Humans ; Immunotherapy/adverse effects* ; Lung Neoplasms/drug therapy*

OBJECTIVETo investigate the autophagy of effector cells in lung tissue at different time points when rats were exposed to free SiO2 dust.

METHODSSixty Wistar rats (220∼230 g) were selected and allocated to experimental group (n = 30) and control group (n = 30). In the experimental group, a rat silicosis model was established by infusing SiO2 suspension into the trachea of rats. Six rats in each group were sacrificed on days 1, 7, 14, 21, or 28 of dust exposure. Lung tissue samples were collected to prepare lung tissue sections. The pulmonary inflammation and fibrosis were observed by HE staining. The proautophagosome, autophagosome, and autophagolysosome in lung tissue sections were observed under a transmission electron microscope.

RESULTSOn day 1 of dust exposure, many proautophagosomes and autophagosomes were seen in both experimental group and control group. On day 7 of dust exposure, the experimental group had more autophagosomes in lung tissue than the control group. On day 14 of dust exposure, the experimental group had fewer autophagosomes than the control group. On days 21 and 28, autophagolysosomes were seen in macrophage plasma in both experimental group and control group; the autophagolysosomes in experimental group showed cloudy swelling and expansion, and some were vacuolated, and these changes were more significant on day 28.

CONCLUSIONFree SiO2 dust can induce autophagy in the lung tissue of rats, with varying degrees at different time points of dust exposure.

Animals ; Autophagy ; drug effects ; Dust ; Lung ; drug effects ; pathology ; Male ; Rats ; Rats, Wistar ; Silicon Dioxide ; toxicity

OBJECTIVEThis study aimed to explore the effects of hyperoxia on the development of fetal lung by investigating the changes of morphological and cell proliferation induced by hyperoxia in cultured fetal lungs as well as the effects of dexamethasone on hyperoxia-exposed lungs.

METHODSHuman fetal lung explants at the pseudoglandular stage of development were cultured randomly either in normoxia (21% O2/5% CO2) or hyperoxia (95% O2/5% CO2) for 72 hrs. Dexamethasone was added into the feeding medium at the concentration of 10(-6)M. Harvested tissues were stained for pancytokeratin to identify epithelial cells, with Ki-67 as a marker of proliferation. The effects of lung morphometry were analyzed using computer assisted image analysis. The mean airway thickness, the proportion of the surface area occupied by airways, the mean airway surface area and the index of the epithelium proliferation were measured.

RESULTSThe lung architectures remained unchanged after 72 hrs normoxia culture, whereas hyperoxia culture resulted in significant dilation of airways and thinning of epithelium, with the surface area of airways of 6662 microm(2) vs 2728 microm(2) and the thickness of airways of 7.8 microm vs 8.1 microm (P < 0.05). Hyperoxia culture also resulted in an increase in the proportion of the surface area occupied by airways than normoxia culture (35.2% vs 23.4%; P < 0.05). The surface area of airways (3174 microm(2)) and the proportion of the surface area occupied by airways (23.9%) decreased significantly in hyperoxia-cultured lungs after dexamethasone administration (P < 0.05). The epithelium proliferation index in hyperoxia-cultured lungs (21.8%) was higher than that in normoxia-cultured lungs (5.1%) and dexamethasone-treated hyperoxia-cultured lungs (7.4%) (P < 0.05).

CONCLUSIONSThe exposure of pseudoglandular lungs to hyperoxia modulates the lung architecture to resemble saccular lungs with higher epithelium proliferation index. Dexamethasone may inhibit the effects induced by hyperoxia.

Cell Differentiation ; drug effects ; Dexamethasone ; pharmacology ; Female ; Humans ; Hyperoxia ; pathology ; Lung ; drug effects ; embryology ; pathology ; Pregnancy

To investigate the effect of Brucea javanica oil emulsion on proliferation, migration and autophagy of non-small cell lung cancer A549 cells.
 Methods: First, A549 cells were divided into a control group and a low, medium or high dose of Brucea javanica oil emulsion groups (0, 2.5, 5.0 or 10.0 mg/mL); then, the cells were divided into a 3-MA+Brucea javanica oil emulsion group and a Brucea javanica oil emulsion group in the presence or absence of 3-methyl adenine (3-MA). Cell counting kit-8 (CCK-8) and clone formation assay were used to detect cell proliferation, while the wound scratch and Transwell assay were used to measure cell migration. Cell immunofluorescence and Western blot were used to analyze autophagy.
 Results: Compared with the control group, the numbers of cell proliferation and colony-formation, the relative cell migration rate and numbers of trans-membrane cells were reduced in a dose-dependent manner in the Brucea javanica oil emulsion groups (all P<0.05). Meanwhile, compared with the control group, the aggregation of microtubule associated protein 1 light chain3 (LC3) green fluorescence and the LC3-II/LC3-I ratios were increased, while p62 level was decreased (all P<0.05) in the high dose group. Compared with the Brucea javanica oil emulsion group (5.0 mg/mL), the cell proliferation, numbers of cell clone formation, cell migration rate and numbers of Transwell transmembrane cells were increased in the 3-MA+Brucea javanica oil emulsion group (all P<0.05).
 Conclusion: Brucea javanica oil emulsion can promote the autophagy of non-small cell lung cancer A549 cells and inhibit the cell proliferation and migration.
A549 Cells ; Autophagy ; drug effects ; Brucea ; chemistry ; Carcinoma, Non-Small-Cell Lung ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Humans ; Lung Neoplasms ; Plant Oils ; pharmacology

No abstract available.
Animals ; Cyclophosphamide/*pharmacology ; Immunosuppressive Agents/*pharmacology ; Lung/*drug effects ; Lung Injury/*drug therapy ; Male ; *Paraquat ; Pulmonary Edema/*drug therapy

OBJECTIVETo assess the effects of tumor necrosis factor-α (TNF-α) in enhancing the radiosensitivity of lung cancer cells in vitro.

METHODSA549 cells were exposed to γ-ray with or without TNF-α treatment. MTT assay was used to evaluate the cell viability, and flow cytometry was performed to assess the cell apoptosis. Western blotting was used to observe the expression of caspase-3 protein in the exposed cells.

RESULTSCompared with the exposed cells without TNF-α treatment, the cells treated with TNF-α showed significantly suppressed cell proliferation, increased the cell apoptosis, altered cell cycle, and increased caspase-3 protein expression after γ-ray exposure.

CONCLUSIONTNF-α can enhance the radiosensitivity of A549 cells to increase the efficiency of radiotherapy with γ-ray irradiation.

Apoptosis ; drug effects ; radiation effects ; Cell Cycle ; drug effects ; radiation effects ; Cell Line, Tumor ; Gamma Rays ; Humans ; Lung Neoplasms ; Radiation Tolerance ; drug effects ; Tumor Necrosis Factor-alpha ; pharmacology

People complain about nasal stuffiness after SO2 exposure. This study was to investigate the acute effects of SO2 on nasal vascular and airway resistances in anaesthetized pigs for elucidating the underlying vascular and control mechanisms. Controlled ventilation was passed to the lungs or retrogradely through each nasal cavity. Nasal airway and lower airway pressures were measured to reflect airflow resistance changes. Systemic arterial pressure and nasal arterial flow were measured to calculate nasal vascular resistance. Nasal and pulmonary SO2 challenges were given. At 2 ppm, SO2 decreased systemic blood pressure and nasal vascular resistance but increased nasal airway and lower airway resistances. With increasing level to 8 ppm, SO2 increased systemic arterial pressure, nasal vascular and lower airway resistances but decreased nasal airway resistance. Nasal and pulmonary challenges induced similar responses. Ipsilateral nasal challenge elicited bilateral responses. Ruthenium red abolished the responses to nasal challenges. Bilateral vagosympathectomy eliminated the responses to lung challenges. Hence, SO2 at 2 ppm causes nasal congestion through sensory reflex vasodilatation but at higher levels nasal decongestion through sensory reflex vasoconstriction. Nasal congestion coupled with bronchoconstriction at levels of SO2 below short-term exposure limit (STEL) (≤ 2 ppm) would limit SO2 entering the lungs. Nasal decongestion at levels of SO2 beyond STEL (> 2 ppm) can effectively decrease total airway resistance as concurrent strong bronchoconstriction may impair ventilation.
Administration, Inhalation ; Airway Resistance ; drug effects ; Animals ; Lung ; drug effects ; Nasal Cavity ; drug effects ; Respiration ; Sulfur Dioxide ; pharmacology ; Swine ; Vascular Resistance ; drug effects ; Vasodilation

Animals ; Inflammation ; chemically induced ; Lung ; drug effects ; Oligodeoxyribonucleotides ; pharmacology ; Pulmonary Alveoli ; drug effects ; pathology ; Silicon Dioxide ; adverse effects

OBJECTIVETo investigate the antitumor effect of apigenin on human lung cancer cells.

METHODSThe anti-proliferation and sensitization effects of apigenin on human lung cancer cells was accessed by counting cells after Trypan blue staining and MTS assay.

RESULTS(1) Apigenin significantly suppressed the proliferation of four types of human lung cancer cells (A549:P=0.041, H460:P=0.050, LTEP-a2:P=0.039, H292:P=0.016); (2) Apigenin significantly increased the susceptibility of human lung cancer cells to antitumor drugs (P<0.05 or P<0.01) in a synergistic way (almost all of the combination index values are less than 1).

CONCLUSIONApigenin widely inhibits cell proliferation of various lung cancer cell lines in a dose-dependent manner and the combination treatment of apigenin and antitumor drugs is very effective in human lung cancer cells, and Nrf2-ARE pathway may contribute to the mechanism.

Antineoplastic Agents ; pharmacology ; Apigenin ; pharmacology ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; drug effects ; Drug Synergism ; Humans ; Lung Neoplasms ; pathology

To investigate the effects of cigarette smoking in different manners on acute lung injury in rats.The commercially available cigarettes with tar of 1,5, 11 mg were smoked in Canada depth smoking (health canada method, HCM) manner, and those with tar of 11 mg were also smoked in international standard (ISO) smoking manner. Rats were fixed and exposed to mainstream in a manner of nose-mouth exposure. After 28 days, the bronchoalveolar lavage fluids from left lung were collected for counting and classification of inflammatory cells and determination of pro-inflammatory cytokines IL-1β and TNF-α. The right lungs were subjected to histological examination and determination of myeloperoxidase (MPO) and superoxide dismutase (SOD) activities and glutathione, reactive oxygen species (ROS) and malondialdehyde (MDA) levels.In both HCM and ISO manners, the degree of lung injury was closely related to the tar content of cigarettes, and significant decrease in the body weight of rats was observed after smoking for one week. In a HCM manner, smoking with cigarette of 11 mg tar resulted in robust infiltration of macrophages, lymphocytes and neutrophils into lungs, significant increase in IL-1β and TNF-α levels and MPO activities, and significant decrease in GSH levels and SOD activities and increase in ROS and MDA levels (all<0.05). Smoking with cigarette of 5 mg tar led to moderate increase in IL-1β and TNF-α levels, and MPO activities (all<0.05), and moderate decrease in GSH levels and SOD activities and increase of ROS and MDA levels (all<0.05). However, smoking with cigarette of 1 mg tar affected neither inflammatory cell infiltration nor IL-1β and TNF-α levels.Cigarette smoking in nose-mouth exposure manner can induce acute lung injury in rats; and the degree of lung injury is closely related to the content of tar and other hazards in cigarettes.
Acute Lung Injury ; etiology ; pathology ; physiopathology ; Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; cytology ; Chemotaxis, Leukocyte ; drug effects ; Glutathione ; analysis ; drug effects ; Interleukin-1beta ; analysis ; drug effects ; Lung ; chemistry ; pathology ; Lymphocytes ; drug effects ; pathology ; Macrophages ; drug effects ; pathology ; Male ; Malondialdehyde ; analysis ; Neutrophil Infiltration ; drug effects ; Neutrophils ; drug effects ; pathology ; Peroxidase ; analysis ; drug effects ; Rats ; Reactive Oxygen Species ; analysis ; Smoking ; adverse effects ; Superoxide Dismutase ; analysis ; drug effects ; Tobacco Products ; adverse effects ; classification ; Tumor Necrosis Factor-alpha ; analysis ; drug effects ; Weight Loss ; drug effects