Direct in vivo evidence for the susceptibility of human neuronal cells to dengue virus has not been reported.In this study, we demonstrated that type 2 dengue (DEN-2) virus infection induced extensive apoptosis in the human neuroblastoma cell line SK-N-SH. Phospholipase A 2 (PLA 2 ) was activated by DEN-2 infection, which led to the generation of arachidonic acid (AA). Inhibition of PLA 2 activity by the PLA 2 inhibitors, AACOCF 3 and ONO-RS-082, diminished DEN-2 virus-induced apoptosis. In contrast, the cyclooxygenase inhibitors aspirin and indomethacin, thought to increase AA accumulation by blocking AA catabolism, enhanced apoptosis. Exogenous AA induced apoptosis in a dose-dependent manner. Superoxide anion, which is thought to be generated through the AA-activated NADPH oxidase, was increased after infection. Pretreatment with superoxide dismutase (SOD) protected cells against DEN-2 virus-induced apoptosis. Furthermore, generation of superoxide anion was blocked by AACOCF 3 . In addition, the transcription factors, NF-B and c-Jun, were found to be activated after DEN-2 virus infection. However, pretreatment of cells with oligodeoxynucleotides containing NF-B, but not c-Jun, binding sites (transcription factor decoy) strongly prevented dengue virusinduced apoptosis. The finding that AACOCF 3 and SOD significantly block activation of NF-B suggests that this activation is derived from the AA-superoxide anion pathway. Our results indicate that DEN-2 virus infection of human neuroblastoma cells triggers an apoptotic pathway through PLA 2 activation to superoxide anion generation and subsequently to NF-B activation. This apoptotic effect can be either directly derived from the action of AA and superoxide anion on mitochondria or indirectly derived from the products of apoptosis-related genes activated by NF-B.Dengue virus, a mosquito-borne human pathogen, is a member of the Flaviviridae and is classified into four serotypes (Dengue virus type 1 through 4, designated here DEN-1, -2, -3, and -4 virus) (27,74). Dengue disease, which is caused by dengue virus infection, is considered a major public health problem in Southeast Asia and Central America (25, 58). As a consequence of increasing travel to areas of endemicity, dengue infection has been imported to many parts of the world. Classic dengue fever generally presents in older children and adults with high fever, severe headache and retro-orbital pain, myalgia, arthralgia, nausea, and rash. The acute phase may last for up to a week, but prolonged recovery is common and is sometimes associated with fatigue and depression. In some cases, hemorrhagic manifestations (dengue hemorrhagic fever) and signs of circulatory failure occur, leading to sudden and often hypovolemic shock (dengue shock syndrome) (26,88). An increasing number of cases have been reported with manifestations of encephalopathy and encephalitis, which cover a wide range of symptoms and signs from headache and clouded sensorium to convulsion, spasticity, and coma (34,49,73,79). As a result, the etiolo...
Reductive dechlorination of carbon tetrachloride (CT) and tetrachloroethylene (PCE) by zerovalent silicon (ZVS, Si0) and the combination of Si0 with metal iron (Fe0) was investigated as potential reductants for chlorinated hydrocarbons. The X-ray photoelectron spectroscopy (XPS) was used to identify the surface characteristics of Si0. CT and PCE can be completely degraded via sequential reductive dechlorination to form lesser chlorinated homologues by Si0. Productions of chloroform (CF) and trichloroethylene (TCE) accounted for 80% of CT and 65% of PCE dechlorination, respectively. The degradation of CT and PCE by Si0 at pH 8.3 followed pseudo-first-order kinetics, and the normalized surface rate constants (k(sa)) were 0.288 and 0.003 L m(-2) h(-1), respectively, which react more efficiently than zerovalent iron in CT and PCE dechlorination. A linear relationship was also established between pH and the k(sa) value. The XPS results showed that the hydrogenated silicon surface and silicon oxides on the silicon surface were removed during the dechlorination processes, thus providing a relatively clean silicon surface for dechlorination reactions. The combination of zerovalent silicon with iron influences both the dechlorination rate and the distribution of products. Sequential reductive dechlorination was still the main reaction for CT dechlorination by Si0/Fe0, while reductive dechlorination and beta-elimination were the dominant reaction pathways for PCE dechlorination with ethane and ethene as the major end products. Also, the combination of silicon and iron constitutes a buffer system to maintain the pH at a stable value. A 0.3 unit of pH changed upon increasing the amount of Fe by a factor of 35 was observed, depicting that Si0 serves as a pH buffer in Si0/Fe0 system during dechlorination processes.
Recent studies have demonstrated beneficial effects of specific probiotics on alleviating obesity-related disorders. Here we aimed to identify probiotics with potential antiobesity activity among 88 lactic acid bacterial strains via in vitro screening assays, and a Lactobacillus plantarum strain K21 was found to harbor abilities required for hydrolyzing bile salt, reducing cholesterol, and inhibiting the accumulation of lipid in 3T3-L1 preadipocytes. Furthermore, effects of K21 on diet-induced obese (DIO) mice were examined. Male C57Bl/6J mice received a normal diet, high-fat diet (HFD), or HFD with K21 administration (109 CFU in 0.2 mL PBS/day) for eight weeks. Supplementation of K21, but not placebo, appeared to alleviate body weight gain and epididymal fat mass accumulation, reduce plasma leptin levels, decrease cholesterol and triglyceride levels, and mitigate liver damage in DIO mice. Moreover, the hepatic expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) related to adipogenesis was significantly downregulated in DIO mice by K21 intervention. We also found that K21 supplementation strengthens intestinal permeability and modulates the amount of Lactobacillus spp., Bifidobacterium spp., and Clostridium perfringens in the cecal contents of DIO mice. In conclusion, our results suggest that dietary intake of K21 protects against the onset of HFD-induced obesity through multiple mechanisms of action.
DAS prevents IL-1beta and MSU crystal induced COX-2 upregulation in synovial cells and chondrocytes and ameliorates crystal induced synovitis potentially through a mechanism involving NF-kappaB. Anti-inflammatory actions of DAS may be of value in treatment of joint inflammation.
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