Article
Biochemistry & Molecular Biology
Junya Suzuki, Kosuke Kaji, Norihisa Nishimura, Takahiro Kubo, Fumimasa Tomooka, Akihiko Shibamoto, Satoshi Iwai, Yuki Tsuji, Yukihisa Fujinaga, Koh Kitagawa, Tadashi Namisaki, Takemi Akahane, Hitoshi Yoshiji
Summary: The renin-angiotensin-aldosterone system plays an important role in liver fibrosis and HSC activation. The natriuretic peptide system acts as a counter-regulatory hormone and is regulated by neprilysin. The combination of an angiotensin receptor and a neprilysin inhibitor has shown potential therapeutic effects on liver fibrosis.
Article
Nanoscience & Nanotechnology
Yao-Wen Zhang, Li-Shuang Hou, Jie-Hua Xing, Tang-Rui Zhang, Si-Yuan Zhou, Bang-Le Zhang
Summary: Liver fibrosis is a common and prevalent chronic liver disease with no effective therapeutic drugs. This study proposes a targeted delivery system with autophagy inhibition, which shows synergistic effects in anti-liver fibrosis. This provides a potential treatment approach for liver fibrosis.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Chemistry, Multidisciplinary
Yumei Hao, Kaichao Song, Xiaochuan Tan, Ling Ren, Xiuping Guo, Chuchu Zhou, He Li, Jin Wen, Ya Meng, Mingbao Lin, Yujia Zhang, Hongdong Huang, Lulu Wang, Wensheng Zheng
Summary: Hepatic fibrosis is a chronic liver disease that lacks effective pharmacotherapeutic treatments. Researchers have designed targeted and reactive oxygen species (ROS)-responsive micelles for the specific delivery of resveratrol (RES), a traditional Chinese medicine, to activated hepatic stellate cells (aHSCs) for the treatment of liver fibrosis. In vitro and in vivo experiments demonstrate that these micelles enhance the targeted delivery of RES to aHSCs, reduce collagen accumulation, and protect hepatocytes from damage.
Review
Gastroenterology & Hepatology
Leke Wiering, Pallavi Subramanian, Linda Hammerich
Summary: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease with a wide range of severity, from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH). NASH can lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma, making hepatic fibrosis an important predictor of outcomes. Recent advancements in understanding the activation and inactivation of hepatic stellate cells, which drive fibrosis development, have shed light on the disease progression in NAFLD/NASH.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Gastroenterology & Hepatology
Jialiang Luo, Lei Li, Bo Chang, Zhengyumeng Zhu, Fan Deng, Mengyao Hu, Yu Yu, Xiao Lu, Zhengliang Chen, Daming Zuo, Jia Zhou
Summary: This study reveals the important role of the interaction between MBL and hepatic stellate cells in controlling the progression of liver fibrosis. MBL can promote senescence in hepatic stellate cells by interacting with cell surface receptors, exacerbating liver fibrosis. Restoring MBL expression in the liver or eliminating senescent cells can inhibit the development of liver fibrosis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Jordi Ribera, Clara Vilches, Vanesa Sanz, Ignacio de Miguel, Irene Portoles, Bernat Cordoba-Jover, Esther Prat, Virginia Nunes, Wladimiro Jimenez, Romain Quidant, Manuel Morales-Ruiz
Summary: Liver fibrosis is a significant health issue with limited treatment options. Targeting hepatic stellate cells and using gold nanorods may be promising strategies for reducing fibrosis. Gold nanorods have shown potential in decreasing fibrosis, hepatic inflammation, and hepatocyte injury.
Article
Biochemistry & Molecular Biology
Sam Seok Cho, Ji Hye Yang, Ji Hyun Lee, Jin Sol Baek, Sae Kwang Ku, Il Je Cho, Kyu Min Kim, Sung Hwan Ki
Summary: The study suggests that ferroptosis contributes to the progression of hepatic fibrosis by activating hepatic stellate cells and increasing the expression of fibrosis markers.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Aiting Yang, Xuzhen Yan, Hufeng Xu, Xu Fan, Mengyang Zhang, Tao Huang, Weiyu Li, Wei Chen, Jidong Jia, Hong You
Summary: The deficiency of HSCs-specific Loxl1 can prevent CCl4-induced hepatic fibrosis and reduce fibrosis and inflammation in liver tissue, with ITGA8/FAK/PI3K/AKT/HIF1a being essential for the function and expression of LOXL1. The study suggests novel mechanisms and potential targets for the treatment of fibrosis in the future.
Article
Biochemistry & Molecular Biology
Floris Haijer, Shiva Koets-Shajari, Janette Heegsma, Sandra Serna-Salas, Tjasso Blokzijl, Manon Buist-Homan, Han Moshage, Klaas Nico Faber
Summary: Liver fibrosis is caused by excessive proliferation and collagen production by hepatic stellate cells (HSCs) due to chronic liver injury. Hydroxyurea, an anti-proliferative drug, showed inhibitory effects on HSC proliferation and fibrosis development in both in vitro and in vivo experiments. This study provides evidence for the therapeutic potential of hydroxyurea in treating liver fibrosis.
Article
Engineering, Biomedical
Yanping Li, Ting Zhang, Jinhang Zhang, Qinhui Liu, Qingyi Jia, Wenfei Chen, Qin Tang, Yimin Xiong, Yan Xia, Ying Xu, Li Mo, Yuan Huang, Jinhan He
Summary: A multitask nanoparticle system called CCR was developed to target the Golgi apparatus of activated hepatic stellate cells (HSCs) for liver fibrosis treatment. The CCR nanoparticles specifically recognized and accumulated in the Golgi apparatus by binding to fibronectin and CD44 on activated HSCs. Treatment with CCR nanoparticles loaded with a hedgehog inhibitor effectively suppressed HSC activation and extracellular matrix secretion, inhibiting liver fibrosis progression.
Article
Cell Biology
Yiming Zhu, Chihao Zhang, Mingzhe Huang, Jiayun Lin, Xiao Fan, Tao Ni
Summary: In this study, the researchers found that TRIM26 promotes HSCs ferroptosis through mediating the ubiquitination of SLC7A11, thereby suppressing liver fibrosis. The targeted suppression of SLC7A11 by TRIM26 could be a novel therapeutic strategy for liver fibrosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Jieun Kim, Chanbin Lee, Jinsol Han, Hayeong Jeong, Sihyung Wang, Yung Hyun Choi, Youngmi Jung
Summary: Liver fibrosis is primarily caused by activated hepatic stellate cells (HSCs), and targeting these cells is crucial in preventing liver fibrosis. This study investigated the in vivo functions of thymosin beta 4 (T β 4) in liver fibrosis by generating T β 4 conditional knockout mice. The selective deletion of T β 4 in activated HSCs attenuated liver injury and fibrosis by repressing Hedgehog signaling. Re-expression of T β 4 reversed the effect of HSC-specific T β 4 deletion and led to liver fibrosis with Hedgehog activation. These findings suggest T β 4 as a potential therapeutic target for liver fibrosis.
Article
Plant Sciences
Ke Chen, Weiran Guo, Rongxin Li, Yueqing Han, Qi Gao, Shuzhen Wang
Summary: This study investigates the antifibrotic properties of T-96 and its underlying molecular mechanisms. The results show that T-96 can inhibit the proliferation, migration, and activation of hepatic stellate cells and alleviate liver injury, inflammation, and fibrosis progression in a CCl4-induced liver fibrosis mouse model. Mechanistic studies reveal that the antifibrotic effect of T-96 is mediated by suppressing the expression of AGAP2 and inhibiting the phosphorylation of FAK and AKT.
Article
Chemistry, Multidisciplinary
Mahmoud A. Younis, Yusuke Sato, Yaser H. A. Elewa, Hideyoshi Harashima
Summary: This article reports a novel strategy for treating liver fibrosis by reprogramming activated Hepatic Stellate Cells (aHSCs) into quiescent Hepatic Stellate Cells (qHSCs) using siRNA-loaded lipid nanoparticles (LNPs). The optimized LNPs enable ligand-free, selective, and potent siRNA delivery to aHSCs, resulting in the reversal of liver fibrosis and restoration of normal liver function in mice. This scalable and ligand-free platform has potential for clinical translation.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Biochemistry & Molecular Biology
Tian-tian Sun, Xu-ling Liu, Guang-yue Yang, Wei Zhang, Le Tao, Wen-ting Ma, Liu Wu, Qigen Li, Cheng Liu
Summary: This study found that patients with hepatic fibrosis had significantly higher levels of neurokines, and that hepatic stellate cells interact with nerves to produce neurogenic substances that promote liver fibrosis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)