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Cells
Special Issues
Liver Diseases: From Molecular Mechanism to Therapeutic Aspect
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Liver Diseases: From Molecular Mechanism to Therapeutic Aspect

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Tissues and Organs".

Deadline for manuscript submissions: closed (15 March 2023) | Viewed by 15141

Special Issue Editor

Dr. Fabrizio Bronte

E-Mail Website
Guest Editor
Ospedali Riuniti Villa Sofia-V. Cervello, Università degli Studi di Palermo, Palermo, Italy
Interests: liver; hepatitis; gastroenterology; autoimmune; hepatocellular carcinoma Interests: cancer; Hepatitis B and C; autoimmune hepatitis; hepatocellular carcinoma; pancreatitis; cholangitis

Special Issue Information

Dear Colleagues,

In recent years, many studies have made it possible to understand the molecular mechanisms underlying viral, autoimmune, and neoplastic pathologies of the liver and therefore to be able to develop targeted therapies. This has made it possible to modify the natural history of liver diseases by reducing their complications and increasing survival. 

In this Special Issue, we want to focus on the molecular mechanisms that underlie the main hepatic diseases from HCV, HBV, autoimmune diseases (AH) such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), and their complications (cirrhosis, portal hypertension, hepatorenal, hepato-pulmonary and hepato-cardiac syndrome, acute on chronic liver failure, spontaneous bacterial peritonitis), as well as the mechanisms that underlie hepatocarcinoma and cholangiocarcinoma by evaluating their therapeutic implications. 

Dr. Fabrizio Bronte
Guest Editor

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Keywords

  • liver disease
  • molecular mechanism
  • therapeutic aspect
  • hepatitis
  • HBV
  • HCV
  • autoimmune hepatitis
  • primary biliary cholangitis (PBC)
  • primary sclerosing cholangitis (PSC)
  • cirrhosis
  • portal hypertension
  • hepatorenal syndrome
  • hepato-pulmonary syndrome
  • hepato-cardiac syndrome
  • acute-on-chronic liver failure
  • spontaneous bacterial peritonitis (SBP)

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Published Papers (5 papers)

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Research

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19 pages, 9482 KiB  
Article
Fermented Soybean Paste Attenuates Biogenic Amine-Induced Liver Damage in Obese Mice
by Ju-Hwan Yang, Eun-Hye Byeon, Dawon Kang, Seong-Geun Hong, Jinsung Yang, Deok-Ryong Kim, Seung-Pil Yun, Sang-Won Park, Hyun-Joon Kim, Jae-Won Huh, So-Yong Kim, Young-Wan Kim and Dong-Kun Lee
Cells 2023, 12(5), 822; https://doi.org/10.3390/cells12050822 - 6 Mar 2023
Cited by 8 | Viewed by 2695
Abstract
Biogenic amines are cellular components produced by the decarboxylation of amino acids; however, excessive biogenic amine production causes adverse health problems. The relationship between hepatic damage and biogenic amine levels in nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, mice were [...] Read more.
Biogenic amines are cellular components produced by the decarboxylation of amino acids; however, excessive biogenic amine production causes adverse health problems. The relationship between hepatic damage and biogenic amine levels in nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, mice were fed a high-fat diet (HFD) for 10 weeks to induce obesity, presenting early-stage of NAFLD. We administered histamine (20 mg/kg) + tyramine (100 mg/kg) via oral gavage for 6 days to mice with HFD-induced early-stage NAFLD. The results showed that combined histamine and tyramine administration increased cleaved PARP-1 and IL-1β in the liver, as well as MAO-A, total MAO, CRP, and AST/ALT levels. In contrast, the survival rate decreased in HFD-induced NAFLD mice. Treatment with manufactured or traditional fermented soybean paste decreased biogenically elevated hepatic cleaved PARP-1 and IL-1β expression and blood plasma MAO-A, CRP, and AST/ALT levels in HFD-induced NAFLD mice. Additionally, the biogenic amine-induced reduction in survival rate was alleviated by fermented soybean paste in HFD-induced NAFLD mice. These results show that biogenic amine-induced liver damage can be exacerbated by obesity and may adversely affect life conservation. However, fermented soybean paste can reduce biogenic amine-induced liver damage in NAFLD mice. These results suggest a beneficial effect of fermented soybean paste on biogenic amine-induced liver damage and provide a new research perspective on the relationship between biogenic amines and obesity. Full article
(This article belongs to the Special Issue Liver Diseases: From Molecular Mechanism to Therapeutic Aspect)
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15 pages, 7736 KiB  
Article
Immunomodulation of Natural Killer Cell Function by Ribavirin Involves TYK-2 Activation and Subsequent Increased IFN-γ Secretion in the Context of In Vitro Hepatitis E Virus Infection
by Paul Kupke, Akinbami Adenugba, Mathias Schemmerer, Florian Bitterer, Hans J. Schlitt, Edward K. Geissler, Jürgen J. Wenzel and Jens M. Werner
Cells 2023, 12(3), 453; https://doi.org/10.3390/cells12030453 - 31 Jan 2023
Cited by 5 | Viewed by 2362
Abstract
Hepatitis E virus (HEV) is a major cause of acute hepatitis globally. Chronic and fulminant courses are observed especially in immunocompromised transplant recipients since administration of ribavirin (RBV) does not always lead to a sustained virologic response. By in vitro stimulation of NK [...] Read more.
Hepatitis E virus (HEV) is a major cause of acute hepatitis globally. Chronic and fulminant courses are observed especially in immunocompromised transplant recipients since administration of ribavirin (RBV) does not always lead to a sustained virologic response. By in vitro stimulation of NK cells through hepatoma cell lines inoculated with a full-length HEV and treatment with RBV, we analyzed the viral replication and cell response to further elucidate the mechanism of action of RBV on immune cells, especially NK cells, in the context of HEV infection. Co-culture of HEV-infected hepatoma cells with PBMCs and treatment with RBV both resulted in a decrease in viral replication, which in combination showed an additive effect. An analysis of NK cell functions after stimulation revealed evidence of reduced cytotoxicity by decreased TRAIL and CD107a degranulation. Simultaneously, IFN-ɣ production was significantly increased through the IL-12R pathway. Although there was no direct effect on the IL-12R subunits, downstream events starting with TYK-2 and subsequently pSTAT4 were upregulated. In conclusion, we showed that RBV has an immunomodulatory effect on the IL-12R pathway of NK cells via TYK-2. This subsequently leads to an enhanced IFN-ɣ response and thus, to an additive antiviral effect in the context of an in vitro HEV infection. Full article
(This article belongs to the Special Issue Liver Diseases: From Molecular Mechanism to Therapeutic Aspect)
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13 pages, 869 KiB  
Article
Multiplexed Digital Spatial Protein Profiling Reveals Distinct Phenotypes of Mononuclear Phagocytes in Livers with Advanced Fibrosis
by Jaejun Lee, Chang Min Kim, Jung Hoon Cha, Jin Young Park, Yun Suk Yu, Hee Jung Wang, Pil Soo Sung, Eun Sun Jung and Si Hyun Bae
Cells 2022, 11(21), 3387; https://doi.org/10.3390/cells11213387 - 26 Oct 2022
Cited by 9 | Viewed by 3929
Abstract
Background and Aims: Intrahepatic mononuclear phagocytes (MPs) are critical for the initiation and progression of liver fibrosis. In this study, using multiplexed digital spatial protein profiling, we aimed to derive a unique protein signature predicting advanced liver fibrosis. Methods: Snap-frozen liver tissues from [...] Read more.
Background and Aims: Intrahepatic mononuclear phagocytes (MPs) are critical for the initiation and progression of liver fibrosis. In this study, using multiplexed digital spatial protein profiling, we aimed to derive a unique protein signature predicting advanced liver fibrosis. Methods: Snap-frozen liver tissues from various chronic liver diseases were subjected to spatially defined protein-based multiplexed profiling (Nanostring GeoMXTM). A single-cell RNA sequencing analysis was performed using Gene Expression Omnibus (GEO) datasets from normal and cirrhotic livers. Results: Sixty-four portal regions of interest (ROIs) were selected for the spatial profiling. Using the results from the CD68+ area, a highly sensitive and specific immune-related protein signature (CD68, HLA-DR, OX40L, phospho-c-RAF, STING, and TIM3) was developed to predict advanced (F3 and F4) fibrosis. A combined analysis of single-cell RNA sequencing data from GEO datasets (GSE136103) and spatially-defined, protein-based multiplexed profiling revealed that most proteins upregulated in F0–F2 livers in portal CD68+ cells were specifically marked in tissue monocytes, whereas proteins upregulated in F3 and F4 livers were marked in scar-associated macrophages (SAMacs) and tissue monocytes. Internal validation using mRNA expression data with the same cohort tissues demonstrated that mRNA levels for TREM2, CD9, and CD68 are significantly higher in livers with advanced fibrosis. Conclusions: In patients with advanced liver fibrosis, portal MPs comprise of heterogeneous populations composed of SAMacs, Kupffer cells, and tissue monocytes. This is the first study that used spatially defined protein-based multiplexed profiling, and we have demonstrated the critical difference in the phenotypes of portal MPs between livers with early- or late-stage fibrosis. Full article
(This article belongs to the Special Issue Liver Diseases: From Molecular Mechanism to Therapeutic Aspect)
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Review

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19 pages, 1328 KiB  
Review
The Role of Non-Coding RNAs in Liver Disease, Injury, and Regeneration
by Melissa M. Rowe and Klaus H. Kaestner
Cells 2023, 12(3), 359; https://doi.org/10.3390/cells12030359 - 18 Jan 2023
Cited by 7 | Viewed by 2487
Abstract
Non-coding RNAs (ncRNAs) have diverse functions in health and pathology in many tissues, including the liver. This review highlights important microRNAs (miRs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in liver disease and regeneration. Greater attention is given to more prevalent and [...] Read more.
Non-coding RNAs (ncRNAs) have diverse functions in health and pathology in many tissues, including the liver. This review highlights important microRNAs (miRs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in liver disease and regeneration. Greater attention is given to more prevalent and well characterized RNAs, including: miR-122, miR-21, the let-7 family of miRs, miR-451a, miR-144, and MALAT1. Full article
(This article belongs to the Special Issue Liver Diseases: From Molecular Mechanism to Therapeutic Aspect)
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24 pages, 1437 KiB  
Review
Immunological Tolerance in Liver Transplant Recipients: Putative Involvement of Neuroendocrine-Immune Interactions
by Jaciara Fernanda Gomes Gama, Liana Monteiro da Fonseca Cardoso, Rodrigo da Cunha Bisaggio, Jussara Lagrota-Candido, Andrea Henriques-Pons and Luiz A. Alves
Cells 2022, 11(15), 2327; https://doi.org/10.3390/cells11152327 - 29 Jul 2022
Cited by 2 | Viewed by 2983
Abstract
The transplantation world changed significantly following the introduction of immunosuppressants, with millions of people saved. Several physicians have noted that liver recipients that do not take their medication for different reasons became tolerant regarding kidney, heart, and lung transplantations at higher frequencies. Most [...] Read more.
The transplantation world changed significantly following the introduction of immunosuppressants, with millions of people saved. Several physicians have noted that liver recipients that do not take their medication for different reasons became tolerant regarding kidney, heart, and lung transplantations at higher frequencies. Most studies have attempted to explain this phenomenon through unique immunological mechanisms and the fact that the hepatic environment is continuously exposed to high levels of pathogen-associated molecular patterns (PAMPs) or non-pathogenic microorganism-associated molecular patterns (MAMPs) from commensal flora. These components are highly inflammatory in the periphery but tolerated in the liver as part of the normal components that arrive via the hepatic portal vein. These immunological mechanisms are discussed herein based on current evidence, although we hypothesize the participation of neuroendocrine-immune pathways, which have played a relevant role in autoimmune diseases. Cells found in the liver present receptors for several cytokines, hormones, peptides, and neurotransmitters that would allow for system crosstalk. Furthermore, the liver is innervated by the autonomic system and may, thus, be influenced by the parasympathetic and sympathetic systems. This review therefore seeks to discuss classical immunological hepatic tolerance mechanisms and hypothesizes the possible participation of the neuroendocrine-immune system based on the current literature. Full article
(This article belongs to the Special Issue Liver Diseases: From Molecular Mechanism to Therapeutic Aspect)
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