Decreased expression of SFTPC by TGF-β1 treatment was restored by TSA via hyperacetylation of histone H4 in the promoter region. TSA partially attenuated pulmonary fibrosis and increased Sftpc mRNA in ATII. Our findings suggest that the epigenetic restoration of SP-C would be a therapeutic target for pulmonary fibrosis.
Circulating endothelial microparticles (EMPs) are considered to be markers of endothelial injury, and lung microvascular endothelial cells express higher levels of angiotensin-converting enzyme (ACE). The aim of this study is to examine whether the number of ACE+ microvascular EMPs could be a prognostic marker for the development of acute respiratory distress syndrome (ARDS) in septic patients.The numbers of EMPs and ACE+ EMPs in the culture supernatant from human microvascular endothelial cells, as well as in the blood of mouse lung injury models and septic patients (n=82), were examined using flow cytometry.ACE+ EMPs in the culture supernatant from pulmonary microvascular endothelial cells increased after exposure to an inflammatory stimulus. In the mouse lung injury models, the circulating ACE+ EMPs and ACE+ EMP/EMP ratio were higher than in the controls (p<0.001). The ACE+ EMP/EMP ratio was correlated with the wet/dry lung ratio (rs=0.775, p<0.001). The circulating ACE+ EMPs and ACE+ EMP/EMP ratio on admission were significantly increased in septic patients who developed ARDS compared with septic patients who did not (p<0.001).Therefore, circulating ACE+ EMPs may be a prognostic marker for the development of ARDS in the septic patients.
CYFRA 21-1 is a new tumor marker using two different monoclonal antibodies which recognize the divergent epitope on the N- or C-terminal region of domain 2 of cytokeratin 19 fragment, respectively. In this study, we investigated the relationship between levels of CYFRA 21-1 and survival duration, as well as the efficacy of chemotherapy associated with changes in CYFRA 21-1. Serum samples were obtained from 87 patients with nonoperable lung cancer (35 cases with squamous-cell carcinoma, 33 with adenocarcinoma, 3 with large-cell carcinoma, and 16 with small-cell carcinoma). The cutoff point was set at 3.5 ng/ml. In a CYFRA 21-1 assay, significantly more patients with squamous-cell carcinoma and adenocarcinoma were positive compared to patients with small-cell and large-cell carcinomas (p = 0.0017). Following chemotherapy, blood levels of CYFRA 21-1 decreased significantly in responders versus nonresponders (p = 0.0246). A significant correlation was noted between survival periods and pretreatment levels of CYFRA 21-1 (p = 0.0036). The present study suggests that CYFRA 21-1 might be useful as a possible indicator of survival and therapeutic effect for lung cancer.
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