Primary immune thrombocytopenia (ITP) is one of the most common blood diseases as well as the commonest acquired bleeding disorder in childhood. Although the etiology of ITP is unclear, in the pathogenesis of the disease, both environmental and genetic factors including polymorphisms of TNF-a, IL-10, and IL-4 genes have been suggested to be involved. In this study, we investigated the rs2424913 single-nucleotide polymorphism (SNP) (C46359T) in DNA methyltransferase 3B (DNMT3B) gene promoter and the VNTR polymorphism of IL-1 receptor antagonist (IL-1 Ra) intron-2 in 32 children (17 boys) with the diagnosis of ITP and 64 healthy individuals. No significant differences were found in the genotype distribution of DNMT3B polymorphism between the children with ITP and the control group, whereas the frequency of allele T appeared significantly increased in children with ITP (P = 0.03, OR = 2, 95% CI: 1.06–3.94). In case of IL-1 Ra polymorphism, children with ITP had a significantly higher frequency of genotype I/II, compared to control group (P = 0.043, OR = 2.60, 95% CI: 1.02–6.50). Moreover, genotype I/I as well as allele I was overrepresented in the control group, suggesting that allele I may have a decreased risk for development of ITP. Our findings suggest that rs2424913 DNMT3B SNP as well as IL-1 Ra VNTR polymorphism may contribute to the susceptibility to ITP.

Breast milk is the ideal food for infants and undoubtedly has immediate and long-term benefits. Breast milk contains extracellular vesicles (EVs) i.e., exosomes secreted by maternal breast cells. Exosomes carry genetic material, such as long non-coding RNAs (lncRNAs), which possibly participate in cell-to-cell communications, as they are known to regulate critical gene pathways. The aim of the present study was to screen human breastmilk exosomes for their lncRNA cargo and to examine exosomal lncRNA levels associated with milk obtained from mothers that gave birth at term or prematurely (<37 weeks of gestation). Samples were collected at 3 weeks postpartum from 20 healthy, breastfeeding mothers; 10 mothers had given birth at full-term and 10 mothers preterm. Exosomal RNA was extracted from all samples and the expression of 88 distinct lncRNAs was determined using reverse transcription-quantitative PCR. A total of 13 lncRNAs were detected in ≥85% of the samples, while 31 were detected in ≥50% of the samples. Differential expression analysis of the lncRNAs between the two groups revealed ≥2-fold differences, with generally higher lncRNA concentrations found in the milk of the mothers that gave birth at term compared with those that gave birth preterm. Among these, the non-coding RNA activated at dNA damage (NORAD) was prominently detected in both groups, and its expression was significantly downregulated in the breast milk exosomes of mothers who delivered preterm. On the whole, the present study demonstrates that breast milk lncRNAs may be important factors of normal early human development. collectively, the presence of lncRNAs in human breast milk may explain the consistent inability of researchers to fully 'humanize' animal milk.

Objective:Mesenchymal stromal cells (MSCs) have a supportive role in hematopoiesis and as components of the bone marrow (BM) microenvironment may present alterations during acute lymphoblastic leukemia (ALL) and be affected by chemotherapeutic agents. We examined the biological and functional characteristics of MSCs in ALL diagnosis and treatment and their effect on MSC qualitative properties.Materials and Methods:Immunophenotypic characterization, evaluation of clonogenicity, and proliferative capacity were measured. Apoptotic features, cell-cycle analysis, and stromal cell-derived factor 1α and angiopoietin-1 levels in MSC supernatant at diagnosis and in different phases of treatment were assessed. Chemotherapy was administered according to the Berlin-Frankfurt-Munster-2000 protocol. BM samples from children with solid tumors without BM involvement were used as the control group.Results:The morphology, the immunophenotypic profile, and the apoptotic characteristics of the MSCs were not affected by leukemia. The secretion of factors involved in the trafficking of hematopoietic cells in the BM seems to be upregulated at diagnosis in comparison to the treatment phases. MSCs are influenced by the disease in terms of their functional characteristics such as clonogenicity and proliferation rate. These effects cease as soon as treatment is initiated. Chemotherapy does not seem to exert any effect on any of the MSC features examined.Conclusion:MSCs from children with ALL are affected by their interaction with the leukemic environment, but this phenomenon ceases upon treatment initiation, while no effect is observed by chemotherapy itself.

Mesenchymal stromal cells (MSCs) comprise a promising source for cellular therapy due to their ability to be readily isolated from various tissues and expand ex vivo. A unique property of these cells is the modulation of immune responses, making them attractive candidates for the treatment of autoimmune diseases. Recently, several clinical trials, mainly in adults, suggest the use of MSCs for therapy of refractory autoimmune diseases. There are a very limited number of reports in the literature addressing the cellular therapy options for pediatric patients with autoimmune diseases refractory to standard therapy. This review discusses the possible mechanisms underlying the immunosuppressive effects of MSCs on almost all cell types, and also the recent advances in cellular therapy of autoimmune diseases using MSCs as modulators of immune response, especially in children.