RETRACTED ARTICLE: Silencing of EPCAM suppresses hepatic fibrosis and hepatic stellate cell proliferation in mice with alcoholic hepatitis via the PI3K/Akt/mTOR signaling pathway

Zhang, Zhi; Wen, Huiqing; Weng, Jun; Feng, Lei; Liu, Hongya; Hu, Xiaojun; Zeng, Fanhong

doi:10.1080/15384101.2019.1642067

Cited by 22 publications

(13 citation statements)

References 34 publications

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“…And our data strongly indicated that RUT could partly participate in the palliation of the damage caused by ethanol though anti-apoptosis. The present findings also revealed that ethanol inhibited PI3K/ AKT pathway, which is consistent with previous literature (Zhang et al, 2019). In fact, the activation of PI3K/AKT pathway is essential for cell resistance to oxidation and apoptosis (Arab et al, 2019;Cao et al, 2020).…”

Section: Discussionsupporting

confidence: 93%

Rutaecarpine Ameliorates Ethanol-Induced Gastric Mucosal Injury in Mice by Modulating Genes Related to Inflammation, Oxidative Stress and Apoptosis

Ren

Wei

et al. 2020

Front. Pharmacol.

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Background: Rutaecarpine (RUT), a major quinazolino carboline alkaloid compound from the dry unripe fruit Tetradium ruticarpum (A. Juss.) T. G. Hartley, has various pharmacological effects. The aim of this present study was to investigate the potential gastroprotective effect of rutaecarpine on ethanol-induced acute gastric mucosal injury in mice and associated molecular mechanisms, such as activating Nrf2 and Bcl-2 via PI3K/AKT signaling pathway and inhibiting NF-κB.Methods: Gastric ulcer index and histopathology was carried out to determine the efficacy of RUT in gastric ulceration, and the content of SOD, GSH in serum and CAT, MDA, MPO, TNF-α, IL-6, IL-1β in tissue were measured by kits. Besides, in order to illustrate the potential inflammatory, oxidative, and apoptotic perturbations, the mRNA levels of NF-κB p65, PI3K, AKT, Nrf2, Nqo1, HO-1, Bcl-2 and Bax were analyzed. In addition, the protein expression of NF-κB p65 and Nrf2 in cytoplasm and nucleus, AKT, p-AKT, Bcl-2 Bax and Caspase 3 were analyzed for further verification. Finally, immunofluorescence analysis was performed to further verify nuclear translocation of NF-κB p65.Results: Current data strongly demonstrated that RUT alleviated the gross gastric damage, ulcer index and the histopathology damage caused by ethanol. RUT inhibited the expression and nuclear translocation of NF-κB p65 and the expression of its downstream signals, such as TNF-α, IL-6, IL-1β and MPO. Immunofluorescence analysis also verifies the result. In the context of oxidative stress, RUT improved the antioxidant milieu by remarkably upregulating the expression Nqo1 and HO-1 with activating Nrf2, and could remarkably upregulate antioxidant SOD, GSH, CAT and downregulate levels of MDA. Additionally, RUT activate the expression of Bcl-2 and inhibited the expression of downstream signals Bax and Caspase 3 to promote gastric cellular survival. These were confirmed by RUT activation of the PI3K/AKT pathway manifested by enhanced expression of PI3K and promotion of AKT phosphorylation.Conclusion: Taken together, these results strongly demonstrated that RUT exerted a gastroprotective effect against gastric mucosal injury induced by ethanol. The underlying mechanism might be associated with the improvement of anti-inflammatory, anti-oxidation and anti-apoptosis system.

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Section: Discussionsupporting

confidence: 93%

Rutaecarpine Ameliorates Ethanol-Induced Gastric Mucosal Injury in Mice by Modulating Genes Related to Inflammation, Oxidative Stress and Apoptosis

Ren

Wei

et al. 2020

Front. Pharmacol.

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“…et al, 2017 ), CXCL12 ( Semaan et al, 2017 ), and SENP2 ( Shen et al, 2012 ) were also reported to participate in the pathogenesis of liver cirrhosis and HCC. Zhang et al (2019) confirmed that silencing EPCAM can inhibit hepatic fibrosis and hepatic stellate cell proliferation in mice with alcoholic hepatitis through the PI3K/Akt/mTOR signaling pathway. Wenfang Tian et al (2016) also found that WDR5 is an important epigenetic factor in the process of liver fibrosis.…”

Section: Resultsmentioning

confidence: 64%

Identification and Analysis of the Blood lncRNA Signature for Liver Cirrhosis and Hepatocellular Carcinoma

Xia

Shu

et al. 2020

Front. Genet.

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As one of the most common malignant tumors, hepatocellular carcinoma (HCC) is the fifth major cause of cancer-associated mortality worldwide. In 90% of cases, HCC develops in the context of liver cirrhosis and chronic hepatitis B virus (HBV) infection is an important etiology for cirrhosis and HCC, accounting for 53% of all HCC cases. To understand the underlying mechanisms of the dynamic chain reactions from normal to HBV infection, from HBV infection to liver cirrhosis, from liver cirrhosis to HCC, we analyzed the blood lncRNA expression profiles from 38 healthy control samples, 45 chronic hepatitis B patients, 46 liver cirrhosis patients, and 46 HCC patients. Advanced machine-learning methods including Monte Carlo feature selection, incremental feature selection (IFS), and support vector machine (SVM) were applied to discover the signature associated with HCC progression and construct the prediction model. One hundred seventy-one key HCC progression-associated lncRNAs were identified and their overall accuracy was 0.823 as evaluated with leave-one-out cross validation (LOOCV). The accuracies of the lncRNA signature for healthy control, chronic hepatitis B, liver cirrhosis, and HCC were 0.895, 0.711, 0.870, and 0.826, respectively. The 171-lncRNA signature is not only useful for early detection and intervention of HCC, but also helpful for understanding the multistage tumorigenic processes of HCC.

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“…The JAK-STAT pathway is one of the most studied pathways in cell signal transduction and plays a variety of roles in physiological processes. 33 In addition, we found that caspase-3, which is associated with cell apoptosis, was upregulated after Rab40b knockdown. Therefore, the exact regulation between Rab40b and cleaved caspase-3 needs further investigation.…”

Section: Discussionmentioning

confidence: 77%

<p>Overexpression of Rab40b Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis via PI3K/AKT Signaling Pathway</p>

Shi

Zhang

Zhong

et al. 2020

CMAR

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Background: Rab40b is an evolutionarily conserved Rab GTPase that plays an important role in intracellular trafficking and is closely related to cancer progression. However, the role and potential molecular mechanism of Rab40b in hepatocellular carcinoma (HCC) have not yet been elucidated. Materials and Methods: The expression of Rab40b in HCC tissues and peritumour tissues was tested by qRT-PCR, Western blotting and histological analysis. A Kaplan-Meier survival curve was generated based on the expression of Rab40b in the HCC samples. Cell proliferation assays, wound healing assays, and transwell assays are used to examine the effect of Rab40b on HCC cell growth in vitro. The effect of Rab40b on cell cycle was examined by flow cytometry. A xenograft implantation model was used to assess the effect of Rab40b on the development of HCC cells in vivo. Results: Rab40b protein expression is upregulated in HCC tissues, and this upregulation is associated with high pathological stage and poor prognosis in HCC patients. Rab40b overexpression promotes the proliferation and metastasis of HCC cells by upregulating cyclin D1, cyclin E1 and matrix metalloproteinase 2 (MMP2) through the PI3K/AKT signalling pathway. Conversely, Rab40b inhibitors can significantly inhibit the proliferation and metastasis of HCC cell lines and induce G0/G1 cell cycle arrest and apoptosis. Studies of a nude mouse xenograft model demonstrated that Rab40b knockdown can significantly inhibit the proliferation and progression of HCC tumours in vivo. Conclusion: Overall, this study demonstrates that Rab40b is an important oncoprotein that promotes HCC progression by regulating the expression of cyclin D1, cyclin E1, p21 and MMP2 through the PI3K/AKT signalling pathway.

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RETRACTED ARTICLE: Silencing of EPCAM suppresses hepatic fibrosis and hepatic stellate cell proliferation in mice with alcoholic hepatitis via the PI3K/Akt/mTOR signaling pathway

Cited by 22 publications

References 34 publications

Rutaecarpine Ameliorates Ethanol-Induced Gastric Mucosal Injury in Mice by Modulating Genes Related to Inflammation, Oxidative Stress and Apoptosis

Rutaecarpine Ameliorates Ethanol-Induced Gastric Mucosal Injury in Mice by Modulating Genes Related to Inflammation, Oxidative Stress and Apoptosis

Identification and Analysis of the Blood lncRNA Signature for Liver Cirrhosis and Hepatocellular Carcinoma

<p>Overexpression of Rab40b Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis via PI3K/AKT Signaling Pathway</p>

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