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The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor initially identified as the receptor for dioxin. Almost half a century after its discovery, AHR is now recognized as a receptor for multiple physiological ligands, with important roles in health and disease. In this review, we discuss the role of AHR in the gut–brain axis and its potential value as a therapeutic target for immune-mediated diseases.

An increasing number of innovative therapies have emerged in the field of wound healing. Nanostructured systems have been used to improve wound healing at different stages. The drug itself may be formulated at a nanoscale such that it can function as its own “carrier” or nanomaterials may be used as drug delivery vehicles. The present work covers the latest advancements on innovative nano‐based organic and inorganic materials. These novel drug delivery systems possess high stability, large surface area and tunable compositions and have demonstrated their wound‐healing properties using in vitro and in vivo models. Key areas in the development of new systems for wound care are the assessment of biological compatibility, the evaluation of anti‐microbial activity and the in vivo efficacy assessment using full‐thickness skin models. Due to the multifactorial nature of chronic wound occurrence robust models should support the investigation of new materials in order to elucidate mechanisms involved in the sequence of physiologic processes that take place at wound healing. Although several nanoparticles have been successfully tested both in vitro and in vivo, researchers are still investigating the approaches to implementing large scale production of nanotechnological platforms to wound healing treatments. Several nanomaterials have been employed in wound healing in each type of healing phase (Hemostasis, Inflammation, Proliferation, Remodeling). The rationale for using each material strongly depends on the phase but also the duration of the therapeutic effect, dose, deepness and mechanism of action. NPs, nanoparticles.

Tumor-associated macrophages (TAMs) play an important role in the immune response to cancer, but the mechanisms by which the tumor microenvironment controls TAMs and T cell immunity are not completely understood. Here we report that kynurenine produced by glioblastoma cells activates aryl hydrocarbon receptor (AHR) in TAMs to modulate their function and T cell immunity. AHR promotes CCR2 expression, driving TAM recruitment in response to CCL2. AHR also drives the expression of KLF4 and suppresses NF-κB activation in TAMs. Finally, AHR drives the expression of the ectonucleotidase CD39 in TAMs, which promotes CD8+ T cell dysfunction by producing adenosine in cooperation with CD73. In humans, the expression of AHR and CD39 was highest in grade 4 glioma, and high AHR expression was associated with poor prognosis. In summary, AHR and CD39 expressed in TAMs participate in the regulation of the immune response in glioblastoma and constitute potential targets for immunotherapy.Using animal models and clinical samples, the authors report that glioblastoma metabolites activate the transcription factor aryl hydrocarbon receptor in tumor-associated macrophages to modulate their function and T cell immunity, promoting tumor growth.

Zika virus (ZIKV) is a flavivirus linked to multiple birth defects including microcephaly, known as congenital ZIKV syndrome. The identification of host factors involved in ZIKV replication may guide efficacious therapeutic interventions. In genome-wide transcriptional studies, we found that ZIKV infection triggers aryl hydrocarbon receptor (AHR) activation. Specifically, ZIKV infection induces kynurenine (Kyn) production, which activates AHR, limiting the production of type I interferons (IFN-I) involved in antiviral immunity. Moreover, ZIKV-triggered AHR activation suppresses intrinsic immunity driven by the promyelocytic leukemia (PML) protein, which limits ZIKV replication. AHR inhibition suppressed the replication of multiple ZIKV strains in vitro and also suppressed replication of the related flavivirus dengue. Finally, AHR inhibition with a nanoparticle-delivered AHR antagonist or an inhibitor developed for human use limited ZIKV replication and ameliorated newborn microcephaly in a murine model. In summary, we identified AHR as a host factor for ZIKV replication and PML protein as a driver of anti-ZIKV intrinsic immunity.Giovannoni et al. report that the aryl hydrocarbon receptor (AHR) is a novel host factor exploited by Zika virus and dengue virus to evade the immune response. AHR is a candidate target for the treatment of Zika virus congenital syndrome and dengue fever.

Acetaminophen (APAP) is usually safe when administrated in therapeutic doses; however, APAP overdose can lead to severe liver injury. APAP can cause direct hepatocyte damage, and stimulates an inflammatory response leading to oxidative stress. Supressor of Cytokine Signaling (SOCS) 2 modulates cytokine and growth factor signaling, and plays a role in the regulation of hepatic cellular processes. Our study evaluated the role of SOCS2 in APAP liver injury. The administration of a toxic dose (600 mg/kg) of APAP caused significant liver necrosis in WT mice. In SOCS2 mice, there was significantly more necrosis, neutrophil recruitment, and expression of the neutrophil-active chemokine CXCL-1. Expression of proinflammatory cytokines, such as TNF-α and IL-6, was elevated, while expression of anti-inflammatory cytokines, IL-10 and TGF-β, was diminished. , SOCS2 hepatocytes expressed more p-NF-kB and produced more ROS than WT hepatocytes when exposed to APAP. SOCS2 hepatocytes were more sensitive to cell death in the presence of IL-6 and hydrogen peroxide. The administration of catalase and resulted in a pronounced reduction of cells/mice death and necrosis in the SOCS2 group. We have demonstrated that SOCS2 has a protective role in the liver by controlling pro-oxidative and inflammatory mechanisms induced by APAP.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

In the version of this article initially published, author Alexandre Prat’s surname was misspelled. The error has been corrected in the HTML and PDF versions of the article.

A construção civil é um dos setores onde mais se registam acidentes de trabalho, muitas das vezes graves e até fatais. Isto deve-se às condições de trabalho que expõem os trabalhadores a riscos elevados, com expressão visível e frequentemente dramática na sua saúde. Ademais, e agravando este panorama, muitas empresas não adotam um plano de regresso ao trabalho após a ocorrência de um acidente, apesar da reconhecida importância da adoção do mesmo.Este estudo tem como objetivo explorar a atividade de trabalho dos trabalhadores da construção civil, especialmente no que concerne aos riscos profissionais, impactos para a saúde, nomeadamente, aqueles que são decorrentes de acidentes de trabalho, de acordo com o ponto de vista destes trabalhadores. O estudo incluiu um total de 12 participantes, sendo que o método de recolha de dados consistiu na realização de entrevistas individuais a trabalhadores da construção civil de uma empresa de pequena dimensão. Os resultados demonstram que os participantes reconhecem as condições penosas em que trabalham, os riscos a que se encontram expostos e os impactos desta atividade para a sua saúde. Para além disso, foi possível compreender que existe uma incompatibilidade entre as condições de trabalho e o uso dos Equipamentos de Proteção Individual (EPIs). Ademais, verificou-se ainda a inexistência de um plano de regresso ao trabalho após acidente, ajustado às necessidades dos trabalhadores. Tendo isto em consideração, é urgente que se invista em melhores condições para estes trabalhadores a fim de proporcionar um local de trabalho mais seguro e sustentável.

A pele atua como a primeira linha de proteção contra o ambiente externo e fornece funções essenciais. Quando a sua integridade é comprometida devido a complicações mecânicas, físicas ou relacionadas com o metabolismo, é geralmente observado um maior risco de danos adicionais. Além disso, vários fatores levam ao comprometimento do processo de cicatrização, o que pode levar a feridas crónicas e, consequentemente, causar sofrimento, aumentar a suscetibilidade a infeções e diminuir a qualidade de vida dos doentes.A presente tese de mestrado descreve brevemente a anatomia e fisiologia da pele, as mudanças estruturais e funcionais desta ao longo do tempo, a patogénese das feridas crónicas e as abordagens terapêuticas desenvolvidas para tratar infeções e estimular o processo de cicatrização. Assim, nesta tese de mestrado, focámo-nos em terapias mais tradicionais (como por exemplo, enxertos e pensos) e em abordagens inovadoras, das quais fazem parte os substitutos cutâneos e sistemas nanotecnológicos. Outros tipos de estratégias avançadas no tratamento de feridas incluem terapias com células estaminais e fatores de crescimento, terapia génica, terapia por pressão negativa, oxigenoterapia hiperbárica e outras.De forma geral, esta dissertação cobre os recentes avanços tecnológicos nas duas últimas décadas e discute possíveis perspetivas no tratamento de feridas.

The banana (Musa spp.) under water deficit may occur a significant reduction in productivity and fruit quality, as the water deficit during the vegetative period affects the rate of leaf development, influencing the number of flowers and therefore the number of bunches and the production of fruit. The objective of this study was to evaluate the characterization of post-harvest fruits of banana cv. Pacovan Apodi, in the third cycle of production under different irrigation levels in the conditions of the plateau region of Apodi-Ceará. The experiment was conducted at the experimental area of agroempresa Frutacor in Limoeiro do Norte – CE (05°06' S, 37º52' W, 151 m) in the period of june/07 to july/08. The water depth accounted for 50, 75, 100, 125 and 150% of ETc of lysimeter drainage. The crop was irrigated by a drip irrigation system, consisting of five emitters per plant, with nominal flow of 2.3 L h- 1 and PS 20 m.c.a. The water depth influenced significantly (p <0.05) in the potassium content in fruits and TSS (ºBrix), pH and ATT were not influenced significantly by the irrigation water.