Article
Biochemistry & Molecular Biology
Zixiong Zhou, Jing Qi, Yajiao Wu, Chutao Li, Wenqiang Bao, Xiaohuang Lin, An Zhu
Summary: This study investigated the hepatoprotective effects of nuciferine (Nuci) against acetaminophen (APAP)-induced acute liver injury (ALI) and explored its underlying mechanisms. The results showed that Nuci significantly attenuated APAP-induced ALI by reducing tissue pathological damage, inhibiting oxidative stress and inflammation, and regulating glutathione metabolism, anti-inflammatory responses, and autophagy.
Article
Biochemistry & Molecular Biology
Xiyue Shen, Saddam Muhammad Ishaq, Qiao'e Wang, Juntao Yuan, Junling Gao, Zhongbing Lu
Summary: DDAH1 plays a protective role in APAP-induced liver injury by attenuating oxidative stress, inflammation, and damage to the liver through influencing xenobiotic metabolism and glutathione metabolism pathways. Increasing hepatic DDAH1 expression and activity may be a novel approach for treating drug-induced acute liver injury.
Editorial Material
Cell Biology
Xiaojuan Chao, Hong-Min Ni, Wen-Xing Ding
Summary: SQSTM1/p62 is a receptor protein degraded by selective autophagy, whose accumulation activates multiple cell survival signaling pathways including NF Kappa B, MTOR, and NFE2L2. Deletion of Sqstm1 improves hepatic metabolic reprogramming and cell repopulation in mice with liver-specific defects, but also promotes liver tumorigenesis. This highlights the complex interplay among autophagy, SQSTM1, and MTORC1 in liver tumorigenesis.
Article
Multidisciplinary Sciences
Jianfang Ye, Jie Chen, Yun Li, Liao Sun, Hongyun Lu
Summary: This study aimed to investigate whether hepatocyte-specific HIF-2a deficiency could improve CCl4-induced liver fibrosis in mice. The results showed that hepatocyte-specific HIF-2a knockout had no effect on mouse growth, liver function, glucose or lipid metabolism. CCl4-treated knockout and wild-type mice exhibited similar patterns of liver injury and inflammatory cell infiltration. Therefore, hepatocyte HIF-2a expression may not be a key factor in the initiation of liver fibrogenesis.
Article
Biochemistry & Molecular Biology
Jing Li, Xuewen Tang, Xing Wen, Xiaoyuan Ren, Huihui Zhang, Yatao Du, Jun Lu
Summary: Acetaminophen overdose is a common cause of drug-induced liver injury. The reaction between APAP metabolite and thiol molecules is the main cause of APAP-induced hepatotoxicity, but the role of other thiol-related regulators is unclear. In this study, the deletion of the Glrx2 gene worsened APAP-induced liver damage by interrupting the thiol-redox compensatory response and enhancing the AIF pathway-mediated oxidative damage.
Article
Cell Biology
Laura Mainz, Mohamed A. F. E. Sarhan, Sabine Roth, Ursula Sauer, Charis Kalogirou, Markus Eckstein, Elena Gerhard-Hartmann, Helen-Desiree Seibert, Hans-Ulrich Voelker, Carol Geppert, Andreas Rosenwald, Martin Eilers, Almut Schulze, Markus Diefenbacher, Mathias T. Rosenfeldt
Summary: The potential therapeutic target of macroautophagy/autophagy for various diseases, including cancer, is mainly based on preclinical mouse studies. This study introduces a shRNA transgenic mouse model that allows simultaneous knockdown of Atg7 in most organs, providing a valuable tool for further understanding of the role of autophagy impairment at different disease stages.
Article
Neurosciences
Xin Zhu, Mei Yang, Liu Yang
Summary: The purpose of this study was to investigate the effect of isoflurane postconditioning on neuron injury and its mechanism of affecting autophagy through miR-384-5p/ATG5. HT22 cells were exposed to isoflurane after oxygen-glucose deprivation/reoxygenation. The level of miR-384-5p was detected and ATG5 was confirmed as a target molecule downstream of miR-384-5p. Isoflurane postconditioning regulated miR-384-5p/ATG5 and inhibited apoptosis-related proteins expression, as well as inhibited autophagy. In MCAO rats, isoflurane post-conditioning regulated miR-384-5p and inhibited apoptosis, as well as inhibited autophagy. The molecular mechanism behind isoflurane post-conditioning in alleviating ischemic neuronal injury may be related to miR-384-5p/ATG5-mediated autophagy regulation.
Article
Cell Biology
John D. Griffin, Eloy Bejarano, Xiang-Dong Wang, Andrew S. Greenberg
Summary: The data suggest that protection against NAFLD in the absence of hepatic PLIN2 is driven by the integrated actions of both ATGL and lipophagy, with increased autophagy contributing to enhanced cellular fatty acid oxidation in PLIN2(LKO) hepatocytes. Inhibiting either ATGL or autophagy blunted the increased FA oxidation, while combined inhibition of both pathways reduced FA oxidation to the same extent as treatment with either inhibitor alone.
Article
Nanoscience & Nanotechnology
Xiaopeng Cai, Shiyuan Hua, Jingwen Deng, Zhen Du, Dongxiao Zhang, Zhenfeng Liu, Nazif Ullah Khan, Min Zhou, Zhi Chen
Summary: Astaxanthin (ASX) can prevent APAP-induced liver injury (AILI) by activating the Nrf2/HO-1 pathway, and the ASX-loaded hollow mesoporous silica nanoparticles (HMSN@ASX) can improve the solubility of ASX and target delivery to the liver, significantly improving the therapeutic effects.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Pharmacology & Pharmacy
Hui Qian, Qingyun Bai, Xiao Yang, Jephte Y. Akakpo, Lili Ji, Li Yang, Thomas Rulicke, Kurt Zatloukal, Hartmut Jaeschke, Hong-Min Ni, Wen-Xing Ding
Summary: The study revealed the crucial role of p62 in APAP-induced liver injury (AILI), showing that it inhibits the late injury phase by enhancing autophagic selective removal of APAP adducts and mitochondria while impairing the recovery phase likely by enhancing hepatic blood coagulation.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Biochemistry & Molecular Biology
Shasha Liu, Ruohan Cheng, Hui He, Kunming Ding, Rongmi Zhang, Yuanyuan Chai, Qinwei Yu, Xin Huang, Luyong Zhang, Zhenzhou Jiang
Summary: This study investigated the effect and mechanism of 8-methoxypsoralen (8-MOP) on acetaminophen (APAP)-induced hepatotoxicity in mice. It was found that treatment with different doses of 8-MOP reduced liver damage caused by APAP, as evidenced by decreased serum transaminase levels and histopathological liver necrosis area. 8-MOP achieved this by inhibiting the enzymatic activities of Cyp2e1 and reducing the production of the toxic metabolite APAP-CYS. The results suggest that 8-MOP could be a potential therapeutic agent for APAP-induced liver toxicity.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Pharmacology & Pharmacy
Peng Jiang, Zhenghong Liu, Tingyu Fang, Zhidan Zhang, Yu Zhang, Dongdong Wang, Peter J. Little, Suowen Xu, Jianping Weng
Summary: Despite an increase in Gdf15 levels after APAP overdose, this study concluded that Gdf15 is not involved in APAP-induced liver injury. The study also suggests that genomic analysis of mRNA expression after APAP overdose is of limited relevance unless followed up by a functional analysis of candidate genes in vivo.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Zhimin Gao, Wei Yi, Junyuan Tang, Yuling Sun, Jianrong Huang, Tian Lan, Xiaoyan Dai, Suowen Xu, Zheng-Gen Jin, Xiaoqian Wu
Summary: Urolithin A (UA), a metabolite of ellagitannin natural products, protects against acetaminophen-induced liver injury (AILI) and is superior to N-acetylcysteine (NAC) in dosage and therapeutical time window. UA promotes mitophagy and activated Nrf2/ARE signaling in the liver, leading to alleviation of acetaminophen-induced oxidative stress and hepatic necrosis.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Oncology
Vangelis Kondylis, Farina Schneider, Fabian Schorn, Nikos Oikonomou, Beate Katharina Straub, Sabine Werner, Philip Rosenstiel, Manolis Pasparakis
Summary: In the absence of autophagy defects, activation of p62 and Nrf2 exacerbates liver disease phenotype and can lead to early death. Expression of a p62 mutant exacerbates hepatocarcinogenesis, while forced activation of Nrf2 itself does not increase liver injury or tumor burden.
Article
Endocrinology & Metabolism
Yongting Zhao, Ruxin Wang, Qi Qin, Jiaojiao Yu, Hui Che, Lihong Wang
Summary: Diabetic cardiomyopathy (DCM) is a serious complication of diabetes mellitus caused by hyperglycemia. Transfer RNA-derived fragments (tRFs) play a crucial role in the dysfunction of cardiomyocytes during DCM progression. High glucose treatment induces abnormalities in cardiomyocytes and differential expression of tRFs, including upregulated tRFs involved in cardiac dysfunction-related processes. The most significantly upregulated tRF, tRF-5014a, negatively regulates autophagy and its inhibition attenuates cardiomyocyte injury under high glucose conditions.
FRONTIERS IN ENDOCRINOLOGY
(2023)