Modulation of miR-10a-mediated TGF-ß1/Smads signaling affects atrial fibrillation-induced cardiac fibrosis and cardiac fibroblast proliferation.

Atrial fibrillation (AF) rat models and rat cardiac fibroblasts (CFs) with overexpressed or inhibited miR-10a were used to investigate the possible role of miR-10a-mediated transforming growth factor-ß (TGF-ß1)/Smads signaling in cardiac fibrosis and fibroblast proliferation in rats with AF. Gene ontology and pathway enrichment analyses were used to identify the possible function of miR-10a in cardiac fibrosis. The results showed that overexpressed miR-10a significantly prolonged the duration of AF, further elevated the collagen volume fraction (CVF), and increased the viability of CFs in AF rats; these findings were in contrast with the findings for rats with inhibition of miR-10a (all P<0.05). Moreover, miR-10a overexpression could promote miR-10a, collagen-I, collagen III, α-SMA, and TGF-ß1 protein expression and increase the levels of hydroxyproline but reduced Smad7 protein expression in atrial tissues and CFs in AF rats. Not surprisingly, inhibiting miR-10a led to completely contrasting results (all P<0.05). Moreover, TGF-ß1 treatment could reverse the inhibitory effect of miR-10a down-regulation on cardiac fibrosis in CFs. Bioinformatics analysis and luciferase reporter assay results demonstrated that miR-10a bound directly to the 3'-UTR of BCL6, which is involved in cell growth and proliferation. Thus, our study indicate that down-regulation of miR-10a may inhibit collagen formation, reduce atrial structure remodeling, and decrease proliferation of CFs, eventually suppressing cardiac fibrosis in AF rats via inhibition of the TGF-ß1/Smads signaling pathway.

[Relationship between radial growth of Abies georgei and climate factors at different altitudes on the eastern slope of Yulong Snow Mountain, China.] / çŽ‰é¾™é›ªå±±ä¸œå¡ä¸åŒæµ·æ‹”é•¿è‹žå†·æ‰å¾„å‘ç”Ÿé•¿ä¸Žæ°”å€™å› å­çš„å ³ç³».

Based on dendrochronological methods, we established residual chronologies (RES) of Abies georgei at low, middle and high altitudes with ring width data on the eastern slope of Yulong Snow Mountain. We examined the relationship between the radial growth and climate factors (temperature and precipitation) by response function analysis and redundancy analysis (RDA) to identify the key climatic factors driving the radial growth of A. georgei. The results showed that the responses of radial growth of A. georgei to climates were consistent at three altitudes, which was jointly controlled by temperature and precipitation. This consistency was related to the steep terrain of Yulong Snow Mountain, the high-altitude distribution, and shallow root characteristics of A. georgei. At all three altitudes, tree growth showed significantly positive correlation with mean temperature of the current July, mean temperature of the previous November, and precipitation of the current January, but negative correlation with precipitation of the current June. The comprehensive application of response function analysis and redundancy analysis could accurately reveal the relationship between tree growth and climatic factors along environmental gradients. Our results provided a scientific basis for climatic reconstruction and forest management in the area.

[Comparison of the exposure rates of risk factors and inducing factors of acute myocardial infarction between younger and aged adults].

OBJECTIVE: To study the clinical characteristics of acute myocardial infarction (AMI) among younger adults and to explore the possible mechanisms of early myocardial infarction, combined with the newly discovered risk factors of coronary heart disease. METHODS: Data on comparative analysis to the exposure rates of the risk factors and inducing factors of non-CAD patients with two groups of AMI patients including younger adults group (< or =40 years old) and aged adults group (> or =50 years old). Coronary angiography was applied. RESULTS: There were differences noticed between the frequencies of risk factors of the two AMI groups. In younger adults group the exposure rates of smoking, hyperlipidemia, positive family history, C-reactive protein (CRP) and fibrinogen were markedly higher, while in elderly group the exposure rates of hypertension, smoking, hyperlipidemia, diabetes, CRP, fibrinogen and homocysteine (HCY) were markedly higher (P < 0.05). Although the clustering status of risk factors of the younger adult group was not higher than that of the elderly group. There were obvious inducing factors before the patients were attacked by AMI and the inducing factors inclined to cluster, which had obvious dose-reaction relationships with the occurrence of AMI in young people. CONCLUSION: Early AMI of younger adults might relate to the clustering status of inducing factors. The coexistence of several kinds of inducing factors was resulted in the occurrence of AMI of the atherosclerosis (As) and non-As patients by means of myocardial ischemia accumulation effect.

[Studies of the possible mechanisms for protective effects of recombinant human growth hormone on intestinal mucosa barrier in rat sepsis].

OBJECTIVE: To investigate the protective effects of recombinant human growth hormone (rhGH) on intestinal mucosal barrier in rat sepsis and explore its possible mechanisms. METHODS: E. coli was injected intraperitoneally to produce rats sepsis models. Forty-two female SD rats were randomly divided into the control group (group C), sepsis group (group S) and treatment group (group T). Group S and group T were further divided into 1 d and 3 d subgroups (T1d,T3d, Sld, S3d), respectively. The expression of IGF-1 mRNA in liver, expression of Bcl-2 protein in intestine, bacteria translocation, the levels of growth hormone(GH) and insulin-like growth factor-1 (IGF-1) in plasma, and the histological appearance of intestine were determined dynamically by means of RT-PCR, radioimmunoassay, immunohistochemical staining and other corresponding methods, respectively. RESULTS: (1) rhGH could significantly attenuate intestinal mucosal injuries and ameliorate bacteria translocation on sepsis rats. (2) The levels of Bcl-2 protein expression in intestine in group T (T1d:2441 +/- 117; T3d: 3628 +/- 235) were obviously higher than those of group S (S1d: 321 +/- 36; S3d: 1873 +/- 57) (P < 0.01). (3) The plasma levels of GH in group T (T1d: 1.28 +/- 0.24 microg/L; T3d: 2.14 +/- 0.48 microg/L) increased markedly than those of group S (S1d: 0.74 -/+ 0.12 microg/L; S3d: 0.60 +/- 0.18 microg/L) (P < 0.01). (4) The plasma levels of IGF-1 in group T (Tld: 168.94 +/- 65.67 microg/L; T3d: 201.56 +/- 64.98 microg/L) elevated significantly than those of group S (Sld: 116.72 +/- 13.96 microg/L; S3d:107.50 +/- 23.53 microg/L) (P < 0.05). (5) The levels of liver IGF-1 mRNA in group T (Tld: 0.98 +/- 0.20; T3d: 1.76 +/- 0.17) were significantly higher than those in group S (S1d: 0.38 +/- 0.09; S3d: 0.46 +/- 0.10) (P < 0.01). CONCLUSION: rhGH conferred protective efficacy in maintaining the integrity of intestinal mucosal barrier against sepsis in rat. The possible mechanisms might involve the rhGH-diminished apoptosis of intestinal mucosa cells and the rhGH-maintained intestinal mucosa barrier via the roles of GH and IGF-1.