Circ_0006873 suppresses the osteogenic differentiation of human-derived mesenchymal stem cells through mediating miR-20a/SMURF2 axis in vitro.

The clinical application of human-derived mesenchymal stem cells (hMSCs) in osteoporosis (OP) treatment is promising. We aimed to uncover the role of circular RNA 0006873 (circ_0006873) in OP progression using hMSCs. The levels of circ_0006873, pantothenate kinase 2 (PANK2) messenger RNA (mRNA), microRNA-20a (miR-20a), SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) mRNA and the mRNA levels of osteogenesis-related markers were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of osteogenesis-related markers and SMURF2 was detected by Western blot assay. Alkaline phosphatase (ALP) staining and activity were determined using an ALP staining Kit and an ALP Colorimetric Assay Kit. Circ_0006873 was highly expressed in the serum samples and bone tissue samples of OP patients compared with control cases. Circ_0006873 overexpression down-regulated the expression of osteogenesis-related markers and reduced ALP staining and activity. Circ_0006873 down-regulated miR-20a level through its interaction with miR-20a in hMSCs. Circ_0006873 suppressed osteogenic differentiation through targeting miR-20a. SMURF2 was a molecular target of miR-20a, and miR-20a promoted osteogenic differentiation through targeting SMURF2. Circ_0006873 suppressed the osteogenic differentiation of hMSCs by upregulating SMURF2 level via sponging miR-20a in vitro.

[Changes of the characteristics of sleep apnea in heart failure patients and the associated factors].

OBJECTIVE: To investigate the changes of the characteristics of sleep apnea in heart failure patients with periodic breathing disorder and to explore the influencing factors. METHODS: According to the characteristics of sleep apnea after polysomnography (PSG) for 2 nights, 54 patients with heart failure were divided into 3 groups: obstructive sleep apnea (OSA), central sleep apnea (CSA) and OSA-CSA switching groups, with 18 patients each. t test was used for comparison between the first and the second PSG data, left ventricular ejection fraction (LVEF), periodic breathing cycle length (PBCL) and lung to finger circulation time (LFCT) in the same patient. Analysis of variance was performed for comparison within groups and Pearson correlation test was used for correlation analysis between 2 variables. RESULTS: When the events of sleep apnea changed from OSA to CSA, the mean wake and sleep stage II (S2) PtcCO(2) decreased significantly [(41.0 +/- 1.3) cm H(2)O vs (34.9 +/- 1.0) cm H(2)O, 1 cm H(2)O = 0.098 kPa, P < 0.01;(42.1 +/- 1.2) cm H(2)O vs (36.3 +/- 1.1) cm H(2)O, P < 0.01], while PBCL and LCFT increased significantly [(51.9 +/- 2.1) s vs (62.3 +/- 1.9) s, P < 0.01, (54.4 +/- 1.8) s vs (65.3 +/- 1.6) s, P < 0.01]. Furthermore, there was a significant decrease in LVEF [(32.1 +/- 2.5)% vs (19.9 +/- 3.5)%, P < 0.05], and LVEF was negatively correlated with PBCL and LFCT (r = 0.687, P < 0.05;r = -0.591, P < 0.05). When sleep apnea changed from CSA to OSA, the mean wake and S2 PtcCO(2) increased significantly [(39.2 +/- 0.5) cm H(2)O vs (42.7 +/- 1.0) cm H(2)O, P < 0.05], while PBCL and LFCT decreased significantly [(61.5 +/- 3.4) s vs (49.7 +/- 2.8) s, P < 0.05, (66.1 +/- 2.1) s vs (52.1 +/- 1.6) s, P < 0.01)]. In addition, there was a negative correlation between PtcCO(2) and PBCL (r = -0.586, P < 0.05). However, PtcCO(2) showed no significant correlation with LFCT (r = -0.381, P > 0.05). There were no statistical differences between the first and the second mean wake and S2 PtcCO(2), PBCL and LFCT in the OSA and the CSA group, but AHI showed a significant correlation with LVEF in the CSA group (r = -0.474, P < 0.05). CONCLUSIONS: The characteristics of sleep apnea can change when periodic breathing happens in heart failure patients with OSA or CSA. The change can be affected by wake and sleep PtcCO(2), PBCL and LFCT, and possibly by heart function.

Subjective sleepiness in heart failure patients with sleep-related breathing disorder.

BACKGROUND: Previous studies show that sleep-related breathing disorder (SRBD) is common in patients with heart failure (HF) and is associated with increased mortality. This study aimed to determine whether there was significant difference of subjective daytime sleepiness between HF patients with and without SRBD. METHODS: We enrolled, prospectively, 195 consecutive HF patients with left ventricular ejection fractions (LVEF) < or = 45% and all subjects underwent polysomnography to measure the sleep structure between 2005 and 2008. Patients were then assigned to those with SRBD including obstructive and central sleep apnea (apnea-hypopnea index (AHI) > or = 5/hour of sleep) and those without SRBD (AHI < 5/hour) according to the sleep study. The subjective sleepiness was assessed with Epworth sleepiness scale (ESS). RESULTS: Among 195 HF patients, the prevalence of obstructive sleep apnea (OSA) was 53% and of central sleep apnea (CSA) was 27%. There was no significant difference of ESS scores between patients without SRBD (NSA) and with SRBD (NSA vs OSA: 6.7 +/- 0.6 vs 7.6 +/- 0.4, P = 0.105 and NSA vs CSA: 6.7 +/- 0.6 vs 7.4 +/- 0.5, P = 0.235, respectively), indicating that SRBD patients had no more subjective daytime sleepiness. Compared with NSA, patients with SRBD had increased arousal index (ArI) (NSA vs OSA: 14.1 +/- 1.4 vs 26.3 +/- 1.5, P < 0.001 and NSA vs CSA: 14.1 +/- 1.4 vs 31.3 +/- 3.5, P < 0.001, respectively), more awake number after sleep onset (NSA vs OSA: 19.2 +/- 1.5 vs 26.2 +/- 1.4, P = 0.01 and NSA vs CSA: 19.2 +/- 1.5 vs 36.9 +/- 4.4, P < 0.001, respectively), and reduced proportion of slow-wave sleep (SWS) (NSA vs OSA: 13.8 +/- 1.7 vs 9.3 +/- 0.7, P = 0.024 and NSA vs CSA: 13.8 +/- 1.7 vs 8.9 +/- 0.9, P = 0.024, respectively). CONCLUSIONS: OSA and CSA remain common in patients with HF on optimal contemporary therapy. Patients with both HF and SRBD have no significant subjective daytime sleepiness compared with patients without SRBD, despite of significantly increased awake number, arousal and decreased proportion of deep sleep stages. It is not a credible way and means to exclude SRBD in patients with HF according to the absence of subjective daytime sleepiness.