Tiotropium in Patients with Bronchiectasis: A Prospective Cohort Study.

PURPOSE: There are limited studies on the use of bronchodilators for the treatment of bronchiectasis. This study investigated the efficacy of tiotropium in patients with bronchiectasis and airflow limitation. METHODS: This study was a prospective cohort study, including 169 patients with bronchiectasis and airflow limitation from 2015 to 2019. The clinical outcomes observed in our study were the effect of tiotropium on the frequency of moderate exacerbations, the time to the first severe exacerbation, and the annual decline in FEV1. RESULTS: After 12 months, the annual decline in the FEV1 after bronchodilator use was 27.08 ml or 42.9 ml per year in the group with or without tiotropium, respectively. Treatment with tiotropium was associated with a decreased risk of moderate exacerbation of bronchiectasis (Adjusted RR 0.618 95% CI 0.493-0.774; P < 0.005). The time to the first severe acute exacerbation of bronchiectasis in the tiotropium group was longer than the non-tiotropium group (Adjusted HR 0.333 95% CI 0.219-0.506; P < 0.001). CONCLUSION: In conclusion, prospective cohort study showed that tiotropium effectively ameliorated the annual decline in the FEV1, with a lower-risk rate of moderate exacerbations and prolonging the time to the first-time severe exacerbation in patients with bronchiectasis and airflow limitation.

Injectable hydrogel-mediated combination of hyperthermia ablation and photo-enhanced chemotherapy in the NIR-II window for tumor eradication.

Local administration of therapeutic agents with long-term retention capabilities efficiently avoids nonspecific distribution in normal organs with an increased drug concentration in pathological tissue. Herein, we developed an injectable and degradable alginate-calcium (Ca2+) hydrogel for the local administration of corn-like Au/Ag nanorods (NRs) and doxorubicin hydrochloride (DOX·HCl). The immobilized Au/Ag NRs with strong absorbance in the near-infrared II (NIR-II) window efficiently ablated the majority of tumor cells after 1064 nm laser irradiation and triggered the release of DOX to kill residual tumor cells. As a result, injectable hydrogel-mediated NIR-II photothermal therapy (PTT) and chemotherapy efficiently inhibited tumor growth, resulting in the complete eradication of tumors in most of the treated mice. Furthermore, owing to the confinement of the Au/Ag NRs and DOX·HCl within the hydrogel, such treatment exhibited excellent biocompatibility.

Hesperidin attenuates influenza A virus (H1N1) induced lung injury in rats through its anti-inflammatory effect.

BACKGROUND: Influenza A viruses (IAV) can cause pandemics and are big threats to human health. Inflammation is the main pathological process in the lungs after IAV infection. We aimed to investigate whether hesperidin, a well-known anti-inflammatory compound, could be effective in improving IAV-induced lung injury. METHODS: We generated a rat model using H1N1 virus infection, and intraperitoneally injected different doses of hesperidin for 5 days. Pulmonary function was analysed. Local inflammatory state was profiled by immune cells and cytokines. Pulmonary microvascular endothelial cells were isolated from rats and used to test the effects of hesperidin in vitro. RESULTS: Hesperidin showed efficacy in improving H1N1-induced impairment of pulmonary function in a dose-dependent manner. Local numbers of immune cells and concentrations of cytokines were significantly limited by hesperidin. However, we found that hesperidin neither inhibited virus replication, nor rescued infected pulmonary microvascular endothelial cells. Rather, we observed that hesperidin reduced pro-inflammatory cytokine production by suppressing mitogen-activated protein kinase (MAPK) signalling pathways. CONCLUSIONS: Hesperidin could alleviate H1N1-induced impairment of pulmonary function by inhibiting cytokine production in pulmonary microvascular endothelial cells through MAPK signalling pathways.

Silymarin mitigates lung impairments in a rat model of acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a deadly disease and lacks effective treatments. Inflammation and oxidative stress play key roles in ARDS development. We aimed to evaluate the efficacy of pretreatment of silymarin, which has capacities of anti-inflammatory and anti-oxidative stress, in ARDS. We used lipopolysaccharide (LPS) to generate an ARDS rat model, which was pretreated with silymarin. Lung wet/dry ratio and broncho-alveolar lavage fluid (BALF) analyses were performed. Histological changes of the lungs were evaluated using hematoxylin and eosin staining. Cells and proteins in BALF were determined. Protein levels in the lungs were assessed using immunoblotting. LPS administration significantly caused an increased lung wet/dry ratio, an elevated protein level in BALF, and an impaired pulmonary function in the rats. Silymarin mitigated these changes in a dose-dependent manner. Silymarin ameliorated LPS-induced histological changes of the lungs, and reduced infiltration of lymphocytes, macrophages, and neutrophils. Consistently, concentrations of pro-inflammatory cytokines such as interferon-γ, interleukin (IL)-6, and tumor necrosis factor (TNF)-α were increased, while that of anti-inflammatory cytokine IL-10 was decreased in BALF. Additionally, silymarin pretreatment partially inactivated multiple mitogen-activated protein kinase signaling pathways in the lungs. Silymarin mitigated LPS-induced lung impairments by down-regulating inflammation in a rat model.

A Method to Encapsulate Small Organic Molecules in Calcium Phosphate Nanoparticles Based on the Supramolecular Chemistry of Cyclodextrin.

Calcium phosphate nanoparticles (CPNPs) encapsulating small organic molecules, such as imaging agents and drugs, are considered to be ideal devices for cancer diagnosis or therapy. However, it is generally difficult to encapsulate small organic molecules in CPNPs because of the lack of solubility in water or binding affinity to calcium phosphate. To solve these issues, we utilized the carboxymethyl ß-cyclodextrin (CM-ß-CD) to increase the solubility and binding affinity to small organic molecules for the encapsulation into CPNPs in this work. The results indicated that the model molecules, hydrophilic rhodamine B (RB) and hydrophobic docetaxel (Dtxl), are successfully encapsulated into CPNPs with the assistance of CM-ß-CD. We also demonstrated the CPNPs could be remarkably internalized into A549 cells, resulting in the efficient inhibition of tumor cells' growth.

Expression variations of connective tissue growth factor in pulmonary arteries from smokers with and without chronic obstructive pulmonary disease.

Cigarette smoking contributes to the development of pulmonary hypertension (PH) complicated with chronic obstructive pulmonary disease (COPD), and the pulmonary vascular remodeling, the structural basis of PH, could be attributed to abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs).In this study, morphometrical analysis showed that the pulmonary vessel wall thickness in smoker group and COPD group was significantly greater than in nonsmokers. In addition, we determined the expression patterns of connective tissue growth factor (CTGF) and cyclin D1 in PASMCs harvested from smokers with normal lung function or mild to moderate COPD, finding that the expression levels of CTGF and cyclin D1 were significantly increased in smoker group and COPD group. In vitro experiment showed that the expression of CTGF, cyclin D1 and E2F were significantly increased in human PASMCs (HPASMCs) treated with 2% cigarette smoke extract (CSE), and two CTGF siRNAs with different mRNA hits successfully attenuated the upregulated cyclin D1 and E2F, and significantly restored the CSE-induced proliferation of HPASMCs by causing cell cycle arrest in G0. These findings suggest that CTGF may contribute to the pathogenesis of abnormal proliferation of HPASMCs by promoting the expression of its downstream effectors in smokers with or without COPD.