CytoDyn Announces First Patient Enrolled in Phase II Trial for NASH

CytoDyn, Inc. announced the first patient first visit metric was met for the company’s Phase II clinical trial for the treatment of nonalcoholic steatohepatitis (NASH). The Phase II trial is designed to test whether leronlimab may inhibit the devastating liver fibrosis associated with NASH.
[CytoDyn, Inc.]
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Proline-Rich Tyrosine Kinase 2 Mediates Transforming Growth Factor-Beta-Induced Hepatic Stellate Cell Activation and Liver Fibrosis

The impact of ECM on TGF-β-mediated fibrogenic signaling pathway in hepatic stellate cells (HSCs) has remained obscure. Investigators studied the role of non-receptor tyrosine kinase focal adhesion kinase family members in TGF-β-signaling in HSCs.
[Scientific Reports]
Kim, J., Kang, W., Kang, S. H., Park, S. H., Kim, J. Y., Yang, S., Ha, S. Y., & Paik, Y.-H. (2020). Proline-rich tyrosine kinase 2 mediates transforming growth factor-beta-induced hepatic stellate cell activation and liver fibrosis. Scientific Reports, 10(1), 21018. https://doi.org/10.1038/s41598-020-78056-0 Cite
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Regulation of Peroxisome Proliferator-Activated Receptor-Gamma Activity Affects the Hepatic Stellate Cell Activation and the Progression of NASH via TGF-β1/Smad Signaling Pathway

PAR-γ agonist was found to inhibit primary HSCs and NIH/3T3 fibroblast activation and reverted their phenotypical morphology induced by TGF-β1 in vitro. In addition to this, PPAR-γ agonist decreased expression of TGF-β1 and phosphorylation of Smad2/3 while increased expression of Smad7.
[Journal of Physiology and Biochemistry]
Ni, X.-X., Li, X.-Y., Wang, Q., & Hua, J. (2020). Regulation of peroxisome proliferator-activated receptor-gamma activity affects the hepatic stellate cell activation and the progression of NASH via TGF-β1/Smad signaling pathway. Journal of Physiology and Biochemistry. https://doi.org/10.1007/s13105-020-00777-7 Cite
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AdipoR1/AdipoR2 Dual Agonist Recovers Nonalcoholic Steatohepatitis and Related Fibrosis via Endoplasmic Reticulum-Mitochondria Axis

Investigators synthesized and reported an adiponectin-based agonist JT003, which potently improved insulin resistance in high fat diet induced nonalcoholic steatohepatitis mice and suppresses hepatic stellate cells activation in CCl4 induced liver fibrosis.
[Nature Communications]
Xu, H., Zhao, Q., Song, N., Yan, Z., Lin, R., Wu, S., Jiang, L., Hong, S., Xie, J., Zhou, H., Wang, R., & Jiang, X. (2020). AdipoR1/AdipoR2 dual agonist recovers nonalcoholic steatohepatitis and related fibrosis via endoplasmic reticulum-mitochondria axis. Nature Communications, 11(1), 5807. https://doi.org/10.1038/s41467-020-19668-y Cite
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Endothelial p300 Promotes Portal Hypertension and Hepatic Fibrosis through CCL2-Mediated Angiocrine Signaling

In vitro, epigenome‐editing of carbon tetrachloride (CCL2) enhancer and promoter regions by CRISPR‐dCas9‐KRAB technology repressed TNFα‐induced CCL2 transcription via H3K9 tri‐methylation.
[Hepatology]
Gao, J., Wei, B., Liu, M., Hirsova, P., Sehrawat, T. S., Cao, S., Hu, X., Xue, F., Yaqoob, U., Kang, N., Cui, H., Pomerantz, W. C. K., Kostallari, E., & Shah, V. H. (n.d.). Endothelial p300 promotes portal hypertension and hepatic fibrosis through CCL2-mediated angiocrine signaling. Hepatology, n/a(n/a). https://doi.org/https://doi.org/10.1002/hep.31617 Cite
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Neutrophils in Liver Diseases: Pathogenesis and Therapeutic Targets

Currently, neutrophils, with their autocrine, paracrine, and immune modulation functions, have been shown to be involved in liver diseases, including viral hepatitis, nonalcoholic steatohepatitis, alcoholic liver disease, liver fibrosis, cirrhosis, liver failure, and liver cancer. Accordingly, this review summarizes the role of neutrophils in liver diseases.
[Cellular & Molecular Immunology]
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MicroRNAs as Regulators, Biomarkers and Therapeutic Targets in Liver Diseases

Investigators review recent advances regarding the regulation and function of miRNAs in liver diseases with a major focus on miRNAs that are specifically expressed or enriched in hepatocytes, neutrophils, hepatic stellate cells, immune cells and in circulation.
[Gut]
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β-Arrestin2 Deficiency Attenuates Oxidative Stress in Mouse Hepatic Fibrosis through Modulation of NOX4

Hepatic fibrosis is a disease characterized by excessive deposition of ECM in the liver. The authors investigated whether β-arrestin2 regulated oxidative stress in hepatic fibrosis.
[Acta Pharmacologica Sinica]
Du, J., Sun, J., Li, N., Li, X., Sun, W., & Wei, W. (2020). β-Arrestin2 deficiency attenuates oxidative stress in mouse hepatic fibrosis through modulation of NOX4. Acta Pharmacologica Sinica, 1–11. https://doi.org/10.1038/s41401-020-00545-9 Cite
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Georgia State Start-Up Awarded NIH Grant To Develop Contrast Agent for Early Detection of Liver Disease

Inlighta Biosciences, LLC, a start-up company led by Jenny Yang, Regents’ Professor of Chemistry at Georgia State University, has been awarded a National Institute of Health grant to accelerate development of a magnetic resonance imaging contrast agent to detect liver fibrosis, formation of scar tissue in the liver caused by alcoholic and non-alcoholic fatty liver disease.
[Georgia State University]
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Nonalcoholic Steatohepatitis: The Role of Peroxisome Proliferator-Activated Receptors

The authors summarize and discuss the current literature on nonalcoholic fatty liver disease (NAFLD) as the liver manifestation of the systemic metabolic syndrome and focuses on the role of peroxisome proliferator-activated receptors in the pathomechanisms as well as in the potential targeting of disease.
[Nature Reviews Gastroenterology & Hepatology]
Francque, S., Szabo, G., Abdelmalek, M. F., Byrne, C. D., Cusi, K., Dufour, J.-F., Roden, M., Sacks, F., & Tacke, F. (2020). Nonalcoholic steatohepatitis: the role of peroxisome proliferator-activated receptors. Nature Reviews Gastroenterology & Hepatology, 1–16. https://doi.org/10.1038/s41575-020-00366-5 Cite
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Hepatic Stem Cell Numb Gene Is a Potential Target of Huang Qi Decoction Against Cholestatic Liver Fibrosis

Cholestatic liver fibrosis rats transplanted into rat bone marrow-derived mesenchymal stem cells with knocked down Numb gene were treated with Huang Qi Decoction.
[Scientific Reports]
Hepatic stem cell Numb gene is a potential target of Huang Qi Decoction against cholestatic liver fibrosis | Scientific Reports. (n.d.). Retrieved October 19, 2020, from https://www.nature.com/articles/s41598-020-74324-1 Cite
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