RNAi-Mediated c-Rel Silencing Leads to Apoptosis of B Cell Tumor Cells and Suppresses Antigenic Immune Response In Vivo

c-Rel is a member of the Rel/NF-κB transcription factor family and is predominantly expressed in lymphoid and myeloid cells, playing a critical role in lymphocyte proliferation and survival. Persistent activation of the c-Rel signal transduction pathway is associated with allergies, inflammation, autoimmune diseases, and a variety of human malignancies. To explore the potential of targeting c-Rel as a therapeutic agent for these disorders, we designed a small interfering RNA (siRNA) to silence c-Rel expression in vitro and in vivo. C-Rel-siRNA expression via a retroviral vector in a B cell tumor cell line leads to growth arrest and apoptosis of the tumor cells. Silencing c-Rel in primary B cells in vitro compromises their proliferative and survival response to CD40 activation signals, similar to the impaired response of c-Rel knockout B cells. Most important, in vivo silencing of c-Rel results in significant impairment in T cell-mediated immune responses to antigenic stimulation. Our study thus validates the efficacy of c-Rel-siRNA, and suggests the development of siRNA-based therapy, as well as small molecular inhibitors for the treatment of B cell tumors as well as autoimmune diseases

The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis

The proto-oncogene RAS, coding for a 21 kDa protein (p21), is mutated in 20% of lung cancer. However, the literature remains controversial on its prognostic significance for survival in lung cancer. We performed a systematic review of the literature with meta-analysis to assess its possible prognostic value on survival. Published studies on lung cancer assessing prognostic value of RAS mutation or p21 overexpression on survival were identified by an electronic search. After a methodological assessment, we estimated individual hazard ratios (HR) estimating RAS protein alteration or RAS mutation effect on survival and combined them using meta-analytic methods. In total, 53 studies were found eligible, with 10 concerning the same cohorts of patients. Among the 43 remaining studies, the revelation method was immunohistochemistry (IHC) in nine and polymerase chain reaction (PCR) in 34. Results in terms of survival were significantly pejorative, significantly favourable, not significant and not conclusive in 9, 1, 31, 2, respectively. In total, 29 studies were evaluable for meta-analysis but we aggregated only the 28 dealing with non-small-cell lung cancer (NSCLC) and not the only one dealing with small-cell-lung cancer (SCLC). The quality scores were not statistically significantly different between studies with or without significant results in terms of survival, allowing us to perform a quantitative aggregation. The combined HR was 1.35 (95% CI: 1.16–1.56), showing a worse survival for NSCLC with KRAS2 mutations or p21 overexpression and, particularly, in adenocarcinomas (ADC) (HR 1.59; 95% CI 1.26–2.02) and in studies using PCR (HR 1.40; 95% CI 1.18–1.65) but not in studies using IHC (HR 1.08; 95% CI 0.86–1.34). RAS appears to be a pejorative prognostic factor in terms of survival in NSCLC globally, in ADC and when it is studied by PCR

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Out-of-hospital cardiopulmonary resuscitation in four Serbian university cities: Outcome follow-up according to the «Utstein style»

Aims: To investigate the return of spontaneous circulation (ROSC), survival to discharge, six-month and one-year survival of patients with out-of-hospital cardiac arrest in four university cities in Serbia. Methods: A prospective, two-year, multicentre study was designed. Using the Utstein template, we recorded out-of-hospital cardiopulmonary (CPR) and its outcomes, and analyzed the immediate survival (ROSC>20 min.), short-term survival (to discharge), long-term survival (one year after discharge), or death following out-of-hospital CPR. Results: During the study period, 591 patients met the inclusion criteria for enrollment and out-of-hospital CPR. The etiology of arrest was cardiac in 33.8% of patients. Cardiac arrest was witnessed by the advanced life support (ALS) team in 15.6% of cases. Asystole was the most frequent initial rhythm at time of arrest (46.4%). The highest survival rate (P<0,001) was observed in cases with initial VF and pulseless VT, while patients with asystole and pulseless electrical activity (PEA) had theleast chance of survival. Within the whole group of patients, ROSC was detected with a frequency of 69.7%. The frequency of patients who died in the field or during admission to hospital was 58.9%, while 28.6% of admitted patients died before discharge. Thirteen percent of patients survived until discharge, and the overall six-month and one-year survival rates were 11.3% and 10%, respectively. No statistical difference in survival rates among the cities was found. Conclusion: The Utstein template should be implemented in the form of an official protocol for out-of-hospital CPR follow-up in all emergency medical services in Serbia

Anomalous trends in conductivity during epoxy-amine reactions

Measurements were carried out of conductivity due to migrating charges as a function of extent of reaction for a series of epoxy-amine formulations. All systems were characterised by the reaction mechanism common to this generic group of materials and ~y an increase in the steady shear viscosity during reaction. The measured conductivity, however, followed one of three distinct patterns as a function of extent of reaction. Intuitively unexpected, and hence particularly interesting, was the observed increase in conductivity during reaction in sew~ral formulations. This communication marks the first time that such response has been reported in the literature. An explanation of the observed trends was offered in terms of an interplay between the contributions of extrinsic and intrinsic migrating charges to the overall (measured) conductivity. Without such information, all con'elations between the measured conductivity and the major processing parameters (viscosity, extent of reaction) remain strictly batch-specific and empirical

The efficacy of a posterior sub-tenon’s capsule triamcinolone injection in patients with non-infectious intermediate uveitis and posterior uveitis

© 2017, University of Kragujevac, Faculty of Science. All rights reserved. To investigate the efficacy of a posterior sub-Tenon’s capsule triamcinolone injection for treating eyes with non-infectious posterior and intermediate uveitis. A total of 31 eyes from 20 patients with non-infectious posterior uveitis and 18 eyes from 10 patients with non-infectious intermediate uveitis that inadequately responded to treatment with systemic corticosteroids and second-line immunosuppressive agents were enrolled in the study. All patients received a posterior sub-Tenon’s injection of 20 mg/ml triamcinolone. The parameters we examined included the following: best corrected visual acuity, central foveal thickness, fluorescein angiography score and intraocular pressure. The mean best corrected visual acuity was significantly improved from the control visit, 0.15±0.30 logMAR (Snellen equivalent 0.7), compared to the baseline measurements, 0.60±0.30 logMAR (Snellen equivalent 0.25; P<0.05). The mean central foveal thickness (CFT) and the mean score for fluorescein angiography (FA) were significantly decreased from the baseline (CFT: 320±34 μm; FA mean score: 5.9±1.9) compared to the twelve-week control visit (CFT: 235±30 μm; FA mean score: 1.2±1.1; P<0.001). Five eyes had intraocular pressure spikes that required a topical anti-glaucomatous treatment. A posterior sub-Tenon’s injection of triamcinolone can significantly improve visual acuity and decrease macular oedema in patients with non-infectious posterior and intermediate uveitis. Complications were minimal, and there were no eyes that required surgical treatment for elevated intraocular pressure. The results suggest that the posterior sub-Tenon’s injection of triamcinolone is an important form of therapy for non-infectious posterior and intermediate uveitis

SCI-based LINUX PC-Clusters as a Platform for Electromagnetic Field Calculations

this paper we have described the process of eddy-current simulations based on new algorithms developed by ETH Z\u7furich. Using a high bandwidth and low latency network like SCI, a signi cant speedup in the solver computation times has been achieved. Recently the LINUX PC cluster has been upgraded to 16 nodes yielding a total main memory of 16GB. Therefore, it will be possible to compute even larger eddy current problems as the coecient matrices will t into the cluster&apos;s main memor