Article
Chemistry, Multidisciplinary
Ludi Zhang, Jian-Yun Ge, Yun-Wen Zheng, Zhen Sun, Chenhua Wang, Zhaoliang Peng, Baihua Wu, Mei Fang, Kinji Furuya, Xiaolong Ma, Yanjiao Shao, Nobuhiro Ohkohchi, Tatsuya Oda, Jianglin Fan, Guoyu Pan, Dali Li, Lijian Hui
Summary: Liver-humanized rats were generated using CRISPR/Cas9 technology, with an optimized liver injury preconditioning protocol leading to increased human hepatocyte repopulation in the rat livers. This model is preferred for pharmacological studies and human hepatocyte production, showcasing potential for pharmacokinetic profiling of human-specific metabolites and informative implications for hepatocyte transplantation in other large-sized species.
Article
Biochemistry & Molecular Biology
Maria Teresa Pagano, Katia Fecchi, Marina Pierdominici, Elena Ortona, Daniela Peruzzu
Summary: Silibinin exhibits immunosuppressive activity by inhibiting the maturation and activation of human dendritic cells, suggesting its potential application as an adjuvant therapy for autoimmune diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Annie S. P. Yang, Devanjali Dutta, Kai Kretzschmar, Delilah Hendriks, Jens Puschhof, Huili Hu, Kim E. Boonekamp, Youri van Waardenburg, Susana M. Chuva de Sousa Lopes, Geert-Jan van Gemert, Johannes H. W. de Wilt, Teun Bousema, Hans Clevers, Robert W. Sauerwein
Summary: Researchers have found that hepatocytes derived from human hepatocyte organoids (HepOrgs) can support the development of Plasmodium falciparum, and have identified the importance of the host factor scavenger receptor B1 (SRB1) in parasite development.
NATURE COMMUNICATIONS
(2023)
Review
Cell Biology
David A. A. Shafritz, Mo R. R. Ebrahimkhani, Michael Oertel
Summary: Progenitor cells isolated from the fetal liver have the potential to generate new healthy tissue mass. Transplanted fetal liver cells can repopulate the liver and differentiate into functional hepatic cells, leading to anti-fibrotic effects. This approach holds great potential for developing novel cell-based therapies for liver disease.
Article
Medicine, Research & Experimental
Wenqin Zhang, Minjie Luo, Yuexue Zhou, Jie Hu, Caiyan Li, Ke Liu, Meidong Liu, Yaxi Zhu, Huan Chen, Huali Zhang
Summary: The study demonstrates that the LXR agonist GW3965 improves survival in septic mice by reducing multi-organ injury and inflammatory cytokine levels, as well as decreasing MDSC abundance in spleen and enhancing bacteria clearance in tissues. GW3965 activates LXR beta and ABCA1 to induce apoptosis of spleen MDSCs, offering a potential approach to target sepsis-induced immunosuppression.
Article
Gastroenterology & Hepatology
Stephanie May, Miryam Mueller, Callum R. Livingstone, George L. Skalka, Peter J. Walsh, Colin Nixon, Ann Hedley, Robin Shaw, William Clark, Johan Vande Voorde, Leah Officer-Jones, Fiona Ballantyne, Ian R. Powley, Thomas M. Drake, Christos Kiourtis, Andrew Keith, Ana Sofia Rocha, Saverio Tardito, David Sumpton, John Le Quesne, Martin Bushell, Owen J. Sansom, Thomas G. Bird
Summary: By characterizing and comparing the Axin2CreERT2 model, conflicting results regarding the crucial subpopulations of hepatocytes involved in liver regeneration were reconciled. This study highlights the importance of detailed preclinical model characterization and the pitfalls that may arise from comparing across sexes and backgrounds of mice and the effects of genetic insertion into native loci.
JOURNAL OF HEPATOLOGY
(2023)
Article
Cell & Tissue Engineering
Yifan Wang, Qiang Zheng, Zhen Sun, Chenhua Wang, Jin Cen, Xinjie Zhang, Yan Jin, Baihua Wu, Tingting Yan, Ziyuan Wang, Qiuxia Gu, Xingyu Lv, Junjie Nan, Zhongyu Wu, Wenbin Sun, Guoyu Pan, Ludi Zhang, Lijian Hui, Xiujun Cai
Summary: Liver resection is the preferred treatment for primary liver cancers, but concerns about post-hepatectomy liver failure have limited the number of eligible patients. A bioartificial liver device using human-induced hepatocytes showed promising results in a PHLF model and in a small study of patients undergoing liver resection. These findings suggest that this treatment could potentially expand the population eligible for liver resection.
Article
Biochemistry & Molecular Biology
Miey Park, Anshul Sharma, Hana Baek, Jin-Young Han, Junho Yu, Hae-Jeung Lee
Summary: Lipophagy, a type of autophagy that breaks down lipid droplets, plays a crucial role in regulating lipid accumulation and free fatty acid levels. This study investigated the effects of Stevia rebaudiana Bertoni and stevioside on hepatic steatosis and autophagy. The results showed that they reduced body and liver weight, as well as serum triglyceride and cholesterol levels, while increasing the levels of fatty acid oxidase, PPAR alpha, and microtubule-associated protein light chain 3 B. Additionally, they enhanced the expression of Beclin 1, lysosomal associated membrane protein 1, and phosphorylated adenosine monophosphate-activated protein kinase. This study suggests that PPAR alpha-dependent lipophagy is involved in hepatic steatosis and that stevioside could be a potential therapeutic option.
Review
Immunology
Ning Wang, Yongling Lu, Jiang Zheng, Xin Liu
Summary: Prolonged immunosuppression is the main cause of late phase and long-term mortality in sepsis. Although murine models cannot consistently and stably recapitulate the immunopathology of human sepsis, their feasibility can be increased by minimizing inconsistency and increasing clinical relevance.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Marisa Carbonaro, Kehui Wang, Hui Huang, Davor Frleta, Aditi Patel, Alexander Pennington, Mathieu Desclaux, Sven Moller-Tank, Justin Grindley, Judith Altarejos, Jun Zhong, Greg Polites, William Poueymirou, Stephen Jaspers, Christos Kyratsous, Brian Zambrowicz, Andrew Murphy, John C. Lin, Lynn E. Macdonald, Christopher Daly, Mark Sleeman, Gavin Thurston, Zhe Li
Summary: Liver steatosis is a serious health issue without many treatment options due to lack of experimental models. Abnormal lipid accumulation in human hepatocytes transplanted into rodent models is associated with compromised IL-6-GP130 signaling caused by incompatibility between host rodent IL-6 and human IL-6R. Restoring hepatic IL-6-GP130 signaling reduces hepatosteatosis, and providing human Kupffer cells also corrects the abnormality. This study suggests the importance of the IL-6-GP130 pathway in regulating lipid accumulation and provides potential therapeutic options for human liver steatosis.
Article
Cell & Tissue Engineering
Gajendra W. Suryawanshi, Hubert Arokium, Sanggu Kim, Wannisa Khamaikawin, Samantha Lin, Saki Shimizu, Koollawat Chupradit, YooJin Lee, Yiming Xie, Xin Guan, Vasantika Suryawanshi, Angela P. Presson, Dong-Sung An, Irvin S. Y. Chen
Summary: This study utilizes humanized mice models and develops a new method to track the clonal dynamics of human HSPC in a mouse environment. The results show that human cell repopulation in mice is polyclonal and stabilizes more rapidly than previously observed in humans.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Gastroenterology & Hepatology
Adam M. Passman, Magnus J. Haughey, Emanuela Carlotti, Marc J. Williams, Bianca Cereser, Meng-Lay Lin, Shruthi Devkumar, Jonathan P. Gabriel, Enrico Gringeri, Umberto Cillo, Francesco Paolo Russo, Matthew Hoare, Joanne ChinAleong, Marnix Jansen, Nicholas A. Wright, Hermant M. Kocher, Weini Huang, Malcolm R. Alison, Stuart A. C. McDonald
Summary: The origin and expansion dynamics of hepatocyte clones in the normal human liver have been determined using lineage tracing, methylation sequence analysis, and next-generation sequencing. Clonal patches of hepatocytes commonly associate with portal tracts and can lineage-trace with cholangiocytes, indicating a common ancestor at this niche. The patterns of mitochondrial DNA variants reveal spatially restricted mutations and limited clonal mutations, indicating slow growth and quiescence of clonal patches.
JOURNAL OF HEPATOLOGY
(2023)
Article
Plant Sciences
Yuan-Yuan Hao, Wen-Wen Cui, Huai-Lin Gao, Ming-Ye Wang, Yan Liu, Cui-Ru Li, Yun-Long Hou, Zhen-Hua Jia
Summary: JLD, a traditional Chinese medicine formula used to treat T2DM, has shown anti-obesity effects. This study investigated its therapeutic effects on NAFL in a mouse model. Results demonstrated that JLD improved liver injury, decreased body weight, enhanced insulin sensitivity, and suppressed pyroptosis, suggesting its potential as a novel treatment for NAFLD.
PHARMACEUTICAL BIOLOGY
(2022)
Article
Cell Biology
Natalia N. Bezborodkina, Sergey V. Okovityi, Boris N. Kudryavtsev
Summary: The study indicated that liver cirrhosis caused by chronic hepatitis results in alterations in glycogen metabolism, leading to a significant increase in glycogen content in hepatocytes in both humans and rats. This increase may be attributed to a decrease in glycogenolysis due to reduced activity of G6Pase and GP.
Article
Engineering, Biomedical
Jennifer S. Liu, Liszt Y. C. Madruga, Yang Yuan, Matt J. Kipper, Salman R. Khetani
Summary: Due to differences in liver functions across species, in vitro human liver models are used for various purposes. However, the scaffold used for these models often fails to mimic the native liver ECM's complex composition and nanofibrous topography. This study develops novel methods to create decellularized porcine liver ECM (PLECM) and collagen I nanofibers without synthetic polymer blends, which significantly enhance and stabilize the functions of primary human hepatocytes (PHHs) for several weeks. This nanofiber platform can be used for screening compounds, modeling diseases, and understanding cell-ECM interactions in the human liver.
ADVANCED HEALTHCARE MATERIALS
(2023)
Review
Gastroenterology & Hepatology
Kirk J. Wangensteen, Kyong-Mi Chang
Article
Biochemistry & Molecular Biology
Gabriel Martinez-Galvez, Parnal Joshi, Iddo Friedberg, Armando Manduca, Stephen C. Ekker
Summary: Gene-editing experiments often result in error-prone DSB repair, with MMEJ offering more predictable outcomes. A comparison of three repair prediction algorithms found MENTHU to have the highest sensitivity in identifying homogeneous genotypes. The new algorithm MENdel, combining MENTHU and Lindel, showed the most predictive coverage in large datasets for gene editing applications.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Maira P. Almeida, Jordan M. Welker, Sahiba Siddiqui, Jon Luiken, Stephen C. Ekker, Karl J. Clark, Jeffrey J. Essner, Maura McGrail
Summary: In this study, we successfully targeted a 2A-Cre recombinase transgene into zebrafish proneural genes using CRISPR/Cas9 technology, resulting in transgenic lines expressing functional Cre recombinase. This approach provides a new method for generating cell type-specific zebrafish Cre drivers that mimic the spatial and temporal restricted expression of endogenous genes.
SCIENTIFIC REPORTS
(2021)
Review
Oncology
Emanuela Ricciotti, Kirk J. Wangensteen, Garret A. FitzGerald
Summary: Aspirin shows promise as a preventative agent for cancer, particularly in individuals at high risk of colorectal cancer due to Lynch syndrome and in reducing the risk of sporadic colorectal cancer. Additionally, it has been shown to have a beneficial effect as a chemopreventive or adjuvant therapeutic agent in hepatocellular carcinoma (HCC).
Article
Multidisciplinary Sciences
Krishanu Saha, Erik J. Sontheimer, P. J. Brooks, Melinda R. Dwinell, Charles A. Gersbach, David R. Liu, Stephen A. Murray, Shengdar Q. Tsai, Ross C. Wilson, Daniel G. Anderson, Aravind Asokan, Jillian F. Banfield, Krystof S. Bankiewicz, Gang Bao, Jeff W. M. Bulte, Nenad Bursac, Jarryd M. Campbell, Daniel F. Carlson, Elliot L. Chaikof, Zheng-Yi Chen, R. Holland Cheng, Karl J. Clark, David T. Curiel, James E. Dahlman, Benjamin E. Deverman, Mary E. Dickinson, Jennifer A. Doudna, Stephen C. Ekker, Marina E. Emborg, Guoping Feng, Benjamin S. Freedman, David M. Gamm, Guangping Gao, Ionita C. Ghiran, Peter M. Glazer, Shaoqin Gong, Jason D. Heaney, Jon D. Hennebold, John T. Hinson, Anastasia Khvorova, Samira Kiani, William R. Lagor, Kit S. Lam, Kam W. Leong, Jon E. Levine, Jennifer A. Lewis, Cathleen M. Lutz, Danith H. Ly, Samantha Maragh, Paul B. McCray, Todd C. McDevitt, Oleg Mirochnitchenko, Ryuji Morizane, Niren Murthy, Randall S. Prather, John A. Ronald, Subhojit Roy, Sushmita Roy, Venkata Sabbisetti, W. Mark Saltzman, Philip J. Santangelo, David J. Segal, Mary Shimoyama, Melissa C. Skala, Alice F. Tarantal, John C. Tilton, George A. Truskey, Moriel Vandsburger, Jonathan K. Watts, Kevin D. Wells, Scot A. Wolfe, Qiaobing Xu, Wen Xue, Guohua Yi, Jiangbing Zhou
Summary: The NIH's SCGE Consortium aims to develop safer and more effective methods to edit disease-relevant somatic cell genomes in patients, even in hard-to-reach tissues. Their approach includes rigorous validation of technology through third-party testing in animals to accelerate clinical development of new therapies.
Article
Biology
Meredith H. Wilson, Stephen C. Ekker, Steven A. Farber
Summary: This study developed a suite of tools using zebrafish as a model to study lipid droplets in real time, revealing dynamic changes of perilipin 3 loading on intestinal lipid droplets after a high-fat meal and its substitution by perilipin 2.
Article
Green & Sustainable Science & Technology
Joanna Yang Yowler, Kit Knier, Zachary WareJoncas, Shawna L. Ehlers, Stephen C. Ekker, Fabiola Guasp Reyes, Bruce F. Horazdovsky, Glenda Mueller, Adriana Morales Gomez, Amit Sood, Caroline R. Sussman, Linda M. Scholl, Karen M. Weavers, Chris Pierret
Summary: When worldwide cancellations of summer research immersion programs occurred in 2020 due to COVID-19, Mayo Clinic launched a virtual program called Summer Foundations in Research (SFIR) to ensure science pathways training for undergraduate scientists and support their mental wellbeing. Results showed significant increases in knowledge and interest in careers involving biomedical research, as well as improved research skills confidence, among participants. Additionally, positive shifts in mental wellbeing, including decreases in stress and increases in resilience and life satisfaction, were observed.
Article
Biology
Fang Liu, Sekhar Kambakam, Maira P. Almeida, Zhitao Ming, Jordan M. Welker, Wesley A. Wierson, Laura E. Schultz-Rogers, Stephen C. Ekker, Karl J. Clark, Jeffrey J. Essner, Maura McGrail
Summary: The ability to regulate gene activity spatially and temporally is crucial for investigating cell-type-specific gene function. In this study, researchers successfully generated stable, Cre/lox-regulated zebrafish alleles using the GeneWeld CRISPR-Cas9 targeted integration strategy, providing conditional inactivation and rescue capability.
Article
Genetics & Heredity
Ankit Sabharwal, Jarryd M. Campbell, Tanya L. Schwab, Zachary WareJoncas, Mark D. Wishman, Hirotaka Ata, Wiebin Liu, Noriko Ichino, Danielle E. Hunter, Jake D. Bergren, Mark D. Urban, Rhianna M. Urban, Shannon R. Holmberg, Bibekananda Kar, Alex Cook, Yonghe Ding, Xiaolei Xu, Karl J. Clark, Stephen C. Ekker
Summary: Mitochondria are a dynamic eukaryotic innovation that play diverse roles in biology and disease. Mitochondrial disorders are amongst the most prevalent inherited diseases, affecting roughly 1 in every 5000 individuals. Mitochondrial dysfunction is also a common component of a wide variety of other human illnesses.
Review
Biochemistry & Molecular Biology
Bibekananda Kar, Santiago R. Castillo, Ankit Sabharwal, Karl J. Clark, Stephen C. Ekker
Summary: Mitochondria are crucial organelles involved in energy generation and cell functionality, as well as producing important signaling molecules. They can vary between cells, tissues, and organs, and undergo changes due to disease, aging, and environmental factors. Human mitochondrial DNA can have single nucleotide variants that are linked to life-threatening diseases. Mitochondrial DNA base editing tools have proven useful in creating disease models and offer potential for personalized gene therapies targeting mtDNA-based disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Correction
Biology
Meredith H. Wilson, Stephen C. Ekker, Steven A. Farber
Article
Gastroenterology & Hepatology
Mara Sophie Vell, Arunkumar Krishnan, Kirk Wangensteen, Marina Serper, Katharina Sophie Seeling, Leonida Hehl, Miriam Daphne Rendel, Inuk Zandvakili, Marijana Vujkovic, Eleonora Scorletti, Kate Townsend Creasy, Christian Trautwein, Daniel James Rader, Saleh Alqahtani, Kai Markus Schneider, Carolin Victoria Schneider
Summary: Regular aspirin use is associated with a reduced risk of liver disease in men without an elevated risk of gastrointestinal bleeding or ulcers. The protective effect of aspirin appears to be dependent on the duration of intake, and there may be sex-related differences in its effects.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Bibekananda Kar, Ankit Sabharwal, Santiago Restrepo-Castillo, Brandon W. Simone, Karl J. Clark, Stephen C. Ekker
Summary: The FusX TALE Based Editor is a programmable base editing platform for introducing specific genetic variations in mitochondrial DNA. This article provides a protocol for synthesizing and testing FusXTBE plasmids in cultured human cell lines.
Review
Gastroenterology & Hepatology
Agnes Holczbauer, Kirk J. Wangensteen, Soona Shin
Summary: Hepatocellular carcinoma (HCC), originating from the liver, is a major primary cancer and a leading cause of cancer-related death worldwide. The cellular origin of HCC is still controversial, with conflicting views on whether it begins in hepatocytes, biliary cells, or facultative stem cells. Most HCCs develop in the setting of chronic liver injury caused by various factors. Understanding the cellular origin of HCC is crucial for prevention and treatment.
Article
Genetics & Heredity
Ankit Sabharwal, Bibekananda Kar, Santiago Restrepo-Castillo, Shannon R. Holmberg, Neal D. Mathew, Benjamin Luke Kendall, Ryan P. Cotter, Zachary WareJoncas, Christoph Seiler, Eiko Nakamaru-Ogiso, Karl J. Clark, Stephen C. Ekker
Summary: The FusXTBE is a new gene editing toolkit that facilitates broad-based access to TALE mitochondrial base editing technology. It has shown comparable activity to the initial base editor in human cells and high editing efficiency in zebrafish embryos, providing a promising tool for exploring important questions in mitochondrial biology and genetics. The tool enables precise editing specificity at the single nucleotide level and nondestructive genotyping for downstream biological functional genomic applications.
