hUC-MSCs secreted exosomes inhibit the glioma cell progression through PTENP1/miR-10a-5p/PTEN pathway.

OBJECTIVE: The mesenchymal stem cells (MSCs) have been widely studied for their anti-tumor property, due to the characteristic of homing towards tumor sites and immunosuppression. Nevertheless, the underlying molecular mechanisms that link MSCs to the targeted tumor cells, such as glioma, are not clear. MATERIALS AND METHODS: Here, we examined the inhibitory properties and new molecular mechanisms of the human umbilical cord (hUC-MSCs) derived exosomes on the human glioma U87 cells using a co-culture system in vitro. The cell counting kit-8 (CCK-8) assay was performed to measure the anti-tumor activity of hUC-MSCs derived exosomes. The cell apoptosis was assessed by flow cytometry and the immunoblotting assay was applied in order to assess the associated proteins level. The data revealed that hUC-MSCs derived exosomes could repress cell proliferation and induce cell apoptosis. RESULTS: Mechanistically, we identified that lncRNA PTENP1 could be packaged into exosome from hUC-MSCs, transferred to U87 cells, and then stabilized PTEN by binding miR-10a-5p competitively. CONCLUSIONS: Therefore, our data suggested that the exosomes from hUC-MSCs possess a higher anti-tumor capacity, at least partially, via regulating miR-10a-5p/PTEN signaling, which thereby may represent a possible target for early diagnosis and treatment of glioma clinically.

Significance of inducible ventricular fibrillation in patients with coronary artery disease and unexplained syncope.

OBJECTIVES: This study was designed to determine the incidence and prognostic significance of inducible ventricular fibrillation (VF) in patients with coronary artery disease (CAD) and unexplained syncope. BACKGROUND: Current American College of Cardiology/American Heart Association practice guidelines recommend implantation of internal cardioverter-defibrillators (ICDs) in patients with unexplained syncope in whom either ventricular tachycardia (VT) or VF is inducible during electrophysiologic (EP) testing. Although the prognostic significance of inducible monomorphic VT is known, the significance of inducible VF remains undefined. METHODS: We evaluated 118 consecutive patients with CAD and unexplained syncope who underwent EP testing. Sustained monomorphic VT was inducible in 53 (45%) patients; in 20 (17%) patients, VF was the only inducible arrhythmia; and no sustained ventricular arrhythmia was inducible in the remaining 45 (38%) patients. The latter two groups of 65 (55%) patients make up the study population. RESULTS: There were 16 deaths among the study population during a follow-up period of 25.3 +/- 19.6 months. The overall one- and two-year survival in these patients was 89% and 81%, respectively. No significant difference in survival was observed between patients with and without inducible VF (80% power to detect a fourfold survival difference). CONCLUSIONS: In 17% of patients with CAD and unexplained syncope, VF is the only inducible ventricular arrhythmia. Within the limits of this pilot study, long-term follow-up of patients with and without inducible VF demonstrates no difference in survival between the two groups. Therefore, the practice of ICD implantation in patients with CAD, unexplained syncope and inducible VF, especially with triple ventricular extrastimuli, may merit reconsideration.

Spontaneous interpolated atrial premature complex detected by 12-lead ambulatory monitoring.

Spontaneous occurrence of an interpolated atrial premature complex, an unusual finding outside of the experimental electrophysiology laboratory, was detected and confirmed by evaluation of P-wave morphology in a patient who underwent 12-lead ambulatory electrocardiography.

Glucocorticoid resistance caused by reduced expression of the glucocorticoid receptor in cells from human vascular lesions.

Mechanisms that control the balance between cell proliferation and death are important in the development of vascular lesions. Rat primary smooth muscle cells were 80% inhibited by low microgram doses of hydrocortisone (HC) and 50% inhibited by nanogram concentrations of transforming growth factor-beta1 (TGF-beta1), although some lines acquired resistance in late passage. However, comparable doses of HC, or TGF-beta1, failed to inhibit most human lesion-derived cell (LDC) lines. In sensitive LDC, HC (10 microg/mL) inhibited proliferation by up to 50%, with obvious apoptosis in some lines, and TGF-beta1 inhibited proliferation by more than 90%. Collagen production, as measured by [3H]proline incorporation or RIA for type III pro-collagen, was either unaffected or increased in the LDCs by HC. These divergent responses between LDC lines were partially explained by the absence of the glucocorticoid receptor (GR) and heat shock protein 90 mRNA in 10 of 12 LDC lines, but the presence of the mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type II. Western blot analysis confirmed the absence of the GR protein in cells lacking GR mRNA. Immunohistochemistry of human carotid lesions showed high levels of GR in the tunica media, but large areas lacking GR in the fibrous lesion. Considering the absence of the GR in most lines, the effects of HC may be elicited through the mineralocorticoid receptor. Functional resistance to the antiproliferative and antifibrotic effects of HC may contribute to excessive wound repair in atherosclerosis and restenosis.