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Introduction: Acquired aplastic anemia (AA), a heterogeneous bone marrow (BM) failure disease, is mainly mediated by the immune destruction of hematopoietic stem cells (HSCs). Given the predominant role of immunosuppressive therapy (IST) in AA, it is sensible to theorize that variants of cytokine genes might affect the outcome of IST. Methods: In this study, we analyzed three single nucleotide polymorphisms (SNPs) of interleukin (IL)‐10 gene in promoter region to clarify their relationship with susceptibility, clinical efficacy and prognosis of AA. Results: We observed that CT genotype of IL‐10 rs1800896 was associated with a decreased risk of AA (adjusted OR = 0.541 [95% CI 0.295–0.993], p =.047). Besides, the disease severity differed considerably by IL‐10 gene promoter genotypes and alleles. Furthermore, IL‐10 SNPs influenced efficacy of IST, with unfavorable response exhibited by rs1800871 and rs1800872 in dominant models (GG + AG vs. AA, adjusted OR = 0.409 [95% CI 0.178–0.943, p =.036] for rs1800871 and GG + GT vs. TT, adjusted OR = 0.396 [95% CI 0.173–0.909, p =.028] for rs1800872, respectively). Conclusion: The polymorphisms of IL‐10 promoter region were informatively genetic risk factors which might be conducive to the insights into the mechanisms of AA and the design of individual regimens. [ABSTRACT FROM AUTHOR]

By the design of suitable starting materials, a silver(I)-catalyzed epoxide ring-opening/1,2-acyl migration/cyclization cascade has been developed, which allowed us to systematically prepare unsymmetrical 3-formylfurans. Various 3-formylfurans were prepared in good to excellent yields. In addition, the distinct fluorescence properties of 3-formylfurans in solution and the solid state are disclosed. [ABSTRACT FROM AUTHOR]

Acquired aplastic anemia ( AA) is an immune-mediated bone marrow failure syndrome. 1 α,25-Dihydroxyvitamin D3 [1,25( OH)2D3], the biologically active metabolite of vitamin D, is a critical modulator of immune response via binding with vitamin D receptor ( VDR). Previous studies have established that 1,25( OH)2D3 and VDR were involved in the pathogenesis of some autoimmune diseases. In this study, we evaluated the involvement of 1,25( OH)2D3 and VDR on T-cell responses in AA. Plasma 25( OH)D3 levels were comparable between patients with AA and healthy controls. Surprisingly, VDR mRNA was significantly lower in untreated patients with AA than in healthy controls. Subsequent in vitro experiments revealed that 1,25( OH)2D3 treatment suppressed the proliferation of lymphocytes and inhibited the secretion of interferon- γ, tumor necrosis factor- α, and interleukin-17A, meanwhile promoting the production of transforming growth factor- β1 in patients with AA. Moreover, 1,25( OH)2D3 inhibited the differentiation of type 1 and Th17 cells but induced the differentiation of type 2 and regulatory T cells. Interestingly, VDR mRNA was elevated in healthy controls after 1,25( OH)2D3 treatment, but not in patients with AA. In conclusion, decreased expression of VDR might contribute to the hyperimmune status of AA and appropriate vitamin D supplementation could partly correct the immune dysfunction by strengthening signal transduction through VDR in patients with AA. [ABSTRACT FROM AUTHOR]

Objective Recently enhanced T-helper type 17 (Th17) immune responses and deficient CD4+ CD25hiFoxP3+ regulatory T cells (Tregs) have been reported in acquired aplastic anemia ( AA). Interleukin-21 ( IL-21), a CD4+ T-cell-derived proinflammatory cytokine, modulates the balance between Th17 cells and Tregs. However, its role in AA remains unclear. Methods IL-21 gene expression was examined by quantitative real-time PCR. Cytokines in plasma and cell culture supernatants were detected by ELISA. Cytokines-producing T cells and Tregs were evaluated by flow cytometry. Results IL-21 mRNA levels in circulating CD4+ T cells and IL-21 levels in blood plasma were markedly increased in patients with newly diagnosed AA. Moreover, elevated IL-21-producing CD4+ T cells were accompanied by Th17 cells accumulation and Tregs decrease, and correlated with AA activity. In vitro, IL-21 not only inhibited the expression of FoxP3, but also induced the expression of IL-17 in CD4+ T cells of AA patients. More importantly, we found that T cells within the bone marrow (BM) of AA patients were in a heightened activation state, which may be related to IL-21. Conclusion Our data suggested a critical role of IL-21 in breaking immune homeostasis in AA by promoting Th17 cells, activating BM T cells and suppressing Tregs. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 10-year-old girl who was diagnosed with Iron-refractory iron deficiency anaemia (IRIDA), an autosomal recessive genetic disorder caused by mutation in TMPRSS6 gene. It reports that to confirm the diagnosis of IRIDA, the hormone hepcidin level in serum was measured using enzyme-linked immunosorbent assay and TMPRSS6 mutations were screened by DNA sequencing. Further it mentions that she was given glucocorticoids which leads to decrease in serum hepcidin.

The article reports the use of immunosuppressant drug cyclosporin in combination with antihelminthic drug levamisole for aplastic anaemia. It mentions that the treatment was done with immunosuppressive therapy (IST) by anti-thymocyte globulin (ATG), infusion of horse or rabbit-derived antibodies against human T cells, and cyclosporin. Several tables related to patient's characteristics and the pretreatment blood count and results of patients are depicted.

Summary: Securely performing nearest neighbor query over encrypted data in cloud is an important topic in the area of cloud computing, for which Wang et al recently put forward a scheme (ie, CloudBI‐II) to address the challenging security problem: resisting the collusion of cloud server and query users. In this paper, we propose an efficient attack method that indicates CloudBI‐II will reveal the difference vectors under the collusion attack. Furthermore, we show that the difference vector disclosure will result in serious privacy breach and, thus, attain an efficient attack method to break CloudBI‐II. Namely, CloudBI‐II cannot achieve their declared security. Through theoretical analysis and experiment evaluation, we confirm that our proposed attack approach can fast recover the original data from the encrypted data set in CloudBI‐II. Finally, we provide an enhanced scheme that can efficiently resist the collusion attack. [ABSTRACT FROM AUTHOR]

Aplastic anaemia (AA) is considered as an immune-mediated bone marrow failure syndrome. The mechanism is involved with a variety of immune molecules including interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α) and interleukins (ILs). IL-27 is a novel member of the IL-12 family, which mediates T cell response and enhances the production of IFN-γ. However, little is known about the role of IL-27 in the development of AA. This study investigated the role of IL-27 and its receptor IL-27R in the pathogenesis of AA. Both the mRNA expression of IL-27/IL-27R subunits in the bone marrow mononuclear cells (BMMNCs) and the levels of IL-27 in the marrow plasma in AA were found to be higher than in controls. Increased IL-27 correlated with the disease severity of AA. Subsequently, we stimulated marrow T lymphocytes with recombinant human (rh)IL-27 and found that rhIL-27 enhanced the production of TNF-α and IFN-γ in both CD4(+) and CD8(+) T lymphocytes from AA patients. We also detected increased TNF-α and IFN-γ in the supernatants of BMMNCs from AA patients after IL-27 stimulation. In conclusion, our data suggest that elevated IL-27 and IL-27-induced TNF-α and IFN-γ overproduction might be involved in the pathogenesis of AA., (© 2011 Blackwell Publishing Ltd.)