Recently, statins have been shown to have anti-inflammatory effects on lung inflammatory diseases. However, the mechanisms of action of simvastatin in viral pneumonia have yet to be elucidated, although viral infection remains a considerable health threat. In this study, we hypothesised that simvastatin inhibits polyinosinic-polycytidylic acid (poly I:C)-induced airway inflammation, such as RANTES (regulated on activation, normal T-cell expressed and secreted) expression and inflammatory cell recruitment.In bronchial cells, the effect of simvastatin on poly I:C-induced RANTES expression and signal transducer and activator of transcription (STAT)3-mediated signal transduction was determined using an ELISA and short hairpin (sh)RNA system. In a poly I:C-induced pneumonia mouse model, immunological changes in the lungs after simvastatin inhalation, such as inflammatory cell recruitment and cytokine/chemokine release, were examined.In poly I:C-stimulated bronchial cells, RANTES secretion was increased by STAT3 activation, and simvastatin suppressed poly I:C-induced STAT3 activation, resulting in inhibition of RANTES expression. In BALB/c mice stimulated with inhaled poly I:C, RANTES expression and neutrophil infiltration into the airway were elevated. However, simvastatin treatment attenuated STAT3 activation, RANTES release and subsequent neutrophilia in the lungs.These findings suggest that simvastatin inhibits airway inflammation, but there are other mechanisms that need to be fully elucidated.

In an attempt to identify compounds with antihepatotoxic activity, carbon tetrachloride-induced cytotoxicity in primary cultured rat hepatocytes has been adopted as a screening system. Using this screening system, an antihepatotoxic compound from the aerial parts of Epimedium koreanum has been isolated. This compound, icariin, is a flavonol glycoside. Its antihepatotoxic activity was first evaluated by measuring the release of glutamic pyruvic transaminase and sorbitol dehydrogenase from CCl4-intoxicated rat hepatocytes into the culture medium. Icariin significantly reduced the level of glutamic pyruvic transaminase and sorbitol dehydrogenase released resulting in a 76% protection from toxicity at concentration ranges from 1 microM to 20 microM. The antihepatotoxic activity of icariin was also estimated by the determination of total cytochrome P-450 content and glutathione-S-transferase activity in the CCl4-intoxicated hepatocytes.

Cells surviving crisis are often tumorigenic and their telomeres are commonly maintained through the reactivation of telomerase. However, surviving cells occasionally activate a recombination-based mechanism called alternative lengthening of telomeres (ALT). Here we establish stably maintained survivors in telomerase-deleted Caenorhabditis elegans that escape from sterility by activating ALT. ALT survivors trans-duplicate an internal genomic region, which is already cis-duplicated to chromosome ends, across the telomeres of all chromosomes. These ‘Template for ALT' (TALT) regions consist of a block of genomic DNA flanked by telomere-like sequences, and are different between two genetic background. We establish a model that an ancestral duplication of a donor TALT region to a proximal telomere region forms a genomic reservoir ready to be incorporated into telomeres on ALT activation.

ObjectiveStereotactic radiosurgery (SRS) is an emerging treatment modality for malignant spinal tumors. After SRS, some patients suffered from pain aggravation due to development of vertebral compression fracture (VCF). In these cases, surgery should be considered.MethodsThis study consisted of 72 patients who underwent SRS due to spinal tumors. In them, whether post-SRS VCF developed or not was investigated. We retrospectively analyzed their medical records and radiological imaging data. VCF was diagnosed with X-ray and magnetic resonance imaging (MRI). The incidence, time to development and risk factors for VCF were investigated. Age, sex, whole vertebral body involvement rate, vertebral body osteolysis rate, pre-SRS spinal deformity, spinal instability neoplastic score (SINS), spinal canal encroachment, lesion level, and radiation dose were analyzed as potential risk factors. A multi-variate logistic regression model was used for statistical analysis.ResultsIn our study population, VCF was observed in 26 patients (36%). The mean time to VCF development was 1.5 months. Using uni-variate analyses, the significant risk factors were pre-SRS spinal deformity, SINS, vertebral body osteolysis rate, and whole vertebral body involvement rate. However, using multi-variate analyses, the only significant risk factor was vertebral body osteolysis rate. The patients whose vertebral body was destroyed by more than 60% showed an 8.4 times higher risk of VCF than those who had vertebral body destruction of less than 60%(p=0.016).ConclusionThe most significant prognostic factor for post-SRS VCF was vertebral body osteolysis rate, rather than whole vertebral body involvement rate. When more than 60% of the vertebral body was destroyed, the risk of VCF or spinal deformity was high.

Abstract. The generally accepted hypothesis for the pathogenesis of alcoholic liver disease (ALD) is the two-hit model, which proposes that fat accumulation in the liver increases the sensitivity of the liver to a second hit that leads to inflammatory liver cell damage. In this study we evaluated the effects of Magnolia officinalis (MO), which contains honokiol and magnolol as the primary pharmacological components, to eradicate fatty liver in rats fed an ethanol diet. In vitro studies showed that MO was able to protect RAW 264.7 cells from ethanol-induced production of tumor necrosis factor-α, reactive oxygen species, and superoxide anion radicals; the activation of NADPH oxidase; and subsequent cell death. We also investigated the therapeutic effects of MO on alcoholic fatty liver in Lieber-DeCarli ethanol diet-fed rats. MO treatment of the rats for the last 2 weeks of ethanol feeding completely reversed all the serum, hepatic parameters, and fatty liver changes. The increased maturation of sterol regulatory elementbinding protein-1c in the liver by ethanol treatment was completely inhibited by treatment with MO. Therefore, MO may be a promising candidate for development as a therapeutic agent for ALD.