Two Separate Effects Contribute to Regulatory T Cell Defect in Systemic Lupus Erythematosus Patients and Their Unaffected Relatives

Forkhead box P3 (FoxP3)+ regulatory T cells (Tregs ) are functionally deficient in systemic lupus erythematosus (SLE), characterized by reduced surface CD25 [the interleukin (IL)-2 receptor alpha chain]. Low-dose IL-2 therapy is a promising current approach to correct this defect. To elucidate the origins of the SLE Treg phenotype, we studied its role through developmentally defined regulatory T cell (Treg ) subsets in 45 SLE patients, 103 SLE-unaffected first-degree relatives and 61 unrelated healthy control subjects, and genetic association with the CD25-encoding IL2RA locus. We identified two separate, uncorrelated effects contributing to Treg CD25. (1) SLE patients and unaffected relatives remarkably shared CD25 reduction versus controls, particularly in the developmentally earliest CD4+ FoxP3+ CD45RO- CD31+ recent thymic emigrant Tregs . This first component effect influenced the proportions of circulating CD4+ FoxP3high CD45RO+ activated Tregs . (2) In contrast, patients and unaffected relatives differed sharply in their activated Treg CD25 state: while relatives as control subjects up-regulated CD25 strongly in these cells during differentiation from naive Tregs , SLE patients specifically failed to do so. This CD25 up-regulation depended upon IL2RA genetic variation and was related functionally to the proliferation of activated Tregs , but not to their circulating numbers. Both effects were found related to T cell IL-2 production. Our results point to (1) a heritable, intrathymic mechanism responsible for reduced CD25 on early Tregs and decreased activation capacity in an extended risk population, which can be compensated by (2) functionally independent CD25 up-regulation upon peripheral Treg activation that is selectively deficient in patients. We expect that Treg -directed therapies can be monitored more effectively when taking this distinction into account.info:eu-repo/semantics/publishedVersio

Fauna used in popular medicine in Northeast Brazil

<p>Abstract</p> <p>Background</p> <p>Animal-based remedies constitute an integral part of Brazilian Traditional Medicine. Due to its long history, zootherapy has in fact become an integral part of folk medicine both in rural and urban areas of the country. In this paper we summarize current knowledge on zootherapeutic practices in Northeast of Brazil, based on information compiled from ethnobiological scientific literature.</p> <p>Methods</p> <p>In order to examine the diversity of animals used in traditional medicine in Northeast of Brazil, all available references or reports of folk remedies based on animals sources were examined. 34 sources were analyzed. Only taxa that could be identified to species level were included in assessment of medicinal animal species. Scientific names provided in publications were updated.</p> <p>Results</p> <p>The review revealed that at least 250 animal species (178 vertebrates and 72 invertebrates) are used for medicinal purposes in Northeast of Brazil. The inventoried species comprise 10 taxonomic categories and belong to 141 Families. The groups with the greatest number of species were fishes (n = 58), mammals (n = 47) and reptiles (n = 37). The zootherapeutical products are used for the treatment of different illnesses. The most widely treated condition were asthma, rheumatism and sore throat, conditions, which had a wide variety of animals to treat them with. Many animals were used for the treatment of multiple ailments. Beyond the use for treating human diseases, zootherapeutical resources are also used in ethnoveterinary medicine</p> <p>Conclusion</p> <p>The number of medicinal species catalogued was quite expressive and demonstrate the importance of zootherapy as alternative therapeutic in Northeast of Brazil. Although widely diffused throughout Brazil, zootherapeutic practices remain virtually unstudied. There is an urgent need to examine the ecological, cultural, social, and public health implications associated with fauna usage, including a full inventory of the animal species used for medicinal purposes and the socio-cultural context associated with their consumption.</p

Impact of TGF-ß1 -509C/T and 869T/C polymorphisms on glioma risk and patient prognosis

Transforming growth factor beta (TGF-ß) plays an important role in carcinogenesis. Two polymorphisms in the TGF-ß1 gene (-509C/T and 869T/C) were described to influence susceptibility to gastric and breast cancers. The 869T/C polymorphism was also associated with overall survival in breast cancer patients. In the present study, we investigated the relevance of these TGF-ß1 polymorphism in glioma risk and prognosis. A case-control study that included 114 glioma patients and 138 cancer-free controls was performed. Single nucleotide polymorphisms (SNPs) were evaluated by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP). Univariate and multivariate logistic regression analyses were used to calculate odds ratio (OR) and 95 % confidence intervals (95 % CI). The influence of TGF-ß1 -509C/T and 869T/C polymorphisms on glioma patient survival was evaluated by a Cox regression model adjusted for patients' age and sex and represented in Kaplan-Meier curves. Our results demonstrated that TGF-ß1 gene polymorphisms -509C/T and 869T/C are not significantly associated with glioma risk. Survival analyses showed that the homozygous -509TT genotype associates with longer overall survival of glioblastoma (GBM) patients when compared with patients carrying CC + CT genotypes (OR, 2.41; 95 % CI, 1.06-5.50; p = 0.036). In addition, the homozygous 869CC genotype is associated with increased overall survival of GBM patients when compared with 869TT + TC genotypes (OR, 2.62; 95 % CI, 1.11-6.17; p = 0.027). In conclusion, this study suggests that TGF-ß1 -509C/T and 869T/C polymorphisms are not significantly associated with risk for developing gliomas but may be relevant prognostic biomarkers in GBM patients.This work was supported by Fundação para a Ciência e Tecnologia, Portugal (PTDC/SAU-GMG/113795/2009 and SFRH/BPD/33612/2009 to B.M.C.; SFRH/BD/88121/2012 to J.V.C.; SFRH/BD/92786/2013 to C.S.G.; PTDC/SAU-ONC/115513/2009 to R.R.)