Volume 1, Issue 1 (September 2023) – 5 articles

Cover Story (View full-size image):
Classification of hepatic stellate cell (HSC) lines. Spontaneously or artificially immortalized HSC lines derived from mouse (yellow), rat (orange) and human (red) can be used in place of primary HSC in biomedical research. Most of them represent a transdifferentiated, highly proliferative, extracellular matrix-producing myofibroblastic phenotype. Some lines can be partly reverted by treatment with retinol, fatty acids, or the latency-associated peptide of TGF-β1 into a quiescent, vitamin A-storing phenotype. However, compared to primary cells, these infinite growing lines do not always accurately replicate the biology of primary HSC and can therefore not fully replace primary cells in hepatology research.

Editorial

16 November 2022

Perspective

07 March 2023

Pulsed Ultraviolet C as a Potential Treatment for COVID-19

Currently, low dose radiotherapy (LDRT) is being tested for treating life-threatening pneumonia in COVID-19 patients. Despite the debates over the clinical use of LDRT, some clinical trials have been completed, and most are still ongoing. Ultraviolet C (UVC) irradiation has been proven to be highly efficient in inactivating the coronaviruses, yet is considerably safer than LDRT. This makes UVC an excellent candidate for treating COVID-19 infection, especially in case of severe pneumonia as well as the post COVID-19 pulmonary fibrosis. However, the major challenge in using UVC is its delivery to the lungs, the target organ of COVID-19, due to its low penetrability through biological tissues. We propose to overcome this challenge (i) by using pulsed UVC technologies which dramatically increase the penetrability of UVC through matter, and (ii) by integrating the pulsed UVC technologies into a laser bronchoscope, thus allowing UVC irradiation to reach deeper into the lungs. Although the exact characteristics of such a treatment should yet to be experimentally defined, this approach might be much safer and not less efficient than LDRT.

Communication

21 March 2023

Established Hepatic Stellate Cell Lines in Hepatology Research

Hepatic stellate cells comprise a minor cell population in the liver that plays a key role in the pathogenesis of hepatic fibrosis. In chronic liver damage, they undergo a transition from a quiescent to a highly proliferative phenotype with the capacity to synthesize large quantities of extracellular matrix compounds such as collagens. Because of their pivotal role in liver disease pathogenesis, this hepatic cell population has become into the focus of liver research for many years. However, the isolation of these cells is time consuming and requires trained laboratory personnel. In addition, working with primary cells requires the following of ethical and legal standards that need to be approved by the respective authorities. Therefore, continuous growing hepatic stellate cells have become very popular in research laboratories because they are widely available, easy to handle, allow a continuous supply of materials, and further allow reduction of lab animal use in biomedical research. This communication provides some general information about immortalized hepatic stellate cell lines from mouse, rats and humans.

Article

19 May 2023

Comprehensive Landscape of Matrix Metalloproteinases in the Pathogenesis of Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic interstitial lung disease with unknown etiology. Matrix metalloproteinases (MMPs) are involved in fibrotic lung tissues, contributing to the initiation, progression, or resolution of chronic inflammatory disease. In present study, comprehensive changes of MMPs expressions were investigated in IPF by integrative analysis of single-cell transcriptome and bulk transcriptome data. 24 of MMPs were altered and the changes could significantly distinguish IPF from normal subjects and other lung diseases. Among them, MMP1, MMP7 and MMP19 were closely associated to lung functions, susceptibility and alveolar surface density. MMP1 and MMP7 as potential diagnostic indicators, MMP1 and MMP19 as prognostic markers in IPF could accurately predict disease progression. Devolution of MMPs at single-cell resolution, MMP19 was highly expressed in macrophages and markedly interfered with TNF signaling pathway which synchronizes fibrotic microenvironment. MMP19+ macrophages were significantly different from MMP19- macrophages in energy metabolism and immune function. The interaction of MMP19+ macrophages with hyperplastic AT2 was mediated by TNFSF12-TNFRSF12A, and further activated the TNFRSF12A receptor to affect cell glucose metabolism and mitochondrial function. In summary, MMPs has great application potential in the diagnosis, treatment, and prognosis of IPF.

Article

16 September 2023

Hepatic Lysosomal Enzyme Activity in Primary Biliary Cholangitis

Background: Lysosomal enzymes are implicated in autophagy and senescence. Hepatic lysosomal enzymes have not been studied in Primary Biliary Cholangitis (PBC). We therefore quantified the activities of lysosomal hydrolases in liver tissue of PBC patients. Methods: We compared enzyme activities in liver tissue from PBC patients with normal livers. Alcoholic liver disease and chronic viral disease served as disease controls. Results: Cathepsin B1 was significantly increased in early PBC (225.1 ± 18.06 mean ± SD, p < 0.0001) and reduced in later stages (66.5 ± 9.7, p = 0.004, controls 130.4 ± 14.9). It was reduced in patients with extensive fibrosis such as alcoholic and viral cirrhosis (p < 0.01 and p = 0.004 respectively) but not in chronic hepatitis. Cathepsin D was increased in early PBC (39 × 103 ± 4.8 SD, p < 0.0001) and less so in later stages (20.1 × 103 ± 3.9, p = 0.05, controls 14.1 × 103 ± 2.9). It was also increased in the presence of histological necro-inflammation in hepatitis. Treatment with ursodeoxycholate (UDCA) restored the abnormal values of enzymes in PBC. Lipid hydrolases mostly paralleled the changes of Cathepsins. Sequential measurements in serum of patients with acute alcoholic hepatitis showed that cathepsin B1 gradually decreases, and esterases increase as aminotransferases improve. Conclusions: The increased activity of lysosomal enzymes in early PBC are possibly on line with increased senescence. Treatment with UDCA restores abnormal values. In chronic liver disease, Cathepsin B1 reduction is associated with fibrosis and increased cathepsin D with necro-inflammation. Abnormalities of lysosomal enzymes indicate impairment of the final stage of autophagy in chronic liver disease.

TOP