Effect of co-treatment with doxorubicin and verapamil loaded into chitosan nanoparticles on diethylnitrosamine-induced hepatocellular carcinoma in mice.

This study aimed to investigate the potential role of co-treatment with doxorubicin (DOX) and verapamil (VRP) nanoparticles in experimentally induced hepatocellular carcinoma in mice and to investigate the possible mechanisms behind the potential favorable effect of the co-treatment. DOX and VRP were loaded into chitosan nanoparticles (CHNPs), and cytotoxicity of loaded and unloaded drugs against HepG2 cells was evaluated. Male albino mice were divided into eight groups (n = 15): (1) normal control, (2) diethylnitrosamine, (3) CHNPs, (4) free DOX, (5) CHNPs DOX, (6) free VRP, (7) CHNPs VRP, and (8) CHNPs DOX + CHNPs VRP. Either VRP or DOX loaded into CHNPs showed stronger growth inhibition of HepG2 cells than their free forms. DOX or VRP nanoparticles displayed pronounced anticancer activity in vivo through the decline of vascular endothelial growth factor and B cell lymphoma-2 contents in liver tissues, upregulation of antioxidant enzymes, and downregulation of multidrug resistance 1. Moreover, reduced cardiotoxicity was evident from decreased level of tumor necrosis factor-α and malondialdehyde in heart tissues coupled with decreased serum activity of creatine kinase-myocardial band and lactate dehydrogenase. Co-treatment with CHNPs DOX and CHNPs VRP showed superior results versus other treatments. Liver sections from the co-treatment group revealed the absence of necrosis, enhanced apoptosis, and nearly normal hepatic lobule architecture. Co-treatment with CHNPs DOX and CHNPs VRP revealed enhanced anticancer activity and decreased cardiotoxicity versus the corresponding free forms.

Serum LINC00305 expression and its genetic variant rs2850711 are associated with clinical and laboratory features of rheumatoid arthritis.

BACKGROUND: Long intergenic non-protein coding (lnc) RNA 00305 (LINC00305) is a pro-inflammatory atherosclerosis-associated lncRNA. We hypothesised that LINC00305 expression and its variant rs2850711 (A/T) are implicated in rheumatoid arthritis (RA) and linked with clinical and routine laboratory markers. METHODS: 100 RA patients and 100 healthy controls were recruited. LINC00305 genotyping and expression were performed using allelic-discrimination PCR and quantitative real-time PCR. LINC00305 diagnostic power was evaluated using area under the receiver operating characteristic curve (AUC). Serum nuclear factor- κB (NF-κB) and matrix metalloproteinase-3 (MMP-3) levels were determined by ELISA, standard laboratory markers by routine methods. RESULTS: LINC00305 expression was significantly increased in RA patients and positively correlated with DAS28, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor and anti-cyclic citrullinated peptide antibody. In multivariate analysis, NF-κB, MMP-3 and LINC00305 were significant predictors of RA (P< 0.0001). Individuals carrying AT and TT genotypes of rs2850711 polymorphism had significantly more likely to have RA than AA genotype carriers (P< 0.05). LINC00305 expression, DAS28 score and serum levels of NF-κB and MMP-3 were significantly increased in the patients carrying LINC00305 AT and TT genotypes as compared with AA genotype patients (P< 0.01). CONCLUSION: Increased expression level of LINC00305 and its rs2850711 genetic variant may play a role in the diagnosis and management of RA, and its severity and activity.

Association of MicroRNA-146a rs2910164 Gene Polymorphism with Metabolic Syndrome.

Alteration in microRNA-146a (miRNA-146a) expression is an important event in the pathogenesis of many human diseases. MiRNA-146a rs2910164 is a functional polymorphism that showed association with several diseases. Metabolic syndrome is an aggregation of multiple risk factors including impaired glucose tolerance, increased highdensity lipoprotein, abdominal obesity, and high blood pressure. The aim of this study was to assess the relation of miRNA-146a rs2910164 with metabolic syndrome and its component traits in Egyptian women from the Suez Canal area. The study included 100 healthy female subjects and 100 metabolic syndrome patients. The component traits of metabolic syndrome were determined and the genotypes of the polymorphisms were assessed using the polymerase chain reaction-restriction fragment length polymorphism technique using the restriction enzyme Hpy188I. The rare C allele had a significantly higher frequency in metabolic syndrome patients (P = 0.013). The heterozygote GC and the rare CC genotypes showed a significant increase in body mass index, waist circumference, triglycerides, total cholesterol, low-density lipoprotein, systolic and diastolic blood pressure. The GC genotype was associated with higher fasting blood glucose, fasting serum insulin and insulin resistance. The carriers of CC genotype had significantly lower HDL compared with the GG genotype carriers. In conclusion, The C allele of miRNA-146a rs2910164 showed positive association with increased susceptibility to metabolic syndrome and its phenotypes in the study population.