The reversibility of non-genotoxic phenotypic changes has been explored in order to develop novel preventive and therapeutic approaches for cancer. Quisinostat (JNJ-26481585), a novel second-generation histone deacetylase inhibitor (HDACi), has efficient therapeutic actions on non-small cell lung cancer (NSCLC) cell. The present study aims at investigating underlying molecular mechanisms involved in the therapeutic activity of quisinostat on NSCLC cells. We found that quisinostat significantly inhibited A549 cell proliferation in dose- and time-dependent manners. Up-acetylation of histones H3 and H4 and non-histone protein α-tubulin was induced by quisinostat treatment in a nanomolar concentration. We also demonstrated that quisinostat increased reactive oxygen species (ROS) production and destroyed mitochondrial membrane potential (ΔΨm), inducing mitochondria-mediated cell apoptosis. Furthermore, exposure of A549 cells to quisinostat significantly suppressed cell migration by inhibiting epithelial-mesenchymal transition (EMT) process. Bioinformatics analysis indicated that effects of quisinostat on NSCLC cells were associated with activated p53 signaling pathway. We found that quisinostat increased p53 acetylation at K382/K373 sites, upregulated the expression of p21(Waf1/Cip1), and resulted in G1 phase arrest. Thus, our results suggest that the histone deacetylase can be a therapeutic target of NSCLC to discover and develop a new category of therapy for lung cancer.Electronic supplementary materialThe online version of this article (doi:10.1007/s10565-016-9347-8) contains supplementary material, which is available to authorized users.

Pulmonary alveolar proteinosis (PAP) is a rare interstitial lung disease characterized by the abnormal alveolar accumulation of surfactant components. The diagnosis of PAP can be easily missed since it is rare and lacks specific clinical symptoms. It is of great importance to have a better understanding of the crucial clue to clinically diagnose PAP and take PAP into consideration in the differential diagnosis of interstitial pulmonary diseases or other diseases with similar manifestations. Here, we analyze the clinical characteristics of 11 cases of PAP patients in local hospital and review the relevant literature in order to provide more information in diagnosis and management of PAP. In our observation, cyfra21-1 and neuron-specific enolase (NSE) known as tumor markers probably can be useful serum markers for diagnosis of PAP. As for the method of pathologic diagnosis, open-lung biopsy was the gold standard but now it is less required because findings on examination of bronchoalveolar lavage fluid (BALF) can help to make the diagnosis. We also have deep experience about when and how to carry out lung lavage.

Acute pancreatitis (AP) is one kind of acute surgical abdominal disease in the world. It causes intestinal damage with subsequent bacterial migration, endotoxemia and secondary pancreatic infections. In this investigation, we determined that edaravone (EDA) reduces pancreatic and intestinal injury after AP in mice. This was demonstrated by a reduction in histological score, apoptosis, interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α, along with obstructing activation of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NFκB). Our study results suggested that EDA exerts its protective effects against pancreatic and intestinal injury after AP via regulation of the TLR4/NFκB pathway. Our findings provide the basis for EDA to treat AP-induced pancreatic and intestinal injury, even might develop as a potential therapy for other inflammatory diseases.

Traumatic brain injury (TBI) is a clinical emergency with a very high incidence, disability, and fatality rate. Minocycline, a widely used semisynthetic second-generation tetracycline antibiotic, has anti-inflammatory and bactericidal effects. However, minocycline has not been explored as a therapeutic drug in TBI and if effective, the related molecular mechanism is also unclear. In this study, we examined the neuroprotective effect and possible mechanism of minocycline, in mice TBI model by studying the trauma-related functional and morphological changes. Also, in vitro cell studies were carried out to verify the animal model data. We found that minocycline significantly improved the neurobehavioral score, inhibited apoptosis, repaired the blood-brain barrier, and reduced the levels of inflammatory factors Interleukin-6 and tumor necrosis factor-α in TBI mice. In vitro, upon oxygen and glucose deprivation, minocycline reduced the levels of cellular inflammatory factors and increased the levels of tight junction and adherens junction proteins, thereby significantly improving the cell viability. Moreover, Mino treatment prevented the loss of tight junction and adherens junction proteins which were markedly reversed by an ER stress activator (tunicamycin) both in vivo and in vitro. Our findings set an effective basis for the clinical use of Mino to treat Traumatic brain injury-induced neurological deficits.

The effect of stress on the crevice corrosion of P110 carbon steel in the CO 2 -saturated 3.5 wt-% NaCl solution with a small amount of thiosulphate/H 2 S was investigated. The results showed that the composition of corrosion products on the steel surface did not change with elastic stress while the mackinawite film formed at the crevice mouth was more easily spalled off under higher stresses. Further, the elastic stress likely promoted localised corrosion but inhibited uniform corrosion both inside and outside crevice. Increasing the applied stress led to a deeper and sharper corrosion groove covering with corrosion products at the crevice mouth, suggesting the crevice corrosion was promoted by the applied stress. This is likely due to the peeling of mackinawite film and stress concentration at the crevice mouth.