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Licofelone is a COX/5-LOX inhibitor, which recently was approved as an effective treatment for osteoarthritis. Beside its analgesic and anti-inflammatory effects, some reports show neuro-protective properties for this agent in central nervous system. Several lines of evidence declare the involvement of COX or LOX isoenzymes in epileptic disorders. To set the foundation for future research into the neurobiology of licofelone as a potential therapeutic agent, we studied the effect of licofelone in an animal model of epilepsy. Although different neurotransmitters and neuro-modulators like nitric oxide were introduced as suggested targets of licofelone, the underlying mechanisms of central effects of this drug are not still fully understood. We have utilized pentylenetetrazole-induced clonic seizure model to investigate the behavioral consequences of licofelone administration and its possible mechanisms in seizure susceptibility. Licofelone revealed anticonvulsant properties at the dose of 10 mg/kg (i.p) or higher in mice. Pre-treatment with NO (nitric oxide) donor, L-arginine, reversed this anticonvulsant effects dose dependently. L-NAME, as a non-selective nitric oxide synthase (NOS) inhibitor, potentiated the anticonvulsant effects of licofelone. A neuronal NOS inhibitor, 7-NI did not affect seizure threshold alone or in combination with licofelone. Using non-effective doses of selective inhibitors of inducible NOS, aminoguanidine or 1400W, significantly increased the seizure threshold when were accompanied by licofelone in low doses. These data support the involvement of NO as an important role player in the central neuro-protective properties of licofelone. Furthermore, it implies that down regulation of iNOS seems crucial for anticonvulsant properties of this COX/5-LOX inhibitor in seizure susceptibility.

The modification of tumor-associated antigen-based vaccine to elicit a more robust immune response has been addressed in several ways. In the present work, we aimed to investigate the immunomodulatory effect of selenium nanoparticles as an immunoadjuvant in formulation of a tumor-associated antigen-based vaccine in a preventive form. Fortyfive female inbred BALB/c mice five-to-seven weeks old were used and divided into three groups of test and control, each containing fifteen mice. Group one injected by PBS and used as a control. Group two injected by breast tumor cell lysate alone as vaccine. Group three injected by SeNPs with tumor cell lysate as vaccine. All injections were carried out on day fourteen, twentyone and twentyeight of the study. Tumor induction was done at day thirty. Twenty days after tumor induction serum samples were gathered to measure the cytokine assay. Tumor growth and weight of mice as well as delayed type hyper sensitivity (DTH) response were monitored during the study. Results of the present work showed a significant increase in the level of serum IFN-γ, IL-2, IL-12 and decreased TGF-β in SeNPs/vaccine injected mice as well as lower tumor volume, more potent DTH responses and longer survival rate in comparison to control and tumor lysate vaccine. Taken together, it can be deduced from this work that SeNPs can be considered as an adjuvant in vaccine in triggering robust immune response against breast cancer. But further evaluations are still needed to find the best formula for this agent in antitumor vaccines.

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