Examinando por Autor "Stoore, Caroll"

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    An Exploration of the Cellular Microenvironment of the Female Pig Urethra: Translational Insights for Urological Research
    (Multidisciplinary Digital Publishing Institute (MDPI), 2025-01) Cartes, Agustín; Stoore, Caroll; Baquedano, María Soledad; Hidalgo, Christian; Lillo, Felipe; Landerer, Eduardo; Ramírez-Toloza, Galia; Paredes, Rodolfo
    Urinary incontinence is a widespread issue, particularly among women, with effective treatments remaining elusive. The pig, and especially the female pig, stands as a promising animal model for the study of this condition, due to its anatomical similarities to humans. The aim of this study was to explore the largely uncharted muscular structure of the female pig urethra, linking urethral muscle dysfunction to incontinence. We examined histological sections from the urethras of six sows using Hematoxylin-Eosin and Masson’s trichrome staining for morphometric analysis. The statistical significance of cellular disposition was determined through analysis of variance (ANOVA), followed by a Tukey post hoc test to elucidate specific inter-group differences. Our analysis revealed segment-specific epithelial differences, including variations in cell layers, sparse acinar glands, rich vasculature, and distinct muscle fibers with diverse regional distributions. Notably, significant differences in muscular area and tissue distribution were identified between the proximal, middle, and distal segments of the urethra (p < 0.001). The observed anatomical variations, along with the cellular similarities between pigs and humans, establish the female pig as a crucial translational model for advancing urological research. Specifically, these findings provide a foundation for the development of innovative therapeutic strategies and surgical techniques that can be directly applied to improve outcomes in human urological conditions. © 2025 by the authors.
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    Cattle co-infection of Echinococcus granulosus and Fasciola hepatica results in a different systemic cytokine profile than single parasite infection
    (Public Library of Science, 2020-09) Corrêa, Felipe; Hidalgo, Christian; Stoore, Caroll; Jiménez, Mauricio; Hernández, Marcela; Paredes, Rodolfo
    E. granulosus is a cestode that causes Cystic Echinococcosis (CE), a zoonotic disease with worldwide presence. The immune response generated by the host against the metacestode induces a permissive Th2 response, as opposed to pro-inflammatory Th1 response. In this view, mixed Th2 and regulatory responses allow parasite survival. Overall, larval Echinococcus infections induce strong regulatory responses. Fasciola hepatica, another common helminth parasite, represents a major infection in cattle. Co-infection with different parasite species in the same host, polyparasitism, is a common occurrence involving E. granulosus and F. hepatica in cattle. ‘While it is known that infection with F. hepatica also triggers a polarized Th2/Treg immune response, little is reported regarding effects on the systemic immune response of this example of polyparasitism. F. hepatica also triggers immune responses polarized to the Th2/ Treg spectrum. Serum samples from 107 animals were analyzed, and were divided according to their infection status and Echinococcal cysts fertility. Cytokines were measured utilizing a Milliplex Magnetic Bead Panel to detect IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-10, IL-12 and IL-18. Cattle infected only with F. hepatica had the highest concentration of every cytokine analyzed, with both 4.24 and 3.34-fold increases in IL-10 and IL-4, respectively, compared to control animals, followed by E. granulosus and F. hepatica co-infected animals with two-fold increase in IL-10 and IL-4, compared to control animals, suggesting that E. granulosus co-infection dampens the cattle Th2/Treg immune response against F. hepatica. When considering Echinococcal cyst fertility and systemic cytokine concentrations, fertile cysts had higher IFN-γ, IL-6 and IL-18 concentrations, while infertile cysts had higher IL-10 concentrations. These results show that E. granulosus co-infection lowers Th1 and Th2 cytokine serological concentration when compared to F. hepatica infection alone. E. granulosus infections show no difference in IFN-γ, IL-1, IL-2, IL-6 and IL-18 levels compared with control animals, highlighting the immune evasion mechanisms of this cestode. © 2020 Corrêa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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    Response patterns in adventitial layer of Echinococcus granulosus sensu stricto cysts from naturally infected cattle and sheep
    (BioMed Central Ltd, 2021-06) Hidalgo, Christian; Stoore, Caroll; Baquedano, María; Pereira, Ismael; Franco, Carmen; Hernández, Marcela; Paredes, Rodolfo
    Cystic echinococcosis is a zoonotic disease caused by the metacestode of Echinococcus granulosus sensu lato. The disease is characterized by the development of cystic structures inside viscera of the intermediate host, mainly liver and lungs. These cysts are formed by three layers: germinal, laminated, and adventitial layer, the latter being the local host immune response. Metacestodes that develop protoscoleces, the infective stage to the definitive host, are termed fertile, whereas cysts that do not produce protoscoleces are termed non-fertile. Sheep usually harbor fertile cysts while cattle usually harbor non-fertile cysts. Adventitial layers with fibrotic resolution are associated to fertile cysts, whereas a granulomatous reaction is associated with non-fertile cysts. The aim of this study was to analyze cellular distribution in the adventitial layer of fertile and non-fertile E. granulosus sensu stricto cysts found in liver and lungs of cattle and sheep. A total of 418 cysts were analyzed, 203 from cattle (8 fertile and 195 non-fertile) and 215 from sheep (64 fertile and 151 non-fertile). Fertile cysts from cattle showed mixed patterns of response, with fibrotic resolution and presence of granulomatous response in direct contact with the laminated layer, while sheep fertile cysts always displayed fibrotic resolution next to the laminated layer. Cattle non-fertile cysts display a granulomatous reaction in direct contact with the laminated layer, whereas sheep non-fertile cysts display a granulomatous reaction, but in direct contact with the fibrotic resolution. This shows that cattle and sheep cystic echinococcosis cysts have distinct local immune response patterns, which are associated to metacestode fertility. © 2021, The Author(s).
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    Simvastatin exhibits antiproliferative effects on spheres derived from canine mammary carcinoma cells
    (Spandidos Publications, 2015-05) Torres, Cristian G.; Olivares, Araceli; Stoore, Caroll
    Mammary cancer is the most frequent type of tumor in the female canine. Treatments are mainly limited to surgery and chemotherapy; however, these tumors may develop clinical recurrence, metastasis and chemoresistance. The existence of a subpopulation of cancer cells with stemness features called cancer stem-like cells, may explain in part these characteristics of tumor progression. The statins, potent blockers of cholesterol synthesis, have also shown antitumor effects on cancer mammary cells, changes mediated by a decrease in the isoprenylation of specific proteins. Few studies have shown that simvastatin, a lipophilic statin, sensitizes cancer stem-like cells eliminating drug resistance. The aim of the present study was to evaluate the effects of simvastatin on spheres derived from CF41-Mg canine mammary tumor cells, which were characterized by phenotypic and functional analyses. Spheres exhibited characteristics of stemness, primarily expressing a CD44+/CD24-/low phenotype, displaying auto-renewal and relative chemoresistance. Exposure to simvastatin induced a decrease in the sphere-forming capacity and cell viability, accompanied by a concentration- and time-dependent increase in caspase-3/7 activity. In addition, modulation of β-catenin and p53 expression was observed. Simvastatin triggered a synergistic effect with doxorubicin, sensitizing the spheres to the cytotoxic effect exerted by the drug. Invasiveness of spheres was decreased in response to simvastatin and this effect was counteracted by the presence of geranylgeranyl pyrophosphate. Our results suggest that simvastatin targets canine mammary cancer stem-like cells, supporting its therapeutical application as a novel agent to treat canine mammary cancer.
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    Weighted gene co-expression network analysis reveals immune evasion related genes in Echinococcus granulosus sensu stricto
    (Frontiers Media SA, 2023) Pereira, Ismael; Prado Paludo, Gabriela; Hidalgo, Christian; Stoore, Caroll; Baquedano, María Soledad; Cabezas, Carolina; Cancela, Martín; Ferreira, Henrique Bunselmeyer; Bastías, Macarena; Riveros, Aníbal; Meneses, Claudio; Sáenz, Leonardo; Paredes, Rodolfo
    Cystic echinococcosis (CE) is a zoonotic disease caused by the tapeworm Echinococcus granulosus sensu lato (s.l). In the intermediate host, this disease is characterized by the growth of cysts in viscera such as liver and lungs, inside of which the parasite develops to the next infective stage known as protoscoleces. There are records that the infected viscera affect the development and morphology of E. granulosus s.l. protoscolex in hosts such as buffalo or humans. However, the molecular mechanisms that drive these differences remains unknown. Weighted gene co-expression network analysis (WGCNA) using a set of RNAseq data obtained from E. granulosus sensu stricto (s.s.) protoscoleces found in liver and lung cysts reveals 34 modules in protoscoleces of liver origin, of which 12 have differential co-expression from protoscoleces of lung origin. Three of these twelve modules contain hub genes related to immune evasion: tegument antigen, tegumental protein, ubiquitin hydrolase isozyme L3, COP9 signalosome complex subunit 3, tetraspanin CD9 antigen, and the methyl-CpG-binding protein Mbd2. Also, two of the twelve modules contain only hypothetical proteins with unknown orthology, which means that there are a group of unknown function proteins co-expressed inside the protoscolex of liver CE cyst origin. This is the first evidence of gene expression differences in protoscoleces from CE cysts found in different viscera, with co-expression networks that are exclusive to protoscoleces from liver CE cyst samples. This should be considered in the control strategies of CE, as intermediate hosts can harbor CE cysts in liver, lungs, or both organs simultaneously. Copyright © 2024 Pereira, Paludo, Hidalgo, Stoore, Baquedano, Cabezas, Cancela, Ferreira, Bastías, Riveros, Meneses, Sáenz and Paredes.
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    γδ T cell distribution in the adventitial layer of non-fertile cystic echinococcosis cysts from cattle livers
    (Nature Research, 0025) Stoore, Caroll; Baquedano, María Soledad; Hidalgo, Christian; Cabello-Verrugio, Claudio; Paredes, Rodolfo
    Cystic Echinococcosis (CE) is a zoonotic disease caused by Echinococcus granulosus sensu lato, forming cysts in ruminants and humans with major health and economic impacts. The immune response to CE cysts is complex, with fertility linked to the host’s inflammatory reaction. This study examines γδ T cell distribution and role within the adventitial layer of non-fertile CE cysts in cattle, including cases co-infected with the trematode Fasciola hepatica (FH), a known immune response modulator. Using immunohistochemistry and double immunofluorescence, we observed γδ T cells dispersed in the adventitial layer, enriched in inflammatory zones. Co-infected cases (CE + FH+) showed a reduced γδ T cell proportion among CD3+ T cells compared to non-coinfected cases, suggesting an immunoregulatory effect of FH. Our findings align with prior studies showing γδ T cell recruitment in granulomatous diseases in ruminants but reveal that co-infection alters this response. This study provides the first detailed characterization of γδ T cells in cattle CE cysts, emphasizing their potential role in granulomatous immune responses. It highlights the need for further research into mechanisms influencing CE cyst fertility and immune modulation in helminth co-infections, advancing our understanding of host-pathogen interactions and informing disease management strategies. © The Author(s) 2025.