Survivin: a dual player in healthy and diseased skin

Survivin belongs to the inhibitor of apoptosis (IAP) protein family, and, in addition to the antiapoptotic functions, it also regulates the cell cycle. The survivin gene generates five major isoforms with diverse and opposite functions. Survivin is highly expressed in cancer and in few normal adult tissues, including skin. It is mostly detected in the nucleus of keratinocyte stem cells (KSCs), but it is also expressed in melanocytes and fibroblasts. Survivin isoforms are differentially detected in subpopulations of human keratinocytes, exerting contrasting activities. Survivin has an important role in the regulation of cell cycle in keratinocytes, and it protects these cells from anoikis and UV-induced apoptosis. In melanoma, survivin is abundantly expressed, and its subcellular localization varies depending upon tumor thickness and invasiveness. Survivin overexpression has been shown in squamous cell carcinoma (SCC), and it is also involved in UVB-induced carcinogenesis. The presence of survivin both in the nucleus and in the cytoplasm throughout the epidermal layers of psoriatic lesions suggests the involvement of this protein in the keratinocyte alterations typical of this disease. Additional studies on the expression of survivin isoforms and their subcellular localization in relation to function will confirm the key role of survivin in the skin and will open the field to new therapeutic strategies for many cutaneous condition

Apoptotic pathways in the pathogenesis of pemphigus: targets for new therapies

Pemphigus is a group of rare autoimmune blistering diseases of the skin in which autoantibodies to desmosome cadherins, desmogleins, induce loss of cell-cell adhesion (acantholysis). In addition to steric hindrance and activation of intracellular phosphorylation cascade signaling pathways, apoptosis has been suggested to contribute to the mechanism by which pathogenic IgG induces acantholysis. We review the literature examining the role of apoptosis in pemphigus. Current data recognize a central role of apoptosis in the mechanisms of blister induction. In particular, here we stress the key role of FasL in pemphigus, as it is able to first induce apoptosis, then acantholysis. Being pro-apoptotic molecules important in blister formation, they could represent new specific targets for pemphigus treatment

CD271 downregulation promotes melanoma progression and invasion in 3-dimensional models and in zebrafish

CD271 is a neurotrophin receptor variably expressed in melanoma. While contradictory data are reported on its role as a marker of tumor initiating cells, little is known on its function in tumor progression. CD271 expression was higher in spheroids derived from freshly isolated cells of primary melanomas and in primary WM115 and WM793-B cell lines, while it decreased during progression to advanced stages in cells isolated from metastatic melanomas and in metastatic WM266-4 and 1205Lu cell lines. Moreover, CD271 was scarcely detected in the highly invasive spheroids (SKMEL28 and 1205Lu). CD271, originally expressed in the epidermis of skin reconstructs, disappeared when melanoma started to invade the dermis. SKMEL8 CD271(-) cells showed greater proliferation and invasiveness in vitro, and were associated with a higher number of metastases in zebrafish, as compared to CD271(+) cells. CD271 silencing in WM115 induced a more aggressive phenotype in vitro and in vivo. On the contrary, CD271 overexpression in SKMEL28 cells reduced invasion in vitro, and CD271 overexpressing 1205Lu cells was associated with a lower percentage of metastases in zebrafish. A reduced cell-cell adhesion was also observed in absence of CD271. Taken together, these results indicate that CD271 loss is critical for melanoma progression and metastasis

Do DLX3 and CD271 Protect Human Keratinocytes from Squamous Tumor Development?

Well-regulated epidermal homeostasis depends on the function of different classes of factors, such as transcription regulators and receptors. Alterations in this homeostatic balance may lead to the development of cutaneous squamous tumorigenesis. The homeobox transcription factor DLX3 is determinant for a p53-dependent regulation of epidermal differentiation and modulates skin carcinogenesis. The maintenance of skin homeostasis also involves the action of neurotrophins (NTs) and their receptors, Trk and CD271. While Trk receptor overexpression is a hallmark of cancer, there are conflicting data on CD271 expression and function in cutaneous SCC (cSCC). Previous studies have reported NT receptors expression in head and neck SSC (HNSCC). We show that CD271 is expressed at low levels in primary cSCC cells and the number of CD271+ cells correlates with cell cohesion in SCC spheroids. In normal epidermis, CD271 is expressed in proliferative progenitor cells and DLX3 in terminally differentiated keratinocytes. Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) increase DLX3 expression. In the absence of a functional BDNF receptor TrkB in keratinocytes, we hypothesize that the BDNF-dependent DLX3 response could be mediated via CD271. Altogether, our results support a putative CD271-DLX3 connection in keratinocytes, which might be crucial to preventing squamous skin cancer

a method to estimate the total voc emission of furniture products

Abstract In the last decade, the environmental sustainability has become an important issue that drives more and more the consumer decisions. Consequently, industrial companies are called to meet the growing demand for more sustainable products. Especially in the furniture sector, customers pay serious attention to the emissions that negatively affect human health and so they request products with low volatile organic compounds (VOCs) emissions. This represents a big challenge because it requires the strictly control of each component provided by all the supply chain actors through expensive laboratory tests. For this aim, the present paper proposes a method to estimate the total VOCs emissions of furniture products starting from the characteristics of all semi-finished products (e.g., geometric features, product composition, process information and functionality) and through the definition of an appropriate impact scale based on historical data. It allows making the supply chain (SC) more sustainable, limiting costly chamber tests

an approach to favor industrial symbiosis the case of waste electrical and electronic equipment

Abstract Waste management, in particular waste electrical and electronic equipment (WEEE), currently represents an important issue for the modern society. A transition toward circular economy and industrial symbiosis models is needed to mitigate the environmental problem and recover value from end of life (EoL) materials/products. This study aims to define an approach and a platform, dedicated to the WEEE sector, to favor the creation of industrial symbiosis opportunities. Through this structured approach, demand of virgin materials and components, and supply of EoL products are linked to find potential collaborations. In this way, EoL components/materials could be reused in different applications, thus closed-loop lifecycles can be created through industrial symbiosis. A case study focused on the reuse of plastics from electrical cables is shown to demonstrate that in the WEEE sector the implementation of industrial symbiosis models can lead to win-win scenarios for all the involved stakeholders

An energy assessment method for SMEs: case study of an Italian mechanical workshop

Abstract Nowadays, climate change requires companies to reduce their energy consumption and make their production systems more efficient. However, the complexity of the methodologies, the lack of transparency or high efforts (personnel/time) make this challenge especially difficult for SMEs. In this context, the present paper proposes a workflow to supports SMEs in a lean energy analysis. Through the implementation of several methodologies, a comprehensive assessment of energy consumption was carried out. The application to a real case study allowed to identify energy inefficiencies and to evaluate the energy saving and performance improvement actions

a method for lean energy assessment of manufacturing systems

Abstract Manufacturing systems are among the main consumers of energy. Several methods and tools have been developed to support companies toward energy efficiency. However, they generally require high computational effort, onerous measurement campaigns or complex models. In this paper, a method to perform a lean energy assessment starting from the asset characteristics is proposed. It is based on a set of corrective factors that consider both technical and productive aspects. The final goal is to overcome the lack of precise data needed to identify hotspots from the energy point of view. A real industrial case study allows implementing the method and demonstrating its usefulness

The electron transfer rate of large TPA based compounds: a joint theoretical and electrochemical approach

A series of triphenylamine (TPA) based compounds is investigated by means of density functional theory and cyclic voltammetry. Using the Nicholson\u27s formalism, the measured D E_p are correlated with B3LYP/6-31G* calculated reorganization energies (lambda), elucidating the trend followed by the self electron transfer rate (k_{ET}) of these compounds. Besides the direct dependency upon the dimension of the cationic fragment contributing to the hole stabilization, the lambdas are tuned by the symmetry local to the TPA units, as evidenced by the structural relaxation of the cations. TAPC turns out to be the most effective compound with respect to the self electron transfer process, while N,N\u27-diphenyl-N,N\u27-bis[N-phenyl-N-3-tolyl(4-aminophenyl)]benzidine (MDTAB) shows the interesting combination of low ionization potential (IP) and high k_{ET}. This can make these compounds interesting for practical applications in organic light emitting diodes (OLEDs) devices, due to the direct correlation of the IP and k_{ET} with the hole transfer efficiency to the anode, along with the hole mobility