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Abstract Background Pirfenidone is a novel anti-fibrotic and anti-inflammatory agent that inhibits the progression of fibrosis in animal models and in patients with idiopathic pulmonary fibrosis (IPF). We previously showed that pirfenidone inhibits the over-expression of collagen type I and of heat shock protein (HSP) 47, a collagen-specific molecular chaperone, in human lung fibroblasts stimulated with transforming growth factor (TGF)-β1 in vitro. The increased numbers of HSP47-positive type II pneumocytes as well as fibroblasts were also diminished by pirfenidone in an animal model of pulmonary fibrosis induced by bleomycin. The present study evaluates the effects of pirfenidone on collagen type I and HSP47 expression in the human alveolar epithelial cell line, A549 cells in vitro. Methods The expression of collagen type I, HSP47 and E-cadherin mRNAs in A549 cells stimulated with TGF-β1 was evaluated by Northern blotting or real-time PCR. The expression of collagen type I, HSP47 and fibronectin proteins was assessed by immunocytochemical staining. Results TGF-β1 stimulated collagen type I and HSP47 mRNA and protein expression in A549 cells, and pirfenidone significantly inhibited this process. Pirfenidone also inhibited over-expression of the fibroblast phenotypic marker fibronectin in A549 cells induced by TGF-β1. Conclusion We concluded that the anti-fibrotic effects of pirfenidone might be mediated not only through the direct inhibition of collagen type I expression but also through the inhibition of HSP47 expression in alveolar epithelial cells, which results in reduced collagen synthesis in lung fibrosis. Furthermore, pirfenidone might partially inhibit the epithelial-mesenchymal transition.

Abstract Background The precise role of capsule endoscopy in the diagnostic algorithm of obscure gastrointestinal bleeding has yet to be determined. Despite the higher diagnostic yield of capsule endoscopy, the actual impact on clinical outcome remains poorly defined. The aim of this study was to evaluate the follow-up results of patients with obscure gastrointestinal bleeding to determine which management strategies after capsule endoscopy reduced rebleeding. Methods All patients in whom the cause of obscure gastrointestinal bleeding was investigated between May 2004 and March 2007 were studied retrospectively. We evaluated the clinical outcome of patients with obscure gastrointestinal bleeding after capsule endoscopy using the rebleeding rate as the primary outcome. Results Seventy-seven patients with obscure gastrointestinal bleeding underwent capsule endoscopy. Capsule endoscopy identified clinically significant findings that were thought to be the sources of obscure gastrointestinal bleeding in 58.4% of the patients. The overall rebleeding rate was 36.4%. The rebleeding rate was significantly higher among patients with insignificant findings than among those with significant findings (p = 0.036). Among the patients in whom capsule endoscopy produced significant findings, the rebleeding rate of the patients who underwent therapeutic interventions was significantly lower than that in those who did not undergo intervention (9.5% vs 40.0%, p = 0.046). Conclusion Follow-up and further aggressive interventions are necessary for patients with obscure gastrointestinal bleeding and significant capsule endoscopy findings to reduce the chance of rebleeding.

Background: The precise role of capsule endoscopy in the diagnostic algorithm of obscure gastrointestinal bleeding has yet to be determined. Despite the higher diagnostic yield of capsule endoscopy, the actual impact on clinical outcome remains poorly defined. The aim of this study was to evaluate the follow-up results of patients with obscure gastrointestinal bleeding to determine which management strategies after capsule endoscopy reduced rebleeding.Methods: All patients in whom the cause of obscure gastrointestinal bleeding was investigated between May 2004 and March 2007 were studied retrospectively. We evaluated the clinical outcome of patients with obscure gastrointestinal bleeding after capsule endoscopy using the rebleeding rate as the primary outcome.Results: Seventy-seven patients with obscure gastrointestinal bleeding underwent capsule endoscopy. Capsule endoscopy identified clinically significant findings that were thought to be the sources of obscure gastrointestinal bleeding in 58.4% of the patients. The overall rebleeding rate was 36.4%. The rebleeding rate was significantly higher among patients with insignificant findings than among those with significant findings (p = 0.036). Among the patients in whom capsule endoscopy produced significant findings, the rebleeding rate of the patients who underwent therapeutic interventions was significantly lower than that in those who did not undergo intervention (9.5% vs 40.0%, p = 0.046).Conclusion: Follow-up and further aggressive interventions are necessary for patients with obscure gastrointestinal bleeding and significant capsule endoscopy findings to reduce the chance of rebleeding. [ABSTRACT FROM AUTHOR]

Death-associated protein kinase 1 (DAPK1) is a phosphotransferase in the serine/threonine kinase family. Inhibiting DAPK1 is expected to be beneficial in treating Alzheimer's disease and protecting neuronal cells during cerebral ischemia. In this study, we demonstrated that the natural chalcone isoliquiritigenin inhibits DAPK1 in an ATP-competitive manner, and we synthesized halogen derivatives to amplify the inhibitory effect. Among the compounds tested, the chlorine, bromine, and iodine derivatives exhibited high DAPK1 inhibitory activity and binding affinity. Crystal structure analysis revealed that this improvement is attributable to the halogen atoms fitting well into the hydrophobic pocket formed by I77, L93, and I160. In particular, the chlorine derivative showed a significant enthalpic contribution to the interaction with DAPK1, suggesting its potential as a primary compound for new DAPK1 inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Gerbode defect is an unusual abnormal communication between the left ventricle and the right atrium and is a serious complication of aortic infective endocarditis. Group B Streptococcus is an uncommon cause of infective endocarditis and has a markedly destructive effect on valvular tissue. Acute fistulation between the left ventricle and the right atrium associated with this form of infective endocarditis is a life-threatening, aggressive complication that often requires urgent surgical intervention. However, the identification of actual communication is often extremely difficult. Herein, we describe an unusual case of Gerbode defect resulting from Group B Streptococcus infective endocarditis and discuss the issues surrounding such a rare cardiac defect and such an infection., Case Presentation: A 60-year-old man with underlying uncontrolled diabetes mellitus underwent endoscopic retrograde biliary drainage for acute cholangitis. On the 10th postoperative day, the patient developed multiple acute cerebral embolisms. Transthoracic echocardiography demonstrated severe aortic regurgitation and a large mobile vegetation near the tricuspid annulus. No obvious fistula between the left ventricle and the right atrium could be demonstrated. The blood culture examination was positive for Group B Streptococcus. The patient was diagnosed with Group B Streptococcus infective endocarditis, and antibiotic therapy was initiated. Transesophageal echocardiogram performed after referral to our hospital confirmed detachment of the right coronary cusp of the aortic valve from the annulus and an abnormal cavity immediately below the right coronary cusp. Color Doppler imaging finally revealed systolic blood flows from the left ventricle into the right atrium through the cavity. Therefore, we diagnosed the patient with Gerbode defect resulting from Group B Streptococcus infective endocarditis. In addition to aortic valve replacement, defect closure and left ventricular outflow tract repair were successfully performed urgently for severely complicated and uncommon infective endocarditis. The patient was uneventfully discharged without any complications., Conclusions: We reported successful surgical treatment of unusual active IE and Gerbode defect caused by GBS. Careful preoperative echocardiographic work-up is imperative for accurate early diagnosis and successful repair., (© 2024. The Author(s).)