Unraveling the Mechanisms of Cutaneous Graft-Versus-Host Disease

The skin is the most common target organ affected by graft-versus-host disease (GVHD), with severity and response to therapy representing important predictors of patient survival. Although many of the initiating events in GVHD pathogenesis have been defined, less is known about why treatment resistance occurs or why there is often a permanent failure to restore tissue homeostasis. Emerging data suggest that the unique immune microenvironment in the skin is responsible for defining location- and context-specific mechanisms of injury that are distinct from those involved in other target organs. In this review, we address recent advances in our understanding of GVHD biology in the skin and outline the new research themes that will ultimately enable design of precision therapies

Dialogue between social movement activists and a Master's Program in youth and adult education

This article presents the results of a qualitative study on the relationship between social movements and a Master's Program in youth and adult education in Bahia, Brazil. It pays particular attention to the importance of antiracism in and the decolonization of the program's curriculum

Diâmetro médio predominante de partículas do solo

Apresenta-se um modelo empírico capaz de representar, analiticamente, a curva de distribuição textural acumulada de partículas de um solo e, a partir desse modelo, obter uma expressão que fornece o diâmetro médio predominante de partículas (∅m), que representa o tamanho médio de partículas que ocorrem com maior freqüência no solo. Essas expressões podem ser aplicadas tanto na física do solo quanto em estudos geológicos, geomorfológicos e sedimentológicos

Plantas medicinais utilizadas para doen?as associadas ao sistema digest?rio no Rio Grande do Sul, Brasil

Data from ethnobotanical?s studies may became an important tool for new medicine researches and nowadays an increasing interest by general public on consumption of herbal medicines has been noticed. The World Health Organization has been including the usage of herbal medicine in natura or of products containing them on the context of traditional medicine. The study?s main objective is to realize a bibliographic survey of medicinal plants used to treat problems on the digestive system in Rio Grande do Sul. Through searches on various data basis it was selected 21 studies on ethnobotanical developed in the State. Analysis revealed 184 species of medicinal plants with any indication for the treatment of digestive tract. Those were grouped in 61 botanical families. The most mentioned species were Achyrocline satureioides (Lam.) DC., Plectranthus barbatus Andrews, Eugenia uniflora L., Artemisia absinthium L., Punica granatum L. The richest of all families were Asteraceae (45 species) and Lamiaceae (24). The most utilized preparation form was infusion, representing 33% of the manners. The leaves, the parts most used on the preparations, represents 44%. Of the amount of species, 52% are exotic. Due to the mass number of medicinal species utilized on diseases/symptoms of the digestive tract, it can be conclude that this therapeutically resource develops an important role on the treatment of such problems at popular medicine in Rio Grande do Sul. It is suggest more profound medicinal plants? studies utilized for these purposes, since there are few studies yet that guarantee the efficiency and safety of the consumption of these species.Os dados dos estudos etnobot?nicos podem ser uma importante ferramenta em pesquisas de novas drogas e atualmente observa-se um crescente interesse da popula??o em geral no consumo de fitoter?picos. A Organiza??o Mundial de Sa?de tem inclu?do o uso de plantas medicinais in natura ou de produtos que as contenham no contexto da medicina tradicional. O principal objetivo deste trabalho ? realizar um levantamento bibliogr?fico das plantas medicinais que s?o utilizadas para problemas do sistema digest?rio no Rio Grande do Sul. Atrav?s de pesquisas em diversos bancos de dados foram selecionados 21 trabalhos etnobot?nicos realizados no Estado. As an?lises revelaram 184 esp?cies de plantas medicinais com alguma indica??o para problemas do aparelho digest?rio. Estas foram agrupadas em 61 fam?lias bot?nicas. As esp?cies mais citadas foram Achyrocline satureioides (Lam.) DC., Plectranthus barbatus Andrews, Eugenia uniflora L., Artemisia absinthium L., Punica granatum L. As duas fam?lias mais ricas foram Asteraceae (45 esp?cies) e Lamiaceae (24). A forma de preparo mais utilizada foi ? infus?o, representando 33% das formas, sendo as folhas, as partes mais utilizadas nas prepara??es, representando 44%. Do total de esp?cies 52% s?o ex?ticas. Devido ao grande n?mero de esp?cies medicinais utilizadas para doen?as/sintomas do aparelho digest?rio, pode-se concluir que este recurso terap?utico desempenha um importante papel nos tratamentos desses problemas na medicina popular no Rio Grande do Sul. Sugerem-se estudos mais aprofundados das plantas medicinais utilizadas para este fim, uma vez que ainda s?o poucos os trabalhos que garantam a efici?ncia e seguran?a no consumo destas esp?cies

Therapeutic strategies for IVD regeneration through hyaluronan/SDF-1-based hydrogel and intravenous administration of MSCs

Intervertebral disc (IVD) degeneration involves a complex cascade of events, including degradation of the native extracellular matrix, loss of water content, and decreased cell numbers. Cell recruitment strategies for the IVD have been increasingly explored, aiming to recruit either endogenous or transplanted cells. This study evaluates the IVD therapeutic potential of a chemoattractant delivery system (HAPSDF5) that combines a hyaluronan-based thermoreversible hydrogel (HAP) and the chemokine stromal cell derived factor-1 (SDF-1). HAPSDF5 was injected into the IVD and was combined with an intravenous injection of mesenchymal stem/stromal cells (MSCs) in a pre-clinical in vivo IVD lesion model. The local and systemic effects were evaluated two weeks after treatment. The hydrogel by itself (HAP) did not elicit any adverse effect, showing potential to be administrated by intradiscal injection. HAPSDF5 induced higher cell numbers, but no evidence of IVD regeneration was observed. MSCs systemic injection seemed to exert a role in IVD regeneration to some extent through a paracrine effect, but no synergies were observed when HAPSDF5 was combined with MSCs. Overall, this study shows that although the injection of chemoattractant hydrogels and MSC recruitment are feasible approaches for IVD, IVD regeneration using this strategy needs to be further explored before successful clinical translation.Funding: This research was funded by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia (IUD/BIM/04293/2019) and by EUROSPINE TRF (2017_05)

Tissue distribution of a plasmid DNA encoding Hsp65 gene is dependent on the dose administered through intramuscular delivery

In order to assess a new strategy of DNA vaccine for a more complete understanding of its action in immune response, it is important to determine the in vivo biodistribution fate and antigen expression. In previous studies, our group focused on the prophylactic and therapeutic use of a plasmid DNA encoding the Mycobacterium leprae 65-kDa heat shock protein (Hsp65) and achieved an efficient immune response induction as well as protection against virulent M. tuberculosis challenge. In the present study, we examined in vivo tissue distribution of naked DNA-Hsp65 vaccine, the Hsp65 message, genome integration and methylation status of plasmid DNA. The DNA-Hsp65 was detectable in several tissue types, indicating that DNA-Hsp65 disseminates widely throughout the body. The biodistribution was dose-dependent. In contrast, RT-PCR detected the Hsp65 message for at least 15 days in muscle or liver tissue from immunized mice. We also analyzed the methylation status and integration of the injected plasmid DNA into the host cellular genome. The bacterial methylation pattern persisted for at least 6 months, indicating that the plasmid DNA-Hsp65 does not replicate in mammalian tissue, and Southern blot analysis showed that plasmid DNA was not integrated. These results have important implications for the use of DNA-Hsp65 vaccine in a clinical setting and open new perspectives for DNA vaccines and new considerations about the inoculation site and delivery system

Outdoor solutions for the seasonal concentration of tourism demand in northern portugal: an integrated approach based on the gini index

Measures that address the seasonality, one of the identified overtourism direct causes, allow making a critical reflection on the application of control policies and monitoring regional measures crucial on a sector with such importance at the regional development analysis. The measures should stimulate or reduce tourism demand during low or peak seasons, respectively, generating a better distribution of tourism flows and eliminating potential overtourism situations. Therefore, this chapter focuses on the development of a Gini Index to analyse the distribution of the seasonality in northern Portugal and through it control current public measures in practice and suggest the implementation of different and more effective policy measures. For instance, the ones that make a clear bet on outdoor tourism activities. It will be used in the Gini Index, by the tourists? market of origin measured by the overnight stays in hotel establishments. The results showed the high seasonal concentration of tourist flows.691D-6753-BE59 | Manuel Jos? Serra da Fonsecainfo:eu-repo/semantics/publishedVersio

Graft-versus-host disease reduces lymph node display of tissue-restricted self-antigens and promotes autoimmunity

Acute graft-versus-host disease (GVHD) is initially triggered by alloreactive T cells, which damage peripheral tissues and lymphoid organs. Subsequent transition to chronic GVHD involves the emergence of autoimmunity although the underlying mechanisms driving this process are unclear. Here, we tested the hypothesis that acute GVHD blocks peripheral tolerance of autoreactive T cells by impairing lymph node (LN) display of peripheral tissue-restricted antigens (PTA). At the initiation of GVHD, LN fibroblastic reticular cells (FRC) rapidly reduced expression of genes regulated by DEAF1, an Autoimmune Regulator-like transcription factor required for intra-nodal expression of PTA. Subsequently, GVHD led to the selective elimination of the FRC population, and blocked the repair pathways required for its regeneration. We used a transgenic mouse model to show that the loss of presentation of an intestinal PTA by FRC during GVHD resulted in the activation of auto-aggressive T cells and gut injury. Finally, we show that FRC normally expressed a unique PTA gene signature that was highly enriched for genes expressed in the target organs affected by chronic GVHD. In conclusion, acute GVHD damages and prevents repair of the FRC network, thus disabling an essential platform for purging auto-reactive T cells from the repertoire