Background: Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system. Cytokines plays critical role in pathogenesis of disease. Until now, serum and Cerebrospinal fluid (CSF) levels of many biomarkers and their correlations with MS features have been evaluated. In this study, we measured serum and CSF levels of C-reactive protein (CRP) and IFN-␥ in patients with Multiple sclerosis and their correlations with paraclinical features of MS have been evaluated. Materials and methods: CSF and serum samples were recruited from relapsing remitting multiple sclerosis patients (n = 40) and healthy subjects (n = 40). CSF and serum level measurement of IFN-␥ and CRP were performed using enzyme-linked immunosorbent assay (ELISA). Results: CSF and serum levels of IFN-␥ and CRP were significantly higher in MS patients compared to healthy control group (P < 0.01). We found positive correlations between the CSF and serum levels of IFN-␥ and expanded disability status scale (EDSS) of the MS patients (r = +0.80, P < 0.01; r = +0.34 and P = 0.03, respectively). Moreover, there was a significant association between the serum levels of CRP and EDSS of the patients (r = +0.54 and P < 0.01). Conclusion: Our findings reveal the increased CSF and serum levels of IFN-␥ and CRP in MS patients. Our data suggest that determining serum levels of IFN-␥ and CRP could be useful for understanding and monitoring the inflammatory response in MS. Furthermore, CSF levels of IFN-␥ is more reliable and useful than its serum levels for monitoring of severity of disability in MS patients.
Listeriolysine-O (LLO) is a 50KDa protein responsible for Listeria monocytogenes pathogenicity. The structure of LLO (PDB ID: 4CDB) with
domains D1 to D4 is known. Therefore, it is of interest to identify conserved regions among LLO variants for destabilizing oligomerization
(50 mer complex) of its monomers using appropriate inhibitors. Therefore, it is of interest to identify suitable inhibitors for inhibiting LLO.
Previous reports suggest the use of flavanoids like compounds for inhibiting LLO. Our interest is to identify improved compounds to
destabilize LLO oligomerization. We used a library (Zinc database) containing 200,000 drug-like compounds against LLO using molecular
docking based screening. This resulted in five hits that were further analyzed for pharmacological properties. The hit #1 (2-methyloctadecane-
1, 3, 4-triol) was further refined using appropriate modifications for creating a suitable pharmacophore model LLO inhibition.
The modified compound (1-(4-Cyclopent-3-enyl-6, 7-dihydroxy-8-hydroxymethyl-nona-2, 8-dienylideneamino)-penta-1,4-dien-3-one)
shows fitting binding properties with LLO with no undesirable pharmacological properties such as toxicity.
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