Effect of icariin on the H2O2-induced proliferation of mouse airway smooth muscle cells through miR-138-5p regulating SIRT1/AMPK/PGC-1α axis.

Icariin exerts antioxidative and anti-inflammatory effects and is used in the treatment of bronchial asthma. However, the specific modes of action are uncertain. In this study, we investigated whether icariin could modulate the silencing information regulator 2-related enzyme 1 (SIRT1)/adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) axis by regulating miR-138-5p during H2O2-induced proliferation of mouse airway smooth muscle cells (ASMCs). Primary BALB/c mouse ASMCs were cultured using the tissue block adherence method and were induced with hydrogen peroxide (H2O2; 200 µmol/L) to establish a bronchial asthma ASMC proliferation model. With the aid of Western Blot and quantitative real-time polymerase chain reaction (qRT-PCR) in H2O2-induced ASMCs, the expression of miR-138-5p, SIRT1, AMPK, PGC-1α, α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1), collagen I, and collagen III protein and mRNA were investigated. The proliferation rate and activities of superoxide dismutase1 (SOD1), reduced glutathione (GSH), malonaldehyde (MDA), and reactive oxygen species (ROS) in ASMCs were determined. The results suggest Compared with the H2O2-induced group, icariin inhibited the miR-138-5p expression; enhanced SIRT1, p-AMPK, and PGC-1α expression; attenuated MDA activity and ROS level; lowered TGF-ß1, collagen I, and collagen III expression levels; and decreased the proliferation of ASMCs induced by H2O2. The dual-luciferase reporter gene assay results showed that SIRT1 is a regulatory target of miR-138-5p.The results suggest that Icariin could improve the H2O2-induced proliferation of ASMCs. The mechanism may be related to the increase of activation of SIRT1/AMPK/PGC-1α axis by suppressing the expression of miR-138-5p. Thus, SIRT1 is the regulatory target of miR-138-5p.

Gefitinib improves severe bronchorrhea and prolongs the survival of a patient with lung invasive mucinous adenocarcinoma: A case report.

BACKGROUND: Lung invasive mucinous adenocarcinoma (LIMA), formerly referred to as mucinous bronchioloalveolar carcinoma, is a rare disease that usually presents as bilateral lung infiltration, is unsuitable for surgery and radiotherapy, and shows poor response to conventional chemotherapy. CASE SUMMARY: We report a 56-year-old Chinese man with a history of smoking and epidermal growth factor receptor mutation-positivity who was initially misdiagnosed as severe pneumonia, but was ultimately diagnosed as a case of invasive mucinous adenocarcinoma of the lung by computed tomography -guided percutaneous lung biopsy. Bronchorrhea and dyspnea were improved within 24 h after initiation of gefitinib therapy and the radiographic signs of bilateral lung consolidation showed visible improvement within 30 d. After more than 11 months of treatment, there is no evidence of recurrence or severe adverse events. CONCLUSION: Although the precise mechanism of the antitumor effects of gefitinib are not clear, our experience indicates an important role of the drug in LIMA and provides a reference for the diagnosis and treatment of this disease.

Maresin-2 alleviates allergic airway inflammation in mice by inhibiting the activation of NLRP3 inflammasome, Th2 type immune response and oxidative stress.

Asthma is a chronic inflammatory disease of the respiratory system. Maresin-2 (MaR2) is biosynthesized from docosahexaenoic acid (DHA) by macrophages, display strong anti-inflammatory and pro-resolving activity. To investigate the therapeutic effect and mechanism of MaR2 on asthmatic mice induced by ovalbumin (OVA) in conjunction with the adjuvant aluminum hydroxide. Twenty four female BALB/c mice were randomly divided into control, OVA, OVA + MaR2, and OVA + dexamethasone (Dexa) groups. MaR2 or Dexa were given as a treatment for OVA-induced asthma. Serum, bronchoalveolar alveolar lavage fluid (BALF) and lung tissue were collected for further analysis. The Pathological changes of lung tissue, proportion of inflammatory cells in BALF, levels of inflammatory cytokines in BALF or serum, oxidative stress indices, and the protein concentration of ASC, MPO, Ly-6G, ICAM-1, NLRP3 and Caspase-1 in lung tissues were evaluated. Compared with the OVA group, both OVA + MaR2 and OVA + Dexa group had reduced inflammation and mucus secretion in lung tissue, number of inflammatory cells in BALF, levels of related inflammatory cytokines in serum or BALF, and expressions of ASC, MPO, Ly-6G, ICAM-1, NLRP3 and Caspase-1 proteins in lung tissue. In addition, the oxidative stress was alleviated as indicated by decreased MDA, and elevated SOD and GSH. MaR2 has an obvious protective effect on OVA-induced bronchial asthma in mice, in a similar manner as Dexa. The mechanism may be related to the inhibition of the Th2 type immune response, the NLRP3 inflammasome activation and oxidative stress.