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.

Objective To compare the diagnostic accuracy of magnifying chromoendoscopy (MCE) and endoscopic ultrasonography (EUS) for preoperative endoscopic assessment of the invasion depth of colorectal laterally spreading tumour(LST).Methods Data of 104 cases of colorectal LST were included.With the final pathological diagnosis as the golden standard,the accuracies of MCE and EUS for preoperative assessment of the invasion depth of colorectal LST were compared.Results The diagnostic accuracies of MCE and EUS for evaluating the invasion depth of LST were 89.4％ (93/104) and 73.1％ (76/104),respectively(P＜0.05).The lesion size and the endoscopist could affect the accuracy of the EUS evaluation (P=0.017,OR=3.561;P=0.035,OR =1.399).The accuracy of EUS seemed to show a downward trend for colorectal LST of larger diameters.Conclusion Both MCE and EUS are effective for evaluating the invasion depth of colorectal LST,but the accuracy of MCE may be higher than that of EUS.Large diameter of the lesion and the doctor's experience inadequacy may be the risk factors for the accuracy of EUS.

Arabidopsis ; chemistry ; genetics ; metabolism ; Arabidopsis Proteins ; chemistry ; genetics ; metabolism ; Crystallography, X-Ray ; Intercellular Signaling Peptides and Proteins ; chemistry ; genetics ; metabolism ; Protein Conformation ; Protein-Serine-Threonine Kinases ; chemistry ; genetics ; metabolism

Autophagy is an evolutionarily conserved cellular process which degrades intracellular contents. The Atg17-Atg31-Atg29 complex plays a key role in autophagy induction by various stimuli. In yeast, autophagy occurs with autophagosome formation at a special site near the vacuole named the pre-autophagosomal structure (PAS). The Atg17-Atg31-Atg29 complex forms a scaffold for PAS organization, and recruits other autophagy-related (Atg) proteins to the PAS. Here, we show that Atg31 is a phosphorylated protein. The phosphorylation sites on Atg31 were identified by mass spectrometry. Analysis of mutants in which the phosphorylated amino acids were replaced by alanine, either individually or in various combinations, identified S174 as the functional phosphorylation site. An S174A mutant showed a similar degree of autophagy impairment as an Atg31 deletion mutant. S174 phosphorylation is required for autophagy induced by various autophagy stimuli such as nitrogen starvation and rapamycin treatment. Mass spectrometry analysis showed that S174 is phosphorylated constitutively, and expression of a phosphorylation-mimic mutant (S174D) in the Atg31 deletion strain restores autophagy. In the S174A mutant, Atg9-positive vesicles accumulate at the PAS. Thus, S174 phosphorylation is required for formation of autophagosomes, possibly by facilitating the recycling of Atg9 from the PAS. Our data demonstrate the role of phosphorylation of Atg31 in autophagy.
Alanine ; chemistry ; metabolism ; Amino Acid Motifs ; Aspartic Acid ; chemistry ; metabolism ; Autophagy ; genetics ; Autophagy-Related Proteins ; Carrier Proteins ; chemistry ; metabolism ; Gene Expression Regulation, Fungal ; Membrane Proteins ; chemistry ; metabolism ; Models, Molecular ; Molecular Sequence Data ; Nitrogen ; deficiency ; Phagosomes ; chemistry ; drug effects ; metabolism ; Phosphorylation ; Protein Transport ; Saccharomyces cerevisiae ; drug effects ; genetics ; metabolism ; Saccharomyces cerevisiae Proteins ; chemistry ; genetics ; metabolism ; Serine ; chemistry ; metabolism ; Signal Transduction ; Sirolimus ; pharmacology

OBJECTIVETo study the surgical treatment for distal humeral fractures in adults according to the follow-up results.

METHODSTwenty-one cases (16 males and 5 females) of distal humeral fracture were included in this study. The average age was 42.5 years (range: 37-52 years). Fractures were classified according to the AO classification system. Nine cases of C1, 8 C2 and 4 C3-type fractures were identified. Open reduction and internal fixation were performed in all cases. A tricep-reflecting approach was adopted, and either the AO orthogonal plating or parallel plating technique was chosen, based on the fracture type. The plaster cast was removed 3 weeks after operation. Rehabilitation was encouraged during this period and afterwards. The average follow-up time was 12.2 months (range: 8-28 months). The outcome was scored according to Aitken and Rorabeek system.

RESULTSNo nerve injury, nonunion or failure of fixation was encountered during the operation and follow-up. However, ossifying myositis occurred in one case.

CONCLUSIONSA triceps-reflecting approach can provide adequate exposure to the joint. The use of AO orthogonal plating or parallel plating techniques based on the type of fractures can provide rigid fixation for the fracture.

Adult ; Female ; Follow-Up Studies ; Fracture Fixation, Internal ; adverse effects ; methods ; Humans ; Humeral Fractures ; surgery ; Male ; Middle Aged

OBJECTIVETo explore the treatment methods and outcome of posterior wall fractures of the acetabulum.

METHODSThe data of 31 patients (25 males and 6 females, aged 19-59 years, mean: 40.5 years) with posterior wall fractures of the acetabulum hospitalized in our department from 2002 to 2006 were analyzed retrospectively in this study. The types of fractures, number of fragments, combined dislocations, and sciatic nerve function were documented before admission. All the fractures were treated with open reduction and internal fixation. Based on the fracture type and site, either screws alone or reconstructive plates were used. The patients were immobilized for an average of 12 weeks before partial weight bearing was permitted. After follow-up for 12-70 months (43.6 months on average), modified Merle d'Aubigne score was adopted to evaluate the outcomes of the operations.

RESULTSThe percentages of the excellent, good, fair and poor results were 48.4%, 41.9%, 6.5%, and 3.3%, respectively, with a good to excellent rate of 90.2%. Idiopathic sciatic nerve injury occurred in only one case.

CONCLUSIONSThe sciatic nerve should be routinely exposed and protected during the surgery. The type of fixation should be based on the fracture type and site. Prolonged immobilization may be helpful in improving the final outcomes.

Acetabulum ; diagnostic imaging ; injuries ; Adult ; Bone Plates ; Bone Screws ; Female ; Fracture Fixation, Internal ; Fractures, Bone ; diagnostic imaging ; surgery ; Humans ; Immobilization ; Male ; Middle Aged ; Radiography ; Retrospective Studies ; Young Adult