{
    "abstract": "Necroptosis is a regulated form of cell death implicated in several pathological conditions, including viral infections. In this study, we investigated the expression and correlation of necroptosis markers MLKL, RIP1 and RIP3 in human liver tissue from fatal cases of yellow fever (YF) using immunohistochemistry (IHC). The liver samples were obtained from 21 YF-positive individuals and five flavivirus-negative controls with preserved liver parenchymal architecture. The cases underwent histopathological analysis, followed by tissue immunostaining with the immunohistochemical method of streptavidin-biotin peroxidase. Using the in situ method, we evaluated the centrilobular zone (Z3), midzonal zone (Z2), periportal zone and portal tract (PT) of human liver parenchyma with markers for necroptosis, RIPK1, RIPK3 and MLKL. A quantitative analysis revealed a significantly higher expression of MLKL, RIP1 and RIP3 in the liver parenchyma of YF cases compared to controls in different zones (Z3, Z2, Z1) and portal tracts (PTs) of the liver, especially in zone 2. Immunostaining confirmed the localization of MLKL, RIP1 and RIP3 in hepatocytes and inflammatory infiltrates, highlighting their involvement in the pathogenesis of YF. A Pearson correlation analysis demonstrated significant correlations among necroptosis markers, which indicates their coordinated regulation during YF-induced liver injury.",
    "authors": [
        {
            "affiliation": "Departmento of Pathology, Evandro Chagas Institute, Ministry of Health, Ananindeua 67030-000, PA, Brazil.",
            "firstname": "Vanessa do Socorro Cabral",
            "initials": "VDSC",
            "lastname": "Miranda"
        },
        {
            "affiliation": "Departmento of Pathology, State University of Para, Belem 66050-540, PA, Brazil.",
            "firstname": "Luiz Fabio Magno",
            "initials": "LFM",
            "lastname": "Falc\u00e3o"
        },
        {
            "affiliation": "Tropical Medicine Center, Federal University of Para, Belem 66055-240, PA, Brazil.",
            "firstname": "Hellen Thais",
            "initials": "HT",
            "lastname": "Fuzii"
        },
        {
            "affiliation": "Departmento of Pathology, Evandro Chagas Institute, Ministry of Health, Ananindeua 67030-000, PA, Brazil.",
            "firstname": "Marcos Luiz Gaia",
            "initials": "MLG",
            "lastname": "Carvalho"
        },
        {
            "affiliation": "Departmento of Pathology, Evandro Chagas Institute, Ministry of Health, Ananindeua 67030-000, PA, Brazil.",
            "firstname": "Jeferson da Costa",
            "initials": "JDC",
            "lastname": "Lopes"
        },
        {
            "affiliation": "Departmento of Pathology, Evandro Chagas Institute, Ministry of Health, Ananindeua 67030-000, PA, Brazil.",
            "firstname": "Arnaldo Jorge Martins",
            "initials": "AJM",
            "lastname": "Filho"
        },
        {
            "affiliation": "Departmento of Pathology, Evandro Chagas Institute, Ministry of Health, Ananindeua 67030-000, PA, Brazil.",
            "firstname": "Ana Cecilia Ribeiro",
            "initials": "ACR",
            "lastname": "Cruz"
        },
        {
            "affiliation": "Departmento of Pathology, Evandro Chagas Institute, Ministry of Health, Ananindeua 67030-000, PA, Brazil.",
            "firstname": "Raimunda do Socorro da Silva",
            "initials": "RDSDS",
            "lastname": "Azevedo"
        },
        {
            "affiliation": "Departmento of Pathology, Evandro Chagas Institute, Ministry of Health, Ananindeua 67030-000, PA, Brazil.\nDepartmento of Pathology, State University of Para, Belem 66050-540, PA, Brazil.\nTropical Medicine Center, Federal University of Para, Belem 66055-240, PA, Brazil.",
            "firstname": "Jorge Rodrigues de",
            "initials": "JR",
            "lastname": "Sousa"
        },
        {
            "affiliation": "Evandro Chagas National Institute of Infectious Diseases (INI-FIOCRUZ), Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil.",
            "firstname": "Mayumi Duarte",
            "initials": "MD",
            "lastname": "Wakimoto"
        },
        {
            "affiliation": "Departmento of Pathology, Evandro Chagas Institute, Ministry of Health, Ananindeua 67030-000, PA, Brazil.\nDepartmento of Pathology, State University of Para, Belem 66050-540, PA, Brazil.",
            "firstname": "Pedro Fernando da Costa",
            "initials": "PFDC",
            "lastname": "Vasconcelos"
        },
        {
            "affiliation": "Departmento of Pathology, Evandro Chagas Institute, Ministry of Health, Ananindeua 67030-000, PA, Brazil.\nDepartmento of Pathology, State University of Para, Belem 66050-540, PA, Brazil.\nTropical Medicine Center, Federal University of Para, Belem 66055-240, PA, Brazil.\nEvandro Chagas National Institute of Infectious Diseases (INI-FIOCRUZ), Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil.\nDepartment of Infectious Disease, School of Medicine, Sao Paulo University, Sao Paulo 01246-930, SP, Brazil.",
            "firstname": "Juarez Ant\u00f4nio Sim\u00f5es",
            "initials": "JAS",
            "lastname": "Quaresma"
        }
    ],
    "conclusions": null,
    "copyrights": null,
    "doi": "10.3390/v17010003\n10.1016/j.cll.2010.01.001\n10.3201/eid1009.040197\n10.1001/jama.300.8.960\n10.1128/JVI.75.15.6999-7008.2001\n10.1038/s41598-017-05186-3\n10.1590/S0037-86822003000200012\n10.1590/s1678-9946201961035\n10.3390/v14081725\n10.1038/ni.2159\n10.3390/v9090243\n10.1016/j.virol.2005.09.058\n10.1126/science.aaf2154\n10.1038/cdd.2014.77\n10.1038/s42003-017-0007-1\n10.3389/fcvm.2021.696362\n10.3390/pathogens11010101\n10.1016/j.actatropica.2005.03.003\n10.1016/j.trstmh.2006.02.019\n10.1016/j.mehy.2006.01.060\n10.1177/29.4.6166661\n10.1038/nrm2970\n10.1073/pnas.1613305114\n10.1186/s12974-018-1235-0\n10.1073/pnas.1806973115\n10.1038/nature00858\n10.1073/pnas.0908698106\n10.1007/s10495-005-6075-6\n10.1371/journal.ppat.1010718\n10.1146/annurev-pathol-052016-100247",
    "journal": "Viruses",
    "keywords": [
        "liver parenchyma",
        "necroptosis",
        "yellow fever"
    ],
    "methods": null,
    "publication_date": "2025-01-25",
    "pubmed_id": "39861792\n20513550\n15498159\n18728272\n11435580\n28687779\n12806465\n31340247\n36016347\n22089220\n28846635\n16278000\n27034377\n24902902\n30271893\n34497836\n35056050\n15829426\n16872652\n16650626\n6166661\n20823910\n28096356\n29980212\n29891719\n12110890\n19918053\n15711936\n35951530\n27959630",
    "results": null,
    "title": "Analysis of MLKL, RIP1 and RIP3 Immunostaining Markers in Human Liver Tissue from Fatal Yellow Fever Cases: Insights into Necroptosis.",
    "xml": "<Element 'PubmedArticle' at 0x7885065d3920>"
}