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      Structural changes and expression of hepatic fibrosis-related proteins in coculture of Echinococcus multilocularis protoscoleces and human hepatic stellate cells

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          Abstract

          Background

          Echinococcus multilocularis is the causative agent of human hepatic alveolar echinococcosis (AE). AE can cause damage to several organs, primarily the liver, and have severe outcomes, such as hepatic failure and encephalopathy. The main purpose of this study was to explore the interactions between hepatic stellate cells (HSCs) and E. multilocularis protoscoleces (PSCs). The results of this study provide an experimental basis for further examination of the pathogenesis of hepatic fibrosis due to AE infection.

          Methods

          We investigated the role of Echinococcus multilocularis (Echinococcus genus) PSCs in hepatic fibrosis by examining structural changes and measuring hepatic fibrosis-related protein levels in cocultures of PSCs and human HSCs. Structural changes were detected by transmission electron microscopy (TEM), and levels of the hepatic fibrosis-related proteins collagen I (Col-I), alpha-smooth muscle actin (α-SMA) and osteopontin (OPN) were measured by western blotting and enzyme-linked immunosorbent assay (ELISA).

          Results

          Under coculture (1) both PSCs and HSCs exhibited morphological changes, as observed by TEM; (2) Col-I, α-SMA, and OPN expression levels, which were determined by western blotting and ELISA, significantly increased after 3 days of incubation.

          Conclusions

          The results of this study provide insights into the molecular mechanisms of AE-induced hepatic fibrosis.

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          Most cited references35

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          MicroRNAs: target recognition and regulatory functions.

          MicroRNAs (miRNAs) are endogenous approximately 23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.
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            Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver.

            The hepatic stellate cell has surprised and engaged physiologists, pathologists, and hepatologists for over 130 years, yet clear evidence of its role in hepatic injury and fibrosis only emerged following the refinement of methods for its isolation and characterization. The paradigm in liver injury of activation of quiescent vitamin A-rich stellate cells into proliferative, contractile, and fibrogenic myofibroblasts has launched an era of astonishing progress in understanding the mechanistic basis of hepatic fibrosis progression and regression. But this simple paradigm has now yielded to a remarkably broad appreciation of the cell's functions not only in liver injury, but also in hepatic development, regeneration, xenobiotic responses, intermediary metabolism, and immunoregulation. Among the most exciting prospects is that stellate cells are essential for hepatic progenitor cell amplification and differentiation. Equally intriguing is the remarkable plasticity of stellate cells, not only in their variable intermediate filament phenotype, but also in their functions. Stellate cells can be viewed as the nexus in a complex sinusoidal milieu that requires tightly regulated autocrine and paracrine cross-talk, rapid responses to evolving extracellular matrix content, and exquisite responsiveness to the metabolic needs imposed by liver growth and repair. Moreover, roles vital to systemic homeostasis include their storage and mobilization of retinoids, their emerging capacity for antigen presentation and induction of tolerance, as well as their emerging relationship to bone marrow-derived cells. As interest in this cell type intensifies, more surprises and mysteries are sure to unfold that will ultimately benefit our understanding of liver physiology and the diagnosis and treatment of liver disease.
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              Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans.

              The earlier recommendations of the WHO-Informal Working Group on Echinococcosis (WHO-IWGE) for the treatment of human echinococcosis have had considerable impact in different settings worldwide, but the last major revision was published more than 10 years ago. Advances in classification and treatment of echinococcosis prompted experts from different continents to review the current literature, discuss recent achievements and provide a consensus on diagnosis, treatment and follow-up. Among the recognized species, two are of medical importance -Echinococcus granulosus and Echinococcus multilocularis - causing cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively. For CE, consensus has been obtained on an image-based, stage-specific approach, which is helpful for choosing one of the following options: (1) percutaneous treatment, (2) surgery, (3) anti-infective drug treatment or (4) watch and wait. Clinical decision-making depends also on setting-specific aspects. The usage of an imaging-based classification system is highly recommended. For AE, early diagnosis and radical (tumour-like) surgery followed by anti-infective prophylaxis with albendazole remains one of the key elements. However, most patients with AE are diagnosed at a later stage, when radical surgery (distance of larval to liver tissue of >2cm) cannot be achieved. The backbone of AE treatment remains the continuous medical treatment with albendazole, and if necessary, individualized interventional measures. With this approach, the prognosis can be improved for the majority of patients with AE. The consensus of experts under the aegis of the WHO-IWGE will help promote studies that provide missing evidence to be included in the next update. Copyright 2009 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                qhmccdp@163.com
                3248088030@qq.com
                Journal
                Parasit Vectors
                Parasit Vectors
                Parasites & Vectors
                BioMed Central (London )
                1756-3305
                2 December 2021
                2 December 2021
                2021
                : 14
                : 593
                Affiliations
                [1 ]GRID grid.443385.d, ISNI 0000 0004 1798 9548, Department of Human Parasitology, , Guilin Medical University, ; Guilin, 541199 Guangxi Zhuang China
                [2 ]GRID grid.262246.6, ISNI 0000 0004 1765 430X, Department of Immunology, Faculty of Medicine, , Qinghai University, ; Xining, 810001 Qinghai China
                [3 ]GRID grid.459333.b, The Key Echinococcosis Laboratory, , Qinghai University Affiliated Hospital, ; Xining, 810001 Qinghai China
                [4 ]GRID grid.459333.b, Department of Hepatobiliary and Pancreatic Surgery, , Qinghai University Affiliated Hospital, ; Xining, 810001 Qinghai China
                [5 ]GRID grid.430813.d, Laboratories Department, Faculty of Medical Sciences, , Taiz University, Turba Branch, ; 70270 Taiz, Yemen
                Author information
                http://orcid.org/0000-0002-1973-8879
                Article
                5037
                10.1186/s13071-021-05037-1
                8641223
                34857049
                52028be7-da0f-4788-bf19-141ecc531fe6
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 12 March 2021
                : 24 September 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100012547, Natural Science Foundation of Guangxi Zhuang Autonomous Region;
                Award ID: 2020GXNSFAA297216
                Award Recipient :
                Funded by: qinghai department of science and technology (cn)
                Award ID: 2020-ZJ-Y01
                Categories
                Research
                Custom metadata
                © The Author(s) 2021

                Parasitology
                echinococcus multilocularis,hepatic stellate cell,hepatic fibrosis,protoscoleces,collagen-i,alpha-smooth muscle actin,osteopontin

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