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Biomedicines
Special Issues
New Strategies and Therapeutic Targets Involved in Liver Fibrosis Management
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New Strategies and Therapeutic Targets Involved in Liver Fibrosis Management

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (15 April 2024) | Viewed by 6682

Special Issue Editors

Dr. Cornel Baltă

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Guest Editor
“Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Revolutiei Av., 310144 Arad, Romania
Interests: regenerative medicine; phytotherapy; liver fibrosis; drug delivery systems
Special Issues, Collections and Topics in MDPI journals
Dr. Oana-Maria Boldura

E-Mail Website
Guest Editor
Faculty of Veterinary Medicine, University of Life Sciences “King Mihai I” from Timișoara, Calea Aradului 119, 300645 Timișoara, Romania
Interests: molecular signaling; inflammation pathways; phytotherapy; liver fibrosis
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Anca Oana Hermenean

E-Mail Website
Guest Editor
Faculty of Medicine, Department of Histology, Vasile Goldis Western University of Arad, Arad, Romania
Interests: histochemistry; immunohistochemistry; microscopy; cell biology; antioxidant activity; phytomedicine; regenerative medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Developing new therapeutic strategies that lead to the good therapeutic management of liver fibrosis requires the co-optation and collaboration of specialists in various fields such as chemistry and biochemistry, pharmacy and phytopharmacy, molecular biology, and clinicians. The development of new molecules that can stop and reverse the fibrotic process by modulating various signaling pathways and extracellular matrix dynamics, as well as the discovery of new molecules that play a crucial role in the pathogenesis and evolution of this disease, can open new avenues for therapeutic approaches. Taking into account multifactorial causality and associated or causative morbidities, the development of these new molecules and therapeutic targets will lead to their integrated use in therapeutic strategies applied in the management of liver fibrosis with a direct effect on patients' quality of life.

The main objective of this Special Issue is to gather high-quality scientific papers in the field and to share the latest discoveries in the sector, thus leading to the progress and development of new therapeutic strategies with direct practical application for the benefit of patients. This volume aims to bring together high-quality scientific papers developed by researchers and leading specialists in the fields of chemistry, biochemistry, pharmacy, phytopharmacy, biology, molecular biology and medicine. High-quality scientific papers of real value will be published in this Special Issue in the prestigious international journal Biomedicines (IF: 4.757).

Original research and review articles addressing new strategies and therapeutic targets involved in managing liver fibrosis are welcome and appreciated.

Dr. Cornel Baltă
Dr. Oana-Maria Boldura
Prof. Dr. Anca Oana Hermenean
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 fibrosis
  • antifibrotic effect of flavonoids
  • antifibrotic stem cell therapy
  • miRNA regulation of liver fibrosis
  • mRNA regulation of liver fibrosis
  • organic compounds used in the prevention of liver fibrosis
  • molecular signaling and pathways involved in fibrogenesis

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Published Papers (3 papers)

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Research

15 pages, 2584 KiB  
Article
The Multicomponent Medicinal Product Hepar Compositum Reduces Hepatic Inflammation and Fibrosis in a Streptozotocin- and High-Fat Diet-Induced Model of Metabolic Dysfunction-Associated Steatotic Liver Disease/Metabolic Dysfunction-Associated Steatohepatitis
by Yvonne Burmeister, Kathrin Weyer, Achim Dörre and Bernd Seilheimer
Biomedicines 2023, 11(12), 3216; https://doi.org/10.3390/biomedicines11123216 - 4 Dec 2023
Cited by 1 | Viewed by 1985
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD)—formerly known as non-alcoholic fatty liver disease (NAFLD)—is the most common chronic liver disease worldwide. Since there is currently no approved pharmacotherapy for MASLD, there is an urgent unmet need for efficacious therapeutics for this disease. Hepar compositum [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD)—formerly known as non-alcoholic fatty liver disease (NAFLD)—is the most common chronic liver disease worldwide. Since there is currently no approved pharmacotherapy for MASLD, there is an urgent unmet need for efficacious therapeutics for this disease. Hepar compositum (HC-24) is a multicomponent medicinal product that consists of 24 natural ingredients. It has been shown to have anti-inflammatory properties in an obesity-associated MASLD mouse model, but its potential to reduce MASLD-associated fibrosis had not been explored before this study. Here, we investigated the hepatic anti-inflammatory and anti-fibrotic potential of HC-24 in a streptozotocin (STZ)- and high-fat diet (HFD)-induced model of MASLD. Mice received a single injection of low-dose STZ at 2 days of age, followed by HFD feeding from 4 to 9 weeks of age. Mice were treated every second day with HC-24 or daily with the positive control telmisartan from 6 to 9 weeks of age. A non-diseased control group was included as a healthy reference. An explorative small-scale pilot study demonstrated that HC-24 improved liver histology, resulting in a lower NAFLD activity score and reduced liver fibrosis. A subsequent full study confirmed these effects and showed that HC-24 reduced hepatic inflammation, specifically reducing T helper cell and neutrophil influx, and decreased hepatic fibrosis (with qualitatively reduced collagen type I and type III immunopositivity) in the absence of an effect on body and liver weight, blood glucose or liver steatosis. These results show that HC-24 has hepatoprotective, anti-inflammatory, and anti-fibrotic properties in an STZ- and HFD-induced model of MASLD/MASH, suggesting that this multicomponent medicine has therapeutic potential for MASLD patients. Full article
(This article belongs to the Special Issue New Strategies and Therapeutic Targets Involved in Liver Fibrosis Management)
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13 pages, 4962 KiB  
Article
Dynamics of Liver Macrophage Subsets in a Novel Mouse Model of Non-Alcoholic Steatohepatitis Using C57BL/6 Mice
by Nana Makiuchi, Shun Takano, Yuki Tada, Kaichi Kasai, Naoya Igarashi, Koudai Kani, Miyuna Kato, Kana Goto, Yudai Matsuura, Mayuko Ichimura-Shimizu, Yukihiro Furusawa, Koichi Tsuneyama and Yoshinori Nagai
Biomedicines 2023, 11(10), 2659; https://doi.org/10.3390/biomedicines11102659 - 28 Sep 2023
Cited by 3 | Viewed by 1505
Abstract
Macrophages are critical for the development of non-alcoholic steatohepatitis (NASH). Our previous findings in TSNO mouse livers showed that an iHFC (high-fat/cholesterol/cholate) diet induced liver fibrosis similar to human NASH and led to the accumulation of distinct subsets of macrophage: CD11c+/Ly6C [...] Read more.
Macrophages are critical for the development of non-alcoholic steatohepatitis (NASH). Our previous findings in TSNO mouse livers showed that an iHFC (high-fat/cholesterol/cholate) diet induced liver fibrosis similar to human NASH and led to the accumulation of distinct subsets of macrophage: CD11c+/Ly6C− and CD11c−/Ly6C+ cells. CD11c+/Ly6C− cells were associated with the promotion of advanced liver fibrosis in NASH. On the other hand, CD11c−/Ly6C+ cells exhibited an anti-inflammatory effect and were involved in tissue remodeling processes. This study aimed to elucidate whether an iHFC diet with reduced cholic acid (iHFC#2 diet) induces NASH in C57BL/6 mice and examine the macrophage subsets accumulating in the liver. Histological and quantitative real-time PCR analyses revealed that the iHFC#2 diet promoted inflammation and fibrosis indicative of NASH in the livers of C57BL/6 mice. Cell numbers of Kupffer cells decreased and recruited macrophages were accumulated in the livers of iHFC#2 diet-fed C57BL/6 mice. Notably, the iHFC#2 diet resulted in the accumulation of three macrophage subsets in the livers of C57BL/6 mice: CD11c+/Ly6C−, CD11c−/Ly6C+, and CD11c+/Ly6C+ cells. However, CD11c+/Ly6C+ cells were not distinct populations in the iHFC-fed TSNO mice. Thus, differences in cholic acid content and mouse strain affect the macrophage subsets that accumulate in the liver. Full article
(This article belongs to the Special Issue New Strategies and Therapeutic Targets Involved in Liver Fibrosis Management)
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17 pages, 8291 KiB  
Article
Phytochemical Profiling and Anti-Fibrotic Activities of the Gemmotherapy Bud Extract of Corylus avellana in a Model of Liver Fibrosis on Diabetic Mice
by Cornel Balta, Hildegard Herman, Alina Ciceu, Bianca Mladin, Marcel Rosu, Alciona Sasu, Victor Eduard Peteu, Sorina Nicoleta Voicu, Mihaela Balas, Mihaela Gherghiceanu, Anca Dinischiotu, Neli Kinga Olah and Anca Hermenean
Biomedicines 2023, 11(6), 1771; https://doi.org/10.3390/biomedicines11061771 - 20 Jun 2023
Cited by 1 | Viewed by 2110
Abstract
In this study, we aimed to explore the hepatoprotective effects of the gemmotherapy bud extract of Corylus avellana in a model of liver fibrosis on diabetic mice. An evaluation of total flavonoids and polyphenols contents and LC/MS analyses were performed. Experimental fibrosis was [...] Read more.
In this study, we aimed to explore the hepatoprotective effects of the gemmotherapy bud extract of Corylus avellana in a model of liver fibrosis on diabetic mice. An evaluation of total flavonoids and polyphenols contents and LC/MS analyses were performed. Experimental fibrosis was induced with CCl4 (2 mL/kg by i.p. injections twice a week for 7 weeks) in streptozotocin-induced diabetic mice. Our results showed a content of 6–7% flavonoids, while hyperoside and chlorogenic acids were highlighted in the bud extract. Toxic administration of CCl4 increased oxidative stress, mRNA expression of the transforming growth factor-β1 (TGF-β1) and Smad 2/3, and reduced Smad 7 expression. Furthermore, up-regulation of α-smooth muscle actin (α-SMA) revealed an activation of hepatic stellate cells (HSCs), while collagen I (Col I) up-regulation and matrix metalloproteinases (MMPs) unbalance led to an altered extracellular matrix enriched in collagen, confirmed as well by a trichrome stain and electron microscopy analysis. Treatment with gemmotherapy extract significantly restored the liver architecture and the antioxidant balance, and significantly decreased collagen deposits in the liver and improved the liver function. Our results suggest that Corylus avellana gemmotherapy extract may have anti-fibrotic effects and could be useful in the prevention and treatment of liver fibrosis. The hepatoprotective mechanism is based on HSC inhibition, a reduction in oxidative stress and liver damage, a downregulation of the TGF-β1/Smad signaling pathway and a MMPs/TIMP rebalance. Full article
(This article belongs to the Special Issue New Strategies and Therapeutic Targets Involved in Liver Fibrosis Management)
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