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Sulforaphane (SFN) is an isothiocyanate compound derived from glucoraphanin, which is found in cruciferous vegetables, and has been heralded as a chemopreventive and/or chemotherapeutic agent. The present study investigated the effects of SFN on enhancing the anticancer role of cisplatin (cis-dichlorodiammineplatinum; CDDP) in H-28 malignant mesothelioma cells. At concentrations demonstrating limited toxicity in MeT-5A normal human mesothelial cells, combination treatment with the two compounds exhibited synergistic growth-inhibiting and apoptosis-promoting activities, as demonstrated by a series of proapoptotic events, including reactive oxygen species accumulation, loss of mitochondrial membrane potential, upregulation of p53 expression, increased B-cell lymphoma 2 (Bcl-2) associated X protein/Bcl-2 ratio, activation of caspase-3, the occurrence of a sub-G0/G1 peak and an increase in cells with pyknotic and fragmented nuclei, Annexin V-phycoerythrin-positive staining and G2/M phase-transition delay in the cell cycle. The phosphorylation levels of Akt and mammalian target of rapamycin were reduced by the combination treatment, which was accompanied by a significant increase in the level of autophagosomal marker protein microtubule-associated protein 1 light chain 3B-II and the accumulation of acidic vesicular organelles. Pretreatment with the antioxidant N-acetylcysteine attenuated both apoptosis and autophagy, whereas inhibition of autophagy by bafilomycin A1 potentiated apoptotic cell death following the combination treatment with SFN and CDDP. Considering the pro-oxidant-based combinational approach, the results of the present study provide a rationale for targeting cytoprotective autophagy as a potential therapeutic strategy for malignant mesothelioma. [ABSTRACT FROM AUTHOR]

Radiation-induced lung injury (RILI) involves pneumonitis and fibrosis, and results in pulmonary dysfunction. Moreover, RILI can be a fatal complication of thoracic radiotherapy. The present study investigated the protective effect of geranylgeranlyacetone (GGA), an inducer of heat shock protein (HSP)70, on RILI using a C57BL/6 mouse model of RILI developing 6 months subsequent to exposure to 12.5 Gy thoracic radiation. GGA was administered 5 times orally prior and subsequent to radiation exposure, and the results were assessed by histological analysis and western blotting. The results show that late RILI was alleviated by GGA treatment, possibly through the suppression of epithelial-to-mesenchymal transition (EMT) marker expression. Based on histological examination, orally administered GGA during the acute phase of radiation injury not only significantly inhibited pro-surfactant protein C (pro-SPC) and vimentin expression, but also preserved E-cadherin expression 6 months after irradiation-induced injury of the lungs. GGA induced HSP70 and inhibited EMT marker expression in L132 human lung epithelial cells following IR. These data suggest that the prevention of EMT signaling is a key cytoprotective effect in the context of RILI. Thus, HSP70-inducing drugs, such as GGA, could be beneficial for protection against RILI. [ABSTRACT FROM AUTHOR]

Lung fibrosis is a major complication in radiation-induced lung damage following thoracic radiotherapy, while the underlying mechanism has remained to be elucidated. The present study performed immunofluorescence and immunoblot assays on irradiated human pulmonary artery endothelial cells (HPAECs) with or without pre-treatment with VAS2870, a novel NADPH oxidase (NOX) inhibitor, or small hairpin (sh)RNA against NOX1, -2 or -4. VAS2870 reduced the cellular reactive oxygen species content induced by 5 Gy radiation in HPAECs and inhibited phenotypic changes in fibrotic cells, including increased alpha smooth muscle actin and vimentin, and decreased CD31 and vascular endothelial cadherin expression. These fibrotic changes were significantly inhibited by treatment with NOX1 shRNA, but not by NOX2 or NOX4 shRNA. Next, the role of NOX1 in pulmonary fibrosis development was assessed in the lung tissues of C57BL/6J mice following thoracic irradiation using trichrome staining. Administration of an NOX1-specific inhibitor suppressed radiation-induced collagen deposition and fibroblastic changes in the endothelial cells (ECs) of these mice. The results suggested that radiation-induced pulmonary fibrosis may be efficiently reduced by specific inhibition of NOX1, an effect mediated by reduction of fibrotic changes of ECs. [ABSTRACT FROM AUTHOR]

At present, the relationship between the morphological characteristics of the sympheseal region and occlusion has not been well documented. The aim of the present study was to investigate the following, using cone-beam computed tomography (CBCT): Interforaminal distance, the anterior loop, labial bone thickness at the tooth apex, cortical bone thickness, and the basal bone height from the apex of the tooth to the base of the mandible. Three-dimensional CBCT was performed on 20 normal occlusion subjects (9 males and 11 females; mean age=21.9±3.0 years); the mean interforaminal distance was 53.1±3.6 mm, with 85% of the participants demonstrating a mental foramen located below the second premolars on both sides. The mean anterior loop was 1.9±0.8 mm, the mean horizontal distance value was 4.5±1.3 mm, and the mean cortical bone thickness value was 2.3±0.5 mm. An increasing tendency for cortical bone thickness was seen from the central incisor to the second premolar. The mean vertical distance value was 20.3±3.1 mm. Decreasing tendency of vertical distance was seen from the central incisor to the second premolar. Furthermore, the width (mental foramina of both sides and their anterior loops), height (teeth apices and the inferior border of the mandible), depth (cortical bone thickness of the symphysis), and safety margins for vital anatomical structures (anterior loop, tooth apex, and inferior border of mandible) should be taken into account prior to symphyseal block-bone harvesting. The results of the present study suggested that a pre-operative evaluation with CBCT may be useful for diagnosis and treatment planning, and for minimizing complications during block-bone graft. [ABSTRACT FROM AUTHOR]