SHYCD induces APE1/Ref-1 subcellular localization to regulate the p53-apoptosis signaling pathway in the prevention and treatment of acute on chronic liver failure

Diao, Jiang; Li, Hai-Ye; Huang, Wei; Ma, Wu; Dai, Huan; Liu, Yawei; Wang, Ming; Hua, He Yu; Ou, Jinying; Sun, Xiaomin; Sun, Xuegang; Yang, Yanlin

doi:10.18632/oncotarget.19891

Cited by 9 publications

(4 citation statements)

References 40 publications

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“…Apart from the regulation of inflammatory response, p53 mostly functions in acute injury by regulating apoptosis and cell arrest. In liver injury model, San huang yin chi decoction has been reported to improve hepatic injury by downregulating p53-mediated apoptosis signaling pathway ( Diao et al, 2017 ). In acute lung injury, Physalis alkekengi L. var.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms Underlying the Effects of Lianhua Qingwen on Sepsis-Induced Acute Lung Injury: A Network Pharmacology Approach

Yang

Wei

et al. 2021

Front. Pharmacol.

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Background and Purpose: Sepsis is a life-threatening condition associated with secondary multiple organ injury. Acute lung injury (ALI) caused by sepsis has high morbidity and mortality in critical care units. Lianhua Qingwen (LHQW) is a traditional Chinese medicine composing of 11 herbs and 2 medicinal minerals. LHQW exhibits anti-inflammatory activity and is effective in treating pneumonia. Our study aimed to evaluate the effect of LHQW on sepsis-induced ALI and its underlying mechanism.Materials and Methods: A network pharmacology approach was used to predict the bioactive components and effective targets of LHQW in treating ALI. We established ALI model C57/BL6 mice via an intraperitoneal injection of LPS and inhibited p53 expression by pifithrin-α, in order to validate the mechanism by which LHQW exerted protective role in ALI. Hematoxylin-eosin staining was conducted to assess the severity of lung injury. The severity of inflammation was evaluated based on MPO (myeloperoxidase) activity. TUNEL assay was employed to detect apoptotic cells. The levels of p53 and caspase-3 were tested by immunohistochemical staining and Western blotting. The expression levels of Bcl-2, Bax, cytochrome C and caspase-9 were detected by Western blotting.Results: A total of 80 genes were associated with LHQW in the treatment of ALI. After PPI network construction, four active components (quercetin, luteolin, kaempferol and wogonin) and 10 target genes (AKT1, TP53, IL6, VEGFA, TNF, JUN, STAT3, MAPK8, MAPK1, and EGF) were found to be essential for ALI treatment. GO and KEGG analyses indicated that apoptosis pathway was mainly involved in the LHQW-ALI network. Animal experiments showed that LHQW was able to attenuate LPS-induced ALI, and medium-dose LHQW exhibited the most prominent effect. LHQW could inhibit the overexpression of p53 induced by LPS and suppress p53-mediated intrinsic apoptotic pathways by decreasing the levels of Bax, caspase-3 and caspase-9, increasing the expression of Bcl-2, and attenuating the release of cytochrome C in ALI mice.Conclusion: This study reveals that LHQW may alleviate LPS-induced ALI via inhibiting p53-mediated intrinsic apoptosis pathways.

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Section: Discussionmentioning

confidence: 99%

Mechanisms Underlying the Effects of Lianhua Qingwen on Sepsis-Induced Acute Lung Injury: A Network Pharmacology Approach

Yang

Wei

et al. 2021

Front. Pharmacol.

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“…As illustrated in Table 1, CCl 4 is the most frequently used method to establish ACLF models. Normally, rats are selected to administrate CCl 4 via intraperitoneal injection, subcutaneous injection, intragastric gavage or inhalation for 6-8 or 8-12 weeks to induce the chronic liver injury with a fibrotic or cirrhotic state (12,(86)(87)(88), then D-GalN alone or D-GalN plus LPS are administrated (86,89). Meanwhile, ACLF models can also be established in mice treated with CCl 4 for 6-8 weeks to a fibrotic state then following the D-GalN/LPS administration (90)(91)(92)(93)(94).…”

Section: + D-galn/lpsmentioning

confidence: 99%

The progress to establish optimal animal models for the study of acute-on-chronic liver failure

Zhai

Zhang²,

Shang³

et al. 2023

Front. Med.

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Acute-on-chronic liver failure (ACLF) defines a complicated and multifaceted syndrome characterized by acute liver dysfunction following an acute insult on the basis of chronic liver diseases. It is usually concurrent with bacterial infection and multi-organ failure resulting in high short-term mortality. Based on the cohort studies in ACLF worldwide, the clinical course of ACLF was demonstrated to comprise three major stages including chronic liver injury, acute hepatic/extrahepatic insult, and systemic inflammatory response caused by over-reactive immune system especially bacterial infection. However, due to the lack of optimal experimental animal models for ACLF, the progress of basic study on ACLF is limping. Though several experimental ACLF models were established, none of them can recapitulate and simulate the whole pathological process of ACLF patients. Recently, we have developed a novel mouse model for ACLF combining chronic liver injury [injection of carbon tetrachloride (CCl4) for 8 weeks], acute hepatic insult (injection of a double dose CCl4), and bacterial infection (intraperitoneal injection of Klebsiella pneumoniae), which could recapitulate the major clinical features of patients with ACLF worsened by bacterial infection.

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“…45 Representatives of CCl 4 -dependent models are summarized in Table 1. [28][29][30]32,[45][46][47][48][49][50][51][52][53][54][55][56]…”

Section: -Based Modelsmentioning

confidence: 99%

Prospect of Animal Models for Acute-on-chronic Liver Failure: A Mini-review

Hassan¹,

Li²

2022

J Clin Transl Hepatol

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Acute-on-chronic liver failure (ACLF) is a clinical syndrome that develops in patients with chronic liver diseases following a precipitating event and associated with a high mortality rate due to systemic multiorgan failure. Establishing a suitable and stable animal model to precisely elucidate the molecular basis of ACLF pathogenesis is essential for the development of effective early diagnostic and treatment strategies. In this context, this article provides a concise and inclusive review of breakthroughs in ACLF animal model development.

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SHYCD induces APE1/Ref-1 subcellular localization to regulate the p53-apoptosis signaling pathway in the prevention and treatment of acute on chronic liver failure

Cited by 9 publications

References 40 publications

Mechanisms Underlying the Effects of Lianhua Qingwen on Sepsis-Induced Acute Lung Injury: A Network Pharmacology Approach

Mechanisms Underlying the Effects of Lianhua Qingwen on Sepsis-Induced Acute Lung Injury: A Network Pharmacology Approach

The progress to establish optimal animal models for the study of acute-on-chronic liver failure

Prospect of Animal Models for Acute-on-chronic Liver Failure: A Mini-review

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