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  1. Article ; Online: Imbalanced IL-1B and IL-18 Expression in Sézary Syndrome

    Kelly Cristina Gomes Manfrere / Marina Passos Torrealba / Frederico Moraes Ferreira / Emanuella Sarmento Alho de Sousa / Denis Miyashiro / Franciane Mouradian Emidio Teixeira / Ricardo Wesley Alberca Custódio / Helder I. Nakaya / Yasmin Alefe Leuzzi Ramos / Mirian Nacagami Sotto / Anders Woetmann / Niels Ødum / Alberto José da Silva Duarte / José Antonio Sanches / Maria Notomi Sato

    International Journal of Molecular Sciences, Vol 24, Iss 4674, p

    2023  Volume 4674

    Abstract: Sézary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma, with an abnormal inflammatory response in affected skin. The cytokines IL-1B and IL-18, as key signaling molecules in the immune system, are produced in an inactive form and ...

    Abstract Sézary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma, with an abnormal inflammatory response in affected skin. The cytokines IL-1B and IL-18, as key signaling molecules in the immune system, are produced in an inactive form and cleave to the active form by inflammasomes. In this study, we assessed the skin, serum, peripheral mononuclear blood cell (PBMC) and lymph-node samples of SS patients and control groups (healthy donors (HDs) and idiopathic erythroderma (IE) nodes) to investigate the inflammatory markers IL-1B and IL-18 at the protein and transcript expression levels, as potential markers of inflammasome activation. Our findings showed increased IL-1B and decreased IL-18 protein expression in the epidermis of SS patients; however, in the dermis layer, we detected increased IL-18 protein expression. In the lymph nodes of SS patients at advanced stages of the disease (N2/N3), we also detected an enhancement of IL-18 and a downregulation of IL-1B at the protein level. Moreover, the transcriptomic analysis of the SS and IE nodes confirmed the decreased expression of IL1B and NLRP3 , whereas the pathway analysis indicated a further downregulation of IL1B -associated genes. Overall, the present findings showed compartmentalized expressions of IL-1B and IL-18 and provided the first evidence of their imbalance in patients with Sézary syndrome.
    Keywords Sézary syndrome ; lymph nodes ; inflammasome ; IL-1B ; IL-18 ; erythroderma skin ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2023-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy.

    Laurie Laugier / Ludmila Rodrigues Pinto Ferreira / Frederico Moraes Ferreira / Sandrine Cabantous / Amanda Farage Frade / Joao Paulo Nunes / Rafael Almeida Ribeiro / Pauline Brochet / Priscila Camillo Teixeira / Ronaldo Honorato Barros Santos / Edimar A Bocchi / Fernando Bacal / Darlan da Silva Cândido / Vanessa Escolano Maso / Helder I Nakaya / Jorge Kalil / Edecio Cunha-Neto / Christophe Chevillard

    PLoS Neglected Tropical Diseases, Vol 14, Iss 12, p e

    2020  Volume 0008889

    Abstract: Chronic Chagas disease cardiomyopathy (CCC), an especially aggressive inflammatory dilated cardiomyopathy caused by lifelong infection with the protozoan Trypanosoma cruzi, is a major cause of cardiomyopathy in Latin America. Although chronic myocarditis ...

    Abstract Chronic Chagas disease cardiomyopathy (CCC), an especially aggressive inflammatory dilated cardiomyopathy caused by lifelong infection with the protozoan Trypanosoma cruzi, is a major cause of cardiomyopathy in Latin America. Although chronic myocarditis may play a major pathogenetic role, little is known about the molecular mechanisms responsible for its severity. The aim of this study is to study the genes and microRNAs expression in tissues and their connections in regards to the pathobiological processes. To do so, we integrated for the first time global microRNA and mRNA expression profiling from myocardial tissue of CCC patients employing pathways and network analyses. We observed an enrichment in biological processes and pathways associated with the immune response and metabolism. IFNγ, TNF and NFkB were the top upstream regulators. The intersections between differentially expressed microRNAs and differentially expressed target mRNAs showed an enrichment in biological processes such as Inflammation, inflammation, Th1/IFN-γ-inducible genes, fibrosis, hypertrophy, and mitochondrial/oxidative stress/antioxidant response. MicroRNAs also played a role in the regulation of gene expression involved in the key cardiomyopathy-related processes fibrosis, hypertrophy, myocarditis and arrhythmia. Significantly, a discrete number of differentially expressed microRNAs targeted a high number of differentially expressed mRNAs (>20) in multiple processes. Our results suggest that miRNAs orchestrate expression of multiple genes in the major pathophysiological processes in CCC heart tissue. This may have a bearing on pathogenesis, biomarkers and therapy.
    Keywords Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
    Subject code 610
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Rheumatic Heart Disease and Myxomatous Degeneration

    Carlo de Oliveira Martins / Lea Demarchi / Frederico Moraes Ferreira / Pablo Maria Alberto Pomerantzeff / Carlos Brandao / Roney Orismar Sampaio / Guilherme Sobreira Spina / Jorge Kalil / Edecio Cunha-Neto / Luiza Guilherme

    PLoS ONE, Vol 12, Iss 1, p e

    Differences and Similarities of Valve Damage Resulting from Autoimmune Reactions and Matrix Disorganization.

    2017  Volume 0170191

    Abstract: Autoimmune inflammatory reactions leading to rheumatic fever (RF) and rheumatic heart disease (RHD) result from untreated Streptococcus pyogenes throat infections in individuals who exhibit genetic susceptibility. Immune effector mechanisms have been ... ...

    Abstract Autoimmune inflammatory reactions leading to rheumatic fever (RF) and rheumatic heart disease (RHD) result from untreated Streptococcus pyogenes throat infections in individuals who exhibit genetic susceptibility. Immune effector mechanisms have been described that lead to heart tissue damage culminating in mitral and aortic valve dysfunctions. In myxomatous valve degeneration (MXD), the mitral valve is also damaged due to non-inflammatory mechanisms. Both diseases are characterized by structural valve disarray and a previous proteomic analysis of them has disclosed a distinct profile of matrix/structural proteins differentially expressed. Given their relevance in organizing valve tissue, we quantitatively evaluated the expression of vimentin, collagen VI, lumican, and vitronectin as well as performed immunohistochemical analysis of their distribution in valve tissue lesions of patients in both diseases. We identified abundant expression of two isoforms of vimentin (45 kDa, 42 kDa) with reduced expression of the full-size protein (54 kDa) in RHD valves. We also found increased vitronectin expression, reduced collagen VI expression and similar lumican expression between RHD and MXD valves. Immunohistochemical analysis indicated disrupted patterns of these proteins in myxomatous degeneration valves and disorganized distribution in rheumatic heart disease valves that correlated with clinical manifestations such as valve regurgitation or stenosis. Confocal microscopy analysis revealed a diverse pattern of distribution of collagen VI and lumican into RHD and MXD valves. Altogether, these results demonstrated distinct patterns of altered valve expression and tissue distribution/organization of structural/matrix proteins that play important pathophysiological roles in both valve diseases.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Rheumatic Heart Disease and Myxomatous Degeneration

    Carlo de Oliveira Martins / Lea Demarchi / Frederico Moraes Ferreira / Pablo Maria Alberto Pomerantzeff / Carlos Brandao / Roney Orismar Sampaio / Guilherme Sobreira Spina / Jorge Kalil / Edecio Cunha-Neto / Luiza Guilherme

    PLoS ONE, Vol 12, Iss 1, p e

    Differences and Similarities of Valve Damage Resulting from Autoimmune Reactions and Matrix Disorganization.

    2017  Volume 0170191

    Abstract: Autoimmune inflammatory reactions leading to rheumatic fever (RF) and rheumatic heart disease (RHD) result from untreated Streptococcus pyogenes throat infections in individuals who exhibit genetic susceptibility. Immune effector mechanisms have been ... ...

    Abstract Autoimmune inflammatory reactions leading to rheumatic fever (RF) and rheumatic heart disease (RHD) result from untreated Streptococcus pyogenes throat infections in individuals who exhibit genetic susceptibility. Immune effector mechanisms have been described that lead to heart tissue damage culminating in mitral and aortic valve dysfunctions. In myxomatous valve degeneration (MXD), the mitral valve is also damaged due to non-inflammatory mechanisms. Both diseases are characterized by structural valve disarray and a previous proteomic analysis of them has disclosed a distinct profile of matrix/structural proteins differentially expressed. Given their relevance in organizing valve tissue, we quantitatively evaluated the expression of vimentin, collagen VI, lumican, and vitronectin as well as performed immunohistochemical analysis of their distribution in valve tissue lesions of patients in both diseases. We identified abundant expression of two isoforms of vimentin (45 kDa, 42 kDa) with reduced expression of the full-size protein (54 kDa) in RHD valves. We also found increased vitronectin expression, reduced collagen VI expression and similar lumican expression between RHD and MXD valves. Immunohistochemical analysis indicated disrupted patterns of these proteins in myxomatous degeneration valves and disorganized distribution in rheumatic heart disease valves that correlated with clinical manifestations such as valve regurgitation or stenosis. Confocal microscopy analysis revealed a diverse pattern of distribution of collagen VI and lumican into RHD and MXD valves. Altogether, these results demonstrated distinct patterns of altered valve expression and tissue distribution/organization of structural/matrix proteins that play important pathophysiological roles in both valve diseases.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Serum from dengue virus-infected patients with and without plasma leakage differentially affects endothelial cells barrier function in vitro.

    Francielle Tramontini Gomes de Sousa Cardozo / Gyulnar Baimukanova / Marion Christine Lanteri / Sheila Marie Keating / Frederico Moraes Ferreira / John Heitman / Cláudio Sérgio Pannuti / Shibani Pati / Camila Malta Romano / Ester Cerdeira Sabino

    PLoS ONE, Vol 12, Iss 6, p e

    2017  Volume 0178820

    Abstract: BACKGROUND:Although most of cases of dengue infections are asymptomatic or mild symptomatic some individuals present warning signs progressing to severe dengue in which plasma leakage is a hallmark. METHODOLOGY/PRINCIPAL FINDINGS:The present study used ... ...

    Abstract BACKGROUND:Although most of cases of dengue infections are asymptomatic or mild symptomatic some individuals present warning signs progressing to severe dengue in which plasma leakage is a hallmark. METHODOLOGY/PRINCIPAL FINDINGS:The present study used Electric Cell-substrate Impedance Sensing (ECIS®) which allows for electrical monitoring of cellular barrier function measuring changes in Transendothelial Electric Resistance (TEER) to investigate the parameters associated with dengue induced leakage. Three groups of individuals were tested: dengue-positives with plasma leakage (leakage), dengue-positives without plasma leakage (no leakage), and dengue-negatives (control). Data show that TEER values of human umbilical vein endothelial cells (HUVECs) was significantly lower after incubation with serum from subjects of the leakage group in comparison to the no leakage or control groups. The serum levels of CXCL1, EGF, eotaxin, IFN-γ, sCD40L, and platelets were significantly decreased in the leakage group, while IL-10, IL-6, and IP-10 levels were significantly increased. We also found a strong correlation between TEER values and augmented levels of IP-10, GM-CSF, IL-1α, and IL-8, as well as decreased levels of CXCL1 and platelets. CONCLUSIONS/SIGNIFICANCE:The present work shows that the magnitude of the immune response contributes to the adverse plasma leakage outcomes in patients and that serum components are important mediators of changes in endothelial homeostasis during dengue infections. In particular, the increased levels of IP-10 and the decreased levels of CXCL1 and platelets seem to play a significant role in the disruption of vascular endothelium associated with leakage outcomes after DENV infection. These findings may have important implications for both diagnostic and therapeutic approaches to predict and mitigate vascular permeabilization in those experiencing the most severe clinical disease outcomes after dengue infection.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610 ; 630
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Integration of miRNA and gene expression profiles suggest a role for miRNAs in the pathobiological processes of acute Trypanosoma cruzi infection

    Ludmila Rodrigues Pinto Ferreira / Frederico Moraes Ferreira / Laurie Laugier / Sandrine Cabantous / Isabela Cunha Navarro / Darlan da Silva Cândido / Vagner Carvalho Rigaud / Juliana Monte Real / Glaucia Vilar Pereira / Isabela Resende Pereira / Leonardo Ruivo / Ramendra Pati Pandey / Marilda Savoia / Jorge Kalil / Joseli Lannes-Vieira / Helder Nakaya / Christophe Chevillard / Edecio Cunha-Neto

    Scientific Reports, Vol 7, Iss 1, Pp 1-

    2017  Volume 12

    Abstract: Abstract Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America. Its acute phase is associated with high parasitism, myocarditis and profound myocardial gene expression changes. A chronic phase ensues where 30% develop ... ...

    Abstract Abstract Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America. Its acute phase is associated with high parasitism, myocarditis and profound myocardial gene expression changes. A chronic phase ensues where 30% develop severe heart lesions. Mouse models of T. cruzi infection have been used to study heart damage in Chagas disease. The aim of this study was to provide an interactome between miRNAs and their targetome in Chagas heart disease by integrating gene and microRNA expression profiling data from hearts of T. cruzi infected mice. Gene expression profiling revealed enrichment in biological processes and pathways associated with immune response and metabolism. Pathways, functional and upstream regulator analysis of the intersections between predicted targets of differentially expressed microRNAs and differentially expressed mRNAs revealed enrichment in biological processes and pathways such as IFNγ, TNFα, NF-kB signaling signatures, CTL-mediated apoptosis, mitochondrial dysfunction, and Nrf2-modulated antioxidative responses. We also observed enrichment in other key heart disease-related processes like myocarditis, fibrosis, hypertrophy and arrhythmia. Our correlation study suggests that miRNAs may be implicated in the pathophysiological processes taking place the hearts of acutely T. cruzi-infected mice.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2017-12-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Distinct Mitral Valve Proteomic Profiles in Rheumatic Heart Disease and Myxomatous Degeneration

    Carlo de Oliveira Martins / Keity Souza Santos / Frederico Moraes Ferreira / Priscila Camillo Teixeira / Pablo Maria Alberto Pomerantzeff / Carlos M. A. Brandão / Roney Orismar Sampaio / Guilherme S. Spina / Jorge Kalil / Luiza Guilherme / Edecio Cunha-Neto

    Clinical Medicine Insights: Cardiology, Vol 2014, Iss 8, Pp 79-

    2014  Volume 86

    Keywords Diseases of the circulatory (Cardiovascular) system ; RC666-701 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R
    Language English
    Publishing date 2014-08-01T00:00:00Z
    Publisher Libertas Academica
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: MicroRNA Transcriptome Profiling in Heart of Trypanosoma cruzi-Infected Mice

    Isabela Cunha Navarro / Frederico Moraes Ferreira / Helder I Nakaya / Monique Andrade Baron / Gláucia Vilar-Pereira / Isabela Resende Pereira / Ana Maria Gonçalves Silva / Juliana Monte Real / Thales De Brito / Christophe Chevillard / Joseli Lannes-Vieira / Jorge Kalil / Edecio Cunha-Neto / Ludmila Rodrigues Pinto Ferreira

    PLoS Neglected Tropical Diseases, Vol 9, Iss 6, p e

    Parasitological and Cardiological Outcomes.

    2015  Volume 0003828

    Abstract: Chagas disease is caused by the parasite Trypanosoma cruzi, and it begins with a short acute phase characterized by high parasitemia followed by a life-long chronic phase with scarce parasitism. Cardiac involvement is the most prominent manifestation, as ...

    Abstract Chagas disease is caused by the parasite Trypanosoma cruzi, and it begins with a short acute phase characterized by high parasitemia followed by a life-long chronic phase with scarce parasitism. Cardiac involvement is the most prominent manifestation, as 30% of infected subjects will develop abnormal ventricular repolarization with myocarditis, fibrosis and cardiomyocyte hypertrophy by undefined mechanisms. Nevertheless, follow-up studies in chagasic patients, as well as studies with murine models, suggest that the intensity of clinical symptoms and pathophysiological events that occur during the acute phase of disease are associated with the severity of cardiac disease observed during the chronic phase. In the present study we investigated the role of microRNAs (miRNAs) in the disease progression in response to T. cruzi infection, as alterations in miRNA levels are known to be associated with many cardiovascular disorders. We screened 641 rodent miRNAs in heart samples of mice during an acute infection with the Colombiana T.cruzi strain and identified multiple miRNAs significantly altered upon infection. Seventeen miRNAs were found significantly deregulated in all three analyzed time points post infection. Among these, six miRNAs had their expression correlated with clinical parameters relevant to the disease, such as parasitemia and maximal heart rate-corrected QT (QTc) interval. Computational analyses identified that the gene targets for these six miRNAs were involved in networks and signaling pathways related to increased ventricular depolarization and repolarization times, important factors for QTc interval prolongation. The data presented here will guide further studies about the contribution of microRNAs to Chagas heart disease pathogenesis.
    Keywords Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
    Subject code 610
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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