Snail mucus is a mixture of active substances commonly thought to have healthy properties for the treatment of skin disorders. Although snail mucus is an ingredient of several cosmetic and para-pharmaceutic products, a comprehensive characterization of chemical composition and biological effects is still missing. Crude purified extracts from Helix aspersa muller mucus (HelixComplex) were prepared and, after chemical characterization, tested on in vitro experimental models. Differently from what expected, HelixComplex was characterized by the presence of small amounts of glycolic acid and allantoin. By using different in vitro assays on fibroblast cultures, we found that HelixComplex lacked of cytotoxicity, protected cells from apoptosis (p < 0.05) and, importantly, was able to significantly induce cell proliferation and migration through direct and indirect mechanisms. These effects were associated to morphological changes, cytoskeleton re-organization and release of cytokines. In conclusion, our findings suggest that snail mucus biological effects are attributable to cell proliferation and migration, and pave the way for further investigating snail mucus potential as therapeutic agent.

The key role of T cells in the pathogenesis of cutaneous psoriasis has been well described in the last decade and the knowledge of the relative role of the different subsets of T cells in psoriasis pathogenesis has considerably evolved. Now, it is clear that IL-17A-producing T cells, including Th17/Tc17, have a central role in the pathogenesis of cutaneous psoriasis and therapies blocking the IL-17A pathway show high clinical efficacy. By contrast, the contribution of IFNγ-producing T cells has progressively become less clear because of the lack of efficacy of anti-IFNγ antibodies in clinical studies. In parallel, the role of CD8⁺ T cells specific for self-antigens has been revived and increasing evidence now indicates that in psoriatic skin the majority CD8⁺ T cells are present in the form of epidermal tissue-resident memory T cells. In the last years it also emerged the possibility of a contribution of T cell recirculation in the pathogenesis of psoriasis and its systemic manifestations. The aim of this review is to define a hierarchy for the different subsets of T cells in the T cell-mediated inflammatory cascade in psoriatic skin. This analysis will possibly help to distinguish the subsets that initiate the disease, those involved in the establishment of the self-sustaining amplification loop that leads to the cutaneous clinical manifestations and finally the subsets that act as downstream players in established lesions. Specific T cell subpopulations finally will be considered for their possible role in propagating inflammation at distant sites and for representing a link with systemic inflammation and cardiovascular comorbidities.

The aim of this study is to identify subsets of T cells differentially represented in the circulation of patients with psoriatic arthritis and to evaluate the possibility that they can recirculate between peripheral blood and the inflamed joints. We analyzed the phenotype and cytokine expression in circulating CD8⁺ and CD4⁺ T cells in 69 subjects: 28 with cutaneous psoriasis, 15 patients with psoriatic arthritis, and 26 healthy subjects. In the circulation, the percentage of each subset was compared among the groups and correlation was calculated with the serum concentration of C-reactive protein. To investigate the migration of T cells towards the inflamed joints, we performed a transwell migration assay towards patient serum and synovial fluid. In selected patients we analyzed in parallel T cells from peripheral blood and from synovial fluid. In the circulation, we found increased percentage of CD8⁺ CCR6⁺ T cell effectors expressing CD69 and of IL-17-producing T cells in patients with psoriatic arthritis. CD8⁺ effector/effector memory T cells showed increased migration towards synovial fluid. Finally, in synovial fluid we found accumulation of CXCR3⁺ CD8⁺ T cells and CD69⁺ cells. CD4⁺ T cells in the two compartments shared many similarities with CD8⁺ T cells. The results indicate a role for memory T cell effectors in systemic and joint manifestations of psoriatic arthritis.

Silica-based luminescent nanoparticles (SiNPs) show promising prospects in nanomedicine in light of their chemical properties and versatility. In this study, we have characterized silica core–PEG shell SiNPs derivatized with PEG moieties (NP-PEG), with external amino- (NP-PEG-amino) or carboxy-groups (NP-PEG-carbo), both in cell cultures as well as in animal models. By using different techniques, we could demonstrate that these SiNPs were safe and did not exhibit appreciable cytotoxicity in different relevant cell models, of normal or cancer cell types, growing either in suspension (JVM-2 leukemic cell line and primary normal peripheral blood mononuclear cells) or in adherence (human hepatocarcinoma Huh7 and umbilical vein endothelial cells). Moreover, by multiparametric flow cytometry, we could demonstrate that the highest efficiency of cell uptake and entry was observed with NP-PEG-amino, with a stable persistence of the fluorescence signal associated with SiNPs in the loaded cell populations both in vitro and in vivo settings suggesting this as an innovative method for cell traceability and detection in whole organisms. Finally, experiments performed with the endocytosis inhibitor Genistein clearly suggested the involvement of a caveolae-mediated pathway in SiNP endocytosis. Overall, these data support the safe use of these SiNPs for diagnostic and therapeutic applications.

Redox regulation plays a key role in several physiopathological contexts and free radicals, from nitric oxide and superoxide anion up to other forms of reactive oxygen species (ROS), have been demonstrated to be involved in different biological and regulatory processes. The data reported in the current literature describe a link between ROS, inflammation and programmed cell death that is attracting interest as new pathways to be explored and targeted for therapeutic purposes. In this light, there is also growing attention to the involvement of this link in the activity of the TNF-related apoptosis inducing ligand (TRAIL). TRAIL is a member of the TNF ligands super family able to mediate multiple intracellular signals, with the potential to lead to a range of biological effects in different cell types. In particular, the hallmark of TRAIL is the ability to induce selective apoptosis in transformed cells leaving normal cells almost unaffected and this feature has already opened the door to several clinical studies for cancer treatment. Moreover, TRAIL plays a role in several physiological and pathological processes of both innate and adaptive immune systems and of the cardiovascular context, with a strong clinical potential. Nonetheless, several issues still need to be clarified about the signaling mediated by TRAIL to gain deeper insight into its therapeutic potential. In this light, the aim of this review is to summarize the main preclinical evidences about the interplay between TRAIL and redox signaling, with particular emphasis to the implications in vascular physiopathology and cancer.

The chemokine receptor CCR4 has emerged as a skin-homing molecule important for the migration of T cells from the blood to the dermis. From our previous data on psoriasis patients, CCR4⁺ memory T cells emerged as a putative recirculating population between skin and blood. Here we focused our attention on the expression of CCR4 and skin-tropic molecules in the different stages of memory T cell differentiation. We analyzed the chemokine receptor profile in CD8⁺ and CD4⁺ CD45RA⁻CCR7⁺ (T_CM) and CD45RA⁻CCR7⁻ (T_EM) cells. Subpopulations were further divided on the basis of CD62L expression, and the distribution among the subsets of the skin-homing molecule CLA (Cutaneous Lymphocyte Antigen) was evaluated. The characterization was performed on peripheral blood mononuclear cells isolated from 21 healthy subjects and 24 psoriasis patients. The results indicate that (i) the skin-homing CCR4 marker is mainly expressed in T_CM cells, (ii) CCR4⁺ T_CM cells also express high level of CLA and that (iii) the more differentiated phenotype T_EM expresses CXCR3 and CCR5 but lower level of CCR4 and CLA. This indicates that progressive stages of memory T cell differentiation have profoundly different chemokine receptor patterns, with CD8⁺ T_CM displaying a marked skin-tropic phenotype CLA⁺CCR4⁺. Differential skin-tropic phenotype between T_CM and T_EM cells was observed in both healthy subjects and psoriasis patients. However, patients showed an expanded circulating population of CD8⁺ T_CM cells with phenotype CCR4⁺CXCR3⁺ that could play a role in the pathophysiology of psoriasis and possibly in disease recurrence.