Idiopathic pulmonary fibrosis is a progressive and fatal disease with a poor prognosis. Matrix metalloproteinase-2 is involved in the pathogenesis of organ fibrosis. The role of matrix metalloproteinase-2 in lung fibrosis is unclear. This study evaluated whether overexpression of matrix metalloproteinase-2 affects the development of pulmonary fibrosis. Lung fibrosis was induced by bleomycin in wild-type mice and transgenic mice overexpressing human matrix metalloproteinase-2. Mice expressing human matrix metalloproteinase-2 showed significantly decreased infiltration of inflammatory cells and inflammatory and fibrotic cytokines in the lungs compared to wild-type mice after induction of lung injury and fibrosis with bleomycin. The computed tomography score, Ashcroft score of fibrosis, and lung collagen deposition were significantly reduced in human matrix metalloproteinase transgenic mice compared to wild-type mice. The expression of anti-apoptotic genes was significantly increased, while caspase-3 activity was significantly reduced in the lungs of matrix metalloproteinase-2 transgenic mice compared to wild-type mice. Active matrix metalloproteinase-2 significantly decreased bleomycin-induced apoptosis in alveolar epithelial cells. Matrix metalloproteinase-2 appears to protect against pulmonary fibrosis by inhibiting apoptosis of lung epithelial cells.

This work investigates the soot formation process in diesel jet flame using a detailed kinetic soot model implemented into the KIVA-3V multidimensional CFD code and 2D imaging by use of time-resolved laser induced incandescence (LII). The numerical model is based on the KIVA code which is modified to use CHEMKIN as the chemistry solver using Message Passing Interface (MPI). This allows for the chemical reactions to be simulated in parallel on multiple CPUs. The detailed soot model used is based on the method of moments, which begins with fuel pyrolysis, followed by the formation of polycyclic aromatic hydrocarbons, their growth and coagulation into spherical particles, and finally, surface growth and oxidation of the particles. The model can describe the spatial and temporal characteristics of soot formation processes such as soot precursors distributions, nucleation rate and surface reaction rate. The experiments by use of laser induced incandescence were conducted using a constant volume combustion vessel which simulated diesel engine conditions. The distribution of soot volume fraction and particle diameter in diesel jet was revealed by time-resolved LII measurements, and qualitative agreement was obtained between the experimental and simulation results. The experimental results show that the smaller particles are made up of majority of soot formation region in the jet at the early time of the start of soot formation, which become larger around the periphery of the soot formation region with transition to the diffusion combustion phase, and rapidly transform the large particle after the end of injection. Also, simulation results show that the soot particles are formed to surround the soot precursor formation region and to extend downstream. It was also found that the dominant soot growth process differs by the region in the fuel jet. The particle inception is fast around the central region of the jet, and C2H2 surface reaction rate becomes higher toward the periphery of the jet.

We propose a new concept on simultaneous reduction of NO and soot emissions in Diesel engine exhaust by use of the diesel fuel oil (n-Tridecane) with liquefied CO2 dissolved. The CO2 dissolved component is expected to undergo flash boiling or gas separation when being injected into the combustion chamber, and improve spray atomization and mixing process both of which are primary factors to govern soot formation. Further, the internal EGR effect caused by CO2 component injected with the fuel is expected for NO formation. In order to assess this concept, spray dynamics measurement was conducted in the constant volume vessel with a variation of ambient pressure and temperature. Further, combustion experiments were carried out by using a rapid compression and expansion machine. Here, characteristics of the evaporative mixed fuel spray were examined by shadowgraph photography. And flame characteristics were measured by direct photography and two-color method to assess the qualitative flame temperature and soot concentration. From the results, it is revealed that the Diesel fuel - liquefied CO2 mixed fuel can successfully reduce NO and soot emissions in Diesel combustion process with keeping and improving the combustion coefficient.

Crizotinib is highly effective against anaplastic lymphoma kinase-positive and c-ros oncogen1-positive non-small cell lung cancer. Renal dysfunction is associated with crizotinib therapy but the mechanism is unknown. Here, we report a case of anaplastic lymphoma kinase positive non-small cell lung cancer showing multiple cysts and dysfunction of the kidneys during crizotinib administration. We also present results demonstrating that long-term crizotinib treatment induces fibrosis and dysfunction of the kidneys by activating the tumor necrosis factor-α/nuclear factor-κB signaling pathway. In conclusion, this study shows the renal detrimental effects of crizotinib, suggesting the need of careful monitoring of renal function during crizotinib therapy.

Apoptosis is a programmed cell death involved in embryogenesis and tissue homeostasis under physiological conditions. However, abnormalities in the process of apoptosis are implicated in the pathogenesis of various diseases. The human microbiota may release products that induce apoptosis of host cells. We recently identified a novel microbiome-derived peptide called corisin that worsens lung fibrosis by inducing apoptosis of lung epithelial cells. We hypothesized that corisin and a corisin-like peptide might also induce apoptosis of cells from different tissues. We cultured podocytes, renal tubular epithelial cells, keratinocytes, retinal and intestinal cells treated with corisin and evaluated apoptosis by flow cytometry and Western blotting. Although at different grades, flow cytometry analysis and Western blotting showed that corisin and a corisin-like peptide induced apoptosis of podocytes, keratinocytes, tubular epithelial cells, retinal, and intestinal cells. In addition, we found that corisin synergistically enhances the proapoptotic activity of transforming growth factor-β1 on podocytes. In conclusion, these results suggest that corisin and corisin-like peptides may play a role in the pathogenesis of disease in different organs by promoting apoptosis of parenchymal cells.

Epithelial-mesenchymal transition is currently recognized as an important mechanism for the increased number of myofibroblasts in cancer and fibrotic diseases. We have already reported that epithelial-mesenchymal transition is involved in airway remodeling induced by eosinophils. Procaterol is a selective and full β2 adrenergic agonist that is used as a rescue of asthmatic attack inhaler form and orally as a controller. In this study, we evaluated whether procaterol can suppress epithelial-mesenchymal transition of airway epithelial cells induced by eosinophils. Epithelial-mesenchymal transition was assessed using a co-culture system of human bronchial epithelial cells and primary human eosinophils or an eosinophilic leukemia cell line. Procaterol significantly inhibited co-culture associated morphological changes of bronchial epithelial cells, decreased the expression of vimentin, and increased the expression of E-cadherin compared to control. Butoxamine, a specific β2-adrenergic antagonist, significantly blocked changes induced by procaterol. In addition, procaterol inhibited the expression of adhesion molecules induced during the interaction between eosinophils and bronchial epithelial cells, suggesting the involvement of adhesion molecules in the process of epithelial-mesenchymal transition. Forskolin, a cyclic adenosine monophosphate-promoting agent, exhibits similar inhibitory activity of procaterol. Overall, these observations support the beneficial effect of procaterol on airway remodeling frequently associated with chronic obstructive pulmonary diseases.