Chronic infection with the Hepatitis B Virus (HBV) is a major cause of liver-related morbidity and mortality. One peculiar observation in cells infected with HBV (or with closely‑related animal hepadnaviruses) is the presence of viral DNA integration in the host cell genome, despite this form being a replicative dead-end for the virus. The frequent finding of somatic integration of viral DNA suggests an evolutionary benefit for the virus; however, the mechanism of integration, its functions, and the clinical implications remain unknown. Here we review the current body of knowledge of HBV DNA integration, with particular focus on the molecular mechanisms and its clinical implications (including the possible consequences of replication-independent antigen expression and its possible role in hepatocellular carcinoma). HBV DNA integration is likely to influence HBV replication, persistence, and pathogenesis, and so deserves greater attention in future studies.

https://www.mdpi.com/1999-4915/9/4/75/pdf

HBV DNA Integration: Molecular Mechanisms and Clinical Implications

https://www.gastrojournal.org/article/S0016-5085(06)00012-6/pdf

High Prevalence and Mapping of Pre-S Deletion in Hepatitis B Virus Carriers With Progressive Liver Diseases

Hepatitis B virus PreS/S gene variants: Pathobiology and clinical implications

http://ir.lib.ncku.edu.tw/bitstream/987654321/45245/1/7010100503016.pdf

Endoplasmic reticulum stress stimulates the expression of cyclooxygenase-2 through activation of NF-κB and pp38 mitogen-activated protein kinase

https://www.gastrojournal.org/article/S0016-5085(07)01643-5/pdf

Pre-S deletion and complex mutations of hepatitis B virus related to advanced liver disease in HBeAg-negative patients.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1053/jhep.2001.21163

Prevalence and significance of hepatitis B virus (HBV) pre-S mutants in serum and liver at different replicative stages of chronic HBV infection☆

A new mode of electromembrane extraction (EME) has been developed for detection via matrix-assisted laser desorption/ionization mass spectrometry (MALDI/MS). Posaconazole, extracted from 8 mL of a 10 mM trifluoroacetic acid solution onto a thin polyvinylidene difluoride (PVDF) membrane, was used as a model analyte. The transport was forced by an electrical potential difference between two electrodes inside the lumen of a hollow fiber and glass tube. Under an application of 80 V, cationic posaconazole in the sample solution moved toward the negative electrode inside the glass tube and was trapped by the PVDF membrane on the side. After 15 min of extraction, 3 μL of α-cyano-4-hydroxycinnamic acid (CHCA) solution was applied on top of the membrane, which was then analyzed by MALDI/MS. Under optimal extraction conditions, the calibration curve of posaconazole was linear over a concentration range of 0.10–100.00 nM. The limit of detection (LOD) at a signal-to-noise ratio of 3 was 0.03 nM with an enhancement factor of 138 for posaconazole. The application of this method to the determination of posaconazole in human serum samples was also successfully demonstrated.

/pdf/electromembrane-extraction-of-posaconazole-for-matrix-3uugj6tj.pdf

Electromembrane Extraction of Posaconazole for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometric Detection

A rapid and sensitive protein determination method that uses electromembrane extraction (EME) and is coupled with matrix-assisted laser desorption/ionization mass spectrometry (MALDI/MS) is developed. A flat nylon membrane is used to collect proteins from an aqueous solution and is directly analyzed by MALDI/MS after the addition of the MALDI matrix. Insulin is used as a model protein to investigate the optimum extraction of the parameters. The optimum EME conditions are obtained at 12 V of voltage, 10 min of extraction time, 12 mL sample volume, and 400 rpm agitation rate. The linear dynamic range (LDR) of insulin in an aqueous solution is in the range of 1.0–100.0 nM. The limit of detection (LOD) for insulin in an aqueous solution is 0.3 nM with 103-fold signal-to-noise (S/N) ratio enhancement. Furthermore, the applicability of this method to determine insulin in complicated sample matrices is also investigated. The LDR of insulin in human urine samples is in the range of 5.0–100.0 nM, and the LOD of insulin in urine samples is calculated to be 1.5 nM. The precision and accuracy of this method are evaluated at three different concentration levels, and the coefficient of variation (CV) and relative error are less than 6%. This approach is time-efficient and economical, as the flat membrane mode of EME coupled with MALDI/MS is suitable.

/pdf/nylon-membrane-based-electromembrane-extraction-coupled-with-1odg41o0.pdf

Nylon Membrane-Based Electromembrane Extraction Coupled with Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry for the Determination of Insulin

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Papers

Prevalence and significance of hepatitis B virus (HBV) pre-S mutants in serum and liver at different replicative stages of chronic HBV infection☆

Electromembrane Extraction of Posaconazole for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometric Detection

Nylon Membrane-Based Electromembrane Extraction Coupled with Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry for the Determination of Insulin