Altered PGE2-EP2 is associated with an excessive immune response in HBV-related acute-on-chronic liver failure

Wang, Yunyun; Chen, Chao; Qi, Jinjin; Wu, Fengtian; Guan, Jun; Chen, Zhi; Zhu, Haihong

doi:10.1186/s12967-019-1844-0

Cited by 12 publications

(16 citation statements)

References 31 publications

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“… 69 Stimulating DRD1 negatively regulates the activation of NLRP3 inflammatory bodies through cAMP, thereby regulating the occurrence of inflammation. 70 In addition, DR exists in a variety of immune cells, such as regulatory T cells (Tregs), effector T cells (Teffs), and NK cells. DRD1 involves the inhibition of CD4 + and CD8 + T cells.…”

Section: Discussionmentioning

confidence: 99%

Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology

Li¹,

Wang²,

Li³

et al. 2021

DDDT

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Background Rhubarb, as a traditional Chinese medicine, is the preferred drug for the treatment of stagnation and constipation in clinical practice. It has been reported that rhubarb possesses hepatotoxicity, but its mechanism in vivo is still unclear. Methods In this study, the chemical components in rhubarb were identified based on UPLC-Q-TOF/MS combined with data postprocessing technology. The metabolic biomarkers obtained through metabolomics technology were related to rhubarb-induced hepatotoxicity. Furthermore, the potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology involving the above components and metabolites. Meanwhile, GO gene enrichment analysis and KEGG pathway analysis were performed on the common targets. Results Twenty-eight components in rhubarb were identified based on UPLC-Q-TOF/MS, and 242 targets related to rhubarb ingredients were predicted. Nine metabolic biomarkers obtained through metabolomics technology were closely related to rhubarb-induced hepatotoxicity, and 282 targets of metabolites were predicted. Among them, the levels of 4 metabolites, namely dynorphin B (10–13), cervonoyl ethanolamide, lysoPE (18:2), and 3-hydroxyphenyl 2-hydroxybenzoate, significantly increased, while the levels of 5 metabolites, namely dopamine, biopterin, choline, coenzyme Q9 and P1, P4-bis (5ʹ-uridyl) tetraphosphate significantly decreased. In addition, 166 potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology. The KEGG pathway analysis was performed on the common targets to obtain 46 associated signaling pathways. Conclusion These data suggested that rhubarb may cause liver toxicity due to its action on dopamine D1 receptor (DRD1), dopamine D2 receptor (DRD2), phosphodiesterase 4B (PDE4B), vanilloid receptor (TRPV1); transient receptor potential cation channel subfamily M member 8 (TRPM8), prostanoid EP2 receptor (PTGER2), acetylcholinesterase (ACHE), muscarinic acetylcholine receptor M3 (CHRM3) through the cAMP signaling pathway, cholinergic synapses, and inflammatory mediators to regulate TRP channels. Metabolomics technology and network pharmacology were integrated to explore rhubarb hepatotoxicity to promote the reasonable clinical application of rhubarb.

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Section: Discussionmentioning

confidence: 99%

Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology

Li¹,

Wang²,

Li³

et al. 2021

DDDT

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“…Extensive production of inflammatory mediators including cytokines, chemokines, growth factors, bioactive lipid mediators, and expression of chemokine receptors by different immune cells induce systemic inflammation, immune-mediated tissue damage, and subsequently liver failure (14)(15)(16)(17)(18)(19). Activated immune cells release other mediators such as proteases, reactive oxygen species (ROS), prostaglandins, and leukotrienes that further aggravate tissue damage (16,20).…”

Section: Pathophysiological Mechanisms In Aclf Systemic Inflammationmentioning

confidence: 99%

Acute-on-Chronic Liver Failure: Pathophysiological Mechanisms and Management

Khanam

Kottilil

2021

Front. Med.

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Acute-on-chronic liver failure (ACLF) is a multifaceted condition with poor treatment options and high short-term mortality. ACLF can develop in patients with or without liver cirrhosis, where patients with decompensated cirrhosis display a higher risk of short-term mortality. Pathophysiological mechanisms include systemic inflammation due to bacterial and fungal infections and acute hepatic insult with drug, alcohol, and viral hepatitis. Cryptogenic factors also contribute to the development of ACLF. The clinical outcome of patients with ACLF gets further complicated by the occurrence of variceal hemorrhage, hepatorenal syndrome, hepatic encephalopathy, and systemic immune dysfunction. Regardless of the better understanding of pathophysiological mechanisms, no specific and definitive treatment is available except for liver transplantation. The recent approach of regenerative medicine using mesenchymal stem cells (MSCs) could be advantageous for the treatment of ACLF as these cells can downregulate inflammatory response by inducing antiinflammatory events and prevent hepatic damage and fibrosis by inhibiting hepatic stellate cell activation and collagen synthesis. Moreover, MSCs are involved in tissue repair by the process of liver regeneration. Considering the broad therapeutic potential of MSCs, it can serve as an alternative treatment to liver transplant in the near future, if promising results are achieved.

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“…Currently, oxidative stress is believed to play an important role in liver failure [ 4 ]. During ACLF, injured/dead hepatocytes significantly increase oxidative stress, which leads to additional hepatocyte loss and inhibits regeneration, resulting in a vicious cycle [ 5 , 6 ]. Recent studies have shown that scoring systems for assessing severity and disease outcomes of ACLF have been developed [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Association between plasma level of superoxide dismutase and survival of patients with acute-on-chronic liver failure

Tian

Yao

et al. 2022

BMC Gastroenterol

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Background Fewer than 50% of patients with acute-on-chronic liver failure (ACLF) recover spontaneously, and ACLF has high mortality without liver transplantation. Oxidative stress has been shown to mediate hepatic inflammation during acute liver failure (ALF). We wanted to see if a biomarker for oxidative stress might be used to measure the severity and prognosis of ACLF patients. Methods A retrospective cohort of 124 ACLF patients, as well as healthy individuals, liver cirrhosis and ALF patients, was studied between January 2015 and September 2018. The levels of plasma superoxide dismutase (SOD) were detected using an ELISA commercial kit, and the Kaplan–Meier method was used for survival analysis. Results Patients with ACLF had statistically higher plasma SOD levels than the controls did (healthy controls and liver cirrhosis patients); however, the levels did not differ from those in patients with ALF. The plasma SOD level may be an inexpensive, easily accessible, and significant independent prognostic index for mortality on multivariate analysis (HR = 1.201, 95% CI 1.001–1.403, P < 0.01) as well as the model for end-stage liver disease (MELD) score. A level of SOD > 428 U/mL was linked to a statistically significant increase in the likelihood of death or liver transplantation in ACLF patients. Combination of plasma SOD levels and MELD scores improved performance in measuring the severity and prognosis of ACLF patients. Conclusion Patients with ACLF can be classified into high-risk and low-risk groups based on their plasma SOD levels at the time of admission to the hospital. The patient outcome is more closely connected with the combination of SOD level and MELD score than either value alone. This approach might be used to predict patient prognoses and prioritize liver transplant candidates.

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Altered PGE2-EP2 is associated with an excessive immune response in HBV-related acute-on-chronic liver failure

Cited by 12 publications

References 31 publications

Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology

Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology

Acute-on-Chronic Liver Failure: Pathophysiological Mechanisms and Management

Association between plasma level of superoxide dismutase and survival of patients with acute-on-chronic liver failure

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