Article
Chemistry, Medicinal
Ui-Jin Bae, Byung-Hyun Park, Min Kyung Cho, Eun Ju Bae
Summary: This study investigated the effects of Acer tegmentosum Maxim extract (ATE) on liver injury and fibrosis in mice with bile duct ligation (BDL)-induced cholestasis. ATE treatment significantly attenuated hepatocellular necrosis, reduced serum bile acids and bilirubin levels, and decreased liver inflammation, oxidative stress, and fibrosis. These effects were mediated through the decreased expression of genes involved in the NF-kappa B pathway. These findings suggest that ATE could be a potential therapeutic agent for cholestasis-induced liver injury and fibrosis.
JOURNAL OF MEDICINAL FOOD
(2022)
Article
Biochemistry & Molecular Biology
Xueqian Zhou, Xiaoxun Zhang, Nan Zhao, Liangjun Zhang, Wen Qiu, Chunwei Song, Jin Chai, Shiying Cai, Wensheng Chen
Summary: Bile components are important in maintaining gut microbiota homeostasis. In cholestasis, impaired bile secretion leads to liver injury. However, it is unclear whether gut microbiota plays a role in cholestatic liver injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Nasrin Shakerinasab, Mahdokht Azizi, Mahboubeh Mansourian, Hossein Sadeghi, Shirvan Salaminia, Reza Abbasi, Mohammad Esmaeil Shahaboddin, Amir Hossein Doustimotlagh
Summary: This study aimed to investigate the effects of empagliflozin on cholestatic liver injury in rats. The results showed that empagliflozin has protective effects on the liver by reducing inflammation and oxidative stress.
CURRENT PHARMACEUTICAL DESIGN
(2022)
Article
Nutrition & Dietetics
Zihang Yuan, Jie Wang, Haoran Zhang, Yingying Miao, Qianhui Tang, Ziqiao Yuan, Cheng Nong, Zhicheng Duan, Luyong Zhang, Zhenzhou Jiang, Qinwei Yu
Summary: In this study, researchers investigated the effects of triptolide (TP), a compound found in Tripterygium wilfordii Hook.f, on cholestasis-induced liver injury. They found that TP reduced liver enzyme levels and necrosis in a mouse model of common bile duct ligation (BDL) cholestasis. TP also inhibited cholangiocyte proliferation and alleviated BDL-induced hepatic fibrosis and inflammation by reducing the expression of RelB.
FRONTIERS IN NUTRITION
(2022)
Article
Biochemistry & Molecular Biology
Fatemeh Alaei Faradonbeh, Ivone Igreja Sa, Hana Lastuvkova, Jolana Cermanova, Milos Hroch, Hana Faistova, Jaroslav Mokry, Zuzana Nova, Martin Uher, Petr Nachtigal, Petr Pavek, Stanislav Micuda
Summary: Metformin was found to stimulate bile secretion in healthy mice by increasing liver bile acid synthesis and intestinal bile acid reabsorption. However, when used in combination with estrogen, metformin exacerbated bile secretion impairment and led to a significant increase in plasma bile acid concentrations.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Pharmacology & Pharmacy
Chang Hun Lee, Yunjung Choi, Hyewon Cho, In Hyuk Bang, Lihua Hao, Seung-Ok Lee, Raok Jeon, Eun Ju Bae, Byung-Hyun Park
Summary: The synthesized HDAC8 inhibitor SPA3014 demonstrated therapeutic efficacy against cholestatic liver injury and fibrosis in mice, suggesting its potential as a new therapeutic strategy for cholestatic liver disease.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sharmila Fagoonee, Maddalena Arigoni, Marta Manco, Martina Olivero, Francesca Bizzaro, Cinzia Magagnotti, Annapaola Andolfo, Barbara Miniscalco, Marco Forni, Stefano Todeschi, Emanuela Tolosano, Elena Bocchietto, Raffaele Calogero, Fiorella Altruda
Summary: Analysis of mRNA and miRNA contained in circulating extracellular vesicles (EVs) can detect early cholestatic liver injury and fibrosis in mice, offering promising biomarkers for severe cholestasis-induced liver fibrosis in humans.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Cell Biology
Trinh Van Le, Hong-Thuy Phan-Thi, My-Xuan Huynh-Thi, Thanh Minh Dang, Ai Xuan Le Holterman, Gabriele Grassi, Thao-Uyen Nguyen-Luu, Nhung Hai Truong
Summary: Chloroquine (CQ) treatment has been shown to prevent hepatic stellate cell (HSC) activation and autophagy, leading to a reduction in liver fibrogenesis. In both in vitro and in vivo experiments, CQ inhibited HSC activation, improved liver function, and reduced liver injury.
Article
Pharmacology & Pharmacy
Chang Ke, Jianlong Gao, Jiyuan Tu, Yan Wang, Yangxin Xiao, Yuan Wu, Yanju Liu, Zhongshi Zhou
Summary: This study aimed to investigate the protective effect of Ganfule capsule (GFL) on liver fibrosis and its possible mechanism. The cholestatic liver fibrosis model was prepared by bile duct ligation (BDL) in mice. The results showed that GFL could alleviate liver injury and fibrosis caused by BDL. Metabonomic analysis revealed metabolic disorder after surgery, which could be alleviated by GFL through regulation of glutamine metabolism and other pathways. GFL inhibited the activity of glutaminase 1 (GLS1) and the NF-kappa B pathway, leading to the alleviation of liver fibrosis.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Plant Sciences
Jingyi Cai, Jiasheng Wu, Su Fang, Shaoyong Liu, Tianming Wang, Yuanyuan Li, Juan Zou, Rong Shi, Zhengtao Wang, Li Yang, Yueming Ma
Summary: CBBP treatment alleviates ANIT-induced cholestasis and liver injury by reducing hepatocyte inflammation and apoptosis.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Cell Biology
Sujit K. Mohanty, Bryan Donnelly, Haley Temple, Alexander Bondoc, Monica McNeal, Greg Tiao
Summary: Biliary atresia is an obstructive neonatal cholangiopathy leading to liver cirrhosis and end stage liver disease. The transcription factor T-bet plays a critical role in the progression of BA. Analysis showed that T-bet knockout mice had decreased inflammatory response and altered immune cell profile compared to wild-type mice when infected with RRV, indicating the importance of T-bet in the disease.
Article
Gastroenterology & Hepatology
Jia-Yi Liu, Zhu-Yuan Ding, Zi-Yi Zhou, Sheng-Zhen Dai, Jie Zhang, Hao Li, Qiu Du, Ye-Yu Cai, Quan-Liang Shang, Yong-Heng Luo, En-Hua Xiao
Summary: Bile duct ligation in mice is a classical method for studying cholestatic fibrosis. This study aimed to evaluate the correlation between pathological changes and multiparameter MRI characteristics of liver fibrosis in a BDL mouse model. Results show that MRI parameters correlate with hepatic fibrosis rate and can be used for detecting cholestatic fibrosis.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Gastroenterology & Hepatology
Paula Iruzubieta, Naroa Goikoetxea-Usandizaga, Lucia Barbier-Torres, Marina Serrano-Macia, David Fernandez-Ramos, Pablo Fernandez-Tussy, Virginia Gutierrez-de-Juan, Sofia Lachiondo-Ortega, Jorge Simon, Miren Bravo, Fernando Lopitz-Otsoa, Mercedes Robles, Carlos Ferre-Aracil, Marta Varela-Rey, Natalia Elguezabal, Jose Luis Calleja, Shelly C. Lu, Malgorzata Milkiewicz, Piotr Milkiewicz, Juan Anguita, Maria J. Monte, Jose J. G. Marin, Marcos Lopez-Hoyos, Teresa C. Delgado, Mercedes Rincon, Javier Crespo, Maria Luz Martinez-Chantar
Summary: The study found elevated levels of MCJ in liver tissue of patients with chronic cholestatic liver disease and observed significantly decreased inflammation and apoptosis in MCJ-KO mice after bile duct ligation.
Article
Microbiology
Bowen Yang, Tianning Sun, Yingle Chen, Hongbing Xiang, Jun Xiong, Shiting Bao
Summary: The study confirmed the crucial role of gut microbiota, particularly Bacteroides species, in cognitive dysfunction induced by bile duct ligation in mice.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Cell Biology
Sara Huber, Theresia Fitzner, Rene G. Feichtinger, Sarah Hochmann, Theo Kraus, Karl Sotlar, Barbara Kofler, Martin Varga
Summary: This study characterized the expression of GAL and GAL(1-3)-R in the healthy human bile duct and pCCA, and found that the expression of GAL and GAL(3)-R in tumor cells of pCCA patients could potentially be suitable biomarkers for survival.
Article
Surgery
Lea Penzkofer, Tobias Huber, Jens Mittler, Hauke Lang, Stefan Heinrich
Summary: This study suggests that liver resections in cirrhotic livers are feasible with proper patient selection and limitation of the extent of surgery. Comorbidities increase the postoperative mortality in addition to impaired liver function and should always be considered in the preoperative assessment of patients undergoing liver surgery.
ZENTRALBLATT FUR CHIRURGIE
(2023)
Article
Gastroenterology & Hepatology
Steffie Revia, Agnieszka Seretny, Lena Wendler, Ana Banito, Christoph Eckert, Kersten Breuer, Anand Mayakonda, Pavlo Lutsik, Matthias Evert, Silvia Ribback, Suchira Gallage, Ismaiel Chikh Bakri, Kai Breuhahn, Peter Schirmacher, Stefan Heinrich, Matthias M. Gaida, Mathias Heikenwaelder, Diego F. Calvisi, Christoph Plass, Scott W. Lowe, Darjus F. Tschaharganeh
Summary: Epigenetic modifiers, such as KDM6A, are frequently mutated in human cancer. This study found that Kdm6a deficiency accelerates tumor development in liver and pancreatic cancer models by hyperactivating mTORC1 signaling. KDM6A acts as a tumor suppressor and can be a potential target for mTORC1 inhibition in gastrointestinal cancers with KDM6A-deficient tumors.
Article
Oncology
Dirk Andreas Ridder, Lana Louisa Urbansky, Hagen Roland Witzel, Mario Schindeldecker, Arndt Weinmann, Kristina Berndt, Tiemo Sven Gerber, Bruno Christian Koehler, Federico Nichetti, Annekathrin Ludt, Nadine Gehrke, Joern Markus Schattenberg, Stefan Heinrich, Wilfried Roth, Beate Katharina Straub
Summary: The role of Tak1 in hepatocellular carcinoma (HCC) development has been investigated and it has been found that high nuclear Tak1 expression is associated with poor prognosis and vascular invasion in HCC patients.
Review
Gastroenterology & Hepatology
Richard X. Sousa Da Silva, Achim Weber, Philipp Dutkowski, Pierre-Alain Clavien
Summary: Although liver transplantation is a success, many patients die while waiting for an organ. To address the increasing need for liver grafts, donor criteria have been expanded to include marginal grafts. However, these grafts carry a higher risk of complications. Machine perfusion, a procedure developed years ago, is of great interest in assessing graft viability and improving outcomes for recipients.
Article
Cell Biology
Sophia Pantasis, Juliane Friemel, Salome Mirjam Bruetsch, Zehan Hu, Sabrina Krautbauer, Gerhard Liebisch, Joern Dengjel, Achim Weber, Sabine Werner, Mattia Renato Bordoli
Summary: A study reveals the role of vertebrate lonesome kinase (VLK) in liver homeostasis and regeneration. VLK is highly expressed in neonatal mice hepatocytes but downregulated in adulthood. Knocking out VLK gene in hepatocytes leads to liver steatosis, inflammation, fibrosis, and expansion of liver progenitor cells in mice. These findings highlight the importance of VLK in liver function and repair.
JOURNAL OF CELL SCIENCE
(2022)
Article
Biotechnology & Applied Microbiology
Pierre-Alain Clavien, Philipp Dutkowski, Matteo Mueller, Dilmurodjon Eshmuminov, Lucia Bautista Borrego, Achim Weber, Beat Muellhaupt, Richard X. Sousa Da Silva, Brian R. Burg, Philipp Rudolf von Rohr, Martin J. Schuler, Dustin Becker, Max Hefti, Mark W. Tibbitt
Summary: A human liver has been successfully transplanted using ex situ normothermic machine perfusion, which extends the time window for evaluating the viability of donor organs and transforms the urgency of the surgery to an elective procedure.
NATURE BIOTECHNOLOGY
(2022)
Article
Surgery
Irina Staib-Lasarzik, Sophie Lehr, Ann Kristin Rosner, Ralph Timaru-Kast, Katharina Hoeter, Kai Bruns, Daniel Wollschlaeger, Stefan Heinrich, Serge C. Thal, Kristin Engelhard
Summary: This study found that intraoperative fluid replacement has no effect on postoperative serum levels of ampicillin and is not associated with surgical site infections (SSI). The control of serum levels during surgery does not seem necessary.
Article
Medicine, Research & Experimental
Tobias Huber, Laura Isabel Hanke, Christian Boedecker, Lukas Vradelis, Janine Baumgart, Stefan Heinrich, Fabian Bartsch, Jens Mittler, Alicia Schulze, Christian Hansen, Florentine Huettl, Hauke Lang
Summary: This study compares three different modes of demonstrating 3D reconstructions of liver CT scans and evaluates their applications in liver resection planning. The results of the study will help improve the accuracy and feasibility of liver surgery and provide guidance for teaching.
Article
Surgery
Verena Tripke, Tobias Huber, Janine Baumgart, Stefan Heinrich, Hauke Lang
Summary: This case report presents a rare case of hepatic echinococcosis. Through three-dimensional reconstruction based on preoperative CT scan, complete resection and vascular reconstruction were successfully performed. Liver resection for hepatic echinococcosis may require complex vascular resections and reconstructions.
ZENTRALBLATT FUR CHIRURGIE
(2022)
Article
Surgery
Tobias Huber, Florentine Huettl, Laura Isabel Hanke, Lukas Vradelis, Stefan Heinrich, Christian Hansen, Christian Boedecker, Hauke Lang
Summary: The resectability borders in liver surgery have significantly changed in recent decades due to the optimization of conservative treatment, improvement of imaging methods, and continuous development of surgical techniques. Technical developments such as three-dimensional segmentation, preoperative planning, and intraoperative navigation options have made complex procedures easier and safer. New technologies like 3D printing, virtual and augmented reality provide additional display options for individual patient anatomy. This review article provides an overview of the current state of available technologies and offers insights into the operating theatre of the future.
ZENTRALBLATT FUR CHIRURGIE
(2022)
Article
Oncology
Guillaume Fonteneau, Alexandra Redding, Hannah Hoag-Lee, Edward S. Sim, Stefan Heinrich, Matthias M. Gaida, Elda Grabocka
Summary: This study reveals that stress adaptation through phase-separation organelles SGs mediates PDAC development. Moreover, preexisting stress conditions such as obesity are a driving force behind tumor SG dependence, and enhanced SG levels are key determinants and a chemopreventive target for obesity-associated PDAC.
Article
Cell Biology
Daniela Lenggenhager, Jonas Grossmann, Jerome Gouttenoire, Christine Sempoux, Achim Weber
Summary: Immunohistochemistry for HEV ORF2 protein is a useful tool for tissue-based diagnosis of hepatitis E. However, we report an unexpected immunoreactivity of the HEV ORF2 antibody to CMV proteins. The staining pattern of CMV-infected cells is limited to the nucleus, in contrast to the cytoplasmic and occasional canalicular positivity observed in hepatitis E.
Article
Cell Biology
Simon Haefliger, Juergen Hench, Colm J. O'Rourke, Nathalie Meyer-Schaller, Sarp Uzun, Joan Saldarriaga, Achim Weber, Luca Mazzucchelli, Philip Jermann, Stephan Frank, Jesper B. Andersen, Luigi Terracciano, Christine Sempoux, Matthias S. Matter
Summary: This study analyzed the genetic and epigenetic alterations of hepatocellular adenomas (HCA) with atypical morphological features, and found differences with hepatocellular carcinoma (HCC) or HCA without atypical morphology. Therefore, targeted sequencing and/or combined methylation/copy number profiling should be performed to differentiate between HCC and HCA when diagnosis is difficult.
Article
Medicine, General & Internal
Ladina Vonzun, Romana Brun, Nora Gadient-Limani, Marcel Andre Schneider, Theresia Reding, Rolf Graf, Perparim Limani, Nicole Ochsenbein-Kolble
Summary: This prospective cohort study aimed to generate reference values for serum pancreatic stone protein (PSP) in pregnancy and compare them to the values of the general healthy population. The PSP values in healthy pregnant women (4-12 ng/mL) were within the range of the reference values of the general healthy population (8-16 ng/mL).
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Surgery
Stefan Heinrich, Juliane Theurer, Hauke Lang
Summary: Compared to colorectal and neuroendocrine liver metastases, liver surgery has not yet gained the same status for non-colorectal non-endocrine (NCNE) liver metastases. This is mainly due to different tumor biology and the lack of effective systemic treatment options in the past. However, even chemotherapy-naive patients with NCNE liver metastases can benefit from liver resection. With the significant advancements in systemic treatment in recent years, modern liver surgery will become an integral part of multimodality treatment concepts for several diseases.