Delivery of siRNA using hyaluronic acid-guided nanoparticles for downregulation of CXCR4.

In this study, effective transport of small interfering RNAs (siRNAs) via hyaluronic acid (HA) receptor was carried out with biodegradable HA and low-molecular weight polyethyleneimine (PEI)-based transport systems. Gold nanoparticles (AuNPs) capable of giving photothermal response, and their conjugates with PEI and HA, were also added to the structure. Thus, a combination of gene silencing, photothermal therapy and chemotherapy, has been accomplished. The synthesized transport systems ranged in size, between 25 and 690 nm. When the particles were applied at a concentration of 100 µg mL-1 (except AuPEI NPs) in vitro, cell viability was above 50%. Applying radiation after the conjugate/siRNA complex (especially those containing AuNP) treatment, increased the cytotoxic effect (decrease in cell viability of 37%, 54%, 13%, and 15% for AuNP, AuPEI NP, AuPEI-HA, and AuPEI-HA-DOX, respectively) on the MDA-MB-231 cell line. CXCR4 gene silencing via the synthesized complexes, especially AuPEI-HA-DOX/siRNA was more efficient in MDA-MB-231 cells (25-fold decrease in gene expression) than in CAPAN-1 cells. All these results demonstrated that the synthesized PEI-HA and AuPEI-HA-DOX conjugates can be used as siRNA carriers that are particularly effective, especially in the treatment of breast cancer.

The Investigation of the Cox-2 Selective Inhibitor Parecoxib Effects in Spinal Cord Injury in Rat.

Aim: Today, spinal cord injury (SCI) can be rehabilitated but cannot be treated adequately. This experimental study was conducted to investigate possible beneficial effects of methylprednisolone and parecoxib in treatment of SCI. Materials and methods: Forty-eight male Wistar albino rats were assigned into CONTROL, acute (MP-A, PX-A, and PXMP-A), and subacute (MP-S, PX-S, and PXMP-S) stage groups. Then, to induce SCI, a temporary aneurysm clip was applied to the spinal cord following T7-8 laminectomy, except in the CONTROL group. Four hours later parecoxib, methylprednisolone, or their combination was administered to rats intraperitoneally except CONTROL, SHAM-A, and SHAM-S groups. Rats in the acute stage group were sacrificed 72 h later, and whereas rats in the subacute stage were sacrificed 7 days later for histopathological and biochemical investigation and for gene-expression analyses. Results: Parecoxib and methylprednisolone and their combination could not improve histopathological grades in any stage. They also could not decrease malondialdehyde or caspase-3, myeloperoxidase levels in any stage. Parecoxib and methylprednisolone could decrease the TNF-α gene expression in subacute stage. Methylprednisolone could increase TGF-1ß gene-expression level in acute stage. Conclusion: Neither of the experimental drugs, either alone or in combination, did not show any beneficial effects in SCI model in rats.

Elevated Tear Human Neutrophil Peptides 1-3, Human Beta Defensin-2 Levels and Conjunctival Cathelicidin LL-37 Gene Expression in Ocular Rosacea.

Purpose: To investigate the role of innate immunity in ocular rosacea. Methods: Thirty-two patients with ocular rosacea patients (group-1) and 28 healthy volunteers (group-2) who served as controls were enrolled in the study. Tear function parameters were assessed, conjunctival impression cytology was performed and tear samples were collected. Human-neutrophil-peptides (HNP) 1-3 and human-beta-defensin-2 (hBD-2) levels were measured in tears by using ELISA tests. Cathelicidin leucin-leucin-37 (LL-37), hBD-2, human-beta-defensin-9 (hBD-9) gene expression levels were measured in the conjunctival impression cytology samples using real-time polymerase chain reaction. Results: Tear HNP1-3 (p = 0.024), hBD-2 (p < 0.001), conjunctival LL-37 gene expression rate (p = 0.014) and ocular surface disease index scores (p = 0.001) were higher and the tear break-up time was lower (p = 0.003) in group-1. No other differences were found between the groups. Conclusion: The results of this study suggest the role of abnormal innate immunity in the pathophysiology of ocular rosacea by revealing elevated antimicrobial peptide levels.

Effects of DMSO on a rabbit ear hypertrophic scar model: A controlled randomized experimental study.

Dimethyl sulfoxide (DMSO) is an anti-inflammatory, antibacterial, analgesic drug widely used to treat several diseases as reported in the literature. It has a detractive effect on collagen deposition in the abnormal tissue. This study aimed to investigate the possible therapeutic effects of DMSO on hypertrophic scar formation in rabbits. Twenty-four New Zealand male albino rabbits were randomly divided into four groups: control, sham, DMSO, and TRA (triamcinolone acetonide). Except the control group, punch biopsy defects were created on each animal's right ear. Following the hypertrophic scar formation on day 28, intralesional DMSO and triamcinolone acetonide were administered once a week for 4 weeks into these scars of the DMSO and TRA groups, respectively. No therapeutic agent was administered to the control and sham groups. One week after the last injection, ear samples were collected for histopathological, immunohistochemical, and real-time polymerase chain reaction gene expression analyses. Histopathological examination revealed that the epithelium in the DMSO group was thicker than that in the control and TRA groups, but thinner than that in the sham group. Connective tissue thickness and vascularity level of the sham group were higher than those of the control, DMSO, and TRA groups. The collagen type I immunoreactivity level of the sham and TRA groups was higher than those of the control and DMSO groups. The collagen type III immunoreactivity level was higher in the sham group than in all other groups. Collagen type I/type III immunoreactivity ratios were lower in the DMSO group. The alignment of collagen fibers was normal in the DMSO group, but was irregular in the sham and TRA groups. The collagen type I gene expression levels of the DMSO and TRA groups were lower than that of the sham group. Collagen type III and IFN-γ mRNA expression levels were almost similar among the groups. TGF-1ß mRNA expression levels were higher in the DMSO and TRA groups than in the control and sham groups. On the basis of the results, it can be concluded that intralesional administration of DMSO decreases hypertrophic scar formation easily and safely.