Feeding Diversified Protein Sources Exacerbates Hepatic Insulin Resistance via Increased Gut Microbial Branched-Chain Fatty Acids and mTORC1 Signaling in Obese Mice

Scientists showed that the branched-chain fatty acids, isobutyric and isovaleric acid, increased glucose production and activated mTORC1/S6K1 in hepatocytes.
[Nature Communications]
Choi, B. S.-Y., Daniel, N., Houde, V. P., Ouellette, A., Marcotte, B., Varin, T. V., Vors, C., Feutry, P., Ilkayeva, O., Ståhlman, M., St-Pierre, P., Bäckhed, F., Tremblay, A., White, P. J., & Marette, A. (2021). Feeding diversified protein sources exacerbates hepatic insulin resistance via increased gut microbial branched-chain fatty acids and mTORC1 signaling in obese mice. Nature Communications, 12(1), 3377. https://doi.org/10.1038/s41467-021-23782-w Cite
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Generation of Functional Liver Organoids on Combining Hepatocytes and Cholangiocytes with Hepatobiliary Connections Ex Vivo

Scientists reported the generation of a hepatobiliary tubular organoid using mouse hepatocyte progenitors and cholangiocytes.
[Nature Communications]
Tanimizu, N., Ichinohe, N., Sasaki, Y., Itoh, T., Sudo, R., Yamaguchi, T., Katsuda, T., Ninomiya, T., Tokino, T., Ochiya, T., Miyajima, A., & Mitaka, T. (2021). Generation of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo. Nature Communications, 12(1), 3390. https://doi.org/10.1038/s41467-021-23575-1 Cite
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WSX1 Act as a Tumor Suppressor in Hepatocellular Carcinoma by Downregulating Neoplastic PD-L1 Expression

Mechanistically, WSX1 transcriptionally downregulated an isoform of PI3K—PI3Kδ and thereby inactivated AKT, reducing AKT-induced GSK3β inhibition.
[Nature Communications]
Wu, M., Xia, X., Hu, J., Fowlkes, N. W., & Li, S. (2021). WSX1 act as a tumor suppressor in hepatocellular carcinoma by downregulating neoplastic PD-L1 expression. Nature Communications, 12(1), 3500. https://doi.org/10.1038/s41467-021-23864-9 Cite
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Characterization of a Commercially Available Line of iPSC Hepatocytes as Models of Hepatocyte Function and Toxicity for Regulatory Purposes

The authors assessed similarities and differences between commercially available iPSC hepatocytes and primary human hepatocytes in preliminary assays of drug metabolism, hepatotoxicity, and drug transport.
[Journal of Pharmacological and Toxicological Methods]
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ADAM10 and ADAM17 Regulate EGFR, C-Met and TNF RI Signalling in Liver Regeneration and Fibrosis

Investigators showed that while ablation of ADAM17 resulted in decreased shedding of TNF RI, ADAM10 deficiency led to increased levels of soluble TNF RI in serum.
[Scientific Reports]
Zbodakova, O., Chalupsky, K., Sarnova, L., Kasparek, P., Jirouskova, M., Gregor, M., & Sedlacek, R. (2021). ADAM10 and ADAM17 regulate EGFR, c-Met and TNF RI signalling in liver regeneration and fibrosis. Scientific Reports, 11(1), 11414. https://doi.org/10.1038/s41598-021-90716-3 Cite
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A Novel, Multitargeted Endogenous Metabolic Modulator Composition Impacts Metabolism, Inflammation, and Fibrosis in Nonalcoholic Steatohepatitis-Relevant Primary Human Cell Models

Researchers described a study of a novel EMM composition comprising five amino acids and an amino acid derivative (Leucine, Isoleucine, Valine, Arginine, Glutamine, and N-acetylcysteine [LIVRQNac]) and its systematic evaluation across multiple NASH-relevant primary human cell model systems, including hepatocytes, macrophages, and stellate cells.
[Scientific Reports]
Daou, N., Viader, A., Cokol, M., Nitzel, A., Chakravarthy, M. V., Afeyan, R., Tramontin, T., Marukian, S., & Hamill, M. J. (2021). A novel, multitargeted endogenous metabolic modulator composition impacts metabolism, inflammation, and fibrosis in nonalcoholic steatohepatitis-relevant primary human cell models. Scientific Reports, 11(1), 11861. https://doi.org/10.1038/s41598-021-88913-1 Cite
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The Microbiota in Cirrhosis and Its Role in Hepatic Decompensation

This review focuses on the role of microbiota in decompensation and strategies targeting microbiota to prevent acute decompensation.
[Journal of Hepatology]
Trebicka, J., Macnaughtan, J., Schnabl, B., Shawcross, D. L., & Bajaj, J. S. (2021). The microbiota in cirrhosis and its role in hepatic decompensation. Journal of Hepatology, 75, S67–S81. https://doi.org/10.1016/j.jhep.2020.11.013 Cite
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Liver Regeneration and Inflammation: From Fundamental Science to Clinical Applications

The authors describe the mechanisms of tissue repair following damage, highlighting the close relationship between inflammation and liver regeneration, and discuss how recent findings can help design novel therapeutic approaches.
[Nature Reviews Molecular Cell Biology]
Campana, L., Esser, H., Huch, M., & Forbes, S. (2021). Liver regeneration and inflammation: from fundamental science to clinical applications. Nature Reviews Molecular Cell Biology, 1–17. https://doi.org/10.1038/s41580-021-00373-7 Cite
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Induced Tissue-Specific Stem Cells (iTSCs): Their Generation and Possible Use in Regenerative Medicine

The authors provide a brief overview of iPSCs and discusses recent advances in the establishment of induced nduced tissue-specific stem cells and their possible applications in regenerative medicine.
[Pharmaceutics]
Pharmaceutics | Free Full-Text | Induced Tissue-Specific Stem Cells (iTSCs): Their Generation and Possible Use in Regenerative Medicine | HTML. (n.d.). Retrieved June 2, 2021, from https://www.mdpi.com/1999-4923/13/6/780/htm Cite
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Inhibition of Nuclear Factor (Erythroid-Derived 2)-like 2 Promotes Hepatic Progenitor Cell Activation and Differentiation

Researchers analyzed the oxidative damage in models of liver injury characterized by biliary epithelial cells/hepatic progenitor cells (HPCs) activation and defined the impact of redox balance perturbation on HPC fate. They then identified Nuclear factor (erythroid-derived 2)-like 2 as the main transcription factor involved in the activation of HPCs.
[NPJ Regenerative Medicine]
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The Zinc Finger Protein Miz1 Suppresses Liver Tumorigenesis by Restricting Hepatocyte-Driven Macrophage Activation and Inflammation

Researchers reported that the zinc finger transcription factor Miz1 restricted hepatocyte-driven inflammation to suppress hepatocellular carcinoma, independently of its transcriptional activity.
[Immunity]
Zhang, W., Zhangyuan, G., Wang, F., Jin, K., Shen, H., Zhang, L., Yuan, X., Wang, J., Zhang, H., Yu, W., Huang, R., Xu, X., Yin, Y., Zhong, G., Lin, A., & Sun, B. (2021). The zinc finger protein Miz1 suppresses liver tumorigenesis by restricting hepatocyte-driven macrophage activation and inflammation. Immunity, 0(0). https://doi.org/10.1016/j.immuni.2021.04.027 Cite
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