Plasma Proteome Profiling of Coronary Artery Disease Patients: Downregulation of Transthyretin-An Important Event.

Coronary artery disease (CAD) is a prevalent chronic inflammatory cardiac disorder. An early diagnosis is likely to help in the prevention and proper management of this disease. As the study of proteomics provides the potential markers for detection of a disease, in the present investigation, attempt has been made to identify disease-associated differential proteins involved in CAD pathogenesis. For this study, a total of 200 selected CAD patients were considered, who were recruited for percutaneous coronary intervention (PCI) treatment. The proteomic analysis was performed using two-dimensional gel electrophoresis (2-DE) and MALDI-TOF MS/MS. Samples were also subjected to Western blot analysis, enzyme-linked immunosorbent assay (ELISA), peripheral blood mononuclear cells isolation immunofluorescence (IF) analysis, analytical screening by fluorescence-activated cell sorting (FACS), and in silico analysis. The representative data were shown as mean ± SD of at least three experiments. A total of 19 proteins were identified. Among them, the most abundant five proteins (serotransferrin, talin-1, alpha-2HS glycoprotein, transthyretin (TTR), fibrinogen-α chain) were found to have altered level in CAD. Serotransferrin, talin-1, alpha-2HS glycoprotein, and transthyretin (TTR) were found to have lower level, whereas fibrinogen-α chain was found to have higher level in CAD plasma compared to healthy, confirmed by Western blot analysis. TTR, an important acute phase transport protein, was validated low level in 200 CAD patients who confirmed to undergo PCI treatment. Further, in silico and in vitro studies of TTR indicated a downexpression of CAD in plasma as compared to the plasma of healthy individuals. Lower level of plasma TTR was determined to be an important risk marker in the atherosclerotic-approved CAD patients. We suggest that the TTR lower level predicts disease severity and hence may serve as an important marker tool for CAD screening. However, further large-scale studies are required to determine the clinical significance of TTR.

Evaluation of Anti-inflammatory Effects of Choerospondias axillaris Fruit's Methanolic Extract in Synoviocytes and CIA Rat Model.

BACKGROUND: Rheumatoid Arthritis (RA) is an autoimmune, systemic disease mainly affecting joints. Presently, there is no specific treatment/ drug available for curing RA except few supportive medicines. Therefore, the focus has been shifted to medicinal plants for the treatment of such diseases. Choerospondias axillaris commonly known as Lupsi/Lapsi and has been reported to have several properties for the treatment of various diseases. OBJECTIVE: The present study has been conducted to explore the anti-inflammatory effects of Choerospondias axillaris fruit extract on Synoviocytes (FLS) and Collagen-Induced Arthritis (CIA) rat model. METHODS: Methanolic extract of the Choerospondias axillaris fruit was used for determining phytochemical, antioxidant and anti-inflammatory properties. Antioxidant activity of Choerospondias axillaris fruit was determined by free radicals scavenging assays and bioactive compounds were identified via LC-MS/MS analysis. Anti-inflammatory effect was investigated in RA and Osteo Arthritis (OA) primary cells and also in Collagen Induced Arthritis (CIA) rat models. Further, the medicinal properties of anti-inflammatory bioactive compounds were supported by docking studies. RESULTS: In-vitro and in-vivo studies showed significant decrease in the levels of inflammatory cytokines. Docking analysis revealed that quercetin inhibits TNF-α having -9.1 kcal/mol binding energy and 10.13 µM inhibitory constant. Quercetin also inhibits IL-6 having -6.6 kcal/mol binding energy and 21.9 µM inhibitory constant. CONCLUSION: Observed results suggest that the underutilized fruit Choerospondias axillaris can be used to reduce the inflammation of inflammatory diseases like RA.

Genome Wide Analysis of Chlamydia pneumoniae for Candidate Vaccine Development.

BACKGROUND: Chlamydia pneumoniae (C. pneumoniae) is a pathogen associated with respiratory tract infection of humans and its viable presence in atherosclerotic plaques is also assumed to play significant function in cardiac diseases. Unavailability of effective antimicrobial drugs has implicated the urgent need of some more disease associated vaccines that may provide relief efficiently. Thus, present study has been undertaken to analyse the whole proteome of C. pneumoniae in order to propose bacterial proteins as candidate vaccine for CAD by taking the aid of 'Reverse Vaccinology'. METHODS: Whole proteome of C. pneumoniae was downloaded and redundancy was removed by CD-HIT web server. Similarity search between proteins of C. pneumoniae and Homo sapiens was performed by BLASTP to avoid human similar proteins. Virulent proteins were selected by VirulentPred web server. Sub cellular localization of identified proteins was investigated by LocTree3 and pSORTb servers. Surface accessibility area (SAA) and antigenic epitopes prediction has been undertaken by prediction of protease specificity (POPS) and Ellipro, NetMHCpan 3.0 servers respectively. Functional significance of identified proteins was predicted through 3D model construction followed by the ligand binding site, active site and domain characterization. RESULTS: Three reference proteins RVOM1, RVOM2, RVEC1 were predicted with the crucial role in C. pneumoniae that may be capable of inducing B cell and T cell response. CONCLUSION: Detailed analysis of these proteins indicated that they may be utilized as the vaccine candidates during the chlamydial infection in near future.