SiRNA/DOX lodeded chitosan based nanoparticles: Development, Characterization and in vitro evaluation on A549 lung cancer cell line.

High-mobility group AT-hook2 (HMGA2), involved in epithelial mesenchymal transition (EMT) process, has a pivotal role in lung cancer metastasis. Lung cancer therapy with HMGA2 suppressing small interfering RNA (siRNA) has been introduced recently while doxorubicin (DOX) has been used as a frequent cancer chemotherapy agent. Both reagents have been faced with obstacles in clinic which make them ineffective. NanoParticles (NPs) provided a platform for efficient co delivery of the anticancer drugs. The aim of this study was production and in vitro characterization of different pharmacological groups (siRNA, DOX or siRNA-DOX) of carboxymethyl dextran thrimethyl chitosan nanoparticles (CMDTMChiNPs) on cytotoxicity, gene expression, apoptosis and migration of metastatic lung cancer cell line (A-549). CMDTMChiNPs were synthesized and encapsulated with siRNA, DOX or siRNA-DOX. Then the effects of HMGA2 siRNA and DOX co delivery was assessed in A549 viability and target genes (HMGA2, Ecadherin, vimentin and MMP9) by MTT and real time PCR, respectively. In addition capability of apoptosis induction and anti-migratory features of formulated NPs were analyzed by flowcytometry and wound healing assays. SiRNA-DOX-CMDTM ChiNPs approximate size were 207±5 with poly dispersity index (PDI) and zeta potential of 0.4 and 16.3±0.3, respectively. NPs loaded with DOX and siRNA were the most efficient drug formulations in A549 cell cytotoxicity, altering of EMT markers, apoptosis induction and migration inhibition. Generally our results showed that co delivery of HMGA2 siRNA and DOX by novel designed CMDTMChiNPs is a new therapeutic approach with great potential efficiency for lung cancer treatment.

Tetanus neurotoxin HCC protein commits T cells to IFN-γ producing cells.

A protective response against tetanus toxin and toxoid demands efficient specific T cell and B cell responses. Tetanus neurotoxin (TeNT), a 150 kDa polypeptide, is the main cause of tetanus disease. TeNT consists of two structurally distinct chains, a 50 kDa N-terminal light (L) and a 100 kDa C-terminal heavy (H) chain. C-terminal heavy (H) chain (fragment C) has two sub-domains named as proximal HCN and carboxy sub-domain or HCC. Beside neural binding property, HCC has been recently found as an immunodominant module of TeNT. In the present study, we investigated the effects of recombinant HCC (rHCC) on the expression of lineage specific transcription factors and secretion of a panel of functional cytokines including IFN-γ, IL-4, and IL-17 from purified human T cells. Our results revealed that T-bet transcript level, as TH1 specific transcription factor, was significantly increased in the cells treated with 10 and 20 µg/ml of rHCC following 48 h treatment(p<0.05). Treated purified human T cells with rHCC showed significant increase in IFN-γ mRNA level and cytokine secretion, but not IL-4 and IL-17, following 48 h treatment. In conclusion, our results showed that treatment of T cells with r HCC resulted in development of Th1 lineage phenotype, which might lead to a specific and protective antibody mediated response against tetanus toxin.

Celiac disease and multiple sclerosis in the northwest of Iran.

OBJECTIVE: To compare the frequency of celiac disease (CD) in patients with multiple sclerosis (MS) and healthy controls using tissue transglutaminase IgA antibodies (anti-tTGA) as a screening tool. BACKGROUND: CD and MS are immune-mediated diseases, and it has been hypothesized that the genetic similarities between these conditions can predispose individuals to suffer from both. Data regarding this association are limited, particularly in Eastern countries. METHODS: One hundred clinically defined MS patients were randomly selected from Tabriz, northwest of Iran. The control group consisted of 121 age- and gender-matched healthy individuals. All subjects were screened with anti-tTGA. Total IgA was obtained for investigation of IgA deficiency. RESULTS: The mean age of MS patients (32 male and 68 female) was 33.06±8.79 years; the mean age of controls was 32.98±9.62 years. The mean expanded disability scale score (EDSS) for MS patients was 3.86±1.91. Approximately 78.5 % of MS patients suffered from a remitting relapsing type of MS. All subjects (MS patients and controls) were negative for anti-tTGA. IgA deficiency was demonstrated in 14 % of MS patients and 11 % of controls (p>0.1). No IgA-deficient subjects consented to undergo a duodenal mucosa biopsy. CONCLUSION: The present study failed to demonstrate a positive relationship between MS and CD. Therefore, we conclude that there is no basis for recommending the routine screening of MS sufferers for celiac disease (Ref. 23).

Comparison of outcome and quality of life: haemodialysis versus peritoneal dialysis patients.

INTRODUCTION: Ever since peritoneal dialysis (PD) was introduced as a form of renal replacement therapy, its efficacy and complications have been compared with that of haemodialysis (HD). The aim of this study was to determine the efficacy and outcome of PD in comparison to HD in our region. METHODS: We compared 60 patients on PD with 60 matched patients on HD in Tabriz's Sina Hospital during the period 2004-2006. The technique, patients' survival and quality of life were compared by means of a health-related quality-of-life questionnaire (GHQ-28). RESULTS: There was no significant difference in the mean age and duration of dialysis between patients on PD and HD. Survival of diabetic patients was better with HD than PD, but in non-diabetic patients, there was no difference in the survival rates between the two groups. Among patients on PD, diabetics had a 25 percent higher mortality rate and non-diabetic patients had a three percent higher mortality rate than their corresponding counterparts on HD. In all four axes of the questionnaire, i.e. psychophysical dysfunction, stress and sleep disorders, social dysfunction and major depression, PD patients had lower scores than HD patients (p-values are less than 0.001, less than 0.001, equal to 0.002 and less than 0.001, respectively), indicating that patients on PD had a better quality of life compared to those on HD. CONCLUSION: In this study, technique, patients' survival and their quality of life were better on PD than on HD. However, survival and mortality of diabetic patients on HD were better than those on PD.