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    Circulating arsenic is associated with long-term risk of graft failure in kidney transplant recipients: A prospective cohort study
    (2023-06-23)
    Sotomayor, Camilo G.
    ;
    Groothof, Dion
    ;
    Vodegel, Joppe J.
    ;
    Gacitúa, Tomás A.
    ;
    Gomes-Neto, António W.
      12
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    Association between maternal obesity, essential fatty acids and biomarkers of fetal liver function
    (2023)
    Macarena Ortiz
    ;
    Francisca Sánchez
    ;
    Daniela Álvarez
    ;
    Cristian Flores
    ;
    Francisca Salas-Pérez
      7Scopus© Citations 5
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      10Scopus© Citations 10
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    Administration of Secretome Derived from Human Mesenchymal Stem Cells Induces Hepatoprotective Effects in Models of Idiosyncratic Drug-Induced Liver Injury Caused by Amiodarone or Tamoxifen
    (2023)
    HUANG, YA LIN  
    ;
    Silva Villalobos, Verónica
    ;
    DE GREGORIO CONCHA, CRISTIAN ALEJANDRO  
    ;
    Álvaro A. Elorza
    ;
    Patricio Léniz
    <jats:p>Drug-induced liver injury (DILI) is one of the leading causes of acute liver injury. While many factors may contribute to the susceptibility to DILI, obese patients with hepatic steatosis are particularly prone to suffer DILI. The secretome derived from mesenchymal stem cell has been shown to have hepatoprotective effects in diverse in vitro and in vivo models. In this study, we evaluate whether MSC secretome could improve DILI mediated by amiodarone (AMI) or tamoxifen (TMX). Hepatic HepG2 and HepaRG cells were incubated with AMI or TMX, alone or with the secretome of MSCs obtained from human adipose tissue. These studies demonstrate that coincubation of AMI or TMX with MSC secretome increases cell viability, prevents the activation of apoptosis pathways, and stimulates the expression of priming phase genes, leading to higher proliferation rates. As proof of concept, in a C57BL/6 mouse model of hepatic steatosis and chronic exposure to AMI, the MSC secretome was administered endovenously. In this study, liver injury was significantly attenuated, with a decrease in cell infiltration and stimulation of the regenerative response. The present results indicate that MSC secretome administration has the potential to be an adjunctive cell-free therapy to prevent liver failure derived from DILI caused by TMX or AMI.</jats:p>
      24Scopus© Citations 14
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    Autoantibodies Against Proteins Previously Associated With Autoimmunity in Adult and Pediatric Patients With COVID-19 and Children With MIS-C
    (2022)
    Peter D. Burbelo
    ;
    Riccardo Castagnoli
    ;
    Chisato Shimizu
    ;
    Ottavia M. Delmonte
    ;
    Kerry Dobbs
    <jats:p>The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren’s syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring <jats:italic>in vivo</jats:italic> decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring &amp;gt;100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.</jats:p>
    Scopus© Citations 25  1
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    Complement Component C3 Participates in Early Stages of Niemann–Pick C Mouse Liver Damage
    (2020)
    Andrés D. Klein
    ;
    Javier González de la Vega
    ;
    Silvana Zanlungo
    <jats:p>Niemann–Pick type C (NPC), a lysosomal storage disorder, is mainly caused by mutations in the NPC1 gene. Niemann–Pick type C patients and mice show intracellular cholesterol accumulation leading to hepatic failure with increased inflammatory response. The complement cascade, which belongs to the innate immunity response, recognizes danger signals from injured tissues. We aimed to determine whether there is activation of the complement system in the liver of the NPC mouse and to assess the relationship between C3 activation, a final component of the pathway, and NPC liver pathology. Niemann–Pick type C mice showed high levels of C3 staining in the liver which unexpectedly decreased with aging. Using an inducible NPC1 hepatocyte rescue mouse model, we restored NPC1 expression for a short time in young mice. We found C3 positive cells only in non-rescued cells, suggesting that C3 activation in NPC cells is reversible. Then, we studied the effect of C3 ablation on NPC liver damage at two postnatal time points, P56 and P72. Deletion of C3 reduced the presence of hepatic CD68-positive cells at postnatal day 56 and prevented the increase of transaminase levels in the blood of NPC mice. These positive effects were abrogated at P72, indicating that the complement cascade participates only during the early stages of liver damage in NPC mice, and that its inhibition may serve as a new potential therapeutic strategy for the disease.</jats:p>
    Scopus© Citations 14  2
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    Failing to Make Ends Meet: The Broad Clinical Spectrum of DNA Ligase IV Deficiency. Case Series and Review of the Literature
    (2019)
    Aidé Tamara Staines Boone
    ;
    Ivan K. Chinn
    ;
    Carmen Alaez-Versón
    ;
    Marco A. Yamazaki-Nakashimada
    ;
    Karol Carrillo-Sánchez
      2Scopus© Citations 32
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    Platelet Count in Patients with Mild Disease at Admission is Associated with Progression to Severe Hantavirus Cardiopulmonary Syndrome
    (2019)
    LOPEZ HERNANDEZ, RENE RAMON  
    ;
    Mario Calvo
    ;
    VIAL COX, MARIA CECILIA  
    ;
    Marcela Ferrés
    ;
    GRAF SANTOS, JERÓNIMO  
    <jats:p>Background: Hantavirus cardiopulmonary syndrome (HCPS) has a mortality up to 35–40% and its treatment is mainly supportive. A variable to predict progression from mild to severe disease is unavailable. This study was performed in patients with documented infection by Andes orthohantavirus, and the aim was to find a simple variable to predict progression to moderate/severe HCPS in patients with mild disease at admission. Methods: We performed a retrospective analysis of 175 patients between 2001 and 2018. Patients were categorized into mild, moderate, and severe disease according to organ failure and advanced support need at hospital admission (e.g., mechanical ventilation, vasopressors). Progression to moderate/severe disease was defined accordingly. Clinical and laboratory variables associated with progression were explored. Results: Forty patients with mild disease were identified; 14 of them progressed to moderate/severe disease. Only platelet count was different between those who progressed versus those that did not (37 (34–58) vs. 83 (64–177) K/mm3, p &lt; 0.001). A ROC curve analysis showed an AUC = 0.889 (0.78–1.0) p &lt; 0.001, with a platelet count greater than 115K /mm3 ruling out progression to moderate/severe disease. Conclusions: In patients with mild disease at presentation, platelet count could help to define priority of evacuation to tertiary care centers.</jats:p>
    Scopus© Citations 10  4
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    Scopus© Citations 731  3