The association of plasma levels of miR-146a, miR-27a, miR-34a, and miR-149 with coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is considered to be one of the most pivotal causes of death in the world. Over the past two decades, significant changes occurred in the diagnosis, prognosis, and treatment of CAD, which has helped reduce mortality rates. microRNAs (miRs) are a class of more than 5000 non-encoding RNA molecules (21-25 nucleotides across the length) that regulate complex biological processes. Today, miRNAs are used to study cardiovascular diseases. In the present study, the expression of miR-146a،miR-27, miR-149, and miR-34a in plasma suffering from CAD and the control group were investigated. METHODS AND RESULTS: The present research was performed on 30 men with CAD and 30 healthy men as controls. The expression levels of miR-146a, miR-27a, miR-149, and miR-34a in the plasma of patients with CAD and the control group were measured using real-time PCR. Also, the correlation between the expression of circulating miRs levels and biochemical LDL-C, HDL-C, BMI, and total cholesterol was evaluated. The expression of miR-27a in the plasma of the CAD group was higher than in the control group (p = 0.020). The expression of miR-146a was downregulated in CAD patients compared to normal subjects (p = 0. 026). However, the expression of miR-34a, miR-149 in the plasma of CAD patients was not significantly different with the control group. In addition to, a direct correlation was found between the expression of miR-146a and HDL-c, the expression of miR-27a and LDL-C and the expression of miR-34a and total cholesterol. Also, the negative correlation between expressions of miR-149 with BMI was reported. CONCLUSION: The obtained results demonstrated that miRs were closely related to biochemical factors and it points out the fact that miRNAs can be applied as a potential strategy for diagnosis and treatment of CAD.

Targeted delivery of interleukin-12 plasmid into HepG2 cells through folic acid conjugated graphene oxide nanocarrier.

Successful gene therapy relies on carriers to transfer genetic materials with high efficiency and low toxicity in a targeted manner. To enhance targeted cell binding and uptake, we developed and synthesized a new gene delivery vector based on graphene oxide (GO) modified by branched polyethyleneimine (BPEI) and folic acid (FA). The GO-PEI-FA nanocarriers exhibit lower toxicity compared to unmodified PEI, as well as having the potential to efficiently condense and protect pDNA. Interestingly, increasing the polymer content in the polyplex formulation improved plasmid transfer ability. Substituting graphene oxide for PEI at an N/P ratio of 10 in the HepG2 and THP1 cell lines improved hIL-12 expression by up to approximately eightfold compared to simple PEI, which is twice as high as GO-PEI-FA in Hek293 at the same N/P ratio. Therefore, the GO-PEI-FA described in this study may serve as a targeting nanocarrier for the delivery of the hIL-12 plasmid into cells overexpressing folic acid receptors, such as those found in hepatocellular carcinoma.

Folic Acid-Functionalized Albumin/Graphene Oxide Nanocomposite to Simultaneously Deliver Curcumin and 5-Fluorouracil into Human Colorectal Cancer Cells: An In Vitro Study.

Background: Nowadays, due to various inherent properties, graphene-based nanoparticles are widely used in drug delivery research. On the other hand, folate receptors are highly expressed on the surface of human tumor cells. In this work, to enhance the 5-fluorouracil (5FU) and curcumin (Cur) effects on colon cancer, we constructed a folic acid- (FA-) modified codelivery carrier based on graphene nanoparticles (GO-Alb-Cur-FA-5FU). Materials and Methods: The HUVEC and HT-29 were selected for evaluating the antitumor effect of the prepared nanocarriers. The structure of nanocarriers was characterized by FTIR spectroscopy, X-ray diffraction analysis, TEM microscopy, and a DLS analyzer. The efficiency of the prepared carrier was evaluated by fluorescence microscopy using Annexin V and the PI kit. The cytotoxicity of the carrier's component individually and the efficacy of the drug carrier GO-Alb-Cur-FA-5FU were assessed by MTT. Results: The results of the pharmacological tests indicated that the new nanoparticles cause increased apparent toxicity in HT-29 cells. The apoptosis rate of the HT-29 and HUVEC cells treated with IC50 values of GO-Alb-Cur-FA-5FU for 48 h was higher than the cells treated with IC50 values of 5FU and Cur individually, which indicated the greater inhibitory efficacy of GO-Alb-Cur-FA-5FU than free drugs. Conclusion: The designed GO-Alb-CUR-FA-5FU delivery system can be applied for targeting colon cancer cells and can be severe as a potential candidate for future drug development.

Interleukin-12 Plasmid DNA Delivery by N-[(2-Hydroxy-3-trimethylammonium)propyl]chitosan-Based Nanoparticles.

Cationic polysaccharides are capable of forming polyplexes with nucleic acids and are considered promising polymeric gene carriers. The objective of this study was to evaluate the transfection efficiency and cytotoxicity of N-[(2-hydroxy-3-trimethylammonium)propyl] chitosan salt (HTCS), a quaternary ammonium derivative of chitosan (CS), which benefits from non-ionizable positive charges. In this work, HTCS with a full quaternization of amino groups and a molar mass of 130,000 g·mol-1 was synthesized to use for delivery of a plasmid encoding the interleukin-12 (IL-12) gene. Thus, a polyplex based on HTCS and the IL-12 plasmid was prepared and then was characterized in terms of particle size, zeta potential, plasmid condensation ability, and protection of the plasmid against enzymatic degradation. We showed that HTCS was able to condense the IL-12 plasmid by the formation of polyplexes in the range of 74.5 ± 0.75 nm. The level of hIL-12 production following the transfection of the cells with HTCS polyplexes at a C/P ratio of 8:1 was around 4.8- and 2.2-fold higher than with CS and polyethylenimine polyplexes, respectively. These findings highlight the role of HTCS in the formation of polyplexes for the efficient delivery of plasmid DNA.