Bioevaluation of superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with dihexadecyl phosphate (DHP)

Superparamagnetic iron oxide nanoparticles (SPIONs) have been investigated for wide variety of applications. Their unique properties render them highly applicable as MRI contrast agents, in magnetic hyperthermia or targeted drug delivery. SPIONs surface properties affect a whole array of parameters such as: solubility, toxicity, stability, biodistribution etc. Therefore, progress in the field of SPIONs surface functionalization is crucial for further development of therapeutic or diagnostic agents. In this study, SPIONs were synthesized by thermal decomposition of iron (III) acetylacetonate Fe(acac) 3 and functionalized with dihexadecyl phosphate (DHP) via phase transfer. Bioactivity of the SPION-DHP was assessed on SW1353 and TCam-2 cancer derived cell lines. The following test were conducted: cytotoxicity and proliferation assay, reactive oxygen species (ROS) assay, SPIONs uptake (via Iron Staining and ICP-MS), expression analysis of the following genes: alkaline phosphatase (ALPL); ferritin light chain (FTL); serine/threonine protein phosphatase 2A (PP2A); protein tyrosine phosphatase non-receptor type 11 (PTPN11); transferrin receptor 1 (TFRC) via RT-qPCR. SPION-DHP nanoparticles were successfully obtained and did not reveal significant cytotoxicity in the range of tested concentrations. ROS generation was elevated, however not correlated with the concentrations. Gene expression profile was slightly altered only in SW1353 cells

Microarray analysis to investigate the global expression of miRNAs in pediatric T1D patients in comparison to non-diabetic controls.

MicroRNAs (miRNAs) are small non-coding RNAs that target multiple mRNAs and regulate gene expression. The implication of miRNAs in T1D pathogenesis, as potential modulators of immune response genes, remains poorly defined. The aim of this study was to investigate the expression profile of miRNAs in new onset T1D to identify autoimmune associated miRNAs. Total RNA from peripheral blood mononuclear cells of newly diagnosed T1D pediatric patients and age-matched controls was screened for disease-associated miRNAs by a microarray analysis. The comprehensive analysis of miRNA expression profile was determined on Affymetrix GeneChip miRNA 4.0 array

Upregulation of FOXO3 in New-Onset Type 1 Diabetes Mellitus

Forkhead box O (FOXO) transcription factors have been implicated in the development and differentiation of the immune cells. FOXO3 plays a crucial role in physiologic and pathologic immune response. FOXO3, cooperatively with FOXO1, control the development and function of Foxp3+ regulatory T cells (Treg). Since the lack of Treg-mediated control has fundamental impact on type 1 diabetes mellitus (T1DM) development, we investigated FOXO3 expression in patients with T1DM. FOXO3 expression was estimated in peripheral blood mononuclear cells (PBMCs) from newly diagnosed T1DM pediatric patients (n=28) and age-matched healthy donors (n=27) by reahavel-time PCR and TaqMan gene expression assays. Expression analysis revealed significant upregulation of FOXO3 in T1DM (P=0.0005). Stratification of the T1DM group according to the presence of initial diabetic ketoacidosis (DKA) did not indicate differences in FOXO3 expression in patients with DKA compared to a mild T1DM onset (P>0.05). In conclusion, overexpression of FOXO3 is correlated with the ongoing islet autoimmune destruction and might suggest a potential role for this gene in the pathogenesis of type 1 diabetes mellitus

Association between interferon-induced helicase (IFIH1) rs1990760 polymorphism and seasonal variation in the onset of type 1 diabetes mellitus IFIH1 polymorphism and type 1 diabetes onset

BACKGROUND: Infections, mostly of viral origin, may contribute to the seasonal variation in the onset of type 1 diabetes mellitus (T1DM). The rs1990760 (A>G, Ala946Thr) polymorphism (GG genotype) of the interferon induced helicase (IFIH1), a virus recognition receptor, confers a modest protection for T1DM. The aim of our study was to evaluate a possible association between this IFIH1 polymorphism and the seasonal variation in the onset of T1DM. MATERIALS AND METHODS: The IFIH1 rs1990760 polymorphism was genotyped in 1055 patients of Central-Eastern European ancestry with T1DM (median age at diagnosis: 8.2 [interquartile range, IQR 4.8-11.8] years). T1DM onset was recorded in monthly intervals. RESULTS: The IFIH1 genotype distribution was the following: 436 patients (41.3%) had AA genotype, 483 patients (45.8%) had AG genotype, and 136 patients (12.9%) had GG genotype. Significant seasonal variation in manifestation of T1DM (highest rate in winter and lowest rate in summer period) was observed in the total cohort (n = 1055), irrespective of gender. The disease predisposing AA genotype was more frequently found among new cases with onset in summer vs in those with onset in winter (44.3% vs 37.9%); conversely, the protective GG genotype was less frequent (9.3% vs 12.9%, respectively; P = .0268 for trend). Significant effect of genotype (P = .0418) was found on the seasonal variability of T1DM onset in the total cohort. CONCLUSIONS: The IFIH1 rs1990760 polymorphism seems to be associated with the seasonal manifestation of T1DM. Our findings suggest that this virus receptor gene may contribute to T1DM manifestation primarily in the summer period