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Molecular Advances and Insights into Liver Diseases
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Molecular Advances and Insights into Liver Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 September 2025 | Viewed by 5624

Special Issue Editor

Dr. Jacek Baj

E-Mail Website
Guest Editor
Department of Correct, Clinical, and Imaging Anatomy, Medical University of Lublin, 20-090 Lublin, Poland
Interests: fatty liver disease; liver diseases; cholecystectomy; micronutrients; macronutrients
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The increasing incidence rate of various liver diseases is induced by numerous factors and primarily include improper dietary habits, excessive alcohol consumption, the components of the metabolic syndrome such as obesity, or risky behaviors that might result in hepatitis. Although the abovementioned factors are commonly known to be associated with liver dysfunctions, current studies are mostly focused on the molecular mechanisms of liver diseases. Liver diseases might occur due to alcohol consumption, viral infection, or medicine. Further, the occurrence of various hepatic dysfunctions can be a result of genetic (Wilson’s disease, hemochromatosis) or autoimmune (cirrhosis, hepatitis) disorders. The abovementioned conditions could be better understood only by focusing on the pathomechanisms occurring on the molecular level that ultimately induce changes leading to these diseases. A better understanding of such processes will result in improvements in both diagnosis and treatment strategies for the chosen liver diseases.

The major objective of this Special Issue is to provide a space for discussion to clinicians and researchers whose studies are focused on the molecular aspects of the chosen liver diseases. This Special Issue aims to also provide a space for the results of novel studies that were performed to improve the diagnosis of liver diseases and, at the same time, provide novel therapeutic options for patients and expand the knowledge on liver disease pathophysiology. Therefore, we are elated to invite you to submit various types of papers including original papers and narrative and systematic reviews to this Special Issue.

Dr. Jacek Baj
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • liver
  • hepatocellular carcinoma
  • cancer
  • hepatitis
  • cirrhosis
  • encephalopathy
  • non-alcoholic fatty liver disease
  • autoimmune diseases
  • Wilson’s disease
  • fatty liver disease

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Published Papers (4 papers)

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Research

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14 pages, 7475 KiB  
Article
Therapeutic Effects of DNase I on Peripheral and Local Markers of Liver Injury and Neutrophil Extracellular Traps in a Model of Alcohol-Related Liver Disease
by Paulína Belvončíková, Andrej Feješ, Barbora Gromová, Ľubica Janovičová, Anna Farkašová, Pavel Babál and Roman Gardlík
Int. J. Mol. Sci. 2025, 26(5), 1893; https://doi.org/10.3390/ijms26051893 - 22 Feb 2025
Viewed by 840
Abstract
Alcohol-related liver disease (ALD) is a leading cause of chronic liver conditions globally. Chronic alcohol consumption induces liver damage through various mechanisms, including neutrophil extracellular trap (NET) formation. Extracellular DNA (ecDNA), released from damaged hepatocytes and NETotic neutrophils, has emerged as a potential [...] Read more.
Alcohol-related liver disease (ALD) is a leading cause of chronic liver conditions globally. Chronic alcohol consumption induces liver damage through various mechanisms, including neutrophil extracellular trap (NET) formation. Extracellular DNA (ecDNA), released from damaged hepatocytes and NETotic neutrophils, has emerged as a potential biomarker and contributor to liver disease pathology. Enzyme DNases could be an effective therapy for the denaturation of immunogenic ecDNA. This study investigated the circulating ecDNA and NET markers in ALD and therapeutic effect of DNase I in a murine model of ALD. Female C57BL/6J mice were fed a control diet (n = 13) or Lieber–DeCarli ethanol diet for 10 days followed by a binge ethanol dose to mimic acute-on-chronic alcoholic liver injury. From day 5, mice fed ethanol were randomized into an ethanol diet group (n = 17) and ethanol + DNase group (n = 5), which received additional DNase I treatment every 12 h. Liver damage markers were analyzed. Circulating ecDNA and NETosis were measured by fluorometry and cytometry, respectively. DNase I activity was analyzed with single radial enzyme dispersion assay. The ethanol-fed mice exhibited increased mortality, neutrophil infiltration and structural damage in the liver. Total circulating ecDNA levels and NET markers did not differ between groups. DNase activity was higher in ethanol-fed mice compared to controls and additional daily administration of DNase prevented liver injury. These findings suggest that alcohol-induced liver injury modestly influences systemic NETosis and ecDNA levels. However, increased DNase activity can prevent disease progression and enhanced systemic degradation of ecDNA using DNase I. Full article
(This article belongs to the Special Issue Molecular Advances and Insights into Liver Diseases)
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16 pages, 5568 KiB  
Article
Genomic and Transcriptomic Profile of HNF1A-Mutated Liver Adenomas Highlights Molecular Signature and Potential Therapeutic Implications
by Angelo Corso Faini, Francesca Arruga, Michele Pinon, Valeria Bracciamà, Francesco Edoardo Vallone, Fiorenza Mioli, Monica Sorbini, Martina Migliorero, Alessandro Gambella, Damiano Carota, Isaac Giraudo, Paola Cassoni, Silvia Catalano, Renato Romagnoli, Antonio Amoroso, Pier Luigi Calvo, Tiziana Vaisitti and Silvia Deaglio
Int. J. Mol. Sci. 2024, 25(19), 10483; https://doi.org/10.3390/ijms251910483 - 29 Sep 2024
Viewed by 1470
Abstract
Hepatocellular adenomas (HAs) are tumors that can develop under different conditions, including in patients harboring a germline mutation in HNF1A. However, little is known about the pathogenesis of such disease. This work aims to better define what mechanisms lie under the development [...] Read more.
Hepatocellular adenomas (HAs) are tumors that can develop under different conditions, including in patients harboring a germline mutation in HNF1A. However, little is known about the pathogenesis of such disease. This work aims to better define what mechanisms lie under the development of this condition. Six HAs were sampled from the liver of a 17-year-old male affected by diabetes and multiple hepatic adenomatosis harboring the heterozygous pathogenic germline variant c.815G>A, p.(Arg272His) in HNF1A, which has a dominant negative effect. All HAs were molecularly characterized. Four of them were shown to harbor a second somatic HNF1A variant and one had a mutation in the ARID1A gene, while no additional somatic changes were found in the remaining HA and normal parenchyma. A transcriptomic profile of the same HA samples was also performed. HNF1A biallelic mutations were associated with the up-regulation of several pathways including the tricarboxylic acid cycle, the metabolism of fatty acids, and mTOR signaling while angiogenesis, endothelial and vascular proliferation, cell migration/adhesion, and immune response were down-regulated. Contrariwise, in the tumor harboring the ARID1A variant, angiogenesis was up-modulated while fatty acid metabolism was down-modulated. Histological analyses confirmed the molecular data. Independently of the second mutation, energetic processes and cholesterol metabolism were up-modulated, while the immune response was down-modulated. This work provides a complete molecular signature of HNF1A-associated HAs, analyzing the association between specific HNF1A variants and the development of HA while identifying potential new therapeutic targets for non-surgical treatment. Full article
(This article belongs to the Special Issue Molecular Advances and Insights into Liver Diseases)
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Review

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17 pages, 756 KiB  
Review
A Closer Look into Autoimmune Liver Diseases
by Branka Filipovic, Marija Marjanovic-Haljilji, Dragana Blagojevic, Milica Dragovic, Emilija Krsmanovic, Ana Matovic, Natasa Panic, Stanimir Kiurski, Zagor Zagorac, Miljan Milanovic, Olivera Markovic, Aleksandra Djokovic, Tijana Glisic, Sanja Dragasevic and Dusan Popovic
Int. J. Mol. Sci. 2025, 26(5), 1863; https://doi.org/10.3390/ijms26051863 - 21 Feb 2025
Viewed by 564
Abstract
Autoimmune liver diseases involve a heterogeneous group of chronic inflammatory disorders, including autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. Sometimes presented consistently as an overlapping syndrome, their pathogenesis is rather complex and has yet to be fully elucidated, despite extensive research [...] Read more.
Autoimmune liver diseases involve a heterogeneous group of chronic inflammatory disorders, including autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. Sometimes presented consistently as an overlapping syndrome, their pathogenesis is rather complex and has yet to be fully elucidated, despite extensive research efforts. This review article corroborates the molecular mechanisms of autoimmune liver diseases, as well as existing and potential therapeutic modalities. Full article
(This article belongs to the Special Issue Molecular Advances and Insights into Liver Diseases)
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37 pages, 1865 KiB  
Review
Supplementation of Micro- and Macronutrients—A Role of Nutritional Status in Non-Alcoholic Fatty Liver Disease
by Magdalena Tyczyńska, Gabriela Hunek, Martyna Szczasny, Adam Brachet, Jacek Januszewski, Alicja Forma, Piero Portincasa, Jolanta Flieger and Jacek Baj
Int. J. Mol. Sci. 2024, 25(9), 4916; https://doi.org/10.3390/ijms25094916 - 30 Apr 2024
Cited by 3 | Viewed by 2374
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a condition in which the pathological cumulation of fat with coexisting inflammation and damage of hepatic cells leads to progressive dysfunctions of the liver. Except for the commonly well-known major causes of NAFLD such as obesity, dyslipidemia, [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is a condition in which the pathological cumulation of fat with coexisting inflammation and damage of hepatic cells leads to progressive dysfunctions of the liver. Except for the commonly well-known major causes of NAFLD such as obesity, dyslipidemia, insulin resistance, or diabetes, an unbalanced diet and imbalanced nutritional status should also be taken into consideration. In this narrative review, we summarized the current knowledge regarding the micro- and macronutrient status of patients suffering from NAFLD considering various diets and supplementation of chosen supplements. We aimed to summarize the knowledge indicating which nutritional impairments may be associated with the onset and progression of NAFLD at the same time evaluating the potential therapy targets that could facilitate the healing process. Except for the above-mentioned objectives, one of the most important aspects of this review was to highlight the possible strategies for taking care of NAFLD patients taking into account the challenges and opportunities associated with the micronutrient status of the patients. The current research indicates that a supplementation of chosen vitamins (e.g., vitamin A, B complex, C, or D) as well as chosen elements such as zinc may alleviate the symptoms of NAFLD. However, there is still a lack of sufficient data regarding healthy ranges of dosages; thus, further research is of high importance in this matter. Full article
(This article belongs to the Special Issue Molecular Advances and Insights into Liver Diseases)
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