1,721,094 research outputs found
Study of pathogenetic molecular mechanisms and new therapeutic approaches for the treatment of Inflammatory Bowel Disease
Get PDFInflammatory bowel diseases (IBDs), resulting from the interaction between genetic and environmental factors which influence the immune responses, are mainly divided into ulcerative colitis (UC) and Crohn’s disease (CD). New studies have shown that IBD is the most common chronic inflammatory disease worldwide, affecting millions of people mainly in industrialized countries.
The number of people with IBD is increasing rapidly, thus, researchers are trying to identify new mechanisms underlying its pathogenesis and find out new treatments to cure the disease as well as to improve the general health and the quality of life of patients.
High-mobility group box 1 (HMGB1) protein, a nuclear non-histone DNA-binding protein, is released into the extracellular milieu and mediates inflammatory responses contributing to the pathogenesis of IBD.
Treatments based on antagonists specifically targeting extracellular HMGB1 have generated encouraging results in a wide number of experimental models of infectious and sterile inflammation. Interestingly, since the current therapeutic approaches for the management of IBD include drugs (immunosuppressors, steroids) and biological treatments that are often associated with adverse health consequences, the use of natural products is gaining worldwide attention.
Accordingly, the whole purpose of this study is to explore novel strategies for limiting the inflammatory potential of HMGB1. More specifically, we aimed at:
1) to assess the ability of the dipotassium glycyrrhizate (DPG), a salt of the glycoconjugated triterpene glycyrrhizin, that has been shown to inhibit the extracellular HMGB1, to reduce intestinal inflammation and improves the mucosal healing;
2) to investigate the interaction between HMGB1 and Poly (ADP-ribose) polymerase 1 (PARP1), a protein recently involved in the regulation of HMGB1 release, and explore the role of PARP1 as a novel molecular target to control gut inflammation.
The results and conclusion of the first point will be presented attaching the published original paper to the thesis (Stronati L, Palone F, Negroni A, Colantoni E, Mancuso AB, Cucchiara S, Cesi V, Isoldi S, Vitali R. Dipotassium Glycyrrhizate Improves Intestinal Mucosal Healing by Modulating Extracellular Matrix Remodeling Genes and Restoring Epithelial Barrier Functions. Front Immunol. 2019 Apr 26;10:939).
The results of the second point will be presented and discussed in this thesis.
Briefly, to induce a severe colitis, dextran sodium sulphate (DSS) was used in C57BL/6 WT or PARP1−/− mice. Undifferentiated and differentiated colonoid cultures of intestinal stem cells harvested from biopsies of UC patients were treated with cytomix (TNF + IFN) to induce inflammation.
Results show that PARP1−/− mice exhibit a less severe colitis compared to WT mice, as evidenced by the reduction of HMGB1 in the serum and stool samples. 3D colonoid cultures exposed to cytomix show increased levels of IL-1, IL-8, TNF and DUOXA2 as well as extracellular HMGB1. Interestingly, PARP1 specific inhibitor, PJ34, decreases the release of HMGB1 in undifferentiated as well as differentiated colonoids.
In conclusion these data demonstrate that: 1) PARP1 and HMGB1 are closely related; 2) PARP1 contributes to improve inflammation by promoting the release of extracellular HMGB1; 3) inhibition of PARP1 could represent a promising therapeutic approach to control gut inflammation
Amici e fratelli. La rappresentazione pittorica di sé in contesti relazionali differenti.
No full textProbabilistic reliability analysis of a simulated finite-element electromechanical system
No full textDendritic cells in intestinal homeostasis and disease
Get PDFDCs are specialized APCs that orchestrate innate and adaptive immune responses. The intestinal mucosa contains numerous DCs, which induce either protective immunity to infectious agents or tolerance to innocuous antigens, including food and commensal bacteria. Several subsets of mucosal DCs have been described that display unique functions, dictated in part by the local microenvironment. In this review, we summarize the distinct subtypes of DCs and their distribution in the gut; examine how DC dysfunction contributes to intestinal disease development, including inflammatory bowel disease and celiac disease; and discuss manipulation of DCs for therapy
La risalita in quota di specie vegetali: strategie adattative e monitoraggio aerobiologico
No full textAtti del Convegno Evidenze del Cambiamento climatico: dalla scala globale a quella locale
No full text
Effetti top-down sulla biodiversità di comunità di invertebrati in ecosistemi sorgentizi: il ruolo degli acari acquatici
Get PDFGoing Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The one factor libor market model using Monte Carlo simulation: an empirical investigation
No full textThe Libor Market Model (LMM) is an advanced mathematical model
used to price interest rate derivatives. Also known as the BGM model
after its authors (Brace, Gatarek, Musiela, 1997), the LMM has become
hegemonic in the financial markets worldwide. The LMM in reality is
not a single model, but rather as a large family of models (Rebonato
2000, Brigo and Mercurio, 2006). Its many variants include: the number
of factors considered, the type of volatility modelling used, the type of
correlation modelling used, if stochastic volatility or SABR are used, if
forward libor rates or swap rates are used, if semi-analytical or numerical
solution methods are used, among others. The many faces of the LMM
offer the disadvantage of making it difficult to understand for beginners.
It also makes it difficult to clearly see what is the best version to use in
practice. Our aim in this contribution will be to construct the simplest
possible version of the LMM, implement it in C++ and investigate its
accuracy to price real market-quoted interest rate derivatives. We consider
three examples: a plain vanilla interest rate swap (IRS), and IRS
with a CAP and an IRS with a CORRIDOR feature. Our results show
that in these cases our implementation of the LMM1F captures quite well
the market prices of these products, as compared with Bloomberg and
Sungard Monis
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