<Emphasis Type="Italic">N</Emphasis>-(2-Hydroxyphenyl)acetamide: a Novel Suppressor of RANK/RANKL Pathway in Collagen-Induced Arthritis Model in Rats

RANKL and RANK are potential contributors of inflammatory cascade in human and animal model of arthritis. The current study aims to investigate the effect of N-(2-hydroxyphenyl)acetamide (NA-2) on regulation of RANKL pathway in collagen-induced arthritis (CIA) model in rats. CIA was induced using bovine type II collagen in female Wistar rats. The clinical parameters, level of pro-inflammatory and oxidative stress markers were measured to determine the progression of the disease. The mRNA level of RANKL and RANK and downstream mediators of inflammation i.e. c-fos, c-jun, NF-κB and Akt were analysed in spleen tissue using real-time PCR. Immunohistochemical analysis of iNOS, pAkt and c-Fos was also done in spleen tissue. Treatment with NA-2 and indomethacin showed increase in body weight and significant reduction in paw volume and arthritic score (p < 0.0001). Marked reduction in the level of oxidative stress markers, NO, PO and GSH (p < 0.0001), and pro-inflammatory markers, IL-1β (p < 0.0001) and TNF-α (p < 0.01), was also observed. Likewise, NA-2 and indomethacin treatment also significantly suppressed the mRNA expression of RANKL, RANK, c-fos, c-jun, NF-κB (p < 0.0001) and Akt (p < 0.01) and protein expression of iNOS, pAkt and c-Fos (p < 0.0001) compared to the arthritic control group. Our findings suggest that NA-2 is an antiarthritic agent acting in a pleiotropic manner in CIA rats by not only reducing the clinical signs of arthritis, inflammatory cytokines and free radical production but also attenuating the RANK/RANKL signaling pathway.     

Is the IL-10 −819 Polymorphism Associated with Visceral Leishmaniasis?

Previous investigations demonstrated that immune responses play critical roles in the defense against visceral leishmaniasis (VL). A key regulator of immune responses is the cytokine, IL-10 and polymorphisms within its promoter which could alter its expression. Thus, the aim of this study was to examine the correlation between polymorphism at the ?819 position of the IL-10 gene and VL in a selected Iranian population. This cross-sectional study was performed on 100 patients with clinical presentation of VL and seropositive for the leishmania (group 1), 62 patients without clinical presentation but seropositive (group 2), and 128 healthy controls (group 3). The IL-10 ?819 polymorphism was evaluated using the PCR-RFLP technique. The anti-leishmania antibody titration was assessed using an immunofluorescence assay. Our results showed that the polymorphism at IL-10 ?819 (C/T) position was significantly associated with VL, and C/T genotype was significantly higher in VL patients when compared to groups 2 and 3 (p?<?0.001). However, the results demonstrated that the C and T alleles were not associated with VL (p?=?0.855). The data presented here confirm the results of previous reports that polymorphisms at the ?819 position of the IL-10 gene can influence susceptibility to VL suggesting that the C/T genotype may be considered as a risk factor for the disease.     

Evaluation of the effect of static magnetic field in treatment of tendon injuries in dog

To assess the effect of magnetic field in experimental tendon injuries, ten clinically healthy adult indigenous dogs were divided into two equal groups (control and experimental). The left superficial digital flexor tendon was exposed and three windows of 6 mm thickness, 3 mm length, and 2 mm intervals were made under general anesthesia. In the experimental group, the dogs were subjected to a magnetic field of 6?×?800 G for 30 days. The tendon biopsy was collected from the site of operation on the postoperative day 30. Histomorphological changes indicated low rate of inflammatory cells, high rate of mature fibroblast, and increased normal collagen fibers, and these were better in the experimental group. The biomechanical test revealed that the tendons of the dogs in the experimental group were more resistant than tendons of the dogs in the control group. The result of this study indicated that magnetic field therapy reduced edema and local swelling, enhanced proliferation of fibroblasts, and regulated arrangement of collagen fibers, providing a good noninvasive physical therapy for tendinous injuries.     

Recurrent pre‐existing and acquired DNA copy number alterations,including focal TERT gains,in neuroblastoma central nervous system metastases

Stage 4 neuroblastomas have a high rate of local and metastatic relapse and associated disease mortality. The central nervous system (CNS) is currently one of the most common isolated relapse sites, yet the genomic alterations that contribute to these metastases are unknown. This study sought to identify recurrent DNA copy number alterations (CNAs) and target genes relating to neuroblastoma CNS metastases by studying 19 pre‐CNS primary tumors and 27 CNS metastases, including 12 matched pairs. SNP microarray analyses revealed that MYCN amplified (MYCNA) tumors had recurrent CNAs different from non‐MYCNA cohorts. Several CNAs known to be prevalent among primary neuroblastomas occurred more frequently in CNS metastases, including 4p?, 7q+, 12q+, and 19q? in non‐MYCNA metastases, and 9p? and 14q? irrespective of MYCNA status. In addition, novel CNS metastases‐related CNAs included 18q22.1 gains in non‐MYCNA pre‐CNS primaries and 5p15.33 gains and 15q26.1→tel losses in non‐MYCNA CNS metastases. Based on minimal common regions, gene expression, and biological properties, TERT (5p), NR2F2 (15q), ALDH1A3 (15q), CDKN2A (9p), and possibly CDH7 and CDH19 (18q) were candidate genes associated with the CNS metastatic process. Notably, the 5p15 minimal common region contained only TERT, and non‐MYCNA CNS metastases with focal 5p15 gains had increased TERT expression, similar to MYCNA tumors. These findings suggest that a specific genomic lesion (18q22.1 gain) predisposes to CNS metastases and that distinct lesions are recurrently acquired during metastatic progression. Among the acquired lesions, increased TERT copy number and expression appears likely to function in lieu of MYCNA to promote CNS metastasis. © 2013 Wiley Periodicals, Inc.     

Emergence of mupirocin-resistant MRSA among Iranian clinical isolates

Mupirocin is a topical antimicrobial agent which is increasingly used for the treatment and eradication of Staphylococcus aureus colonization from the noses of patients and hospital staff. However, the extensive use of this antibiotic has given rise to mupirocin resistance in S. aureus. The present study evaluated the rate of mupirocin resistance in S. aureus clinical isolates from burns patients. A total of 125 S. aureus nonduplicate consecutive clinical isolates were collected from the burns patients in Iranian Burns Hospital, and the presence of mecA and mupA genes was assessed through polymerase chain reaction. From the 125 isolates, 107 (85.6 %) and 40 (32 %) had the mecA and mupA genes, respectively. The high prevalence of mupirocin-resistant S. aureus in this burns hospital in comparison with other general hospitals in Iran requires revision in the current mupirocin therapy strategies. In tandem with other countries, the rate of mupirocin resistance is increasing in Iran, which necessitates regular monitoring.     

Age of puberty in Iranian girls living in Tehran

The aim of this study was to determine the age of appearance of secondary sexual characteristics in Iranian girls living in Tehran. A cross-sectional study was conducted between 2003 and 2004 on 1420 6–17-year-old females in different parts of Tehran. Data were collected on the basis of a multistage probability sampling. Secondary sexual characteristics were evaluated by inspection and palpation, and were recorded according to Tanner staging. The subjects were asked about the occurrence of menarche and the age of its onset. Generalized additive logistic modelling was used for the analysis of data. The median age (percentile 10–percentile 90) of Tanner 2 of breast development (B2) and Tanner 2 of pubic hair growth (P2) among 1136 girls was 9.74 years (8.23–11.94) and 10.49 years (8.86–12.17), respectively. The ages of the 2.5 percentile for B2 and P2 were 7.42 and 7.03 years, respectively, so the onset of puberty at <7 years and 5 months is considered precocious in this population. The median age of menarche in 399 girls was 12.68 years (11.27–15.96).     

Cell line-dependent internalization pathways and intracellular trafficking determine transfection efficiency of nanoparticle vectors.

It has been suggested that cell physiology may affect the internalization pathways of non-viral vectors, leading to cell line-dependent transfection efficiency. To verify this hypothesis, fluorescently labeled alginate-chitosan nanoparticle complexes were used as non-viral vectors to transfect 293T, COS7, and CHO cells and to observe the cellular interactions and internalization mechanisms of the complexes in each cell line. 293T cells, which demonstrate the highest transfection efficiency, internalize complexes primarily through clathrin-mediated processes. COS7 cells also demonstrate some internalization of complexes through the clathrin-dependent pathway, explaining the moderate transfection exhibited. In contrast, CHO cells internalize complexes predominantly through caveolin-mediated pathways and are not transfected. Results suggest that following clathrin-mediated endocytosis, complexes are trafficked to the endo-lysosomal pathway, where the proton-sponge effect leads to their release into the cytosol. Contrarily, the absence of trafficking to this pathway following caveolin-mediated endocytosis results in vesicle-entrapped complexes that become transfection-incompetent. These results demonstrate that cell physiology is a critical factor in efficient transfection, and that trafficking to the endo-lysosomal pathway through specific internalization mechanisms is essential for transfection with alginate-chitosan nanoparticle complexes.