Senescence and cell death in chronic liver injury: roles and mechanisms underlying hepatocarcinogenesis

Xiao, Meng-Chao; Chen, Wenjian; Wang, Chao; Wu, Yingfu; Zhu, Shiwei; Zeng, Chuyang; Cai, Yongchao; Liu, Changcheng; He, Zhiying

doi:10.18632/oncotarget.23622

Cited by 19 publications

(13 citation statements)

References 113 publications

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“…Necrosis is one of the prominent features in acute liver injury 115. Death of necrotic cells is also a distinct feature of hepatic ischemia/reperfusion injury 86.…”

Section: The Outcomes Of Liver Cell Caused By Mnpsmentioning

confidence: 99%

<p>The Toxicity Of Metallic Nanoparticles On Liver: The Subcellular Damages, Mechanisms, And Outcomes</p>

Ying¹,

Zang²,

Qu³

et al. 2019

IJN

147

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Metallic nanoparticles (MNPs) are new engineering materials with broad prospects for biomedical applications; thus, their biosafety has drawn great concern. The liver is the main detoxification organ of vertebrates. However, many issues concerning the interactions between MNPs and biological systems (cells and tissues) are unclear, particularly the toxic effects of MNPs on hepatocytes and other liver cells. Numerous researchers have shown that some MNPs can induce decreased cell survival rate, production of reactive oxygen species (ROS), mitochondrial damage, DNA strand breaks, and even autophagy, pyroptosis, apoptosis, or other forms of cell death. Our review focuses on the recent researches on the liver toxicity of MNPs and its mechanisms at cellular and subcellular levels to provide a scientific basis for the subsequent hepatotoxicity studies of MNPs.

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“…Necrosis is one of the prominent features in acute liver injury 115. Death of necrotic cells is also a distinct feature of hepatic ischemia/reperfusion injury 86.…”

Section: The Outcomes Of Liver Cell Caused By Mnpsmentioning

confidence: 99%

<p>The Toxicity Of Metallic Nanoparticles On Liver: The Subcellular Damages, Mechanisms, And Outcomes</p>

Ying¹,

Zang²,

Qu³

et al. 2019

IJN

147

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“…The liver can repair and regenerate normally if the damage is mild. But when the degree of damage to the liver is severe, hepatocytes lose regenerative capacity, and undergo necrosis, apoptosis or senescence[11,77].…”

Section: Senescence In the Livermentioning

confidence: 99%

Hepatic senescence, the good and the bad

Huda¹,

Liu²,

Hong³

et al. 2019

WJG

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Gradual alterations of cell’s physiology and functions due to age or exposure to various stresses lead to the conversion of normal cells to senescent cells. Once becoming senescent, the cell stops dividing permanently but remains metabolically active. Cellular senescence does not have a single marker but is characterized mainly by a combination of multiple markers, such as, morphological changes, expression of cell cycle inhibitors, senescence associated β-galactosidase activity, and changes in nuclear membrane. When cells in an organ become senescent, the entire organism can be affected. This may occur through the senescence-associated secretory phenotype (SASP). SASP may exert beneficial or harmful effects on the microenvironment of tissues. Research on senescence has become a very exciting field in cell biology since the link between age-related diseases, including cancer, and senescence has been established. The loss of regenerative and homeostatic capacity of the liver over the age is somehow connected to cellular senescence. The major contributors of senescence properties in the liver are hepatocytes and cholangiocytes. Senescent cells in the liver have been implicated in the etiology of chronic liver diseases including cirrhosis and hepatocellular carcinoma and in the interference of liver regeneration. This review summarizes recently reported findings in the understanding of the molecular mechanisms of senescence and its relationship with liver diseases.

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“…After confirming the potential anti-CLI effect of QDD, we try to focus on the effects and mechanisms of DQQ against apoptosis. Apoptosis is one of the important causes of liver cell damage, and it is known that endotoxin is the second blow to CLI and induces chronic liver disease progression via gut-liver axis [ 36 , 37 ] and directly damage liver cells and induce hepatocyte apoptosis [ 38 , 39 ]. Preclinical evidence showed that LA reduced liver injury and decreased oxidative stress response, excessive inflammatory response, and fibrotic progression via downregulating endotoxin levels [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Based Study on the Molecular Biological Mechanism of Action for Qingdu Decoction against Chronic Liver Injury

Zhao

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Qingdu Decoction (QDD) is a traditional Chinese medicine formula for treating chronic liver injury (CLI). Materials and methods. A network pharmacology combining experimental validation was used to investigate potential mechanisms of QDD against CLI. We firstly screened the bioactive compounds with pharmacology analysis platform of the Chinese medicine system (TCMSP) and gathered the targets of QDD and CLI. Then, we constructed a compound-target network and a protein-protein interaction (PPI) network and enriched core targets in Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways. At last, we used a CLI rat model to confirm the effect and mechanism of QDD against CLI. Enzyme-linked immunosorbent assay (ELISA), western blot (WB), and real-time quantitative polymerase chain reaction (RT-qPCR) were used. Results. 48 bioactive compounds of QDD passed the virtual screening criteria, and 53 overlapping targets were identified as core targets of QDD against CLI. A compound-CLI related target network containing 94 nodes and 263 edges was constructed. KEGG enrichment of core targets contained some pathways related to CLI, such as hepatitis B, tumor necrosis factor (TNF) signaling pathway, apoptosis, hepatitis C, interleukin-17 (IL-17) signaling pathway, and hypoxia-inducible factor (HIF)-1 signaling pathway. Three PPI clusters were identified and enriched in hepatitis B and tumor necrosis factor (TNF) signaling pathway, apoptosis and hepatitis B pathway, and peroxisome pathway, respectively. Animal experiment indicated that QDD decreased serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), endotoxin (ET), and IL-17 and increased prothrombin time activity (PTA) level. WB and RT-qPCR analyses indicated that, compared with the model group, the expression of cysteinyl aspartate specific proteinase-9 (caspase-9) protein, caspase-3 protein, B-cell lymphoma-2 associated X protein (Bax) mRNA, and cytochrome c (Cyt c) mRNA was inhibited and the expression of B-cell lymphoma-2 (Bcl-2) mRNA was enhanced in the QDD group. Conclusions. QDD has protective effect against CLI, which may be related to the regulation of hepatocyte apoptosis. This study provides novel insights into exploring potential biological basis and mechanisms of clinically effective formula systematically.

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Senescence and cell death in chronic liver injury: roles and mechanisms underlying hepatocarcinogenesis

Cited by 19 publications

References 113 publications

<p>The Toxicity Of Metallic Nanoparticles On Liver: The Subcellular Damages, Mechanisms, And Outcomes</p>

<p>The Toxicity Of Metallic Nanoparticles On Liver: The Subcellular Damages, Mechanisms, And Outcomes</p>

Hepatic senescence, the good and the bad

Network Pharmacology-Based Study on the Molecular Biological Mechanism of Action for Qingdu Decoction against Chronic Liver Injury

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