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.

OBJECTIVES: To investigate the mechanism by which Guijianyu ameliorates podocyte injury in a mouse model of diabetic kidney disease (DKD) induced by advanced glycation endproducts (AGEs). METHODS: Sixty db/db mouse models of DKD were randomized equally into 5 groups for treatment with saline, Guijianyu extract at 3 doses or irbesartan for 12 weeks, and the changes in renal pathology and structure were observed using transmission electron microscopy, and the expressions of related genes and key proteins were detected using RT-qPCR and immunohistochemistry. In cultured MPC-5 cells incubated with 50 mg/L AGEs-BSA for 24 h, the effect of different concentrations of Guijianyu extract on cell viability was examined with CCK-8 assay; Western blotting was performed to detect the protein expressions of RAGE, VEGFA, TNF-α, NF-κB(p65), IL-6 and caspase-3, and the mRNA expressions of RAGE, NF-κB (p65), VEGFA and IL-6 were detected with RT-qPCR. RESULTS: In mouse models of DKD, treatment with high-dose Guijianyu extract significantly reduced renal expressions of RAGE, VEGFA, NF-κB(p65), and IL-6 proteins and the mRNA expressions of RAGE, NF-κB, and IL-6. In MPC-5 cells, exposure to AGEs significantly reduced cell viability and increased the protein expressions of RAGE, NF‑κB (p65), VEGFA, TNF-α, IL-6 and caspase-3 (P<0.05) and mRNA expressions of RAGE, NF-κB (p65), VEGFA, and IL-6. Treatment with Guijianyu extract obviously improved cell viability and reduced the expressions of RAGE, NF-κB(p65), VEGFA, TNF-α, IL-6, and caspase-3. Furthermore, Guijianyu extract effectively reversed RAGE agonist-induced elevation of protein expressions of RAGE, VEGFA, TNF-α, IL-6, and caspase-3 and mRNA expressions of RAGE, NF-κB (p65), IL-6, and VEGFA in MPC-5 cells. CONCLUSIONS Guijianyu extract ameliorates AGEs-induced mouse renal podocyte injury in DKD by inhibiting the activation of AGEs-RAGE signaling pathway and reducing the expressions of pro-inflammatory cytokines and vascular endothelial growth factors.
Animals ; Glycation End Products, Advanced ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Signal Transduction/drug effects* ; Podocytes/pathology* ; Diabetic Nephropathies/drug therapy* ; Receptor for Advanced Glycation End Products ; Vascular Endothelial Growth Factor A/metabolism* ; Interleukin-6/metabolism* ; Male

In recent years,the physician-patient relationship has been tense,the physician-patient conflict has been escalating,and the number of irrational medical complaints has been constantly increasing,all of which have a negative impact on the public image of the hospital and the legal environment of medical treatment.From the perspective of behavioral economics,it analyzes the reasons for the occurrence of irrational medical complaints among outpatient patients by applying behavioral economics theories such as bounded rationality,social influence,herd effect,loss aversion,endowment effect,and mental accounting.It constructs a model of irrational complaint behaviors of outpatient patients based on behavioral economics theory,and tries to draw lessons from framing effect and nudge theory to propose countermeasures for hospitals to reduce irrational medical complaints and boost the complaint prevention management of medical institutions.

In recent years,the physician-patient relationship has been tense,the physician-patient conflict has been escalating,and the number of irrational medical complaints has been constantly increasing,all of which have a negative impact on the public image of the hospital and the legal environment of medical treatment.From the perspective of behavioral economics,it analyzes the reasons for the occurrence of irrational medical complaints among outpatient patients by applying behavioral economics theories such as bounded rationality,social influence,herd effect,loss aversion,endowment effect,and mental accounting.It constructs a model of irrational complaint behaviors of outpatient patients based on behavioral economics theory,and tries to draw lessons from framing effect and nudge theory to propose countermeasures for hospitals to reduce irrational medical complaints and boost the complaint prevention management of medical institutions.

In recent years,the physician-patient relationship has been tense,the physician-patient conflict has been escalating,and the number of irrational medical complaints has been constantly increasing,all of which have a negative impact on the public image of the hospital and the legal environment of medical treatment.From the perspective of behavioral economics,it analyzes the reasons for the occurrence of irrational medical complaints among outpatient patients by applying behavioral economics theories such as bounded rationality,social influence,herd effect,loss aversion,endowment effect,and mental accounting.It constructs a model of irrational complaint behaviors of outpatient patients based on behavioral economics theory,and tries to draw lessons from framing effect and nudge theory to propose countermeasures for hospitals to reduce irrational medical complaints and boost the complaint prevention management of medical institutions.

In recent years,the physician-patient relationship has been tense,the physician-patient conflict has been escalating,and the number of irrational medical complaints has been constantly increasing,all of which have a negative impact on the public image of the hospital and the legal environment of medical treatment.From the perspective of behavioral economics,it analyzes the reasons for the occurrence of irrational medical complaints among outpatient patients by applying behavioral economics theories such as bounded rationality,social influence,herd effect,loss aversion,endowment effect,and mental accounting.It constructs a model of irrational complaint behaviors of outpatient patients based on behavioral economics theory,and tries to draw lessons from framing effect and nudge theory to propose countermeasures for hospitals to reduce irrational medical complaints and boost the complaint prevention management of medical institutions.

In recent years,the physician-patient relationship has been tense,the physician-patient conflict has been escalating,and the number of irrational medical complaints has been constantly increasing,all of which have a negative impact on the public image of the hospital and the legal environment of medical treatment.From the perspective of behavioral economics,it analyzes the reasons for the occurrence of irrational medical complaints among outpatient patients by applying behavioral economics theories such as bounded rationality,social influence,herd effect,loss aversion,endowment effect,and mental accounting.It constructs a model of irrational complaint behaviors of outpatient patients based on behavioral economics theory,and tries to draw lessons from framing effect and nudge theory to propose countermeasures for hospitals to reduce irrational medical complaints and boost the complaint prevention management of medical institutions.

In recent years,the physician-patient relationship has been tense,the physician-patient conflict has been escalating,and the number of irrational medical complaints has been constantly increasing,all of which have a negative impact on the public image of the hospital and the legal environment of medical treatment.From the perspective of behavioral economics,it analyzes the reasons for the occurrence of irrational medical complaints among outpatient patients by applying behavioral economics theories such as bounded rationality,social influence,herd effect,loss aversion,endowment effect,and mental accounting.It constructs a model of irrational complaint behaviors of outpatient patients based on behavioral economics theory,and tries to draw lessons from framing effect and nudge theory to propose countermeasures for hospitals to reduce irrational medical complaints and boost the complaint prevention management of medical institutions.

In recent years,the physician-patient relationship has been tense,the physician-patient conflict has been escalating,and the number of irrational medical complaints has been constantly increasing,all of which have a negative impact on the public image of the hospital and the legal environment of medical treatment.From the perspective of behavioral economics,it analyzes the reasons for the occurrence of irrational medical complaints among outpatient patients by applying behavioral economics theories such as bounded rationality,social influence,herd effect,loss aversion,endowment effect,and mental accounting.It constructs a model of irrational complaint behaviors of outpatient patients based on behavioral economics theory,and tries to draw lessons from framing effect and nudge theory to propose countermeasures for hospitals to reduce irrational medical complaints and boost the complaint prevention management of medical institutions.

In recent years,the physician-patient relationship has been tense,the physician-patient conflict has been escalating,and the number of irrational medical complaints has been constantly increasing,all of which have a negative impact on the public image of the hospital and the legal environment of medical treatment.From the perspective of behavioral economics,it analyzes the reasons for the occurrence of irrational medical complaints among outpatient patients by applying behavioral economics theories such as bounded rationality,social influence,herd effect,loss aversion,endowment effect,and mental accounting.It constructs a model of irrational complaint behaviors of outpatient patients based on behavioral economics theory,and tries to draw lessons from framing effect and nudge theory to propose countermeasures for hospitals to reduce irrational medical complaints and boost the complaint prevention management of medical institutions.