Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Excess activation of cardiac fibroblasts inevitably induces cardiac fibrosis. Emodin has been used as a natural medicine against several chronic diseases. The objective of this study is to determine the effects of emodin on cardiac fibrosis and the underlying molecular mechanisms. Intragastric administration of emodin markedly decreased left ventricular wall thickness in a mouse model of pathological cardiac hypertrophy with excess fibrosis induced by transaortic constriction (TAC) and suppressed activation of cardiac fibroblasts induced by angiotensin II (AngII). Emodin upregulated expression of metastasis associated protein 3 (MTA3) and restored the MTA3 expression in the setting of cardiac fibrosis. Moreover, overexpression of MTA3 promoted cardiac fibrosis; in contrast, silence of MTA3 abrogated the inhibitory effect of emodin on fibroblast activation. Our findings unraveled the potential of emodin to alleviate cardiac fibrosis upregulating MTA3 and highlight the regulatory role of MTA3 in the development of cardiac fibrosis.

Objective To observe the temporomandibular joint spaces changes after the plastic surgery of combined zygoma with mandibular angel.Methods We randomly selected 59 patients with prominent zygoma and mandibular angle,screening periodontal disease,TMJ pain and partial jaw.Bilateral zygomatic arch coarctation,jaw edge of the mandibular angle ostectomy and the mandibular body outer panel split were used.All patients accepted CT scan and three-dimensional reconstruction before operation,10 days after operation and 6 months after operation,and then image analysis softwares were used to measure the line distance of corresponding angle (0°,60°,120°,and 180°)at the TMJ sagittal plane.The 0° (EE 'pitch) and 60° (AA'pitch) represented for pre-space,the 60° and 120° (PP'pitch) was upper-space,the 120° and 180° (SS'pitch) was posterior-space.Results 0° and 60° had the same change trend,which slightly increased at 10 days after operation.The difference before operation and 10 days,6 months after operation were not statistically significant (P ＞ 0.05);120° and 180° had the same change trend,which increased at 10 days after operation.The difference between before operation and 10 days after operation was statistically significant (P ＜ 0.05),but the difference between before operation and 6 months after operation was not statistically significant (P＞ 0.05).Conclusions In the short term after plastic surgery of zygoma combined with mandibular angel,the TMJ upper and posterior spaces are changed,and the interspace reduced.This may indicate that the TMJ has compensatory ability,and short-term changes can return to normal.

Objective To detect the change of exoression level of plasma microRNA‐21(miR‐21) and TGF‐β1 in cardiac remode‐lin affer acute myocardial infarction(AMI) of the pateins .Methods 200 pateints with AMI and 100 normal controls(age ,sex matched) were enrolled .Blood samples were obtained from the normal controls and patients with AMI on the 3 days ,7 days and 14 days .Real‐time PCR was developed to detect the expression of miR‐21 and TGF‐β1 in plasma .Results The expression of miR‐21 was significantly up‐regulation in the 3 days ,7 days and 14 days in MI group than that cntrol group ,0 .74 ± 0 .21 vs .2 .62 ± 0 .23 , vs .3 .67 ± 0 .25 ,vs .4 .13 ± 0 .27 up‐regulation in the 3 days ,7 days and 14 days in MI group than that cntrol group ,0 .98 ± 0 .18 vs .2 .35 ± 0 .24 ,vs .3 .67 ± 0 .25 ,vs .4 .13 ± 0 .27 ,P<0 .05 ,respectively .The expression of miR‐21 and TGF‐β1 were up‐regulation with the change of cardiac function .Positive relationship between miRNA‐21 expression and LVDd (r=0 .757 ,P<0 .05);Positive relationship between TGF‐β1 mRNA expression and LVDd(r=0 .701 ,P<0 .05) .Conclusion The expression of miR‐21 and TGF‐β1 were up‐regulation in cardiac remodelin affer AMI of the pateins ,which involved in regulation in cardiac remodelin affer AMI .