- Advanced Glycation End Products research
- Immune cells in cancer
- S100 Proteins and Annexins
- MicroRNA in disease regulation
- Immune Response and Inflammation
- Cardiac Fibrosis and Remodeling
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Epigenetics and DNA Methylation
- Circular RNAs in diseases
- Cardiovascular Function and Risk Factors
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Telomeres, Telomerase, and Senescence
- Fibroblast Growth Factor Research
- Peptidase Inhibition and Analysis
- Parathyroid Disorders and Treatments
- Aortic Thrombus and Embolism
- Congenital heart defects research
- Dermatological and Skeletal Disorders
- Biomarkers in Disease Mechanisms
- Cancer-related gene regulation
- Pancreatic function and diabetes
- Angiogenesis and VEGF in Cancer
- Chemotherapy-induced cardiotoxicity and mitigation
- Immune responses and vaccinations
- Linguistic Studies and Language Acquisition
Centro Cardiologico Monzino
2015-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2022-2023
University of Milan
2018
Regenerative Medicine Institute
2014
San Raffaele University of Rome
2007-2012
Vita-Salute San Raffaele University
2008
New York University
2004-2007
Yale University
2004
Rensselaer Polytechnic Institute
2004
University of Padua
2001
After tissue damage, inflammatory cells infiltrate the and release proinflammatory cytokines. HMGB1 (high mobility group box 1), a nuclear protein released by necrotic severely stressed cells, promotes cytokine via its interaction with TLR4 (Toll-like receptor 4) cell migration an unknown mechanism. We show that HMGB1-induced recruitment of depends on CXCL12. CXCL12 form heterocomplex, which we characterized magnetic resonance surface plasmon resonance, acts exclusively through CXCR4 not...
The receptor for advanced glycation endproducts (RAGE) mediates responses to cell danger and stress. When bound by its many ligands (which include endproducts, certain members of the S100/calgranulin family, extracellular high-mobility group box 1, integrin Mac-1, amyloid beta-peptide fibrils), RAGE activates programs responsible acute chronic inflammation. is therefore also involved in cancer progression, diabetes, atherosclerosis, Alzheimer's disease. has several isoforms deriving from...
The prototypical fibroblast growth factor receptor (FGFR) extracellular domain consists of three Ig domains (D1–D3) which the two membrane-proximal D2 and D3 interconnecting D2–D3 linker bear determinants ligand binding specificity. In contrast, D1 D1–D2 are thought to play autoinhibitory roles in FGFR regulation. Here, we report crystal structure three-Ig form FGFR3c complex with FGF1, an FGF that binds promiscuously each seven principal FGFRs. this structure, completely disordered,...
The human receptor for advanced glycation endproducts (RAGE) is a multiligand cell surface protein belonging to the immunoglobulin superfamily, and involved in inflammatory immune responses. Most importantly, RAGE considered HMGB1 several S100 proteins, which are Damage-Associated Molecular Pattern molecules (DAMPs) released during tissue damage. In this study we show that Ager gene coding first appeared mammals, closely related other genes adhesion (CAMs) such as ALCAM, BCAM MCAM earlier...
Inflammation and tissue regeneration follow damage, but little is known about how these processes are coordinated. High Mobility Group Box 1 (HMGB1) a nuclear protein that, when released on injury, triggers inflammation. We previously showed that HMGB1 with reduced cysteines chemoattractant, whereas disulfide bond makes it proinflammatory cytokine. Here we report fully orchestrates muscle liver via CXCR4, its receptors TLR4/MD-2 RAGE (receptor for advanced glycation end products) not...
Arterial aging is a major risk factor for the occurrence of cardiovascular diseases. The aged artery characterized by endothelial dysfunction and vascular smooth muscle cells altered physiology together with low-grade chronic inflammation. MicroRNA-34a (miR-34a) has been recently implicated in cardiac, endothelial, progenitor cell senescence; however, its contribution to aging-associated phenotype not explored so far. We found that miR-34a was highly expressed aortas isolated from old mice....
Objective- Vascular calcification (VC) is age dependent and a risk factor for cardiovascular all-cause mortality. VC involves the senescence-induced transdifferentiation of vascular smooth muscle cells (SMCs) toward an osteochondrogenic lineage resulting in arterial wall mineralization. miR-34a increases with aortas induces SMC senescence through modulation its target SIRT1 (sirtuin 1). In this study, we aimed to investigate whether regulates VC. Approach Results- We found that Runx2...
Background: Conversion of cardiac stromal cells into myofibroblasts is typically associated with hypoxia conditions, metabolic insults, and/or inflammation, all which are predisposing factors to fibrosis and heart failure. We hypothesized that this conversion could be also mediated by response these mechanical cues through activation the Hippo transcriptional pathway. The objective present study was assess role cellular/nuclear straining forces acting in myofibroblast differentiation under...
Advanced glycation end-products (AGEs) and their interaction with the receptor for advanced (RAGE) play a pivotal role in development progression of type 2 diabetes. In this retrospective cohort study, we explored association circulating levels soluble RAGE (sRAGE) isoforms, i.e., endogenous secretory esRAGE cleaved cRAGE, AGEs respective ratios 15-year all-cause mortality diabetes.Baseline sRAGE isoforms concentration were measured by ELISA 362 patients diabetes 125 age- gender-matched...
Abstract Skeletal development requires the correct balance of osteoblast proliferation, survival, and differentiation which is modulated by a network signaling pathways transcription factors. We have examined role AKT (PKB), ERK1/2 in response to FGFs, inhibit differentiation, IGF‐1 Wnt signaling, promote it. Using osteoblastic cell lines as well primary calvarial osteoblasts, we show that distinct effects FGF‐induced proliferation differentiation. mediator but also contributes while...
Fibroblast growth factors (FGFs) regulate long bone development by affecting the proliferation and differentiation of chondrocytes. FGF treatment inhibits chondrocytes both in vitro vivo, but signaling pathways involved have not been clearly identified. In this report we show that MEK-ERK1/2 p38 MAPK pathways, phospholipase Cγ or phosphatidylinositol 3-kinase, play a role FGF-mediated arrest Chemical inhibitors MEK1/2 applied to rat chondrosarcoma (RCS) significantly prevented FGF-induced...
Abstract The mobilization of dendritic cells (DCs) from peripheral tissues is critical for the establishment T cell-dependent immune responses or tolerance, because physical interaction DCs with naive takes place in cell areas lymph nodes. autocrine/paracrine release high mobility group box 1 (HMGB1) nuclear protein by controls outcome DC–T interaction, influencing priming/Th1 polarization cells. We herein present evidence that receptor advanced glycation end products (RAGE), a multiligand...
Inhibitor of NF-kappaB kinases beta (IKKbeta) and alpha (IKKalpha) activate distinct signaling modules. The IKKbeta/canonical pathway rapidly responds to stress-like conditions, whereas the IKKalpha/noncanonical controls adaptive immunity. Moreover, IKKalpha can attenuate IKKbeta-initiated inflammatory responses. High mobility group box 1 (HMGB1), a chromatin protein, is an extracellular signal tissue damage-attracting cells in inflammation, regeneration, scar formation. We show that IKKbeta...
The aim of the study is to compare qualitative and semi-quantitative profile polyphenol fraction purified from leaf (BLPF) fruit (BFPF) bergamot (Citrus bergamia), evaluate their antioxidant anti-inflammatory activity. analytical was carried out by LC-ESI/MS using three different approaches: targeted (searching analytes already reported in extract), semi-targeted (a selective search 3-hydroxy-3-methylglutarate [HMG] derivatives involved cholesterol reducing activity BPF) untargeted. A total...
Abstract Background Diabetes-induced trained immunity contributes to the development of atherosclerosis and its complications. This study aimed investigate in humans whether epigenetic signals involved immune cell activation inflammation are initiated hematopoietic stem/progenitor cells (HSPCs) transferred differentiated progeny. Methods results High glucose (HG)-exposure cord blood (CB)-derived HSPCs induced a senescent-associated secretory phenotype (SASP) characterized by proliferation...
The receptor for advanced glycation end-products (RAGE) recognizes several ligands involved in inflammatory diseases.Two circulating soluble isoforms exist: esRAGE derived from alternative splicing and cRAGE generated by the membrane-bound RAGE (FL-RAGE) proteolysis.Together, constitute sRAGE function as decoy receptors preventing FL-RAGE/ligands binding.We determined serum concentration of both, cRAGE, their AGEs, HMGB1 S100A8/A9 a healthy population 169 subjects aged 20-90 years.cRAGE...
The senescence of vascular smooth muscle cells (VSMCs), characterized by the acquisition senescence-associated secretory phenotype (SASP), is relevant for VSMCs osteoblastic differentiation and calcification (VC). MicroRNA-34a (miR-34a) a driver such phenomena could play role in inflammaging. Herein, we analyzed relationship between miR-34a prototypical SASP component IL6 vitro vivo models. levels increased positively correlated aortas 21 months-old male C57BL/6J mice human aortic (HASMCs)...
Abstract Background Glucagon like peptide-1 receptor agonists (GLP-1RAs) have shown to reduce mortality and cardiovascular events in patients with type 2 diabetes mellitus (T2DM). Since the impairment number function of vasculotrophic circulating CD34 + hematopoietic stem progenitor cells (HSPCs) T2D has been reported increase (CV) risk, we hypothesized that one mechanisms whereby GLP-1 RAs exert CV protective effects may be related ability improve HSPC function. Methods In cord blood...