: The miR-181a-5p and YY1 levels were determined by quantitative real-time reverse transcription-polymerase chain reaction. Exosomes were identified by transmission electron microscopy, Western blot, and PKH-26 labeling. Mast cells or trophoblast cell malignant phenotype were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, wound healing, and Transwell assays. Quantification of YY1 and metastasis-related proteins was performed using Western blot. TargetScan, JASPAR, dual-luciferase reporter genes, and chromatin immunoprecipitation were exploited to verify the relationship between miR-181a-5p, YY1, and MMP-9. RESULTS: MiR-181a-5p was overexpressed in mast cells of PE patients. Overexpressed miR-181a-5p restrained mast cell viability. Mast cell exosomes were successfully isolated, containing high expressions of CD63 and HSP70 and low expression of Calnexin and could be transported to the cytoplasm of trophoblast cells. Mast cell exosomes attenuated the viability, migration, and invasion of HTR-8/SVneo cells, inhibited YY1, N-cadherin, Vimentin, and MMP-9 protein expressions, and promoted E-cadherin protein expression. The effect of exosomes was enhanced by miR-181a-5p mimic but was reversed by miR-181a-5p inhibitor. MiR-181a-5p targeted YY1 which bound to the MMP-9 promoter. Overexpressed YY1 in HTR-8/SVneo cells accelerated the malignant phenotype of the cells and reversed the regulatory effects of exosomal miR-181a-5p. CONCLUSION: Mast cell-derived exosomal miR-181a-5p modulates HTR-8/SVneo cell viability, migration, and invasion via YY1/MMP-9.

Effects of Enhanced External Counterpulsation With Different Sequential Levels on Lower Extremity Hemodynamics.

Objective: This study aimed to investigate acute hemodynamics of lower extremities during enhanced external counterpulsation with a three-level sequence at the hips, thighs, and calves (EECP-3), two-level sequence at the hips and thighs (EECP-2), and single leg three-level sequence (EECP-1). Methods: Twenty healthy volunteers were recruited in this study to receive a 45-min EECP intervention. Blood flow spectrums in the anterior tibial artery, posterior tibial artery, and dorsalis pedis artery were imaged by Color Doppler ultrasound. Mean flow rate (FR), area, pulsatility index (PI), peak systolic velocity (PSV), end-diastolic velocity (EDV), mean flow velocity (MV), and systolic maximum acceleration (CCAs) were sequentially measured and calculated at baseline during EECP-3, EECP-1, and EECP-2. Results: During EECP-3, PI, PSV, and MV in the anterior tibial artery were significantly higher, while EDV was markedly lower during EECP-1, EECP-2, and baseline (all P < 0.05). Additionally, ACCs were significantly elevated during EECP-3 compared with baseline. Moreover, FR in the anterior tibial artery was significantly increased during EECP-3 compared with baseline (P = 0.048). During EECP-2, PI and MV in the dorsalis pedis artery were significantly higher and lower than those at baseline, (both P < 0.05). In addition, FR was markedly reduced during EECP-2 compared with baseline (P = 0.028). During EECP-1, the area was significantly lower, while EDV was markedly higher in the posterior tibial artery than during EECP-1, EECP-2, and baseline (all P < 0.05). Meanwhile, FR of the posterior tibial artery was significantly reduced compared with baseline (P = 0.014). Conclusion: Enhanced external counterpulsation with three-level sequence (EECP-3), EECP-2, and EECP-1 induced different hemodynamic responses in the anterior tibial artery, dorsalis pedis artery, and posterior tibial artery, respectively. EECP-3 acutely improved the blood flow, blood flow velocity, and ACCs of the anterior tibial artery. In addition, EECP-1 and EECP-2 significantly increased the blood flow velocity and peripheral resistance of the inferior knee artery, whereas they markedly reduced blood flow in the posterior tibial artery.

Islet-1 overexpression in human mesenchymal stem cells promotes vascularization through monocyte chemoattractant protein-3.

The LIM-homeobox transcription factor islet-1 (ISL1) has been proposed to mark a cardiovascular progenitor cell lineage that gives rise to cardiomyocytes, endothelial cells, and smooth muscle cells. The aim of this study was to investigate whether forced expression of ISL1 in human mesenchymal stem cells (hMSCs) influenced the differentiation capacity and angiogenic properties of hMSCs. The lentiviral vector, EF1α-ISL1, was constructed using the Multisite Gateway System and used to transduce hMSCs. We found that ISL1 overexpression did not alter the proliferation, migration, or survival of hMSCs or affect their ability to differentiate into osteoblasts, adipocytes, cardiomyocytes, or endotheliocytes. However, ISL1-hMSCs differentiated into smooth muscle cells more efficiently than control hMSCs. Furthermore, conditioned medium from ISL1-hMSCs greatly enhanced the survival, migration, and tube-formation ability of human umbilical vein endothelial cells (HUVECs) in vitro. In vivo angiogenesis assays also showed much more vascular-like structures in the group cotransplanted with ISL1-hMSCs and HUVECs than in the group cotransplanted with control hMSCs and HUVECs. Quantitative RT-PCR and antibody arrays detected monocyte chemoattractant protein-3 (MCP3) at a higher level in conditioned medium from ISL1-hMSCs cultures than in conditioned medium from control hMSCs. Neutralization assays showed that addition of an anti-MCP3 antibody to ISL1-hMSCs-conditioned medium efficiently abolished the angiogenesis-promoting effect of ISL1-hMSCs. Our data suggest that overexpression of ISL1 in hMSCs promotes angiogenesis in vitro and in vivo through increasing secretion of paracrine factors, smooth muscle differentiation ability, and enhancing the survival of HUVECs.

Expression of cofilin 1 is positively correlated with the differentiation of human epithelial ovarian cancer.

The aim of this study was to examine the correlation between cofilin 1 expression and differentiation of epithelial ovarian cancer in patients. We immunohistochemically analyzed 30 patients with primary ovarian epithelial carcinomas, 14 patients with borderline epithelial ovarian tumors, 13 patients with benign epithelial ovarian tumors and 10 normal ovarian tissues. All ovarian cancer patients received the standard therapy, including staging laparotomy and adjuvant chemotherapy consisting of carboplatin and paclitaxel. Cofilin 1 expression gradually increased in normal ovarian tissues, benign tumors, borderline tumors and carcinomas, respectively, and there were significant differences among them (r= 0.94, P<0.05). This suggests a positive correlation between the expression of cofilin 1 and tumor differentiation (r= 0.97, P<0.05). The expression of cofilin 1 may predict the development of ovarian cancer and may be involved in the progression of patients with ovarian carcinoma.