Sirt1 Protects against Oxidative Stress-Induced Apoptosis in Fibroblasts from Psoriatic Patients: A New Insight into the Pathogenetic Mechanisms of Psoriasis

Psoriasis, a multisystem chronic disease characterized by abnormal keratinocyte proliferation, has an unclear pathogenesis where systemic inflammation and oxidative stress play mutual roles. Dermal fibroblasts, which are known to provide a crucial microenvironment for epidermal keratinocyte function, represented the selected experimental model in our study which aimed to clarify the potential role of SIRT1 in the pathogenetic mechanisms of the disease. We firstly detected the presence of oxidative stress (lipid peroxidation and total antioxidant capacity), significantly reduced SIRT1 expression level and activity, mitochondrial damage and apoptosis (caspase-3, -8 and -9 activities) in psoriatic fibroblasts. Upon SIRT1 activation, redox balance was re-established, mitochondrial function was restored and apoptosis was no longer evident. Furthermore, we examined p38, ERK and JNK activation, which was strongly altered in psoriatic fibroblasts, in response to SIRT1 activation and we measured caspase-3 activity in the presence of specific MAPK inhibitors demonstrating the key role of the SIRT1 pathway against apoptotic cell death via MAPK modulation. Our results clearly demonstrate the involvement of SIRT1 in the protective mechanisms related to fibroblast injury in psoriasis. SIRT1 activation exerts an active role in restoring both mitochondrial function and redox balance via modulation of MAPK signaling. Hence, SIRT1 can be proposed as a specific tool for the treatment of psoriasis

Conservation status of Italian coastal dune habitats in the light of the 4th Monitoring Report (92/43/EEC Habitats Directive)

Coastal dunes are among habitats with the worst conservation status on a global, European and national scale. Monitoring and reporting are of strategic importance to determine the effectiveness of the implementation of Habitats Directive and to preserve the unique biodiversity heritage of the Italian dunes. In this study we show main results of the 4th National Report with specific reference to the macro-habitat “Coastal Sand Dunes and Inland Dunes”, highlighting its updated current conservation status at the national and Biogeographical level. A comprehensive Working Group of territorial experts collected, updated, validated and integrated the data available for 11 Annex I Habitats, distributed in the Alpine, Continental and Mediterranean Biogeographical Regions. The conservation status was evaluated through the following criteria: geographic range, surface area, structure, functions, pressures, threats, conservation measures and prospects. Results highlighted the dramatically bad conservation status of Italian dune Habitats: the overall assessment reported 88% of habitats in bad conservation status and the remaining 12% is in inadequate conditions. Results showed a generalised threat and a worrying conservation status both on herbaceous and wooded communities, in particular in some relevant habitats, such as the shifting dunes. Main pressures and threats were linked to residential, commercial and industrial activities, as well as alien species. Although some of the changes in distribution and trends are probably deriving from more accurate and updated data, the alarming conservation status of Italian sand dunes requires a better knowledge of pressures and threats for further management actions and monitoring plans, inside and outside protected areas

The role of autophagy in resistance to targeted therapies

Autophagy is a self-degradative cellular process, involved in stress response such as starvation, hypoxia, and oxidative stress. This mechanism balances macro-molecule recycling to regulate cell homeostasis. In cancer, autophagy play a role in the development and progression, while several studies describe it as one of the key processes in drug resistance. In the last years, in addition to standard anti-cancer treatments such as chemotherapies and irradiation, targeted therapy became one of the most adopted strategies in clinical practices, mainly due to high specificity and reduced side effects. However, similar to standard treatments, drug resistance is the main challenge in most patients. Here, we summarize recent studies that investigated the role of autophagy in drug resistance after targeted therapy in different types of cancers. We highlight positive results and limitations of pre-clinical and clinical studies in which autophagy inhibitors are used in combination with targeted therapies. Refereed/Peer-reviewe

Adalimumab-Based Treatment Versus Disease-Modifying Antirheumatic Drugs for Venous Thrombosis in Behçet's Syndrome: A Retrospective Study of Seventy Patients With Vascular Involvement

Objective: Since Behçet's syndrome (BS) is the prototype of inflammation-induced thrombosis, immunosuppressants are recommended in place of anticoagulants. We undertook this study to assess the clinical efficacy and the corticosteroid-sparing effect of adalimumab (ADA)–based treatment versus disease-modifying antirheumatic drug (DMARD) therapy in a large retrospective cohort of patients with BS-related venous thrombosis. Methods: We retrospectively collected data on 70 BS patients treated with DMARDs or ADA-based regimens (ADA with or without DMARDs) because of venous complications. Clinical and imaging evaluations were performed to define vascular response. We explored differences in outcomes between ADA-based regimens and DMARDs with respect to efficacy, corticosteroid-sparing role, and time on treatment. We also evaluated the role of anticoagulants as concomitant treatment. Results: After a mean ± SD follow-up period of 25.7 ± 23.2 months, ADA-based regimens induced clinical and imaging improvement of venous thrombosis more frequently (P = 0.001) and rapidly (P < 0.0001) than did DMARDs. The mean dose of corticosteroids administered at the last follow-up visit was significantly lower with ADA-based regimens than with DMARDs (P < 0.0001). The time on treatment was significantly longer with ADA plus DMARDs than with DMARDs alone (P = 0.002). No differences were found in terms of efficacy and time on treatment between DMARDs or ADA-based regimens among patients who received anticoagulants and those who did not. Conclusion: In this large retrospective study, we have shown that ADA-based regimens are more effective and rapid than DMARDs in inducing resolution of venous thrombosis in BS patients, allowing reduction of steroid exposure. Moreover, our findings suggest that anticoagulation does not modify the efficacy of either ADA-based regimens or DMARDs for venous complications

Protocolo de ação do uso de resina poliéster na inclusão de fatias semifinas de encéfalo: uma abordagem de baixo custo no ensino de anatomia macroscópica para o ensino fundamental e médio

No ensino de Biologia e Ciências a compreensão da morfologia macroscópica prioriza a visão bidimensional, muito mais por fatores logísticos do que pedagógicos. Tal visão, oferecida pelos livros didáticos, é o fator limitante mais importante para o domínio destas competências. Modelos tridimensionais de boa qualidade são de custo elevado. Materiais biológicos de procedência conhecida e ética também são infrequentes, sua preparação e conservação exigem mão de obra especializada, curadoria constante e ainda requerem substâncias químicas no seu preparo que são irritantes, tóxicas ou com potencial de abuso, e.g. formol, álcool, clorofórmio. A necessidade de aproximar o estudante do conteúdo ministrado em sala de aula enriquecendo a didática e melhorando o processo ensino-aprendizagem faz com que haja uma busca de novas maneiras e materiais que auxiliem o professor neste desenvolvimento. O protocolo de ação para a produção de material didático, para o ensino de Anatomia, fazendo uso de fatias semifinas de encéfalo de vertebrados, fixado e posteriormente incluídas em resina acrílica de poliéster facilita o contato real do estudante com o exposto teoricamente, desvinculando da necessidade de um laboratório de Ciências e Biologia, uma vez que a resina é um material leve, atóxico, de grande durabilidade e que pode ser levado para dentro da sala de aula. A escolha de peças da neuroanatomia (encéfalos) se mostra interessante devido a sua complexidade estrutural e de nomenclatura que, ao ser vista e manuseada, facilita ao estudante a correlação teórico-prática

Protocolo de ação do uso de resina poliéster na inclusão de fatias semifinas de encéfalo: uma abordagem de baixo custo no ensino de anatomia macroscópica para o ensino fundamental e médio

No ensino de Biologia e Ciências a compreensão da morfologia macroscópica prioriza a visão bidimensional, muito mais por fatores logísticos do que pedagógicos. Tal visão, oferecida pelos livros didáticos, é o fator limitante mais importante para o domínio destas competências. Modelos tridimensionais de boa qualidade são de custo elevado. Materiais biológicos de procedência conhecida e ética também são infrequentes, sua preparação e conservação exigem mão de obra especializada, curadoria constante e ainda requerem substâncias químicas no seu preparo que são irritantes, tóxicas ou com potencial de abuso, e.g. formol, álcool, clorofórmio. A necessidade de aproximar o estudante do conteúdo ministrado em sala de aula enriquecendo a didática e melhorando o processo ensino-aprendizagem faz com que haja uma busca de novas maneiras e materiais que auxiliem o professor neste desenvolvimento. O protocolo de ação para a produção de material didático, para o ensino de Anatomia, fazendo uso de fatias semifinas de encéfalo de vertebrados, fixado e posteriormente incluídas em resina acrílica de poliéster facilita o contato real do estudante com o exposto teoricamente, desvinculando da necessidade de um laboratório de Ciências e Biologia, uma vez que a resina é um material leve, atóxico, de grande durabilidade e que pode ser levado para dentro da sala de aula. A escolha de peças da neuroanatomia (encéfalos) se mostra interessante devido a sua complexidade estrutural e de nomenclatura que, ao ser vista e manuseada, facilita ao estudante a correlação teórico-prática

Behçet's Syndrome as a Model of Thrombo-Inflammation: The Role of Neutrophils

Behçet's syndrome (BS) is a systemic vasculitis, clinically characterized by different organ involvement and often complicated by thrombosis which occurs in vessels of all sizes. Thrombosis is more frequent in male patients with active disease and represents an important cause of morbidity and mortality. Neutrophil involvement in BS has been repeatedly suggested in the last few years. Indeed, neutrophils have been shown to be hyperactivated in BS patients, probably with a HLAB51 related contribution, and represent the main cells infiltrating not only oral and genital ulcers or erythema nodosum, but also other sites. Besides being deputed to host defense against micro-organisms, neutrophils display fundamental roles both in inflammation and tissue damage becoming inappropriately activated by cytokines, chemokines and autoantibodies and subsequently producing large amounts of superoxide anion (O2.) via NADPH oxidase (NOX2). The strict relationship between inflammation and hemostasis has been already demonstrated. Indeed, inflammation and immune-mediated disorders increase the risk of thrombosis, but the pathways that link these processes have not been completely elucidated. In this regard, we recently demonstrated, in a large population of BS patients, a new neutrophil-dependent pathogenetic mechanism of thrombosis. In particular, it was shown that neutrophils, mainly through NADPH oxidase, produce excessive amounts of reactive oxygen species (ROS), which are able to markedly modify the secondary structure of fibrinogen and hence the overall architecture of the fibrin clot that becomes less susceptible to plasmin-induced lysis. These data point out that BS represents “per se” a model of inflammation-induced thrombosis and suggest that neutrophils specifically contribute to thrombo-inflammation in this rare disease. In particular, it is suggested that an alteration in fibrinogen structure and function are associated with enhanced ROS production via neutrophil NADPH oxidase. Altogether, these findings improve our understanding of the intricate pathogenetic mechanisms of thrombo-inflammation and may indicate potential new therapeutic targets

Thrombosis in vasculitis: from pathogenesis to treatment

In recent years, the relationship between inflammation and thrombosis has been deeply investigated and it is now clear that immune and coagulation systems are functionally interconnected. Inflammation-induced thrombosis is by now considered a feature not only of autoimmune rheumatic diseases, but also of systemic vasculitides such as Behçet’s syndrome, ANCA-associated vasculitis or giant cells arteritis, especially during active disease. These findings have important consequences in terms of management and treatment. Indeed, Behçet’syndrome requires immunosuppressive agents for vascular involvement rather than anticoagulation or antiplatelet therapy, and it is conceivable that also in ANCA-associated vasculitis or large vessel-vasculitis an aggressive anti-inflammatory treatment during active disease could reduce the risk of thrombotic events in early stages. In this review we discuss thrombosis in vasculitides, especially in Behçet’s syndrome, ANCA-associated vasculitis and large-vessel vasculitis, and provide pathogenetic and clinical clues for the different specialists involved in the care of these patients