Identification of candidate biomarkers in converting and non-converting clinically isolated syndrome by proteomics analysis of cerebrospinal fluid.

Multiple sclerosis (MS) often starts in the form of clinically isolated syndrome (CIS) and only some of the CIS patients progress to relapsing-remitting MS (RRMS). Biomarkers to predict conversion from CIS to MS are thus greatly needed for making correct treatment decisions. To identify a predictive cerebrospinal fluid (CSF) protein, we analyzed the first-attack CSF samples of CIS patients who converted (CIS-MS) (n = 23) and did not convert (CIS-CIS) (n = 19) to RRMS in a follow-up period of 5 years using proteomics analysis by liquid chromatography tandem-mass spectrometry (LC-MS/MS) and verified by ELISA. Label-free differential proteomics analysis of CSF ensured that 637 proteins were identified and 132 of these proteins were found to be statistically significant. Further investigation with the ingenuity pathway analysis (IPA) software led to identification of three pathway networks mostly comprised proteins involved in inflammatory response, cellular growth and tissue proliferation. CSF levels of four of the most differentially expressed proteins belonging to the cellular proliferation network function, chitinase-3-like protein 1 (CHI3L1), tumor necrosis factor receptor superfamily member 21 (TNFRSF21), homeobox protein Hox-B3 (HOXB3) and iduronate 2-sulfatase (IDS), were measured by ELISA. CSF levels of HOXB3 were significantly increased in CIS-MS patients. Our results indicate that cell and tissue proliferation functions are dysregulated in MS as early as the first clinical episode. HOXB3 has emerged as a potential novel biomarker which might be used for prediction of CIS-MS conversion.

Natural products are the future of anticancer therapy: Preclinical and clinical advancements of Viscum album phytometabolites.

Cancer is a multifaceted and genomically complex disease. Research over the years has gradually provided a near complete resolution of cancer landscape and it is now known that genetic/epigenetic mutations, inactivation of tumor suppressors, Overexpression of oncogenes, spatio-temporally dysregulated intracellular signaling cascades, epithelial to mesenchymal transition (EMT), metastasis and loss of apoptosis are some of the most extensively studied biological mechanisms that underpin cancer development and progression. Increasingly it is being realized that current therapeutic interventions are becoming ineffective because of tumor heterogeneity and rapidly developing resistance against drugs. Considerable biological activities exerted by bioactive ingredients isolated from natural sources have revolutionized the field of natural product chemistry and rapid developments in preclinical studies are encouraging. Viscum album has emerged as a deeply studied natural source with substantial and multifaceted biological activities. In this review we have attempted to provide recent breakthroughs in existing scientific literature with emphasis on targeting of protein network in cancer cells. We partition this review into different sections, highlighting latest information from cell culture studies, preclinical and clinically oriented studies. We summarized how bioactive ingredients of Viscum album modulated extrinsic and intrinsic pathways in cancer cells. However, surprisingly, none of the study reported stimulatory effects on TRAIL receptors. The review provided in-depth analysis of how Viscum album modulated Endoplasmic Reticulum Stress in cancer cells and how bioactive chemicals tactfully targeted cytoskeletal machinery in cancer cells as evidenced by cell culture studies. It is noteworthy that Viscum album has entered into various phases of clinical trials, however, there are still knowledge gaps in our understanding regarding how various bioactive constituents of Viscum album modulate intracellular signaling cascades in cancer. Better and deeper comprehension oncogenic signaling cascades will prove to be helful in getting a step closer to individualized medicine.

Expression levels of elastin and related genes in human varicose veins.

Among the suspected reasons for varicose vein formation are changes in the quantity and content of the elastin protein; however, comprehensive investigations about elastin assembly in varicose vein formation are yet lacking. In this study, we aimed to determine the changes in mRNA levels of elastin and some of its functionally related proteins, fibulin 5, LOXL-1, MMP-2 and MMP-9 in varicose vein formation. We analysed the mRNA levels of elastin, fibulin-5, LOXL1, MMP2 and MMP9 in samples of 35 healthy and 35 varicose great saphenous vein tissues. mRNA levels of these genes were determined by using real-time PCR and normalized with HPRT1. When we compared the patient and control groups, elastin mRNA levels were significantly higher in the patient group than in the control group (P = 0.047), although there were no significant differences in fibulin 5, LOXL1, MMP2 and MMP9 mRNA levels between the patient and control groups. We showed that up-regulation of MMP2 mRNA expression was significantly correlated with hyperlipidaemia (P = 0.029). The up-regulation of elastin expression may play an important role in the pathogenesis of primary varicose veins. Additionally, the up-regulation of MMP2 expression was strongly correlated with hyperlipidaemia in varicose veins.