Epigenetic regulation and its therapeutic potential in hepatitis B virus covalently closed circular DNA.

Human hepatitis B virus (HBV) infection is the major cause of acute and chronic hepatitis B, liver cirrhosis, and hepatocellular carcinoma. Although the application of prophylactic vaccination programs has successfully prevented the trend of increasing HBV infection prevalence, the number of HBV-infected people remains very high. Approved therapeutic management efficiently suppresses viral replication; however, HBV infection is rarely completely resolved.

Colchicine-mediated selective autophagic degradation of HBV core proteins inhibits HBV replication and HBV-related hepatocellular carcinoma progression.

The HBV core protein (HBc) is an important viral protein of HBV that plays an indispensable role in the lifecycle of HBV, including capsid assembly and transport, reverse transcription and virus release. In recent years, evidence has shown that HBc may be involved in the malignant progression of HCC. Thus, HBc is an attractive target for antiviral agents and provides a new strategy for the treatment of HBV-related HCC.

Neuropilin-1 is a novel host factor modulating the entry of hepatitis B virus.

Background & Aims: Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the cellular receptor for HBV. However, hepatocytes expressing NTCP exhibit varying susceptibilities to HBV infection. This study aimed to investigate whether other host factors modulate the process of HBV infection.

HOXA-AS2 Epigenetically Inhibits HBV Transcription by Recruiting the MTA1-HDAC1/2 Deacetylase Complex to cccDNA Minichromosome.

Persistent transcription of HBV covalently closed circular DNA (cccDNA) is critical for chronic HBV infection. Silencing cccDNA transcription through epigenetic mechanisms offers an effective strategy to control HBV. Long non-coding RNAs (lncRNAs), as important epigenetic regulators, have an unclear role in cccDNA transcription regulation.

Kinesin Family Member-18A (KIF18A) Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma.

Background & Aims: Kinesin family member 18A (KIF18A) is notable for its aberrant expression across various cancer types and its pivotal role is driving cancer progression. In this study, we aim to investigate the intricate molecular mechanisms underlying the impact of KIF18A on the progression of HCC.

Methods: Western blotting assays, a quantitative real-time PCR and immunohistochemical analyses were performed to quantitatively assess KIF18A expression in HCC tissues.

ZNF148 inhibits HBV replication by downregulating RXRα transcription.

Background: Progressive hepatitis B virus (HBV) infection can result in cirrhosis, hepatocellular cancer, and chronic hepatitis. While antiviral drugs that are now on the market are efficient in controlling HBV infection, finding a functional cure is still quite difficult. Identifying host factors involved in regulating the HBV life cycle will contribute to the development of new antiviral strategies.

Chromatin binding protein HMGN1 promotes HBV cccDNA transcription and replication by regulating the phosphorylation of histone 3.

Background And Aims: Direct elimination of cccDNA remains a formidable obstacle due to the persistent and stable presence of cccDNA in hepatocyte nuclei. The silencing of cccDNA transcription enduringly is one of alternative strategies in the treatment of hepatitis B. Protein binding to cccDNA plays an important role in its transcriptional regulation; thus, the identification of key factors involved in this process is of great importance.

Inhibiting cholesterol de novo synthesis promotes hepatocellular carcinoma progression by upregulating prostaglandin E synthase 2-mediated arachidonic acid metabolism under high fatty acid conditions.

Inhibition of cholesterol de novo synthesis (DNS) by statins has controversial effects on the treatment of hepatocellular carcinoma (HCC). High fatty acid conditions have been reported to limit the effect of statins on metabolism diseases. Whether high fatty acid conditions interfere with the effect of statins on HCC remains unclear.

Gambogic acid inhibits HBx-mediated hepatitis B virus replication by targeting the DTX1-Notch signaling pathway.

Background & Aims: Current antiviral drugs, including nucleoside analogs and interferon, fail to eliminate the HBV covalently closed circular DNA (cccDNA), which serves as a transcript template in infected hepatocytes. Silencing the HBV X protein, which plays a crucial role in cccDNA transcription, is a promising approach to inhibit HBV replication. Therefore, the identification of novel compounds that can inhibit HBx-mediated cccDNA transcription is critical.

Fault Diagnosis of Planetary Gearbox Based on Dynamic Simulation and Partial Transfer Learning.

To address the problem of insufficient real-world data on planetary gearboxes, which makes it difficult to diagnose faults using deep learning methods, it is possible to obtain sufficient simulation fault data through dynamic simulation models and then reduce the difference between simulation data and real data using transfer learning methods, thereby applying diagnostic knowledge from simulation data to real planetary gearboxes. However, the label space of real data may be a subset of the label space of simulation data. In this case, existing transfer learning methods are susceptible to interference from outlier label spaces in simulation data, resulting in mismatching.

Research on the Influence of Geometric Structure Parameters of Eddy Current Testing Probe on Sensor Resolution.

To study the influence of the geometric structure of the probe coil on the electromagnetic characteristics of the eddy current probe in the process of eddy current testing, based on the principle of eddy current testing, different probe coil models were established using finite element software. These geometric structure parameters include the difference between the inner and outer radius, thickness, and equivalent radius. The magnetic field distribution around the probe is simulated and analyzed under different parameters, and the detection performance of the probe is judged in combination with the change rate of the magnetic field around the probe coil.

Sphondin efficiently blocks HBsAg production and cccDNA transcription through promoting HBx degradation.

Hepatitis B surface antigen (HBsAg) loss and seroconversion, which is considered as functional cure of chronic Hepatitis B virus (HBV) infection, is rarely achieved even after long-term antiviral treatments. Therefore, new antiviral strategies interfering with other HBV replication steps are required, especially those that could efficiently inhibit HBsAg production. Here, we identified novel anti-HBV compounds that could potently block HBsAg expression from cccDNA by screening a natural compound library derived from Chinese traditional medical plants by a novel screening strategy.

Rapamycin inhibits hepatitis B virus covalently closed circular DNA transcription by enhancing the ubiquitination of HBx.

Hepatitis B virus (HBV) infection is still a serious public health problem worldwide. Antiviral therapies such as interferon and nucleos(t)ide analogs efficiently control HBV replication, but they cannot eradicate chronic hepatitis B (CHB) because of their incapacity to eliminate endocellular covalently closed circular DNA (cccDNA). Thus, there is a necessity to develop new strategies for targeting cccDNA.

HBx Mediated Increase of DDX17 Contributes to HBV-Related Hepatocellular Carcinoma Tumorigenesis.

HBV is strongly associated with HCC development and DEAD-box RNA helicase 17 (DDX17) is a very important member of the DEAD box family that plays key roles in HCC development by promoting cancer metastasis. However, the important role of DDX17 in the pathogenesis of HBV-related HCC remains unclear. In this study, we investigated the role of DDX17 in the replication of HBV and the development of HBV-associated HCC.

Pimobendan Inhibits HBV Transcription and Replication by Suppressing HBV Promoters Activity.

Current anti-HBV therapeutic strategy relies on interferon and nucleos(t)ide-type drugs with the limitation of functional cure, inducing hepatitis B surface antigen (HBsAg) loss in very few patients. Notably, the level of HBsAg has been established as an accurate indicator to evaluate the drug efficacy and predict the disease prognosis, thus exploring a novel drug targeting HBsAg will be of great significance. Herein, by screening 978 compounds from an FDA-approved drug library and determining the inhibitory function of each drug on HBsAg level in HepG2.

SIRT2 Promotes HBV Transcription and Replication by Targeting Transcription Factor p53 to Increase the Activities of HBV Enhancers and Promoters.

Chronic hepatitis B (CHB) virus infection is one of the leading causes of cirrhosis and liver cancer. Although the major drugs against CHB including nucleos(t)ide analogs and PEG-interferon can effectively control human hepatitis B virus (HBV) infection, complete cure of HBV infection is quite rare. Targeting host factors involved in the viral life cycle contributes to developing innovative therapeutic strategies to improve HBV clearance.

Glutamate dehydrogenase 1 mediated glutaminolysis sustains HCC cells survival under glucose deprivation.

Besides aerobic glycolysis, glutaminolysis has also become a hot spot in the field of tumor research because of its important role in regulating cell proliferation, apoptosis, and migration and invasion. Meanwhile, it is generally believed that tumor cells could sustain its proliferation and survival according to a so-called metabolic flexibility. How the metabolic flexibility of HCC cells behaves has not yet been fully elucidated.

KAT2A Promotes Hepatitis B Virus Transcription and Replication Through Epigenetic Regulation of cccDNA Minichromosome.

Hepatitis B virus (HBV) infection remains a major health problem worldwide. Sufficient maintenance of the HBV covalently closed circular DNA (cccDNA), which serves as a template for HBV transcription, is responsible for the failure of antiviral therapies. While accumulating evidence suggests that cccDNA transcription is regulated by epigenetic machinery, particularly the acetylation and methylation of cccDNA-bound histone 3 (H3) and histone 4 (H4), the potential contributions of histone succinylation and related host factors remain obscured.

DDX17-regulated alternative splicing that produced an oncogenic isoform of PXN-AS1 to promote HCC metastasis.

Background And Aims: The mechanism underlying HCC metastasis remains unclear, many oncogenes are known to regulate this process. However, the role of alternative splicing (AS) in pro-metastatic HCC is poorly understood.

Approach And Results: By performing RNA sequencing on nine pairs of primary HCC tissues with extrahepatic metastasis (EHMH) and nine pairs of metastasis-free HCC (MFH) tissues, we depicted the AS landscape in HCC and found a higher frequency of AS events in EHMH compared with MFH.