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Biomedicines
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Novel Insights into Liver Metabolism
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Novel Insights into Liver Metabolism

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Endocrinology and Metabolism Research".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 3919

Special Issue Editors

Dr. Agata Michalak

E-Mail Website
Guest Editor
Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, 20-954 Lublin, Poland
Interests: liver; alcohol-related liver disease; liver steatosis; liver fibrosis; autoimmune liver diseases; inflammatory bowel disease
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Halina Cichoż-Lach

E-Mail Website
Guest Editor
Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, 20-954 Lublin, Poland
Interests: chronic liver diseases; liver cirrhosis; alcohol-related liver disease; cholestasis; inflammatory bowel disease; novel markers of liver fibrosis; liver steatosis

Special Issue Information

Dear Colleagues,

Thousands of diverse chemical reactions take place in the liver. Its metabolic role is directly related to the biological processes concerning proteins, lipids, carbohydrates, drugs and toxins. Each reaction might be interrupted by molecular or functional disturbances, which will finally result in the development of hepatic failure. Thus, there is an urgent need to explore new diagnostic and therapeutic strategies that can become more specific and more effective to improve liver metabolism. This Special Issue will gather publications exploring the phenomenon of liver metabolism from various perspectives. Both original articles and  reviews are welcomed.

Potential topics include but are not limited to the following:

  • New biomarkers of acute liver failure, liver steatosis and fibrosis;
  • Novel parameters of hepatic decompensation in the course of chronic liver disorders;
  • A comparison between imaging studies and advanced laboratory tests in the evaluation of the liver function;
  • New agents and medical approaches possibly used in cirrhotic patients to improve the function/metabolism of the liver;
  • Relationships between liver metabolism and other systemic failures due to biochemical processes;
  • The role of miRNAs and other biological particles implied in the natural history of liver failure;
  • Possible novel pathways in the diagnosis and treatment of autoimmune liver diseases;
  • Relationships between impaired liver metabolism and the risk of its cancer;
  • In vitro and in vivo models for studying oxidative stress in the liver;
  • The involvement of microbiota in the impaired liver metabolism.

Dr. Agata Michalak
Prof. Dr. Halina Cichoż-Lach
Guest Editors

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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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
  • metabolism
  • oxidative stress
  • mi-RNAs
  • cirrhosis
  • alcohol-related liver disease
  • autoimmune liver disorders
  • hepatocellular cancer
  • liver steatosis
  • microbiota
  • diagnostic markers

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Published Papers (3 papers)

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Research

12 pages, 1781 KiB  
Article
Improved Translational Relevance of In Vitro Fibrosis Models by Integrating IOX2-Mediated Hypoxia-Mimicking Pathways
by Manuel A. González Hernández, Jennifer Venhorst, Lars Verschuren, Karin Toet, Martien P. M. Caspers, Martine C. Morrison, Beatrice Coornaert, Gerard J. P. van Westen and Roeland Hanemaaijer
Biomedicines 2025, 13(6), 1448; https://doi.org/10.3390/biomedicines13061448 - 12 Jun 2025
Viewed by 372
Abstract
Background/Objectives: Preclinical models of liver fibrosis only partially mimic human disease processes. Particularly, traditional transforming growth factor beta 1 (TGFβ1)-induced hepatic stellate cell (HSC) models lack relevant processes, including hypoxia-induced pathways. Here, the ability of a hypoxia-mimicking compound (IOX2) to more accurately [...] Read more.
Background/Objectives: Preclinical models of liver fibrosis only partially mimic human disease processes. Particularly, traditional transforming growth factor beta 1 (TGFβ1)-induced hepatic stellate cell (HSC) models lack relevant processes, including hypoxia-induced pathways. Here, the ability of a hypoxia-mimicking compound (IOX2) to more accurately reflect the human fibrotic phenotype on a functional level was investigated. Methods: Human primary HSCs were stimulated (TGFβ1 +/− IOX2), and the cell viability and fibrotic phenotype were determined. The latter was assessed as protein levels of fibrosis markers—collagen, TIMP-1, and Fibronectin. Next-generation sequencing (NGS), differential expression analyses (DESeq2), and Ingenuity Pathway Analysis (IPA) were performed for mechanistic evaluation and biological annotation. Results: Stimulation with TGFβ1 + IOX2 significantly increased fibrotic marker levels. Also, fibrosis-related pathways were activated, and hypoxia-related genes and collagen modifications, such as crosslinking, increased dose-dependently. Comparative analysis with human fibrotic DEGs showed improved disease representation in the HSC model in the presence of IOX2. Conclusions: In conclusion, the HSC model better recapitulated liver fibrosis by IOX2 administration. Therefore, hypoxia-mimicking compounds hold promise for enhancing the translational value of in vitro fibrosis models, providing valuable insights in liver fibrosis pathogenesis and potential therapeutic strategies. Full article
(This article belongs to the Special Issue Novel Insights into Liver Metabolism)
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11 pages, 2958 KiB  
Article
Targeted Plasma Bile Acid Metabolomic Analysis in Metabolic Dysfunction-Associated Steatohepatitis and Alcoholic Hepatitis
by Yuta Hirata, Yasunaru Sakuma, Hideo Ogiso, Ryozo Nagai and Kenichi Aizawa
Biomedicines 2025, 13(1), 78; https://doi.org/10.3390/biomedicines13010078 - 31 Dec 2024
Cited by 1 | Viewed by 1268
Abstract
Background: Even though many metabolic liver diseases can now be diagnosed using blood tests and diagnostic imaging, early diagnosis remains difficult. Understanding mechanisms contributing to the progression from Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Alcoholic Hepatitis (AH) to cirrhosis is critical to reduce the [...] Read more.
Background: Even though many metabolic liver diseases can now be diagnosed using blood tests and diagnostic imaging, early diagnosis remains difficult. Understanding mechanisms contributing to the progression from Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Alcoholic Hepatitis (AH) to cirrhosis is critical to reduce the burden of end-stage liver disease. Monitoring individual bile acids has been proposed as a way to distinguish various liver disorders. Methods: This study explored bile acid profiles in patients with MASH and AH. Plasma samples from patients with MASH, AH, and a control group were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify bile acid concentrations. Targeted metabolomic analysis was performed to compare bile acid levels between the hepatitis and control groups. Results: Concentrations of ursodeoxycholic acid (UDCA), chenodeoxycholic acid (CDCA), taurocholic acid (TCA), tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), glycoursodeoxycholic acid (GUDCA), glycochenodeoxycholic acid (GCDCA), and glycocholic acid (GCA) were significantly elevated in the hepatitis group. Correlation analysis revealed strong positive relationships between the total and direct bilirubin levels and TUDCA and GCDCA. Aspartate aminotransferase (AST) showed strong positive correlations with TCDCA and GCDCA. Child–Pugh score, Fibrosis-4 index, and non-alcoholic fatty liver disease fibrosis score were positively correlated with GCA, whereas the aspartate aminotransferase-to-platelet ratio correlated with TCA, TCDCA, and GCA. The model for end-stage liver disease (MELD) score showed a strong positive correlation with GCDCA. Implications: GCDCA may serve as a predictive biomarker for liver damage, potentially enabling early diagnosis and targeted intervention in patients with MASH and AH. Full article
(This article belongs to the Special Issue Novel Insights into Liver Metabolism)
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13 pages, 442 KiB  
Article
microRNAs and Other Serological Markers of Liver Fibrosis in Patients with Alcohol-Related Liver Cirrhosis
by Agata Michalak, Małgorzata Guz, Joanna Kozicka, Marek Cybulski, Witold Jeleniewicz, Karolina Szczygieł, Ewa Tywanek and Halina Cichoż-Lach
Biomedicines 2024, 12(9), 2108; https://doi.org/10.3390/biomedicines12092108 - 16 Sep 2024
Cited by 2 | Viewed by 1478
Abstract
Background: It is essential to identify novel non-invasive markers of liver fibrosis for clinical and scientific purposes. Thus, the goal of our survey was to assess the serological expression of selected microRNAs (miRNAs) in patients with alcohol-related liver cirrhosis (ALC) and to [...] Read more.
Background: It is essential to identify novel non-invasive markers of liver fibrosis for clinical and scientific purposes. Thus, the goal of our survey was to assess the serological expression of selected microRNAs (miRNAs) in patients with alcohol-related liver cirrhosis (ALC) and to correlate them with other existing markers. Methods: Two hundred and thirty-nine persons were enrolled in the study: one hundred and thirty-nine with ALC and one hundred healthy controls. Serological expression of miR-126-3p, miR-197-3p and miR-1-3p was evaluated in all participants. Direct markers of liver fibrosis (PICP, PIIINP, PDGF-AB, TGF-α and laminin) together with indirect indices (AAR, APRI, FIB-4 and GPR) were also assessed. The additional evaluation concerned hematological parameters: MPV, PDW, PCT, RDW, MPR, RPR NLR, PLR and RLR. Results: The expression of miR-197-3p was lower in ALC compared to controls (p < 0.0001). miR-126-3p correlated negatively with AST (p < 0.05) and positively with miR-197-3p (p < 0.001). miR-197-3p correlated with direct markers of liver fibrosis—positively with PDGF-AB (p < 0.005) and negatively with TGF-α (p < 0.01). Significant negative relationships were noticed between miR-1-3p and the number of neutrophils (p < 0.05), TGF-α (p < 0.05) and laminin (p < 0.05). Conclusions: The achieved results and observed correlations prove the potential involvement of the examined miRNAs in the process of liver fibrosis, giving a novel insight into the diagnostics of liver cirrhosis. Full article
(This article belongs to the Special Issue Novel Insights into Liver Metabolism)
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