Article
Gastroenterology & Hepatology
Rohit Loomba, Lei Ling, Duy M. Dinh, Alex M. DePaoli, Hsiao D. Lieu, Stephen A. Harrison, Arun J. Sanyal
Summary: This study investigated the impact of aldafermin on the gut microbiota in patients with NASH. The results showed that aldafermin had a significant effect on the stability of the gut microbial community, leading to an enrichment in the rare genus Veillonella, which may be influenced by aldafermin-mediated suppression of bile acid synthesis.
Review
Medicine, Research & Experimental
Shuni Duan, Xiaojiaoyang Li, Guifang Fan, Runping Liu
Summary: Liver diseases and related complications are major causes of morbidity and mortality worldwide. Effective treatments are limited, highlighting the need for novel therapies. Bile acids (BAs) play important roles in regulating energy and immune homeostasis in various liver diseases, making them attractive therapeutic targets. This review summarizes recent progress in understanding the enterohepatic circulation of BAs, potential targets of BAs signaling, and the development of treatments. The protective effects, molecular mechanisms, and outcomes of clinical trials are discussed, along with future perspectives for the development of these candidates. In conclusion, pharmacological therapies targeting BAs signaling hold promise for the treatment of complex liver disorders.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Daniel Rizzolo, Bo Kong, Rulaiha E. Taylor, Anita Brinker, Michael Goedken, Brian Buckley, Grace L. Guo
Summary: This study utilized a mouse model lacking CYP7A1 and CYP27A1 to demonstrate that female DKO mice exhibit significantly reduced BA concentrations but a similar gene expression pattern to WT mice in relation to BA regulation, synthesis, and transport. Additionally, female DKO mice responded similarly to a synthetic FXR agonist compared to WT mice.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Cell Biology
Jun Wei Chan, Claire Wen Ying Neo, Soumita Ghosh, Hyungwon Choi, Su Chi Lim, E. Shyong Tai, Adrian Kee Keong Teo
Summary: The study reveals the involvement of HNF1A in kidney development and function, and identifies SLC51B as a target gene responsible for E1S uptake in human proximal tubule cells. Dysfunction of this process in MODY3 patients may contribute to the development of renal disease.
CELL DEATH & DISEASE
(2023)
Article
Plant Sciences
Yu Fu, Han Feng, Xue Ding, Qing-Hai Meng, Shu-Rui Zhang, Jun Li, Ying Chao, Ting-Ting Ji, Yun-Hui Bi, Wei-Wei Zhang, Qi Chen, Yu-Han Zhang, You-Long Feng, Hui-Min Bian
Summary: AB23A may prevent postmenopausal atherosclerosis by regulating hepatic farnesoid X receptor, increasing bile acid and cholesterol excretion, and reducing plasma cholesterol levels, providing a potential therapeutic approach.
Article
Biochemistry & Molecular Biology
Javier Martinez-Garcia, Manuela Molina, Leticia Odriozola, Angie Molina, Gloria Gonzalez-Aseguinolaza, Nicholas D. Weber, Cristian Smerdou
Summary: This study evaluated the functionality and bile acid-mediated regulation of minimal versions of the human and mouse BSEP promoters. The minimal mouse BSEP promoter (imPr) showed higher expression and inducibility compared to the minimal human promoter (ihPr) and full-length BSEP promoters in human hepatic cells. The imPr promoter was efficiently regulated by administration of a bile acid-enriched diet in mice receiving an AAV8 vector. The optimized imPr promoter with additional IR-1 repeats provided higher levels of expression both in vitro and in vivo.
CELL AND BIOSCIENCE
(2022)
Article
Gastroenterology & Hepatology
Ruiguang Ma, Qian Li, Guoxian Yu, Jun Wang, Yueyue Li, Xinyan Xu, Yiqing Zhu, Min Dong, Yanjing Gao, Lixiang Li, Zhen Li
Summary: Alterations in gastric mucosal microbiome and transcriptome were identified in patients with liver cirrhosis (LC). Impaired energy metabolism in gastric mucosal cells and bile acids might aggravate gastric mucosal inflammation. Gastric mucosal cells might reduce bile acid toxicity by bile acid efflux and detoxification.
Article
Pharmacology & Pharmacy
Xiao-Rong Lu, Ning Ma, Xi-Wang Liu, Shi-Hong Li, Zhe Qin, Li-Xia Bai, Ya-Jun Yang, Jian-Yong Li
Summary: This study found that AEE has therapeutic effects on hyperlipidemia through regulating amino acid metabolism, glutathione metabolism, energy metabolism, bile acid metabolism, and glycerophospholipid metabolism pathways. AEE decreases FXR and increases CYP7A1 in the liver, accelerating the conversion of cholesterol into bile acids and excretion in feces, thus providing potential molecular mechanisms and targets for anti-hyperlipidemia therapies.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Gastroenterology & Hepatology
Teng Liu, Ren-Xue Wang, Jun Han, Zhong-Die Li, Jonathan A. Sheps, Li -Juan Zheng, Xiao-Xiao Xu, Victor Ling, Jian-She Wang
Summary: Comprehensive bile acid profiling revealed increased bile acid modifications and decreased overall hydrophobicity in ABCB4-mutated patients. However, the concentration of tauro-THBA did not differ significantly among patients with different prognoses. ROC analysis indicated that tauro-THBA levels could be used as a prognostic marker for ABCB11-mutated patients.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tianli Chen, Hongda Liu, Zengli Liu, Kangshuai Li, Ruixi Qin, Yue Wang, Jialiang Liu, Zhipeng Li, Qinglun Gao, Chang Pan, Fan Yang, Wei Zhao, Zongli Zhang, Yunfei Xu
Summary: The study revealed that FGF19 and FGFR4 are adverse prognostic biomarkers for gallbladder carcinoma, with their co-expression being a more sensitive predictor. FGF19 can promote GBC progression by stimulating FGFR4 activation via an autocrine pathway with bile as a potential carrier.
Article
Agriculture, Multidisciplinary
Jiangping Song, Xingyu Lu, Denghong Liu, Yuwei Zhang, Xiaoning Zhai, Liuyang Zhou, Jie Gao
Summary: Our study found that fucogalactan sulfate (FS) from Laminaria japonica can lower dyslipidemia by regulating the gut microbiota and bile acid metabolism pathway. Experimental results on dyslipidemia mice demonstrated that oral administration of FS can reduce serum cholesterol levels and liver fat accumulation. Further investigation showed that FS inhibits hepatic farnesoid X receptor (FXR) and activates the intestinal FXR-FGF19 pathway, leading to the suppression of CYP7A1 and CYP8B1 and potentially reducing bile acid synthesis and lipid absorption.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Agnieszka Kempinska-Podhorodecka, Monika Adamowicz, Ewa Ostrycharz, Mateusz Chmielarz, Maciej Wojcicki, Piotr Milkiewicz, Malgorzata Milkiewicz
Summary: The study found that miR-506 is significantly upregulated in the colon of patients with PSC and PSC+UC, but downregulated in patients with UC. This differential expression may be associated with phenotypic presentations of colonic inflammation and neoplasia. Upregulation of miR-506 in PSC and PSC+UC patients may lead to failure of bicarbonate secretion and inhibition of p53, while downregulation of miR-506 in UC patients enhances S1P production, leading to pro-inflammatory signaling.
SCIENTIFIC REPORTS
(2021)
Article
Gastroenterology & Hepatology
Bo Li, Jun Zhang, Yong Chen, Qixia Wang, Li Yan, Rui Wang, Yiran Wei, Zhengrui You, Yikang Li, Qi Miao, Xiao Xiao, Min Lian, Weihua Chen, Dekai Qiu, Jingyuan Fang, M. Eric Gershwin, Ruqi Tang, Xiong Ma
Summary: The study revealed significant individual variability in the therapeutic effects of cholestyramine in icteric PBC patients. Differences in gut microbial composition and metabolites were observed between patients with superior remission (SR) and inferior remission (IR). Patients in the SR group showed enrichment of specific bacterial species producing short-chain fatty acids (SCFAs), while the IR group exhibited an increase in Klebsiella pneumonia.
Article
Plant Sciences
Tingting Yang, Yiying Wang, Xinyun Cao, Yuting Peng, Jiawan Huang, Li Chen, Jiale Pang, Zhenzhou Jiang, Sitong Qian, Ying Liu, Changjiang Ying, Tao Wang, Fan Zhang, Qian Lu, Xiaoxing Yin
Summary: This study investigates the effects and mechanism of quercetin on type 2 diabetes-associated non-alcoholic fatty liver disease (NAFLD). The results show that quercetin can bind to mTOR and competitively occupy its binding pocket. Quercetin alleviates hepatic lipid accumulation by downregulating the mTOR/YY1 signaling pathway and restoring cholesterol homeostasis.
Review
Biotechnology & Applied Microbiology
Impreet Kaur, Ashwini Vasudevan, Preety Rawal, Dinesh M. Tripathi, Seeram Ramakrishna, Savneet Kaur, Shiv K. Sarin
Summary: Hepatocytes are differentiated cells that make up 80% of the liver volume and perform major liver functions. While adult hepatocytes can proliferate and participate in liver regeneration in vivo, maintaining viable and functional primary hepatocytes in culture has been a major challenge. Recent advancements in technical strategies, such as the use of hydrogels, specific microenvironments, growth factors, and co-culture with supporting cell types, have improved the quantity, lifespan, and hepatic functions of primary hepatocytes in vitro. This review discusses the details, limitations, and prospects of different technical strategies, as well as alternative cellular sources and bioengineering strategies for long-term hepatocyte function.
BIOENGINEERING-BASEL
(2023)
Article
Medicine, General & Internal
H. Johansson, J. F. Svensson, M. Almstrom, N. Van Hui, M. Rudling, B. Angelin, G. Nowak, B. Fischler, E. Ellis
JOURNAL OF INTERNAL MEDICINE
(2020)
Article
Cell Biology
Davide Gnocchi, Ewa C. S. Ellis, Helene Johansson, Mats Eriksson, Giovannella Bruscalupi, Knut R. Steffensen, Paolo Parini
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Mihaela Zabulica, Tomas Jakobsson, Francesco Ravaioli, Massoud Vosough, Roberto Gramignoli, Ewa Ellis, Olav Rooyackers, Stephen C. Strom
Summary: Urea cycle disorders are enzymopathies caused by inherited deficiencies in genes of the cycle, with liver transplantation as the only definitive treatment. A novel approach involving reprogramming patient cells into hepatic organoids could provide models for the investigation of cell-based genetic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Mihaela Zabulica, Raghuraman C. Srinivasan, Pinar Akcakaya, Gabriella Allegri, Burcu Bestas, Mike Firth, Christina Hammarstedt, Tomas Jakobsson, Towe Jakobsson, Ewa Ellis, Carl Jorns, Georgios Makris, Tanja Scherer, Nicole Rimann, Natalie R. van Zuydam, Roberto Gramignoli, Anna Forslow, Susanna Engberg, Marcello Maresca, Olav Rooyackers, Beat Thony, Johannes Haberle, Barry Rosen, Stephen C. Strom
Summary: The study demonstrated the efficacy and safety of ex vivo correction of primary human hepatocytes in restoring urea cycle and improving ammonia clearance and enzyme activity. Liver repopulation with genetically edited patient hepatocytes resulted in normal metabolic function and showed no specific off-target editing effects.
Article
Endocrinology & Metabolism
Helene Johansson, Jonas Norskov Sondergaard, Carl Jorns, Claudia Kutter, Ewa C. S. Ellis
Summary: Bile acids (BAs) are essential for lipid absorption in the intestine, and their metabolism is tightly regulated by feedback mechanisms. FGF19 plays a crucial role in maintaining BA homeostasis, while CDCA can independently regulate BA synthesis by increasing FGF19 expression and subsequently reducing BA synthesis.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Gastroenterology & Hepatology
Valerio Azzimato, Ping Chen, Emelie Barreby, Cecilia Morgantini, Laura Levi, Ana Vankova, Jennifer Jager, Andre Sulen, Marina Diotallevi, Joanne X. Shen, Anne Miller, Ewa Ellis, Mikael Ryden, Erik Naslund, Anders Thorell, Volker M. Lauschke, Keith M. Channon, Mark J. Crabtree, Arvand Haschemi, Siobhan M. Craige, Mattia Mori, Francesco Spallotta, Myriam Aouadi
Summary: This study reveals a novel mechanism by which miR-144 inhibits NRF2 activity through the consumption of fumarate by activation of FH. By activating fumarate hydratase in the TCA cycle, hepatic miR-144 triggers an impaired antioxidant response in obesity.
Article
Cell Biology
Christine L. Zimmer, Erik von Seth, Marcus Buggert, Otto Strauss, Laura Hertwig, Son Nguyen, Alicia Y. W. Wong, Chiara Zotter, Lena Berglin, Jakob Michaelsson, Marcus Reuterwall Hansson, Urban Arnelo, Ernesto Sparrelid, Ewa C. S. Ellis, Johan D. Soderholm, Asa Keita, Kristian Holm, Volkan Ozenci, Johannes R. Hov, Jeff E. Mold, Martin Cornillet, Andrea Ponzetta, Annika Bergquist, Niklas K. Bjorkstrom
Summary: The study on patients with primary sclerosing cholangitis (PSC) revealed the characteristics of the human biliary immunological landscape, highlighting differences in immune cell composition compared to blood and the pathological features of biliary inflammation in PSC patients.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Csaba Adori, Teresa Daraio, Raoul Kuiper, Swapnali Barde, Lubica Horvathova, Takashi Yoshitake, Robert Ihnatko, Ismael Valladolid-Acebes, Pauline Vercruysse, Ashley M. Wellendorf, Roberto Gramignoli, Bela Bozoky, Jan Kehr, Elvar Theodorsson, Jose A. Cancelas, Boris Mravec, Carl Jorns, Ewa Ellis, Jan Mulder, Mathias Uhlen, Christina Bark, Tomas Hokfelt
Summary: Research found that the hepatic nerves in NAFLD pathology show signs of degeneration, with chronic sympathetic hyperexcitation being a key factor in axonal degeneration. In experimental steatohepatitis, severe portal vein contraction was observed, spatially correlated with the extension of remaining nerves around the portal vein, providing insight into a potential intrahepatic neuronal mechanism of portal hypertension.
Article
Cell & Tissue Engineering
Emil Bluhme, Ewa Henckel, Roberto Gramignoli, Therese Kjellin, Christina Hammarstedt, Greg Nowak, Ahmad Karadagi, Helene Johansson, Oystein Jynge, Maria Soderstrom, Bjorn Fischler, Stephen Strom, Ewa Ellis, Boubou Hallberg, Carl Jorns
Summary: This study assessed the metabolic function and suitability of hepatocytes isolated from neonatal livers for transplantation. Despite prolonged warm ischemia time, hepatocytes isolated from neonatal donors showed good viability, function, and engraftment. This suggests that neonatal livers should be considered as a donor source for clinical hepatocyte transplantation.
CELL TRANSPLANTATION
(2022)
Article
Gastroenterology & Hepatology
Christine L. Zimmer, Iva Filipovic, Martin Cornillet, Colm J. O'Rourke, Lena Berglin, Hannes Jansson, Dan Sun, Otto Strauss, Laura Hertwig, Helene Johansson, Erik Seth, Ernesto Sparrelid, Joana Dias, Hans Glaumann, Espen Melum, Ewa C. Ellis, Johan K. Sandberg, Jesper B. Andersen, Annika Bergquist, Niklas K. Bjorkstrom
Summary: The study found that MAIT cells were heterogenously lost from intrahepatic and perihilar cholangiocarcinoma tumors possibly in response to increased bacterial burden, while the residual intratumoral MAIT cells exhibited preserved receptor repertoire for interaction with tumor cells. The high presence of MAIT cells in the livers of iCCA patients predicted long-term survival and was associated with a favorable antitumor immune signature.
Article
Multidisciplinary Sciences
Franziska Hildebrandt, Alma Andersson, Sami Saarenpaa, Ludvig Larsson, Noemi Van Hul, Sachie Kanatani, Jan Masek, Ewa Ellis, Antonio Barragan, Annelie Mollbrink, Emma R. Andersson, Joakim Lundeberg, Johan Ankarklev
Summary: Global transcriptional differences across lobular units in the liver remain unknown. Here the authors perform spatial transcriptomics of liver tissue to delineate transcriptional differences in physical space, confirm lobular zonation along transcriptional gradients and suggest the presence of previously uncharacterized structures within liver tissue.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Andreas Giannisis, Kalicharan Patra, Anna K. Edlund, Lur Agirrezabala Nieto, Joan Benedicto-Gras, Simon Moussaud, Andres de la Rosa, Daniel Twohig, Tore Bengtsson, Yuan Fu, Guojun Bu, Greg Bial, Lander Foquet, Christina Hammarstedt, Stephen Strom, Kristina Kannisto, Jacob Raber, Ewa Ellis, Henrietta M. Nielsen
Summary: Liver-generated plasma apoE, although it does not enter the brain, is correlated with the risk and biomarker levels of Alzheimer's disease (AD). Carriers of APOE ε4, the strongest genetic risk factor for AD, show lower plasma apoE and altered brain integrity even in mid-life. This study investigates the role of liver-derived apoE in promoting neurodegeneration and emphasizes the potential importance of the liver in the APOE ε4-associated risk of neurodegenerative disease.
MOLECULAR PSYCHIATRY
(2022)
Article
Cell Biology
Martin Cornillet, Helen Zemack, Hannes Jansson, Ernesto Sparrelid, Ewa Ellis, Niklas K. Bjorkstrom
Summary: Alpha-1 antitrypsin deficiency (A1ATD) is present in 10.8% of patients with biliary tract cancer (BTC), with no significant clinical differences compared to non-A1ATD BTC. The abundance of A1AT protein is increased in intrahepatic cholangiocarcinoma (iCCA) and is influenced by genomic alterations. A1ATD may be associated with a less aggressive phenotype, while high A1AT expression may contribute to a more aggressive phenotype.
Article
Endocrinology & Metabolism
Emelie Barreby, Benedikt Strunz, Sebastian Nock, Lea Naudet, Joanne X. Shen, Helene Johansson, Isabella Soennerborg, Junjie Ma, Egon Urgard, Laura J. Pallett, Yizhou Hu, Achilleas Fardellas, Valerio Azzimato, Ana Vankova, Laura Levi, Cecilia Morgantini, Mala K. Maini, Per Stal, Stephan P. Rosshart, Jonathan M. Coquet, Greg Nowak, Erik Naeslund, Volker M. Lauschke, Ewa Ellis, Niklas K. Bjoerkstroem, Ping Chen, Myriam Aouadi
Summary: By studying patients undergoing liver transplantation, a specific population of resident liver myeloid cells that protects against metabolic impairment in obesity is identified. These cells, termed liver myeloid cells 2 (LM2), decrease in proportion during obesity but can ameliorate oxidative stress. These findings suggest that targeting resident myeloid cells could be a therapeutic approach for reducing oxidative stress in non-alcoholic fatty liver disease (NAFLD).
Correction
Endocrinology & Metabolism
Cecilia Morgantini, Jennifer Jager, Xidan Li, Laura Levi, Valerio Azzimato, Andre Sulen, Emelie Barreby, Connie Xu, Michaela Tencerova, Erik Naslund, Chanchal Kumar, Francisco Verdeguer, Sara Straniero, Kjell Hultenby, Niklas K. Bjorkstrom, Ewa Ellis, Mikael Ryden, Claudia Kutter, Tracey Hurrell, Volker M. Lauschke, Jeremie Boucher, Ales Tomcala, Gabriela Krejcova, Adam Bajgar, Myriam Aouadi