TY - JOUR T1 - Kinetic Profiles of Inflammatory Mediators in the Conjunctival Sac Fluid of Patients upon Photorefractive Keratectomy. JF - Mediators Inflamm Y1 - 2015 A1 - Tisato, Veronica A1 - Perri, Paolo A1 - Rimondi, Erika A1 - Melloni, Elisabetta A1 - Lamberti, Giuseppe A1 - Milani, Daniela A1 - Secchiero, Paola A1 - Zauli, Giorgio AB -

Photorefractive keratectomy (PRK) represents a therapeutic option to remodel corneal stroma and to compensate refractive errors, which involves inflammatory and/or regenerative processes. In this context, the modulation of cytokines/chemokines in the conjunctival sac fluid and their role in the maintenance of the corneal microenvironment during the healing process upon refractive procedures has not been deeply investigated. In this study, serial samples of conjunctival sac fluid of patients (n = 25) undergoing PRK were harvested before and at different time points after surgery. The levels of 29 cytokines/chemokines/growth factors involved in inflammatory/immune processes were measured with a multiplex array system. The results have firstly highlighted the different pattern of cytokine expression between the microenvironment at the anterior surface of the eye and the systemic circulation. More importantly, the kinetic of modulation of cytokines/chemokines at the conjunctival level following PRK revealed that while the majority of cytokines/chemokines showed a significant decrease, MCP-1 emerged in light of its pronounced and significant increase soon after PRK and during the follow-up. This methodological approach has highlighted the role of MCP-1 in the healing process following PRK and has shown a potential for the identification of expression/modulation of soluble factors for biomarker profiling in ocular surface diseases.

VL - 2015 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26525345?dopt=Abstract ER - TY - JOUR T1 - Pediatric patients with inflammatory bowel disease exhibit increased serum levels of proinflammatory cytokines and chemokines, but decreased circulating levels of macrophage inhibitory protein-1β, interleukin-2 and interleukin-17. JF - Exp Ther Med Y1 - 2015 A1 - Kleiner, Giulio A1 - Zanin, Valentina A1 - Monasta, Lorenzo A1 - Crovella, Sergio A1 - Caruso, Lorenzo A1 - Milani, Daniela A1 - Marcuzzi, Annalisa AB -

Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory condition of the gastrointestinal tract. Although the causative events that lead to the onset of IBD are yet to be fully elucidated, deregulation of immune and inflammatory mechanisms are hypothesized to significantly contribute to this disorder. Since the onset of IBD is often during infancy, in the present study, the serum values of a large panel of cytokines and chemokines in pediatric patients (<18 years; n=26) were compared with age-matched controls (n=37). While elevations in the serum level of several proinflammatory and immune regulating cytokines were confirmed, such as interleukin (IL)-1β, IL-5, IL-7, interferon (IFN)-γ-inducible protein-10, IL-16, cutaneous T-cell-attracting chemokine, leukemia inhibitory factor, monokine induced by γ-IFN, IFN-α2 and IFN-γ, notably decreased levels of IL-2, IL-17 and macrophage inhibitory protein-1β were also observed. Therefore, while a number of proinflammatory cytokines exhibit increased levels in IBD patients, pediatric IBD patients may also exhibit certain aspects of a reduced immunological response.

VL - 9 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26136934?dopt=Abstract ER - TY - JOUR T1 - TNF-related apoptosis inducing ligand in ocular cancers and ocular diabetic complications. JF - Biomed Res Int Y1 - 2015 A1 - Perri, Paolo A1 - Zauli, Giorgio A1 - Gonelli, Arianna A1 - Milani, Daniela A1 - Celeghini, Claudio A1 - Lamberti, Giuseppe A1 - Secchiero, Paola KW - Apoptosis KW - Diabetes Complications KW - Diabetes Mellitus KW - Eye Neoplasms KW - Humans KW - Receptors, TNF-Related Apoptosis-Inducing Ligand KW - TNF-Related Apoptosis-Inducing Ligand AB -

TNF-related apoptosis inducing ligand (TRAIL) is an intensively studied cytokine, in particular for its anticancer activity. The discovery that conjunctival sac fluid contains extremely high levels of soluble TRAIL as compared to other body fluids suggested important implications in the context of the immunological surveillance of the eye, in particular of the anterior surface. In this review, we discuss the potential physiopathologic and therapeutic role of the TRAIL/TRAIL receptor system in a variety of ocular cancers. Moreover, since an increasing amount of data has indicated the important biological activities of the TRAIL/TRAIL receptor systems also in a completely different pathologic context such as diabetes mellitus, in the second part of this review we summarize the currently available data on the involvement of TRAIL in the ocular complications of diabetes mellitus as modulator of the inflammatory and angiogenic response in the eye.

VL - 2015 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25834817?dopt=Abstract ER - TY - JOUR T1 - Two-dimensional gel electrophoresis analysis of the leiomyoma interstitial fluid reveals altered protein expression with a possible involvement in pathogenesis. JF - Oncol Rep Y1 - 2015 A1 - Ura, Blendi A1 - Scrimin, Federica A1 - Zanconati, Fabrizio A1 - Arrigoni, Giorgio A1 - Monasta, Lorenzo A1 - Romano, Andrea A1 - Banco, Rubina A1 - Zweyer, Marina A1 - Milani, Daniela A1 - Ricci, Giuseppe AB -

Uterine leiomyoma is the most common smooth benign neoplasm. In the present study, we analyzed the global interstitial fluid (IF) profile of leiomyoma vs. normal myometrium to identify protein dysregulation involved in leiomyoma pathogenesis. Two-dimensional gel electrophoresis and mass spectrometry were used to generate and compare the global interstitial fluid profiles of the leiomyoma and of the normal tissue. Two proteins were validated by immunohistochemistry. By comparing the interstitial fluid profile of the leiomyoma with that of the normal myometrium, the levels of seven proteins were found to be significantly different: four structural organization proteins (desmin, prelamin-A/C, transgelin and α-actinin-1), an inflammatory response (α1-antitrypsin), a response to oxidative stress (peroxiredoxin-2), and a folding protein (heat shock 70 kDa protein 1A/1B). Desmin, α1-antitrypsin and peroxiredoxin-2 were upregulated in the leiomyoma, whereas heat shock 70 kDa protein 1A/1B, α-actinin-1, prelamin-A/C and transgelin were downregulated. Desmin and α1-antitrypsin were further validated by immunohistochemistry. By identifying proteins with altered expression levels compared to the myometrium from several pathways of the leiomyoma pathogenesis, we found the leiomyoma interstitial fluid to have a characteristic proteomic profile. A better appreciation of the pathophysiology of the disease can be useful in the development of conservative treatments that serve as viable alternatives to hysterectomy.

VL - 33 IS - 5 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25738828?dopt=Abstract ER - TY - JOUR T1 - TRAIL as biomarker and potential therapeutic tool for cardiovascular diseases. JF - Curr Drug Targets Y1 - 2012 A1 - Bernardi, Stella A1 - Milani, Daniela A1 - Fabris, Bruno A1 - Secchiero, Paola A1 - Zauli, Giorgio KW - Biological Markers KW - Cardiovascular Diseases KW - Humans KW - Prognosis KW - TNF-Related Apoptosis-Inducing Ligand AB -

This review focuses on TNF-related apoptosis-inducing ligand (TRAIL), also called Apo2 ligand, a protein belonging to the TNF superfamily. TRAIL can be found either in its transmembrane or circulating form, and its mostly studied peripheral effect is the induction of cellular apoptosis. Here, we discuss the evidences supporting the use of TRAIL as biomarker of cardiovascular diseases as well as the evidences showing the potential beneficial therapeutic effects of TRAIL on cardiovascular diseases and diabetes.

VL - 13 IS - 9 U1 - http://www.ncbi.nlm.nih.gov/pubmed/22676911?dopt=Abstract ER -