Complexity on modulation of NF‐κB pathways by hepatitis B and C: A double‐edged sword in hepatocarcinogenesis

Shokri, Somayeh; Mahmoudvand, Shahab; Taherkhani, Reza; Farshadpour, Fatemeh; Jalalian, Farid Azizi

doi:10.1002/jcp.28249

Cited by 25 publications

(20 citation statements)

References 111 publications

(162 reference statements)

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“…IKBKB, CHUK, and NFKBIA are important genes in the NF-κB pathway that are involved in regulating various proteins involved in physiological and pathological processes such as inflammatory translation, immunity, cell proliferation, differentiation, and apoptosis. If NF-κB is overactivated, it will cause immune liver damage and promote the development of liver fibrosis by inhibiting apoptosis of hepatic stellate cells [48]. This study indicated that IKBKB is regulated by the MOL000422 compound, which acts on 11 pathways.…”

Section: Discussionmentioning

confidence: 75%

Network pharmacology-based study on the mechanism of Yiganling capsule in hepatitis B treatment

Lü

Zhou

et al. 2020

BMC Complement Med Ther

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Background: Yiganling (YGL) capsule is a traditional Chinese medicine preparation consisting of eight herbs that has been clinically proven to have a favorable treatment effect on Hepatitis B (HB). However, due to its multiple targets and multi-pharmacological effects, the mechanisms of YGL capsule in the treatment of HB are unknown. Methods: First, the chemical constituents of YGL capsules were obtained from the Chinese medicine database, and YGL capsules were constructed. Second, active compounds were screened by the ADME model. The target fishing model was used to screen the corresponding targets of active compounds and to construct a compounds and compound targets network. Using human disease databases and literature mining, we systematically identified genes associated with HB, constructed disease-specific protein-protein interaction networks, and performed clustering and enrichment analyses of these networks. These networks were then merged to obtain a compounddisease target network, and cluster and enrichment analyses were performed on the compound-disease target network to acquire a compounds-disease targets-mechanism network and a clustering network. Results: We successfully built eight pharmacological network diagrams, including four primary networks and other network maps. The four dominating network maps included a HB disease-associated protein-protein interaction network, a YGL capsule compounds-target network, a YGL capsule ingredient target-HB disease target network, and a YGL-HB disease mechanism network. Other networks included a pathway of HB disease targets, the HB disease protein-protein interaction cluster analysis network, and the YGL-HB target clustering network. Conclusion: This study successfully forecasted, illuminated, and confirmed the synergistic effects of HB disease molecules and discovered the potential of HB relevant targets, clusters, and target-related biological processes and signaling pathways. Our research not only provides theoretical support for the molecular and pharmacological mechanisms of YGL capsule in HB treatment, but also provides new research methods for the study of the other traditional Chinese medicinal compounds.

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Section: Discussionmentioning

confidence: 75%

Network pharmacology-based study on the mechanism of Yiganling capsule in hepatitis B treatment

Lü

Zhou

et al. 2020

BMC Complement Med Ther

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“…Thus, these viruses can contribute to the oncogenic state either through chronic NF-κB-dependent inflammation or by the sustained activity of viral activators of NF-κB. Examples of virally encoded NF-κB activators include the LMP1 protein of Epstein–Barr virus (B cell lymphoma, nasopharyngeal carcinoma) [ 64 ], the vFLIP protein of Kaposi sarcoma herpesvirus (sarcoma, lymphoma) [ 64 ], the Tax protein of HTLV-1 (T cell leukemia) [ 65 ], the X protein of hepatitis B virus (liver cancer) [ 66 ], and the E6 and E7 proteins of some strains of the human papillomavirus (cervical cancer) [ 67 ].…”

Section: Cancer Cell-induced Activation Of Nf-κbmentioning

confidence: 99%

NF-κB and Human Cancer: What Have We Learned over the Past 35 Years?

Gilmore

2021

Biomedicines

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Transcription factor NF-κB has been extensively studied for its varied roles in cancer development since its initial characterization as a potent retroviral oncogene. It is now clear that NF-κB also plays a major role in a large variety of human cancers, including especially ones of immune cell origin. NF-κB is generally constitutively or aberrantly activated in human cancers where it is involved. These activations can occur due to mutations in the NF-κB transcription factors themselves, in upstream regulators of NF-κB, or in pathways that impact NF-κB. In addition, NF-κB can be activated by tumor-assisting processes such as inflammation, stromal effects, and genetic or epigenetic changes in chromatin. Aberrant NF-κB activity can affect many tumor-associated processes, including cell survival, cell cycle progression, inflammation, metastasis, angiogenesis, and regulatory T cell function. As such, inhibition of NF-κB has often been investigated as an anticancer strategy. Nevertheless, with a few exceptions, NF-κB inhibition has had limited success in human cancer treatment. This review covers general themes that have emerged regarding the biological roles and mechanisms by which NF-κB contributes to human cancers and new thoughts on how NF-κB may be targeted for cancer prognosis or therapy.

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“…Apart from the direct HBV-dependent induction of ROS i.e by HBx, there are indirect mechanisms. Both regulatory proteins of HBV (HBx and LHBs) have the capacity to activate NF-kB [268,300,301,302]. On the one hand, the HBV-dependent activation of NF-kB leads to the induction of proinflammatory cytokines like TNFα, lymphotoxin-α or IL-6 and on the other hand HBx was described to suppress the expression of anti-inflammatory cytokines [302,303,304,305,306].…”

Section: Ros Nrf2 and The Virus-associated Pathogenesismentioning

confidence: 99%

Effect of Hepatitis Viruses on the Nrf2/Keap1-Signaling Pathway and Its Impact on Viral Replication and Pathogenesis

Bender

Hildt

2019

IJMS

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With respect to their genome and their structure, the human hepatitis B virus (HBV) and hepatitis C virus (HCV) are complete different viruses. However, both viruses can cause an acute and chronic infection of the liver that is associated with liver inflammation (hepatitis). For both viruses chronic infection can lead to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Reactive oxygen species (ROS) play a central role in a variety of chronic inflammatory diseases. In light of this, this review summarizes the impact of both viruses on ROS-generating and ROS-inactivating mechanisms. The focus is on the effect of both viruses on the transcription factor Nrf2 (nuclear factor erythroid 2 (NF-E2)-related factor 2). By binding to its target sequence, the antioxidant response element (ARE), Nrf2 triggers the expression of a variety of cytoprotective genes including ROS-detoxifying enzymes. The review summarizes the literature about the pathways for the modulation of Nrf2 that are deregulated by HBV and HCV and describes the impact of Nrf2 deregulation on the viral life cycle of the respective viruses and the virus-associated pathogenesis.

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Complexity on modulation of NF‐κB pathways by hepatitis B and C: A double‐edged sword in hepatocarcinogenesis

Cited by 25 publications

References 111 publications

Network pharmacology-based study on the mechanism of Yiganling capsule in hepatitis B treatment

Network pharmacology-based study on the mechanism of Yiganling capsule in hepatitis B treatment

NF-κB and Human Cancer: What Have We Learned over the Past 35 Years?

Effect of Hepatitis Viruses on the Nrf2/Keap1-Signaling Pathway and Its Impact on Viral Replication and Pathogenesis

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