18 results on '"Agostinis, C"'
Search Results
2. Temperature-related changes in sensory nerve conduction: Studies in normal subjects and in patients with paraproteinaemia
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Alfonsi, E., Giampaolo Merlini, Giorgetti, A., Ceroni, M., Piccolo, G., Agostinis, C., and Savoldi, F.
3. What is hiding behind bubbles of air? An unusual Streptococcus pyogenes meningitis
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Paolo Gritti, Al, Lanterna, Sarnecki T, Brembilla C, Agostinis C, Rizzi M, and Fl, Lorini
4. Superficial siderosis of the CNS: MR diagnosis and clinical findings
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Bracchi, M., Savoiardo, M., Triulzi, F., Daniele, D., Grisoli, M., Gianni Boris Bradac, Agostinis, C., Pelucchetti, D., and Scott, G.
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Journal Article - Abstract
PURPOSE: To report the clinical and neuroradiologic findings of superficial siderosis of the CNS, due to chronic subarachnoid bleeding of unknown origin. MATERIALS AND METHODS: We observed seven cases. The main clinical manifestations were progressive deafness and ataxia. Four patients had had previous cranial or cervical trauma, with root avulsion in two, many years before onset of deafness and ataxia. Neuroradiologic studies included MR (0.5 T in four and 1.5 T in three) and angiography of the brain in all cases, CT in six cases, MR of the spine in six, and myelography in four. RESULTS: MR demonstrated a rim of marked hypointensity in T2-weighted images, consistent with hemosiderin deposits, on the surface of cerebellum, brain stem, inferior part of cerebral hemispheres, and spinal cord. CT showed cerebellar atrophy in five cases, and a rim of mild hyperdensity around the brain stem in two. Angiographic studies were negative. Myelography showed cervical nerve root avulsion in two cases and a cervicodorsal extradural cyst in one. Cerebrospinal fluid contained RBCs in all the six examined cases. CONCLUSION: Although CT may occasionally suggest the diagnosis of superficial siderosis, MR demonstrates this abnormality to better advantage.
5. Protection against inflammation- and antiphospholipid antibody-caused fetal loss by the chemokine decoy receptor D6
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La Torre, Y. Martinez, Buracchi, C., ELENA MONICA BORRONI, Dupor, J., Bonecchi, R., Nebuloni, M., Pasqualini, F., Doni, A., Lauri, E., Agostinis, C., Bulla, R., Cook, D. N., Haribabu, B., Meroni, P. L., Rukavina, D., Vago, L., Tedesco, F., Vecchi, A., Lira, S. A., Locati, M., Mantovani, A., de la Torre, Ym, Buracchi, C, Borroni, Em, Dupor, J, Bonecchi, R, Nebuloni, M, Pasqualini, F, Doni, A, Lauri, E, Agostinis, Chiara, Bulla, Roberta, Cook, Dn, Haribabu, B, Meroni, Pl, Rukavina, D, Vago, L, Tedesco, Francesco, Vecchi, A, Lira, Sa, Locati, M, and Mantovani, A. . . Less
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inflammation ,D6, inflammation, antiphospholipid antibody, fetal loss chemokine ,antiphospholipid antibody ,D6 ,fetal loss chemokine
6. Protective and regenerative effects of a novel medical device against esophageal mucosal damage using in vitro and ex vivo models
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Emiliana Giacomello, Roberta Bulla, Fleur Bossi, Daniele Greco, Andrea Balduit, Francesco De Seta, Dario Voinovich, Giuseppe Ricci, Vito Rodolico, Beatrice Belmonte, Micol Pacor, Chiara Agostinis, Alessandro Mangogna, Agostinis, C., Bossi, F., Mangogna, A., Balduit, A., Pacor, M., Giacomello, E., Belmonte, B., Greco, D., Rodolico, V., Voinovich, D., De Seta, F., Ricci, G., Bulla, R., Agostinis C., Bossi F., Mangogna A., Balduit A., Pacor M., Giacomello E., Belmonte B., Greco D., Rodolico V., Voinovich D., De Seta F., Ricci G., and Bulla R.
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0301 basic medicine ,Esophageal Mucosa ,Hyaluronic acid ,RM1-950 ,Pharmacology ,Permeability ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pepsin ,Cell Line, Tumor ,Digestive disorder ,Medicine ,Humans ,Regeneration ,Esophagus ,Amino Acids ,Hyaluronic Acid ,Evans Blue ,Medical device ,biology ,business.industry ,Bioadhesive polymer ,Gastroesophageal reflux disease (GERD) ,Rice extract ,Plant Extracts ,Adhesiveness ,Oryza ,General Medicine ,medicine.disease ,digestive system diseases ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Equipment and Supplies ,030220 oncology & carcinogenesis ,biology.protein ,GERD ,Gastroesophageal Reflux ,Therapeutics. Pharmacology ,business ,Wound healing ,Ex vivo - Abstract
Gastroesophageal reflux disease (GERD) is a common digestive disorder that causes esophagitis and injuries to the esophageal mucosa. GERD symptoms are recurrent during pregnancy and their treatment is focused on lifestyle changes and nonprescription medicines. The aim of this study was to characterize the mechanism of action of a new patented medical device, an oral formulation containing hyaluronic acid, rice extract, and amino acids dispersed in a bioadhesive polymer matrix, by assessing its protective effects in in vitro and ex vivo models of esophageal mucosa damage. Acidic bile salts and pepsin cocktail (BSC) added to CP-A and COLO-680 N esophagus cells were used as an in vitro GERD model to evaluate the binding capacities, anti-inflammatory effects and reparative properties of the investigational product (IP) in comparison to a viscous control. Our results showed that the IP prevents cell permeability and tight junction dysfunction induced by BSC. Furthermore, the IP was also able to down-regulate IL-6 and IL-8 mRNA expression induced by BSC stimulation and to promote tissue repair and wound healing. The results were confirmed by ex vivo experiments in excised rat esophagi through the quantification of Evans Blue permeability assay. These experiments provided evidence that the IP is able to bind to the human esophagus cells, preventing the damage caused by gastroesophageal reflux, showing potential anti-irritative, soothing, and reparative properties.
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- 2020
7. Prognostic Implications of the Complement Protein C1q in Gliomas
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Uday Kishore, Vito Rodolico, Fabrizio Zanconati, Anna Martorana, Beatrice Belmonte, Chiara Agostinis, Domenico Gerardo Iacopino, Roberta Bulla, Alessandro Mangogna, Paola Zacchi, Deborah Bonazza, Mangogna A., Belmonte B., Agostinis C., Zacchi P., Iacopino D., Martorana A., Rodolico V., Bonazza D., Zanconati F., Kishore U., Bulla R., Mangogna, A., Belmonte, B., Agostinis, C., Zacchi, P., Iacopino, D. G., Martorana, A., Rodolico, V., Bonazza, D., Zanconati, F., Kishore, U., and Bulla, R.
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Male ,0301 basic medicine ,medicine.disease_cause ,Pathogenesis ,bioinformatics analysis ,C1q complement ,gliomas ,prognostic significance of C1q ,survival probability ,0302 clinical medicine ,glioma ,Tumor Microenvironment ,Immunology and Allergy ,Complement C1q ,bioinformatics analysi ,Original Research ,Settore MED/27 - Neurochirurgia ,Brain Neoplasms ,Melanoma ,Bioinformatics analysi ,Glioma ,Prognosis ,Acquired immune system ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Bioinformatics analysis ,Female ,Prognostic significance of C1q ,Databases, Nucleic Acid ,lcsh:Immunologic diseases. Allergy ,Immunology ,Biology ,03 medical and health sciences ,Classical complement pathway ,Biomarkers, Tumor ,medicine ,Humans ,Survival probability ,Gliomas ,medicine.disease ,Complement system ,030104 developmental biology ,Cancer research ,lcsh:RC581-607 ,Carcinogenesis ,030215 immunology - Abstract
The contribution of the complement system in the pathophysiology of brain cancers has been recently considered in light of its well-known involvement in carcinogenesis. Complement system represents an important component of the inflammatory response, which acts as a functional bridge between the innate and adaptive immune response. C1q, the first recognition subcomponent of the complement classical pathway, has recently been shown to be involved in a range of pathophysiological functions that are not dependent on complement activation. C1q is expressed in the microenvironment of various types of human tumors, including melanoma, prostate, mesothelioma, and ovarian cancers, where it can exert a protective or a harmful effect on cancer progression. Despite local synthesis of C1q in the central nervous system, the involvement of C1q in glioma pathogenesis has been poorly investigated. We, therefore, performed a bioinformatics analysis, using Oncomine dataset and UALCAN database in order to assess whether the expression of the genes encoding for the three chains of C1q (C1qA, C1qB, and C1qC) could serve as a potential prognostic marker for gliomas. The obtained results were then validated using an independent glioma cohort from the Chinese Glioma Genome Atlas datasets. Our bioinformatics analysis, coupled with immunohistochemistry and fluorescence microscopy, appears to suggest a positive correlation between higher levels of C1q expression and unfavorable prognosis in a diverse grade of gliomas.
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- 2019
8. Hyaluronic Acid Present in the Tumor Microenvironment Can Negate the Pro-apototic Effect of a Recombinant Fragment of Human Surfactant Protein D on Breast Cancer Cells
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Fanan A. Alaql, Anterpreet Kaur, Valarmathy Murugaiah, Uday Kishore, Beatrice Belmonte, Haseeb A. Khan, Salvatore Vieni, Praveen M. Varghese, Roberta Bulla, Taruna Madan, Chiara Agostinis, Salman H. Alrokayan, Terry Roberts, Murugaiah V., Agostinis C., Varghese P.M., Belmonte B., Vieni S., Alaql F.A., Alrokayan S.H., Khan H.A., Kaur A., Roberts T., Madan T., Bulla R., and Kishore U.
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lcsh:Immunologic diseases. Allergy ,0301 basic medicine ,surfactant protein D ,Immunology ,Collectin ,Apoptosis ,Breast Neoplasms ,03 medical and health sciences ,breast cancer ,0302 clinical medicine ,Epidermal growth factor ,Cell Line, Tumor ,hyaluronic acid ,Tumor Microenvironment ,Humans ,Immunology and Allergy ,skin and connective tissue diseases ,innate immunity ,Original Research ,Tumor microenvironment ,Chemistry ,immune surveillance ,Intrinsic apoptosis ,Cell cycle ,Pulmonary Surfactant-Associated Protein D ,Recombinant Proteins ,030104 developmental biology ,Cell culture ,SKBR3 ,Cancer research ,Female ,lcsh:RC581-607 ,030215 immunology - Abstract
Copyright © 2020 Murugaiah, Agostinis, Varghese, Belmonte, Vieni, Alaql, Alrokayan, Khan, Kaur, Roberts, Madan, Bulla and Kishore. Human surfactant protein D (SP-D) belongs to the family of collectins that is composed of a characteristic amino-terminal collagenous region and a carboxy-terminal C-type lectin domain. Being present at the mucosal surfaces, SP-D acts as is a potent innate immune molecule and offers protection against non-self and altered self-such as pathogens, allergens, and tumour. Here, we examined the effect of a recombinant fragment of human SP-D (rfhSP-D) on a range of breast cancer lines. Breast cancer has four molecular subtypes characterised by varied expression of oestrogen (ER), progesterone (PR) and EGF receptors (HER2). The cell viability of HER2 over-expressing (SKBR3) and triple-positive (BT474) breast cancer cell lines (but not of triple-negative cell line (BT20), was reduced following rfhSP-D treatment at 24h. Upregulation of p21/p27 cell cycle inhibitors and p53 phosphorylation (Ser15) in rfhSP-D-treated BT474 and SKBR3 cell lines signified G2/M cell cycle arrest. Cleaved caspase 9 and 3 were detected in rfhSP-D- treated BT474 and SKBR3 cells, suggesting an involvement of intrinsic apoptosis pathway. However, rfhSP-D-induced apoptosis was nullified in the presence of hyaluronic acid whose increased level in breast tumor microenvironment is associated with malignant tumor progression and invasion. rfhSP-D bound to solid-phase HA and promoted tumor cell proliferation. rfhSP-D-treated SKBR3 cells in the presence of hyaluronic acid showed decreased transcriptional levels of p53 when compared to SKBR3 cells treated with rfhSP-D only. Thus, hyaluronic acid appears to negate the anti-tumorigenic properties of rfhSP-D against HER2-over-expressing and triple-positive breast cancer cells. King Saud University, Riyadh, International Scientific Partnership Program (ISPP) ISPP-145; Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy, RC20/16 and 5MILLE15D.
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- 2020
9. Complement Activation and Thrombin Generation by MBL Bound to β2-Glycoprotein I
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Claudia Grossi, Pier Luigi Meroni, William Planer, Fleur Bossi, Peter Garred, Paolo Durigutto, Nicola Pozzi, Francesco Tedesco, Maria Orietta Borghi, Paolo Macor, Chiara Agostinis, Durigutto, P., Macor, P., Pozzi, N., Agostinis, C., Bossi, F., Meroni, P. L., Grossi, C., Borghi, M. O., Planer, W., Garred, P., and Tedesco, F.
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Endothelium ,Human Umbilical Vein Endothelial Cell ,Immunology ,Plasma protein binding ,Mannose-Binding Lectin ,Article ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Thrombin ,medicine ,Human Umbilical Vein Endothelial Cells ,Immunology and Allergy ,Beta 2-Glycoprotein I ,Humans ,Complement Activation ,Antiphospholipid Syndrome ,Calcium ,Endothelial Cells ,Protein Binding ,Thrombosis ,Tumor Necrosis Factor-alpha ,beta 2-Glycoprotein I ,Mannan-binding lectin ,chemistry.chemical_classification ,Endothelial Cell ,biology ,Lectin ,bacterial infections and mycoses ,Cell biology ,Complement system ,medicine.anatomical_structure ,chemistry ,Thrombosi ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Glycoprotein ,Human ,030215 immunology ,medicine.drug - Abstract
β2-Glycoprotein I (β2-GPI) is an abundant plasma glycoprotein with unknown physiological function and is currently recognized as the main target of antiphospholipid Abs responsible for complement activation and vascular thrombosis in patients with antiphospholipid syndrome (APS). In this study, we provide evidence that mannose-binding lectin (MBL) binds to β2-GPI in Ca++ and a dose-dependent manner and that this interaction activates complement and promotes complement-dependent thrombin generation. Surprisingly, a significant binding was observed between MBL and isolated domains II and IV of β2-GPI, whereas the carbohydrate chains, domain I and domain V, were not involved in the interaction, documenting a noncanonical binding mode between MBL and β2-GPI. Importantly, this interaction may occur on endothelial cells because binding of MBL to β2-GPI was detected on the surface of HUVECs, and colocalization of MBL with β2-GPI was observed on the endothelium of a biopsy specimen of a femoral artery from an APS patient. Because β2-GPI–mediated MBL-dependent thrombin generation was increased after priming the endothelium with TNF-α, our data suggests that this mechanism could play an important yet unrecognized role under physiological conditions and may be upregulated in pathological situations. Moreover, the complement activation and the procoagulant effects of the β2-GPI/MBL complex may contribute to amplify similar activities of anti–β2-GPI Abs in APS and possibly act independently of Abs, raising the issue of developing appropriate therapies to avoid recurrences and disability in patients at risk for these clinical conditions.
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- 2020
10. The Combination of N-Acetyl Cysteine, Alpha-Lipoic Acid, and Bromelain Shows High Anti-Inflammatory Properties in NovelIn VivoandIn VitroModels of Endometriosis
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Roberta Bulla, Chiara Agostinis, Giorgio Zauli, Sonia Zorzet, R. De Leo, F. De Seta, Agostinis, C., Zorzet, Sonia, De Leo, R., Zauli, G., DE SETA, Francesco, and Bulla, Roberta
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Pathology ,Anti-Inflammatory Agents ,Apoptosis ,Mice, SCID ,Pharmacology ,Acetylcysteine ,Mice ,and bromelain ,Endometriosi ,Cells, Cultured ,Caspase ,Microscopy ,Cultured ,Thioctic Acid ,biology ,Bromelains ,endothelial cells ,N-acetyl cystein ,endothelial cell ,Female ,Tumor necrosis factor alpha ,Research Article ,lcsh:RB1-214 ,medicine.drug ,medicine.medical_specialty ,Article Subject ,medicine.drug_class ,Cells ,Immunology ,Endometriosis ,Vascular Cell Adhesion Molecule-1 ,SCID ,Fluorescence ,Anti-inflammatory ,NO ,Proinflammatory cytokine ,In vivo ,lcsh:Pathology ,medicine ,Animals ,Humans ,Animal ,Tumor Necrosis Factor-alpha ,Cell Biology ,inflammation ,alpha-lipoic acid, and bromelain ,business.industry ,alpha-lipoic acid ,Uterus ,Disease Models, Animal ,Endothelial Cells ,Inflammation ,Microscopy, Fluorescence ,In vitro ,Disease Models ,biology.protein ,business - Abstract
To evaluate the efficacy of an association of N-acetyl cystein, alpha-lipoic acid, and bromelain (NAC/LA/Br) in the treatment of endometriosis we set up a newin vivomurine model. We explored the anti-inflammatory and proapoptotic effect of this combination on human endometriotic endothelial cells (EECs) and on endothelial cells isolated from normal uterus (UtMECs). We implanted fragments of human endometriotic cysts intraperitoneally into SCID mice to evaluate the efficacy of NAC/LA/Br treatment. UtMECs and EECs, untreated or treated with NAC/LA/Br, were activated with the proinflammatory stimulus TNF-αand their response in terms of VCAM1 expression was evaluated. The proapoptotic effect of higher doses of NAC/LA/Br on UtMECs and EECs was measured with a fluorogenic substrate for activated caspases 3 and 7. The preincubation of EECs with NAC/LA/Br prior to cell stimulation with TNF-αprevents the upregulation of the expression of the inflammatory “marker” VCAM1. Furthermore NAC/LA/Br were able to induce EEC, but not UtMEC, apoptosis. Finally, the novel mouse model allowed us to demonstrate that mice treated with NAC/LA/Br presented a lower number of cysts, smaller in size, compared to untreated mice. Our findings suggest that these dietary supplements may have potential therapeutic uses in the treatment of chronic inflammatory diseases like endometriosis.
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- 2015
11. Neonatal haemochromatosis with reversible pituitary involvement
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Rita Bèrczes, Alessandro Lucianetti, Michela Bosisio, Giuseppe Indolfi, Cristina Agostinis, M. Zambelli, Lorenzo D'Antiga, Michele Colledan, Isabella Pelliccioli, Massimo Resti, Indolfi, G, Berczes, R, Pelliccioli, I, Bosisio, M, Agostinis, C, Resti, M, Zambelli, M, Lucianetti, A, Colledan, M, and D'Antiga, L
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Male ,Pathology ,medicine.medical_specialty ,Pituitary gland ,Pituitary Diseases ,medicine.medical_treatment ,Iron deposition ,Hypopituitarism ,Disease ,Liver transplantation ,ABO Blood-Group System ,neonatal haemochromatosis ,medicine ,Neonatal hemochromatosis ,Humans ,ABO-incompatible liver transplantation ,Transplantation ,business.industry ,Infant, Newborn ,medicine.disease ,Liver Transplantation ,medicine.anatomical_structure ,hypopituitarism ,Blood Group Incompatibility ,Gestation ,Hemochromatosis ,hypothyroidism ,Siderosis ,business - Abstract
Summary Neonatal haemochromatosis is a rare alloimmune gestational disease with a high mortality. The hallmark of neonatal haemochromatosis is severe neonatal liver failure associated with extrahepatic siderosis. Thus far, no pituitary dysfunction has been reported to result from the tissue damage associated with extrahepatic siderosis. The present report describes a neonate with neonatal haemochromatosis and secondary hypothyroidism associated with pituitary iron deposition. Both the conditions were successfully treated by ABO-incompatible liver transplantation. Pituitary gland dysfunction is another possible extrahepatic manifestation of neonatal haemochromatosis, and it is reversible after liver transplantation.
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- 2014
12. The complement component C3 is expressed by the endometrial ectopic tissue and is involved in the endometriotic lesion formation
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Giuseppe Ricci, D. De Santo, Gabriella Zito, Fleur Bossi, Romana Vidergar, S. Zorzet, Roberta Bulla, Chiara Agostinis, Oriano Radillo, Agostinis, C., Zito, G., De Santo, D., Vidergar, R., Radillo, O., Bossi, F., Zorzet, S., Ricci, G., and Bulla, R.
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endometriosis ,Pathology ,medicine.medical_specialty ,Complement system ,business.industry ,mouse model ,endometriosi ,Immunology ,Endometriosis ,Obstetrics and Gynecology ,C3 ,medicine.disease ,Complement (complexity) ,Endometriotic lesion ,Ectopic tissue ,Reproductive Medicine ,Immunology and Allergy ,Medicine ,business - Abstract
OP28 The complement component C3 is expressed by the endometrial ectopic tissue and is involved in the endometriotic lesion formation C. Agostinis 1, G. Zito 1, D. De Santo1, R. Vidergar2, O. Radillo 1, F. Bossi 1, S. Zorzet2, G. Ricci 1, R. Bulla 2 1 Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy 2 Department of Life Sciences, University of Trieste, Trieste, Italy E-mail address: chiara.agostinis@burlo.trieste.it (C. Agostinis). Background: The complement (C) system is one of the major components of humoral innate immunity, acting as the first lines of defence against microbes. The principal roles of C system are the opsonization and lysis of pathogens, but new roles in inflammatory and immunological processes are emerging. It is involved in numerous inflammatory diseases, such as SLE, PNH and endometriosis (EM). Several groups have been demonstrated that the glandular epithelial cells found in endometriotic implants produce and secrete the C component C3. The aim of this work was to confirm the presence of C3 the in the ectopic tissue compared to the eutopic one, and investigate the role of C3 in the pathogenesis of EM. Methods:Weinvestigated by immunofluorescence, the expression of C3 on sections of endometriotic cysts and healthy uterus; we performed RT-qPCR experiments to highlight the synthesis of this C component at local level. We set up a murine in vivo model of endometriosis based on the injection of minced uterine tissue from a donor mouse, into the peritoneum of a receiving animal. Results: We confirmed the presence of C3 selectively in the ectopic and not in eutopic endometrium, and the local synthesis of C3 in endometriotic tissue. We observed a greater amount of cyst formation in the peritoneum of WT mice compared to C3 KO mice.Conclusion: We concluded that C3 can actually be considered a marker of EM and that the local synthesis of this C component can promote the engraftment of the cysts.
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- 2018
13. C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation
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Damiano Rami, Roberta Bulla, Claudio Tripodo, Marina Botto, Carla Guarnotta, Guang Sheng Ling, Paolo Durigutto, Sonia Zorzet, Chiara Agostinis, Francesco Tedesco, Bulla, Roberta, Tripodo, Claudio, Rami, Damiano, Ling, Guang Sheng, Agostinis, Chiara, Guarnotta, Carla, Zorzet, Sonia, Durigutto, Paolo, Botto, Marina, Tedesco, Francesco, Bulla, R., Tripodo, C., Rami, D., Ling, G., Agostinis, C., Guarnotta, C., Zorzet, S., Durigutto, P., Botto, M., Tedesco, F., and Wellcome Trust
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Genetics and Molecular Biology (all) ,0301 basic medicine ,PROTEIN ,General Physics and Astronomy ,MELANOMA ,Apoptosis ,Inbred C57BL ,Biochemistry ,DISEASE ,Animals ,Cell Line, Tumor ,Cell Movement ,Cell Proliferation ,Complement Activation ,Complement C1q ,Complement C3 ,Complement C5 ,Humans ,Mice ,Mice, Inbred C57BL ,Mice, Knockout ,Neoplasms ,Biochemistry, Genetics and Molecular Biology (all) ,Chemistry (all) ,Physics and Astronomy (all) ,fluids and secretions ,immune system diseases ,IMMUNE-RESPONSE ,skin and connective tissue diseases ,Complement component 5 ,Tumor ,Multidisciplinary ,3. Good health ,Cell biology ,Multidisciplinary Sciences ,DEFICIENCY ,medicine.anatomical_structure ,Science & Technology - Other Topics ,Human ,Knockout ,Science ,chemical and pharmacologic phenomena ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,TROPHOBLAST INVASION ,MECHANISMS ,Cell Line ,03 medical and health sciences ,Classical complement pathway ,Immune system ,INFLAMMATION ,medicine ,Science & Technology ,Animal ,Cell growth ,EFFECTOR SYSTEM ,Apoptosi ,General Chemistry ,Complement system ,030104 developmental biology ,Cancer cell ,Neoplasm ,Bone marrow ,ANTIBODY THERAPY - Abstract
Complement C1q is the activator of the classical pathway. However, it is now recognized that C1q can exert functions unrelated to complement activation. Here we show that C1q, but not C4, is expressed in the stroma and vascular endothelium of several human malignant tumours. Compared with wild-type (WT) or C3- or C5-deficient mice, C1q-deficient (C1qa−/−) mice bearing a syngeneic B16 melanoma exhibit a slower tumour growth and prolonged survival. This effect is not attributable to differences in the tumour-infiltrating immune cells. Tumours developing in WT mice display early deposition of C1q, higher vascular density and an increase in the number of lung metastases compared with C1qa−/− mice. Bone marrow (BM) chimeras between C1qa−/− and WT mice identify non-BM-derived cells as the main local source of C1q that can promote cancer cell adhesion, migration and proliferation. Together these findings support a role for locally synthesized C1q in promoting tumour growth., C1q is known to initiate the activation of the complement classical pathway. Here, the authors show the C1q is expressed in the tumour microenvironment and can promote cancer cell migration and adhesion in a complement activation-independent manner.
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- 2016
14. A non-complement-fixing antibody to β2 glycoprotein I as a novel therapy for antiphospholipid syndrome
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Chiara Agostinis, Francesco Tedesco, Maria Orietta Borghi, Paolo Durigutto, Francesca Pregnolato, Roberta Bulla, Claudia Grossi, Paolo Macor, Filomena Guida, Daniele Sblattero, Pier Luigi Meroni, Agostinis, C., Durigutto, Paolo, Sblattero, Daniele, Borghi, M. O., Grossi, C., Guida, F., Bulla, Roberta, Macor, Paolo, Pregnolato, F., Meroni, P. L., and Tedesco, Francesco
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Male ,Phage display ,Complement system ,Immunology ,Biochemistry ,Autoantigens ,Mice ,Antiphospholipid syndrome ,In vivo ,Human Umbilical Vein Endothelial Cells ,Medicine ,recombinant antibody ,Animals ,Humans ,Complement Activation ,chemistry.chemical_classification ,therapy ,biology ,business.industry ,Antibodies, Monoclonal ,Thrombosis ,Cell Biology ,Hematology ,Complement System Proteins ,medicine.disease ,Antiphospholipid Syndrome ,In vitro ,antiphospholipid syndrome ,Recombinant Proteins ,Rats ,Trophoblasts ,Abortion, Spontaneous ,chemistry ,beta 2-Glycoprotein I ,Immunoglobulin G ,biology.protein ,Antibody ,business ,Glycoprotein ,Protein Binding ,Single-Chain Antibodies - Abstract
A single-chain fragment variable (scFv) recognizing β2-glycoprotein 1 (β2GPI) from humans and other species was isolated from a human phage display library and engineered to contain an IgG1 hinge-CH2-CH3 domain. The scFv-Fc directed against β2GPI domain I-induced thrombosis and fetal loss, thus mimicking the effect of antibodies from patients with antiphospholipid syndrome (APS). Complement is involved in the biological effect of anti-β2GPI scFv-Fc, as demonstrated by its ability to promote in vitro and in vivo complement deposition and the failure to induce vascular thrombosis in C6-deficient rats and fetal loss in C5-depleted mice. A critical role for complement was also supported by the inability of the CH2-deleted scFv-Fc to cause vessel occlusion and pregnancy failure. This antibody prevented the pathological effects of anti-β2GPI antibodies from APS patients and displaced β2GPI-bound patient antibodies. The CH2-deleted antibody represents an innovative approach potentially useful to treat APS patients refractory to standard therapy.
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- 2014
15. An alternative role of C1q in cell migration and tissue remodeling: contribution to trophoblast invasion and placental development
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Helena Stabile, Fleur Bossi, Angela Santoni, Chiara Agostinis, Berhane Ghebrehiwet, Cecilia Garlanda, Paola Spessotto, Angela Gismondi, Guillermina Girardi, Roberta Bulla, Francesco De Seta, Claudio Tripodo, Francesco Tedesco, Carla Guarnotta, Agostinis, C, Bulla, R, Tripodo, C, Gismondi, A, Stabile, H, Bossi, F, Guarnotta, C, Garlanda, C, De Seta, F, Spessotto, P, Santoni, A, Ghebrehiwet, B, Girardi, G, and Tedesco, F
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medicine.medical_specialty ,Immunology ,Cell ,Integrin ,Immunoblotting ,chemical and pharmacologic phenomena ,Biology ,Extracellular matrix ,Mice ,Pre-Eclampsia ,immune system diseases ,Pregnancy ,Internal medicine ,medicine ,Cell Adhesion ,Immunology and Allergy ,Animals ,Humans ,Immunoprecipitation ,skin and connective tissue diseases ,Receptor ,Cell adhesion ,reproductive and urinary physiology ,Microscopy, Confocal ,C1q, placental development ,Reverse Transcriptase Polymerase Chain Reaction ,Complement C1q ,Decidua ,Trophoblast ,Placentation ,Immunohistochemistry ,Cell biology ,Trophoblasts ,Mice, Inbred C57BL ,Chemotaxis, Leukocyte ,medicine.anatomical_structure ,Endocrinology ,embryonic structures ,biology.protein ,Female - Abstract
Fetal trophoblast cells invading the decidua in the early phase of pregnancy establish complex interaction with the maternal extracellular matrix. We discovered that C1q was widely distributed in human decidual stroma in the absence of C4 and C3 and was actively synthesized by migrating extravillous trophoblasts. The cells expressed the messages for the three chains of C1q and secreted this complement component that interacted with the proteins of the decidual extracellular matrix. Solid phase-bound C1q promoted trophoblast adhesion and migration, and cell binding to C1q resulted in activation of ERK1/2 MAPKs. Ab inhibition experiments showed that the receptors for the globular head of C1q/p33 and α4β1 integrin were both involved in this process and were colocalized on the cell surface following binding of C1q to trophoblasts. We also found that C1q−/− mice manifested increased frequency of fetal resorption, reduced fetal weight, and smaller litter sizes compared with wild-type mice. C1q deficiency was associated with impaired labyrinth development and decidual vessel remodeling. Collectively, these data suggest that C1q plays an important role in promoting trophoblast invasion of decidua and that defective local production of C1q may be involved in pregnancy disorders, such as pre-eclampsia, characterized by poor trophoblast invasion.
- Published
- 2010
16. The complement system at the embryo implantation site
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Chiara Agostinis, Roberta Bulla, Agostinis, C., and Bulla, Roberta
- Subjects
Spiral artery ,Pregnancy ,Placenta accreta ,Immunology ,Decidua ,Obstetrics and Gynecology ,Trophoblast ,Placentation ,Biology ,medicine.disease ,trophoblast ,Miscarriage ,Andrology ,medicine.anatomical_structure ,Reproductive Medicine ,complement ,C1q ,decidua ,embryonic structures ,medicine ,Immunology and Allergy ,Decidual cells ,reproductive and urinary physiology - Abstract
The Complement (C) system plays an important role in the control of infectious agents and in the removal of immune complexes and apoptotic cells. Like other components of innate immunity, C is able to recognize the targets through the early components and to attack them through the biologically active products released as a result of activation. While recognition is restricted to harmful agents, the effector phase associated with the activation products of the terminal components is not selective for foreign targets and may also attack host cells. Thus, C can be considered an effective defence system but also a potential danger that may differently affect various tissues and organs. The protective function of the C system is particularly important during pregnancy since the implanted embryo is vulnerable to attack by pathogens that colonize the cervico-vaginal cavity. Uncontrolled complement activation is prevented in successful pregnancy by the regulatory proteins positioned on the surface of several placental cells, however, unrestricted C activation induced by antibody-dependent and independent mechanisms may overcome the neutralizing effect of the C inhibitors and results in tissue damage and poor pregnancy outcome. C components produced at feto-maternal interface serve an important function in placental development. C1q synthesized by decidual endothelial cells and expressed on the cell surface is particularly important in this regard because it acts as a molecular bridge between endovascular trophoblast and endothelial cells. C1q is also produced by trophoblast and is used to favour trophoblast migration through the decidua. Defective expression of C1q by trophoblast is associated with impaired trophoblast invasion of decidua and may have important implications in pregnancy disorders such as preeclampsia characterized by reduced vascular remodeling. In conclusion the C system behaves as a double-edged sword, exerting a protective function and inducing damage in pathological situations that may result in poor pregnancy outcome.
- Published
- 2015
17. Preeclampsia is associated with defective production of C1q by invasive trophoblast
- Author
-
Francesco Tedesco, Paola Spessotto, Marina Botto, F. De Seta, Roberta Bulla, Claudio Tripodo, M. Tonon, Chiara Agostinis, Carla Guarnotta, Agostinis, Chiara, Bulla, Roberta, C., Tripodo, C., Guarnotta, DE SETA, Francesco, M., Tonon, P., Spessotto, M., Botto, Tedesco, Francesco, Agostinis, C, Bulla, R, Tripodo, C, Guarnotta, C, De Seta, F, Tonon, M, Spessotto, P, Botto, M, and Tedesco, F
- Subjects
Invasive trophoblast ,Immunology ,Settore MED/08 - Anatomia Patologica ,complement ,preeclampsia ,Biology ,medicine.disease ,Preeclampsia ,Complement system ,Complement (complexity) ,medicine ,Molecular Biology ,c1q - Published
- 2011
18. A Human Monoclonal Antibody Against Domain I Of beta 2-Glycoprotein I prevents Clotting and Fetal Loss Induced By Polyclonal Anti-Phospholipid Antibodies In Animal Models
- Author
-
Agostinis, Chiara, Durigutto, Paolo, Sblattero, Daniele, Borghi, Maria Orietta, Claudia Grossi, Bulla, Roberta, Macor, Paolo, Meroni, Pier Luigi, Tedesco, Francesco, Agostinis, C, Durigutto, Paolo, Sblattero, Daniele, Borghi, Mo, Grossi, C, Bulla, Roberta, Macor, Paolo, Meroni, Pl, and Tedesco, F.
- Subjects
Anti-Phospholipid Antibodies, Fetal Loss ,Anti-Phospholipid Antibodies ,Fetal Loss
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