المؤلفون: Iuliano, Marco, Grimaldi, Lorenzo, Rosa, Paolo, Scibetta, Sofia, Bernardini, Nicoletta, Proietti, Ilaria, Tolino, Ersilia, Skroza, Nevena, Potenza, Concetta, Mangino, Giorgio, Romeo, Giovanna

المصدر: Frontiers in Immunology; 2024, p1-10, 10p

مصطلحات موضوعية: PSORIASIS, EXTRACELLULAR vesicles, APOPTOTIC bodies, T cells, INFLAMMATORY mediators, PSORIATIC arthritis

مستخلص: Psoriasis is a chronic inflammatory disease affecting skin and joints characterized by a chronically altered immune and inflammatory response. Several factors occur from the onset to the development of this disease due to different types of cells spatially and temporally localized in the affected area, such as, keratinocytes, macrophages, neutrophils and T helper lymphocytes. This scenario leads to the chronic release of high levels of inflammatory mediators (i.e., IL-17, IL-23, IL-22, TNF-α, S100 proteins, Defensins) and lastly parakeratosis and thickening of the stratum spinosum. Extracellular vesicles (EVs) are small double membraned biological nanoparticles that are secreted by all cell types and classified, based on dimension and biogenesis, into exosomes, microvesicles and apoptotic bodies. Their role as vessels for long range molecular signals renders them key elements in the pathogenesis of psoriasis, as well as innovative platforms for potential biomarker discovery and delivery of fine-tuned anti-inflammatory therapies. In this review, the role of EVs in the pathogenesis of psoriasis and the modulation of cellular microenvironment has been summarized. The biotechnological implementation of EVs for therapy and research for new biomarkers has been also discussed. [ABSTRACT FROM AUTHOR]

: Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Capriello, Silvia, Ferrari, Silvia Martina, Gatto, Ilenia, Santaguida, Maria Giulia, Fallahi, Poupak, Antonelli, Alessandro, Mangino, Giorgio, Romeo, Giovanna, Virili, Camilla, Centanni, Marco

المساهمون: Capriello, Silvia, Ferrari, Silvia Martina, Gatto, Ilenia, Santaguida, Maria Giulia, Fallahi, Poupak, Antonelli, Alessandro, Mangino, Giorgio, Romeo, Giovanna, Virili, Camilla, Centanni, Marco

مصطلحات موضوعية: B regulatory cell, Hashimoto’s thyroiditi, Th17, polyautoimmunity, systemic sclerosi, human, interleukin-10, autoimmune disease, B-Lymphocytes, regulatory, Hashimoto disease, scleroderma, systemic

الوصف: Systemic sclerosis (SSc) is a systemic autoimmune disease in which gastrointestinal disorders represent a complication in up to 90% of patients. SSc may associate with thyroid autoimmune disorders, with Hashimoto's thyroiditis (HT) being the more prevalent worldwide. Previous studies have examined the behavior of Th17 lymphocytes and Breg cells in patients with HT and concomitant autoimmune organ-specific disorders. These immune phenotypes seem to play a significant role in the pathogenesis of both these autoimmune processes, but their behavior when these two disorders coexist has not been described. We analyzed Th17 and Breg (CD24hiCD38hi) cell subsets in 50 subjects (45F/5M; median age = 49 years): 18 were healthy donors (HD), 20 had isolated HT, and 12 had SSc, seven of whom had both HT and SSc. Breg cells' function was also evaluated by measuring their IL-10 production when stimulated by specific activators. An increased percentage of Th17 lymphocytes characterized HT patients as compared to both HD and the whole group of SSc patients (p = 0.0018). On the contrary, the percentage of unstimulated Breg cells in SSc patients was higher (p = 0.0260), either associated or not with HT, as compared to both HT patients and HD, which, instead, showed a similar percentage of Breg cells. Following a specific stimulation with CpG, the percentages of Breg cells were increased in the whole sample of SSc patients (p < 0.001) as well as in isolated SSc and in SSc+HT ones as compared to isolated HT. However, qualitative analysis, obtained through the detection of the IL-10-producing phenotype, revealed that the percentage of CpG-stimulated CD24hiCD38hi-IL10+cells was significantly decreased in SSc patients (p < 0.0001) with no difference between isolated SSc and SSc+HT patients. The IL-10-producing phenotype was instead slightly increased in HT patients as compared to HD (4.1% vs. 2.8%). The presence of SSc seems to be characterized by an enrichment of total Breg cells but by a reduced Breg IL-10-producing phenotype, ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35874691; info:eu-repo/semantics/altIdentifier/wos/WOS:000829250800001; volume:13; firstpage:1; lastpage:8; numberofpages:8; journal:FRONTIERS IN IMMUNOLOGY; http://hdl.handle.net/11573/1652724Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85134307246

الإتاحة: https://doi.org/10.3389/fimmu.2022.921260Test
http://hdl.handle.net/11573/1652724Test

المؤلفون: Capriotti, Lorena, Iuliano, Marco, Lande, Roberto, Frasca, Loredana, Falchi, Mario, Rosa, Paolo, Mangino, Giorgio, Romeo, Giovanna

المساهمون: Capriotti, Lorena, Iuliano, Marco, Lande, Roberto, Frasca, Loredana, Falchi, Mario, Rosa, Paolo, Mangino, Giorgio, Romeo, Giovanna

مصطلحات موضوعية: antimicrobial peptide, comorbiditie, cytokine, extracellular vesicle, keratinocyte, pathogenesis of psoriasis

الوصف: Extracellular Vesicles (EVs) are a heterogeneous group of cell-derived membranous nanoparticles involved in several physiopathological processes. EVs play a crucial role in the definition of the extracellular microenvironment through the transfer of their cargo. Psoriasis is a prototypical chronic inflammatory disease characterized by several secreted mediators, among which antimicrobial peptides (AMPs) are considered pivotal in the development of the psoriatic inflammatory microenvironment. The role of EVs in the pathogenesis of psoriasis has not been elucidated yet, even if emerging evidence demonstrated that interleukin-17A (IL-17A), the psoriasis-related principal cytokine, modifies EVs release and cargo content. The aim of this work was to analyze whether, besides IL-17A, other psoriasis-related cytokines (ie, IFN-γ, TNF-α, IL-22 and IL-23) could affect EVs release and their AMPs mRNAs cargo as well as to analyze the potential biological effect due to EVs internalization by different acceptor cells.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/36147689; info:eu-repo/semantics/altIdentifier/wos/WOS:000860005700001; volume:15; firstpage:5387; lastpage:5399; numberofpages:13; journal:JOURNAL OF INFLAMMATION RESEARCH; http://hdl.handle.net/11573/1655349Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85137986138

الإتاحة: https://doi.org/10.2147/JIR.S373150Test
http://hdl.handle.net/11573/1655349Test

المؤلفون: Rosa, Paolo, Scibetta, Sofia, Pepe, Giuseppe, Mangino, Giorgio, Capocci, Luca, Moons, Sam J, Boltje, Thomas J, Fazi, Francesco, Petrozza, Vincenzo, Di Pardo, Alba, Maglione, Vittorio, Calogero, Antonella

المساهمون: Rosa, Paolo, Scibetta, Sofia, Pepe, Giuseppe, Mangino, Giorgio, Capocci, Luca, Moons, Sam J, Boltje, Thomas J, Fazi, Francesco, Petrozza, Vincenzo, Di Pardo, Alba, Maglione, Vittorio, Calogero, Antonella

مصطلحات موضوعية: differentiation, glioblastoma, hypoxia, migration, polysialic acid

الوصف: Gliomas are the most common primary malignant brain tumors. Glioblastoma, IDH-wildtype (GBM, CNS WHO grade 4) is the most aggressive form of glioma and is characterized by extensive hypoxic areas that strongly correlate with tumor malignancy. Hypoxia promotes several processes, including stemness, migration, invasion, angiogenesis, and radio- and chemoresistance, that have direct impacts on treatment failure. Thus, there is still an increasing need to identify novel targets to limit GBM relapse. Polysialic acid (PSA) is a carbohydrate composed of a linear polymer of alpha 2,8-linked sialic acids, primarily attached to the Neural Cell Adhesion Molecule (NCAM). It is considered an oncodevelopmental antigen that is re-expressed in various tumors. High levels of PSA-NCAM are associated with high-grade and poorly differentiated tumors. Here, we investigated the effect of PSA inhibition in GBM cells under low oxygen concentrations. Our main results highlight the way in which hypoxia stimulates polysialylation in U87-MG cells and in a GBM primary culture. By lowering PSA levels with the sialic acid analog, F-NANA, we also inhibited GBM cell migration and interfered with their differentiation influenced by the hypoxic microenvironment. Our findings suggest that PSA may represent a possible molecular target for the development of alternative pharmacological strategies to manage a devastating tumor like GBM.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/36076963; info:eu-repo/semantics/altIdentifier/wos/WOS:000851982200001; volume:23; issue:17; firstpage:1; lastpage:22; numberofpages:22; journal:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; http://hdl.handle.net/11573/1655264Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85137865563

الإتاحة: https://doi.org/10.3390/ijms23179563Test
http://hdl.handle.net/11573/1655264Test

المؤلفون: Iuliano, Marco, Santilli, Valter, Mineo, Andrea, Paoloni, Marco, Rosa, Paolo, Mangino, Giorgio, Romeo, Giovanna

المصدر: Current Medicinal Chemistry ; volume 31, issue 13, page 1740-1753 ; ISSN 0929-8673

الوصف: Background: Low-dose-medicine is based on the administration of low doses of biological regulators to restore the immunologic balance altered in the disease. Cytokines are pivotal regulators of cellular and tissue functions and impaired crosstalk, due to an imbalance between specific cytokines, it is fundamental in acute inflammation and diseases correlated to low-grade chronic inflammation. Osteoarthritis is the most prevalent arthritic disease and a leading cause of disability. In the treatment of muscle- skeletal pathologies, the therapeutic integration of conventional medicine with homotoxicology, or low-dose-medicine appears to be beneficial. Objective: This study aims to get more insights into the role of inflammatory cytokines and chemokines during the development of osteoarthritis and to evaluate a possible blocking strategy using anti-inflammatory molecules, we resort to an in vitro experimental model using an established human chondrosarcoma cell line that underwent to a well known pro-inflammatory stimulus as bacterial lipopolysaccharide. Methods: We tested the production of inflammatory-related cytokines and chemokines, and the efficacy of low-dose (LD) administration of anti-inflammatory compounds, namely IL-10 and anti-IL-1, to block inflammatory cellular pathways. Results: Following an inflammatory insult, chondrocytes upregulated the expression of several pro-inflammatory cyto-/chemokines and this induction could be counteracted by LD IL-10 and anti-IL-1. We reported that these effects could be ascribed to an interfering effect of LD drugs with the NF-κB signaling. Conclusion: Our results provided a good indication that LD drugs can be effective in inhibiting the inflammatory response in chondrocytes opening the way to new therapies for the treatment of diseases such as osteoarthritis.

الإتاحة: https://doi.org/10.2174/0929867330666230407140730Test
https://www.eurekaselect.com/215556/articleTest

المؤلفون: Scibetta, Sofia, Miceli, Martina, Iuliano, Marco, Stefanuto, Luca, Carbone, Elena, Piscopo, Paola, Petrozza, Vincenzo, Romeo, Giovanna, Mangino, Giorgio, Calogero, Antonella, Gasperi, Tecla, Rosa, Paolo

المصدر: Life (2075-1729); Apr2024, Vol. 14 Issue 4, p422, 21p

مصطلحات موضوعية: OXIDANT status, NEURODEGENERATION, OXIDATIVE stress, REACTIVE oxygen species, CENTRAL nervous system, CARBOXYHEMOGLOBIN, CATECHOL

مستخلص: Oxidative stress represents a hallmark for many degenerative pathologies of the Central Nervous System. Throughout life, the constant pressure of noxious stimuli and/or episodes of traumatic events may expose the brain to a microenvironment where the non-balanced reactive oxygen species inevitably lead to neuronal loss and cognitive decline. HO-1, a 32 kDa heat-shock protein catalyzing the degradation of heme into carbon monoxide (CO), iron and biliverdin/bilirubin is considered one of the main antioxidant defense mechanisms playing pivotal roles in neuroprotection. Restoring the redox homeostasis is the goal of many natural or synthetic antioxidant molecules pursuing beneficial effects on brain functions. Here, we investigated the antioxidant capacity of four selected benzofuran-2-one derivatives in a cellular model of neurodegeneration represented by differentiated SH-SY5Y cells exposed to catechol-induced oxidative stress. Our main results highlight how all the molecules have antioxidant properties, especially compound 9, showing great abilities in reducing intracellular ROS levels and protecting differentiated SH-SY5Y cells from catechol-induced death. This compound above all seems to boost HO-1 mRNA and perinuclear HO-1 protein isoform expression when cells are exposed to the oxidative insult. Our findings open the way to consider benzofuran-2-ones as a novel and promising adjuvant antioxidant strategy for many neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

: Copyright of Life (2075-1729) is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Capriotti,Lorena, Iuliano,Marco, Lande,Roberto, Frasca,Loredana, Falchi,Mario, Rosa,Paolo, Mangino,Giorgio, Romeo,Giovanna

مصطلحات موضوعية: Journal of Inflammation Research

الوصف: Lorena Capriotti,1,* Marco Iuliano,1,* Roberto Lande,2 Loredana Frasca,2 Mario Falchi,3 Paolo Rosa,1 Giorgio Mangino,1 Giovanna Romeo1 1Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome – Polo Pontino, Latina, Italy; 2Pharmacological Research and Experimental Therapy Section, National Center for Drug Research and Evaluation, Istituto Superiore di Sanità , Rome, Italy; 3National AIDS Center, Istituto Superiore di Sanità , Rome, Italy*These authors contributed equally to this workCorrespondence: Giorgio Mangino, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome – Polo Pontino, C.so della Repubblica, 79, Latina, 04100, Italy, Tel +39 0773 1757271, Email giorgio.mangino@uniroma1.itPurpose: Extracellular Vesicles (EVs) are a heterogeneous group of cell-derived membranous nanoparticles involved in several physiopathological processes. EVs play a crucial role in the definition of the extracellular microenvironment through the transfer of their cargo. Psoriasis is a prototypical chronic inflammatory disease characterized by several secreted mediators, among which antimicrobial peptides (AMPs) are considered pivotal in the development of the psoriatic inflammatory microenvironment. The role of EVs in the pathogenesis of psoriasis has not been elucidated yet, even if emerging evidence demonstrated that interleukin-17A (IL-17A), the psoriasis-related principal cytokine, modifies EVs release and cargo content. The aim of this work was to analyze whether, besides IL-17A, other psoriasis-related cytokines (ie, IFN-γ, TNF-α, IL-22 and IL-23) could affect EVs release and their AMPs mRNAs cargo as well as to analyze the potential biological effect due to EVs internalization by different acceptor cells.Methods: Nanoparticle tracking analysis (NTA) was performed on supernatants of HaCaT cells stimulated with IL-17A, IFN-γ, TNF-α, IL-22 or IL-23 to enumerate EVs. Real-Time RT-PCR was used for gene expression analysis in cells and EVs. Confocal ...

وصف الملف: text/html

العلاقة: https://www.dovepress.com/potential-pathogenetic-role-of-antimicrobial-peptides-carried-by-extra-peer-reviewed-fulltext-article-JIRTest

الإتاحة: https://doi.org/10.2147/JIR.S373150Test
https://www.dovepress.com/potential-pathogenetic-role-of-antimicrobial-peptides-carried-by-extra-peer-reviewed-fulltext-article-JIRTest

المؤلفون: Bordin, Antonella, Chirivì, Maila, Pagano, Francesca, Milan, Marika, Iuliano, Marco, Scaccia, Eleonora, Fortunato, Orazio, Mangino, Giorgio, Dhori, Xhulio, De Marinis, Elisabetta, D'Amico, Alessandra, Miglietta, Selenia, Picchio, Vittorio, Rizzi, Roberto, Romeo, Giovanna, Pulcinelli, Fabio, Chimenti, Isotta, Frati, Giacomo, De Falco, Elena

المساهمون: Sapienza Università di Roma

المصدر: Cell Proliferation ; volume 55, issue 11 ; ISSN 0960-7722 1365-2184

الوصف: Objectives Extracellular vesicles (EVs) are key biological mediators of several physiological functions within the cell microenvironment. Platelets are the most abundant source of EVs in the blood. Similarly, platelet lysate (PL), the best platelet derivative and angiogenic performer for regenerative purposes, is enriched of EVs, but their role is still too poorly discovered to be suitably exploited. Here, we explored the contribution of the EVs in PL, by investigating the angiogenic features extrapolated from that possessed by PL. Methods We tested angiogenic ability and molecular cargo in 3D bioprinted models and by RNA sequencing analysis of PL‐derived EVs. Results A subset of small vesicles is highly represented in PL. The EVs do not retain aggregation ability, preserving a low redox state in human umbilical vein endothelial cells (HUVECs) and increasing the angiogenic tubularly‐like structures in 3D endothelial bioprinted constructs. EVs resembled the miRNome profile of PL, mainly enriched with small RNAs and a high amount of miR‐126, the most abundant angiogenic miRNA in platelets. The transfer of miR‐126 by EVs in HUVEC after the in vitro inhibition of the endogenous form, restored angiogenesis, without involving VEGF as a downstream target in this system. Conclusion PL is a biological source of available EVs with angiogenic effects involving a miRNAs‐based cargo. These properties can be exploited for targeted molecular/biological manipulation of PL, by potentially developing a product exclusively manufactured of EVs.

الإتاحة: https://doi.org/10.1111/cpr.13312Test

المؤلفون: Chiantore, Maria Vincenza, Iuliano, Marco, Mongiovì, Roberta Maria, Dutta, Sankhadeep, Tommasino, Massimo, Di Bonito, Paola, Accardi, Luisa, Mangino, Giorgio, Romeo, Giovanna

المساهمون: Istituto Superiore di Sanità, Sapienza Universy of Rome, Italy, International Agency for Research on Cancer

المصدر: Infectious Agents and Cancer ; volume 17, issue 1 ; ISSN 1750-9378

مصطلحات موضوعية: Cancer Research, Infectious Diseases, Oncology, Epidemiology

الوصف: Background The β3 human papillomavirus (HPV)49 induces immortalization of primary keratinocytes through the action of E6 and E7 oncoproteins with an efficiency similar to alpha high risk (HR)-HPV16. Since HR-HPV oncoproteins are known to alter microRNA (miRNA) expression and extracellular vesicle (EV) production, we investigated the impact of HPV49 E6 and E7 proteins on miRNA profile and EV expression, and their involvement in the control of cell proliferation. Methods The miRNA expression was evaluated by a miRNA array and validated by RT-qPCR in primary human keratinocytes immortalized by β3 HPV49 (K49) or α9 HR-HPV16 (K16), and in EVs from K49 and K16. The modulation of miRNA target proteins was investigated by immunoblotting analyses. Results By comparing miRNA expression in K49 and K16 and the derived EVs, six miRNAs involved in HPV tumorigenesis were selected and validated. MiR-19a and -99a were found to be upregulated and miR-34a downregulated in both cell lines; miR-17 and -590-5p were upregulated in K49 and downmodulated in K16; miR-21 was downregulated only in K16. As for EV-carried miRNAs, the expression of miR-17, -19a, -21 and -99a was decreased and miR-34a was increased in K49 EVs. In K16 EVs, we revealed the same modulation of miR-19a, -34a, and -99a observed in producing cells, while miR-21 was upregulated. Cyclin D1, a common target of the selected miRNAs, was downmodulated in both cell lines, whereas cyclin-dependent kinase 4 was down-modulated in K49 but upregulated in K16. Conclusion These data suggest that E6 and E7 proteins of β3 HPV49 and α9 HR-HPV16 affect key factors of cell cycle control by indirect mechanisms based on miRNA modulation.

الإتاحة: https://doi.org/10.1186/s13027-022-00445-zTest

المؤلفون: Chiantore, Maria Vincenza, Mangino, Giorgio, Iuliano, Marco, Capriotti, Lorena, Di Bonito, Paola, Fiorucci, Gianna, Romeo, Giovanna

المصدر: Cytokine & Growth Factor Reviews ; volume 51, page 92-98 ; ISSN 1359-6101

مصطلحات موضوعية: General Biochemistry, Genetics and Molecular Biology, Immunology, Immunology and Allergy, Endocrinology, Diabetes and Metabolism

الإتاحة: https://doi.org/10.1016/j.cytogfr.2019.12.009Test
https://api.elsevier.com/content/article/PII:S1359610119301546?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1359610119301546?httpAccept=text/plainTest