ABSTRACT
MicroRNAs (miRNAs) have been reported to be associated with heart valve disease, which can be caused by inflammation. This study aimed to investigate the functional impacts of miR-27a on TNF-α-induced inflammatory injury in human mitral valve interstitial cells (hMVICs). hMVICs were subjected to 40 ng/mL TNF-α for 48 h, before which the expressions of miR-27a and NELL-1 in hMVICs were altered by stable transfection. Trypan blue staining, BrdU incorporation assay, flow cytometry detection, ELISA, and western blot assay were performed to detect cell proliferation, apoptosis, and the release of proinflammatory cytokines. We found that miR-27a was lowly expressed in response to TNF-α exposure in hMVICs. Overexpression of miR-27a rescued hMVICs from TNF-α-induced inflammatory injury, as cell viability and BrdU incorporation were increased, apoptotic cell rate was decreased, Bcl-2 was up-regulated, Bax and cleaved caspase-3/9 were down-regulated, and the release of IL-1β, IL-6, and MMP-9 were reduced. NELL-1 was positively regulated by miR-27a, and NELL-1 up-regulation exhibited protective functions during TNF-α-induced cell damage. Furthermore, miR-27a blocked JNK and Wnt/β-catenin signaling pathways, and the blockage was abolished when NELL-1 was silenced. This study demonstrated that miR-27a overexpression protected hMVICs from TNF-α-induced cell damage, which might be via up-regulation of NELL-1 and thus modulation of JNK and Wnt/β-catenin signaling pathways.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Inflammation/chemically induced , MicroRNAs/metabolism , Mitral Valve/drug effects , Nerve Tissue Proteins/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Apoptosis , Cell Proliferation , Cell Survival , Cytokines/metabolism , Enzyme-Linked Immunosorbent Assay , Heart Valve Diseases/prevention & control , Inflammation/pathology , Mitral Valve/cytology , Mitral Valve/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Transfection , Up-RegulationABSTRACT
Objective: To evaluate the efficacy and safety of dexamethasone in alleviating radiation-induced pain deterioration follow-ing palliative radiotherapy in patients with bone metastases from lung cancer. Methods:A total of 103 patients with bone metastases from lung cancer were randomly assigned into the observation group (n=51) and the control group (n=52). Dexamethasone (5 mg, iv) or placebo (saline, 1 mL) was administered after radiation. The incidence of pain deterionation in the two groups was compared. Re-sults:Of the 51 cases in observation group, 13 (25%) had pain deterioration. While 20 patients (38%) experienced aggravated pain in the control group (P=0.03). Conclusion:Dexamethasone alleviated pain deterioration in patients with bone metastases from lung can-cer following palliative radiotherapy, which needs to be confirmed by further studies.