Association of CD14 and macrophage migration inhibitory factor gene polymorphisms with inflammatory microRNAs expression levels in ankylosing spondylitis and polyarthralgia.

This study aimed to investigate the genetic basis of ankylosing spondylitis (AS) and polyarthralgia (PA) conditions among Indian subjects through genotyping two immune regulatory genes CD14 (-159C>T) and MIF (-173G>C) and find their association with the expression levels of three circulating inflammatory miRNAs. This investigation may provide early genetic cause of these two forms of arthritis and more optimal biological targets to predict early therapeutic outcomes. A total of 140 patients (AS: 70 and PA: 70) and 156 controls were recruited from Indian population. CD14 and MIF genotyping was performed using ARMS-PCR. Expression level of three inflammatory miRNAs (miRNA-146a, miRNA-155 and miRNA-181) was quantified using RT-qPCR. C/T genotype of CD14 gene was found to cause 2.06-fold risk of developing AS (CI 1.06-5.98, p = .04) as compared to others and G/C genotype in MIF also shown significant variation between AS and control subjects. In PA subjects, CD14 genotypes (C/T) was found to be associated with disease susceptibility and G/C genotype of MIF gene polymorphism showed 4.71-fold risk of developing PA (CI 2.58-8.62, p = .0001). The study also revealed significant upregulation of miRNA-155 expression in AS subjects (p = .0001) with more than 1.3-fold difference between AS and PA as compared to the control subjects. miRNA-155 had strong association with AS patients with CD14 genotypes (p < .05) than PA and control subjects. This study provides better understanding of the mechanisms and disease susceptibility for MIF and CD14 genetic variants and inflammatory miRNAs networks involved in AS and PA.

Use of Biocompatible Sorafenib-gold Nanoconjugates for Reversal of Drug Resistance in Human Hepatoblatoma Cells.

The present study identifies the potential of highly biocompatible SF-GNP nano-conjugate to enhance the chemotherapeutic response to combat drug resistance in cancer cells. We developed a stable colloidal suspension of sorafenib-gold nanoconjugate (SF-GNP) of <10 nm size in aqueous medium for reverting the cancer drug resistance in SF-resistant HepG2 cells in a 3D ex-vivo model system. In-vivo biocompatibility assay of SF-GNPs showed absence of systemic toxicological effects including hematological, biochemical and histological parameters. More importantly, the histopathological analysis of vital organs such as liver, brain, lung, kidney and heart showed very least or no sign of inflammation, cell infiltration, necrosis, tissue disorganization or fibrotic reactions after intra-peritoneal administration of SF-GNP nanoconjugates in animals. However, SF-GNP nanoconjugates significantly reduced (>80%) the percentage cell survival and the size and number of SF resistant solid tumor colonies of HepG2 cells in 3D model system. The exposure of SF-GNP nanoconjugate to SF resistant HepG2 cell colonies also provided evidence for anti-proliferative effect and reversal of drug resistance by elucidating the molecular regulatory mechanisms of extracellular matrix factor (CD147), tumor growth factor (TGF-ß), hepatoma upregulated protein (hURP) and drug transporter (ABCG-2).