La DPP-4 è espressa nelle beta cellule pancreatiche umane e la sua inibizione migliora la funzionalità e la sopravvivenza beta cellulare nel diabete di tipo 2.

Recentemente alcuni autori hanno mostrato come le isole pancreatiche umane siano in grado di secernere in maniera regolata il GLP-1. Dal momento che questo ormone viene degradato ad opera dell’enzima DPP-4, ci siamo domandati se anche la DPP-4 fosse presente nell’isola pancreatica e, nel caso, quale fosse il suo ruolo. Nel nostro studio, quindi, abbiamo valutato l’espressione e il ruolo della DPP-4 in isole pancreatiche umane purificate da donatori non diabetici (ND), donatori affetti da diabete di tipo 2 (DT2) e in una linea beta cellulare umana insulino-secernente, la EndoC-βH1. Su questi modelli sono state effettuate analisi morfologiche, ultrastrutturali, funzionali, di sopravvivenza e molecolari in varie condizioni sperimentali. L’analisi immunoistochimica e la microscopia confocale hanno mostrato come la DPP-4 fosse presente nell’isola pancreatica e più dettagliatamente come questa colocalizzasse con glucagone e in misura minore con alcune cellule contenenti insulina. L’analisi mediante immunogold da un lato confermava la presenza della DPP-4 sia nelle cellule alfa che nelle cellule beta, mentre dall’altro mostrava come la proporzione delle cellule alfa e beta DPP-4-positive risultasse significativamente ridotta nel diabete di tipo 2; in accordo, anche l’espressione genica risultava essere inferiore nei campioni DT2. In aggiunta, l’esposizione ad un inibitore della DPP-4 era in grado di proteggere sia le isole umane che la linea beta cellulare dal danno indotto da citochine. L’inibizione, inoltre, era in grado di aumentare la secrezione insulinica, ridurre l’apoptosi e migliorare l’ultrastruttura di isole DT2. Questo studio quindi, dimostra che: 1) la DPP-4 è presente nelle beta cellule umane; 2) la sua espressione è ridotta nelle isole DT2 e 3) la sua inibizione ha effetti positivi sia nelle isole pancreatiche isolate che nella linea beta cellulare. Tutto questo suggerisce che la DPP-4, oltre a giocare un ruolo nell’effetto incretinico, è in grado di influenzare in maniera diretta la fisiopatologia delle beta cellule

Osteogenic differentiation of mesenchymal stem cells from dental bud: Role of integrins and cadherins

Several studies have reported the beneficial effects of mesenchymal stem cells (MSCs) in tissue repair and regeneration. New sources of stem cells in adult organisms are continuously emerging; dental tissues have been identified as a source of postnatal MSCs. Dental bud is the immature precursor of the tooth, is easy to access and we show in this study that it can yield a high number of cells with ≥ 95% expression of mesenchymal stemness makers and osteogenic capacity. Thus, these cells can be defined as Dental Bud Stem Cells (DBSCs) representing a promising source for bone regeneration of stomatognathic as well as other systems. Cell interactions with the extracellular matrix (ECM) and neighboring cells are critical for tissue morphogenesis and architecture; such interactions are mediated by integrins and cadherins respectively. We characterized DBSCs for the expression of these adhesion receptors and examined their pattern during osteogenic differentiation. Our data indicate that N-cadherin and cadherin-11 were expressed in undifferentiated DBSCs and their expression underwent changes during the osteogenic process (decreasing and increasing respectively), while expression of E-cadherin and P-cadherin was very low in DBSCs and did not change during the differentiation steps. Such expression pattern reflected the mesenchymal origin of DBSCs and confirmed their osteoblast-like features. On the other hand, osteogenic stimulation induced the upregulation of single subunits, αV, β3, α5, and the formation of integrin receptors α5β1 and αVβ3. DBSCs differentiation toward osteoblastic lineage was enhanced when cells were grown on fibronectin (FN), vitronectin (VTN), and osteopontin (OPN), ECM glycoproteins which contain an integrin-binding sequence, the RGD motif. In addition we established that integrin αVβ3 plays a crucial role during the commitment of MSCs to osteoblast lineage, whereas integrin α5β1 seems to be dispensable. These data suggest that functionalization of biomaterials with such ECM proteins would improve bone reconstruction therapies starting from dental stem cells

Palmitate-induced lipotoxicity alters acetylation of multiple proteins in clonal β cells and human pancreatic islets

Type 2 diabetes is characterized by progressive β cell dysfunction, with lipotoxicity playing a possible pathogenetic role. Palmitate is often used to examine the direct effects of lipotoxicity and it may cause mitochondrial alterations by activating protein acetylation. However, it is unknown whether palmitate influences protein acetylation in β cells. We investigated lysine acetylation in mitochondrial proteins from INS-1E β cells (INS-1E) and in proteins from human pancreatic islets (HPI) after 24 h palmitate exposure. First, we confirmed that palmitate damages β cells and demonstrated that chemical inhibition of deacetylation also impairs INS-1E function and survival. Then, by 2-D gel electrophoresis, Western Blot and Liquid Chromatography-Mass Spectrometry we evaluated the effects of palmitate on protein acetylation. In mitochondrial preparations from palmitate-treated INS-1E, 32 acetylated spots were detected, with 13 proteins resulting over-acetylated. In HPI, 136 acetylated proteins were found, of which 11 were over-acetylated upon culture with palmitate. Interestingly, three proteins, glutamate dehydrogenase, mitochondrial superoxide dismutase, and SREBP-1, were over-acetylated in both INS-1E and HPI. Therefore, prolonged exposure to palmitate induces changes in β cell protein lysine acetylation and this modification could play a role in causing β cell damage. Dysregulated acetylation may be a target to counteract palmitate-induced β cell lipotoxicity

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

An investigation on financial literacy: The Italian case

Treball Final de Màster Universitari en Economia / Master in Economics. Codi: SRN015. Curs acadèmic 2018-2019In the recent past a lot of studies have been devoted to analyze people’s financial literacy level. According to the results of such studies, Italy is always at the bottom of the list of all the European countries, with one of the lowest level of financial literacy in Europe (see the Program for International Student Assessment survey) and with the evidence of various gaps concerning the gender and respondents’ regional position. A questionnaire with 30 questions concerning both financial literacy and sociodemographic questions has been proposed to a sample of 105 Italian citizens. The main goal is to measure their level of financial literacy and understand their preferences for an innovative tool to increase it. The result of the survey shows that there exists a gender gap in financial literacy in Italy, but there are not enough elements to say that regional position of respondents matters in the sample. Based on the answers collected, people seems to prefer a website to find out information about finance. This result leads to the proposal of an innovative app connected to the national web site “Quello che conta”, to improve the Italian financial literacy

Composizioni comprendenti o costituite da polidatina per uso nel trattamento delle patologie ossee

Composizioni comprendenti o costituite da polidatina per uso nel trattamento delle patologie osse

The Myokine Irisin Promotes Osteogenic Differentiation of Dental Bud-Derived MSCs

The myokine irisin, well known for its anabolic effect on bone tissue, has been demonstrated to positively act on osteoblastic differentiation processes in vitro. Mesenchymal stem cells (MSCs) have captured great attention in precision medicine and translational research for several decades due to their differentiation capacity, potent immunomodulatory properties, and their ability to be easily cultured and manipulated. Dental bud stem cells (DBSCs) are MSCs, isolated from dental tissues, that can effectively undergo osteoblastic differentiation. In this study, we analyzed, for the first time, the effects of irisin on DBSC osteogenic differentiation in vitro. Our results indicated that DBSCs were responsive to irisin, showed an enhanced expression of osteocalcin (OCN), a late marker of osteoblast differentiation, and displayed a greater mineral matrix deposition. These findings lead to deepening the mechanism of action of this promising molecule, as part of osteoblastogenesis process. Considering the in vivo studies of the effects of irisin on skeleton, irisin could improve bone tissue metabolism in MSC regenerative procedures

The Myokine Irisin Promotes Osteogenic Differentiation of Dental Bud-Derived MSCs

The myokine irisin, well known for its anabolic effect on bone tissue, has been demonstrated to positively act on osteoblastic differentiation processes in vitro. Mesenchymal stem cells (MSCs) have captured great attention in precision medicine and translational research for several decades due to their differentiation capacity, potent immunomodulatory properties, and their ability to be easily cultured and manipulated. Dental bud stem cells (DBSCs) are MSCs, isolated from dental tissues, that can effectively undergo osteoblastic differentiation. In this study, we analyzed, for the first time, the effects of irisin on DBSC osteogenic differentiation in vitro. Our results indicated that DBSCs were responsive to irisin, showed an enhanced expression of osteocalcin (OCN), a late marker of osteoblast differentiation, and displayed a greater mineral matrix deposition. These findings lead to deepening the mechanism of action of this promising molecule, as part of osteoblastogenesis process. Considering the in vivo studies of the effects of irisin on skeleton, irisin could improve bone tissue metabolism in MSC regenerative procedures

CAN STEVIA LEAF EXTRACTS PROTECT BETA CELLS AGAINST GLUCO- OR LIPOTOXICITY?

In the present study, the effects of leaf extracts of two Stevia rebaudiana Bertoni biotypes (namely ST2 and ST3) on beta cells exposed to gluco- or lipotoxic conditions have been evaluated. Leaf extracts were obtained through innovative and eco-friendly extraction technologies, able to obtain enriched fractions of desired bioactive compounds. Leaf phytochemical composition was spectrophotometrically assessed, in terms of total phenols and flavonoids as well as for their anti-radical and anti-oxidant activity, evaluated by DPPH radical-scavenging assay and ferric reducing antioxidant power (FRAP), respectively. Furthermore, the content and profile of the main steviol glycosides was analysed by HPLC, using an HILIC column under isocratic conditions, and quantified through standard curves of pure standard mixtures. MTT assay was used in order to evaluate the protection effect of stevia leaf extracts on beta cells exposed to gluco- or lipotoxicity conditions. INS-1E cells were exposed for 4 days to 30 mM glucose or 24h to 0.5 mM palmitate with or without increasing concentrations of stevia leaf extracts.The phytochemical characterisation revealed that ST2 had higher total phenolic and flavonoid content and antioxidant activity, in comparison with ST3. Conversely, ST3 showed higher (p<0.05) concentration of stevioside than ST2. Chronic exposure to high glucose concentration reduced INS-1E cells viability (-40%), that was completely prevented by exposure to 50 or 200 μg/mL ST2 and partially, but significantly, in the presence of ST3 genotype. Similarly, 24h exposure to palmitate resulted in a decrease of INS-1E viability (-20%), that was counteracted by both ST2 and ST3. The study shows that Stevia rebaudiana extracts have beneficial effects on viability of beta cells exposed to gluco- or lipotoxic conditions, possibly depending on their phytochemical composition and related antioxidant capacity