RESUMO
BACKGROUND: Cutaneous bacterial dysbiosis is a characteristic hallmark of atopic dermatitis (AD), and it decisively influences the severity of the disease. Despite this, frequently used murine models of AD have not been characterized regarding the changes in skin microbiome communities. OBJECTIVE: To analyse the skin microbiome of two frequently used murine models for AD for assessing their applicability in translational research. METHODS: AD was induced in mice by topical application of calcipotriol or oxazolone. Following comparable elicitation of AD-like dermatitis, including IgE induction, the skin microbial communities were analysed and compared with human AD. RESULTS: We detected critical differences in the microbiota composition of diseased skin. In contrast to calcipotriol treatment, application of oxazolone induced significant changes in the cutaneous microbiota and a drastic drop of bacterial richness. Furthermore, an expansion of Staphylococci, particularly S. xylosus, was observed in the oxazolone group, also displaying positive correlations with AD key markers including pH, TEWL, IL-4, TSLP and IL-33. CONCLUSIONS: In this article, we show that (a) the model of choice to investigate AD needs to be characterized for the cutaneous microbiota if applicable and (b) the oxazolone-mediated mixed Th1-Th2 immune response triggers microbiota-induced alterations which share similarities to dysbiosis in human AD and represents therefore a suitable model for translational research on AD if alterations of the microbiome are in the focus of the investigation.
Assuntos
Dermatite Atópica , Microbiota , Animais , Bactérias , Citocinas , Modelos Animais de Doenças , Disbiose/induzido quimicamente , Humanos , Interleucina-33 , Interleucina-4 , Camundongos , Oxazolona/efeitos adversos , PeleRESUMO
BACKGROUND: Photodynamic therapy (PDT) is well known for its direct cytotoxicity of the free radical-producing photochemical reaction, indirect mechanisms of action including modulation of intrinsic anti-tumour immune activity, and occlusion of pathologically altered tumour vessels leading to tumour ischaemia. The aim of this work is to critically review the evidence base for the use of vascular targeted PDT (VTP) to treat low-risk prostate cancer, and to discuss perspectives and challenges yet to be overcome. A brief general overview of focal prostate cancer therapy was provided, followed by a discussion of both basic and clinical research pertaining to prostate cancer VTP, with a focus on the palladium-based WST-09 and WST-11 photosensitisers. MATERIALS AND METHOD: Literature on VTP for prostate cancer with the fallowing medical subject headings search terms: prostate cancer, photodynamic therapy, vascular targeted photodynamic therapy, bacteriopheophorbide were reviewed. The articles were selected by their relevance to the topic. RESULTS: The clinical and basic research data available to date show much promise for WST-09, and WST-11 based VTP eventually joining the standard urologist's armamentarium against prostate cancer. With good reported tolerability and efficacy VTP can be proposed as an intermediate treatment for local low risk disease, halfway between watchful waiting and radical therapy.