Non-coding RNAs play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). The aim of this study was to characterize the therapeutic role of melatonin as well as the underlying molecular mechanism (its effects on the expression of H19 and its downstream signaling pathways) in the treatment of PAH. Real-time PCR and western blot analysis were performed to evaluate the expression of H19, miR-200a, miR-675, insulin-like growth factor-1 receptor (IGF1R), and programmed cell death 4 (PDCD4). The value of systolic pulmonary artery pressure (SPAP) and the ratio of medial thickening in the monocrotaline (MCT) group were increased, whereas the melatonin treatment could decrease these values to some extent. The weights of RV (right ventricle), LV (left ventricle) + IVS (interventricular septal), and RV/(LV + IVS) in the MCT group were much higher than those in the MCT + melatonin and control groups. In addition, the expression of H19, miR-675, IGF1R mRNA, and IGF1R protein in the MCT group was the highest, whereas their expression in the control group was the lowest. The expression of miR-200, PDCD4 mRNA, and PDCD4 protein in the MCT group was the lowest, whereas their expression in the control group was the highest. Furthermore, H19 directly suppressed the expression of miR-200a, whereas miR-675-3p and miR-200a directly inhibited the expression of IGF1R and PDCD4, respectively. Finally, melatonin treatment inhibited cell proliferation; upregulated the expression of H19, miR-675-3p, and PDCD4; and downregulated the expression of miR-200a and IGF1R. This study demonstrated the role of H19-miR-675-3p-IGF1R- and H19-miR-200a-PDCD4-signaling pathways in the melatonin treatment of PAH.
Non-coding RNAs play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). This study was performed to investigate the role of PVT1 and miR-146a single nucleotide polymorphisms (SNPs) in the lung function of COPD smokers. Real-time PCR and Western blot analyses were performed to measure the expression of miR-146 and PVT1 SNPs and determine the effect of these SNPs on the pathogenesis of COPD. A total of 100 COPD smokers were enrolled in this study and divided into four groups as follows: Rs2910164CC/GC + Rs13281615GG; Rs2910164CC/GC + Rs13281615GA/AA; Rs2910164GG + Rs13281615GG; and Rs2910164GG + Rs13281615GA/AA. No obvious differences in terms of age, sex, and body height and weight were found among the four groups. However, the Rs2910164GG + Rs13281615GA/AA was associated with the highest stage of the Global Initiative for Chronic Obstructive Lung Disease and the highest values of the forced vital capacity, forced expiratory volume, and diffusing capacity of carbon monoxide, while the lowest values of these parameters were observed in the Rs2910164CC/GC + Rs13281615GG group. In addition, the highest and lowest COX2 levels were observed in the Rs2910164GG + Rs13281615GA/AA and Rs2910164CC/GC + Rs13281615GG groups, respectively. PVT1 directly and negatively regulated the miR-146a expression, which in turn directly and negatively regulated COX2 expression. Thus, the combined actions of SNP in PVT1 Rs13281615 and miR-146a Rs2910164 affected the lung function in COPD smokers.
Pulmonary actinomycosis is a chronic, suppurative, granulomatous disease caused by Actinomyces israelii, an obligate anaerobe. The clinical manifestations and imaging characteristics of pulmonary actinomycosis lack specificity and can lead to confusion with tuberculosis and lung cancer. The present study reported a case of pulmonary actinomycosis diagnosed by transbronchoscopic lung biopsy and reviewed the literature on the disease. The clinical characteristics, signs, laboratory findings as well as progression, diagnosis and treatment in the case of pulmonary actinomycosis were analyzed. The patient was diagnosed by transbronchoscopic lung biopsy. After two weeks of antibiotic therapy, the cough was significantly improved and the patient's temperature returned to normal. Moreover, the lesion in the left lower lung was significantly smaller. Pulmonary actinomycosis is usually confused for tuberculosis and lung cancer. The present findings indicated that transbronchoscopic lung biopsy is a useful tool for diagnosing the disease. To conclude, doctors should have a clear enough understanding of the disease to prescribe empirical antibiotics and avoid unnecessary surgery.
The lymph node status is one of the most critical prognostic factors used in determining adjuvant treatment in endometrial cancer (EC). Lymphadenectomy is associated significant surgical and postoperative risks. The use of sentinel lymph node mapping (SLNM) has emerged as an alternative method to complete lymphadenectomy in EC. However, there remains controversy surrounding the use of SLNM in high-risk disease and its false-negative rate (3%). The authors previously identified miR-204-5p as a tumor-suppressor miRNA associated with lymph node metastasis in EC tissues. The present study demonstrated that serum miR-204-5p in patients with EC has the potential for use as an early diagnostic biomarker combined with SLNM to assess the lymph node status prior to surgery. The present study also aimed to identify the optimal cut-off value of serum miR-204-5p. The relative expression levels of miR-204-5p were detected using reverse transcription-quantitative PCR in the serum of 52 patients with EC (total SLNM). A total of 20 patients diagnosed with ovarian cysts, 20 patients diagnosed with myoma, and 20 participants diagnosed with endometrial polyps or endometrial hyperplasia were included as the control group. miR-204-5p expression was also detected in lymph node tissues using in situ hybridization. The results revealed that serum miR-204-5p expression was downregulated in patients with EC compared with its expression in patients with benign ovarian cysts, myoma and endometrial hyperplasia/polyps (P<0.01). In accordance with the final pathological evaluation, patients with EC with a positive SLN status had a significantly lower level of miR-204-5p compared with those with a negative SLN status (P<0.01). The area under the ROC curve of miR-204-5p was 0.923, 95% CI (0.847-1.000), and the diagnostic value had a sensitivity of 87.2% and specificity of 80.0%, with an optimal cut-off value of 0.253. On the whole, it was demonstrated that a lower miR-204-5p expression is associated with lymph node metastasis in these SLN(+) EC tissues, indicating that the downregulation of serum miR-204-5p in patients with EC has potential for use as an early diagnostic biomarker combined with SLNM. In addition, with a cut-off value of 0.253, it appeared optimal for the prediction of lymph node metastasis in EC.
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