(1) Background: Hepatitis B virus (HBV) belongs to the Hepadnaviridae family of viruses that interact with hepatocytes. HBV infection is a major global health problem. Most adults clear the infection quickly after being infected with HBV, while a few people develop chronic HBV infection. It is well-known that the early innate immune response of host cells plays an important role in the fight against virus infection. However, the interactions between HBV and the intrinsic innate immune system of hepatocytes are still not fully understood. The aim of this study was to confirm the interaction between HBV and hepatocytes, and to identify the interferon-stimulated genes (ISGs) regulated by HBx and their expression in association with HBV-associated HCC (HBV-HCC), so that we can refine our understanding of the interaction between HBV and ISGs and its potential influence on HBV-HCC. (2) Methods: We analyzed data concerning the stimulation of IFN-dependent genes in primary human hepatocytes (PHHs) transfected with pathogen DNA mimetics or infected with HBV in the GSE69590 database. Bioinformatic methods, such as GSEA, GO, and KEGG, were used to analyze the differentially expressed innate immunity genes and their related pathways to identify candidate intrinsic innate immune factors. qPCR on HepG2 and Huh7 cells, which highly express HBx, was used to detect relevant intrinsic innate immune factors. qPCR, RNAi, and Elisa methods were used to identify intrinsic innate immune factors in HBV-integrated HepG2.2.15 cells, and bioinformatics analysis was conducted on the HBV-infected tissues and cells in the GEO database. (3) Results: Inhibition of the JAK-STAT pathway enhanced HBV replication in HepG2 cells transfected with HBV plasmid and HepG2-NTCP cells infected with HBV. GSEA analysis of the GSE69590 data revealed significant changes in intrinsic innate immune pathways during HBV infection with PHH for 40 h. A total of 84 differentially expressed, candidate innate immunity genes were identified in GSE69590. Validation showed that TRIM22 and TRIM56 were down-regulated when HBx was expressed. Consistently, TRIM22 and TRIM56 were up-regulated following inhibition of HBx by transfection of HBx siRNA into HepG2.2.15 cells, and HBV pgRNA was up-regulated following down-regulated expression of TRIM22 and TRIM56 in HEK293 cells. Receiver operating characteristics (ROC) and overall survival (OS) analysis of 204 HBV-HCC patients showed that expression of TRIM22 was closely associated with HBV-HCC, and high expression of TRIM22 was associated with longer survival. (4) Conclusions: Innate immunity genes TRIM22 and TRIM56 are regulated by HBx, and higher expression of TRIM22 is closely related to longer survival of HBV-HCC patients.

Liver disease is a major worldwide health and economic problem. Allograft liver transplant is the only effective therapy for end-stage liver disease. The shortage of donors, the high costs, postoperative complications, and lifelong immunosuppression are rate-limiting factors for this established line of treatment. Hence, searching for therapeutic alternatives is mandatory. Stem cells are attractive candidates for cell-based therapy for their potential to support liver regeneration with few complications. They can differentiate into specialized cells, including hepatocytes to restore liver structure and function. Stem cells originating from different sources have been investigated for the treatment of liver diseases. In this review, we highlight the role of stem cells as an appropriate source for liver cell replacement in different liver diseases.

Vitamin D plays a central role in maintaining calcium, phosphorus, and bone homeostasis in close interaction with the parathyroid hormone. Obesity is a significant health problem worldwide, particularly in developed nations. The current study was carried out to investigate the possible relationship between body mass index (BMI) elevation and differentiation in 25-hydroxyvitamin D (VD), vitamin D receptor (VDR) gene expression, and genetic polymorphism besides oxidative stress in adult Egyptian individuals. This was done to explore the mechanisms underlying the suggested role of the VD/VDR complex in the pathogenesis of obesity. A total of 70 subjects (30 obese, 25 overweight, and 15 normal, age: 20–50 years, without other chronic diseases) were selected. The study focused on the determination of VD, VDR gene polymorphism, VDR gene expression, alkaline phosphatase, calcium, phosphorus, glucose, lipid profile, oxidative stress including, oxidant (malondialdehyde), and anti-oxidants (reduced glutathione and superoxide dismutase). The results showed that elevation in BMI led to the percentage of the Ff 'allele' becoming predominant, while the percentage of the FF 'allele' was in the normal BMI range. Also, BMI elevation caused significant reductions in VD and VDR expression, with significant elevations in alkaline phosphatase and the levels of calcium and phosphate in serum. Also, oxidative stress increases with increasing BMI. Elevation in BMI causes a reduction in VD concentration and VDR gene expression levels. Also, the percentage of heterozygous mutant genotype Ff 'allele' is predominantly in the obese human, in contrast to normal subjects, where the percentage of homozygous wild genotype FF 'allele' is predominant. In general, the genetic expression and polymorphism of VD and VDR can be used as a genetic marker for predisposition, diagnosis, prognosis, and progression of obesity.

A MicroRNA (miRNA) is defined as a small molecule of non-coding RNA (ncRNA). Its molecular size is about 20 nucleotides (nt), and it acts on gene expression's regulation at the post-transcription level through binding to the 3'untranslated regions (UTR), coding sequences, or 5'UTR of the target messenger RNAs (mRNAs), which leads to the suppression or degradation of the mRNA. In recent years, a huge evolution has identified the origin and function of miRNAs, focusing on their important effects in research and clinical applications. For example, microRNAs are key players in HCV infection and have important host cellular factors required for HCV replication and cell growth. Altered expression of miRNAs affects the pathogenicity associated with HCV infection through regulating different signaling pathways that control HCV/immunity interactions, proliferation, and cell death. On the other hand, circulating miRNAs can be used as novel biomarkers and diagnostic tools for HCV pathogenesis and early therapeutic response. Moreover, microRNAs (miRNA) have been involved in hepatitis B virus (HBV) gene expression and advanced antiviral discovery. They regulate HBV/HCV replication and pathogenesis with different pathways involving facilitation, inhibition, activation of the immune system (innate and adaptive), and epigenetic modifications. In this short review, we will discuss how microRNAs can be used as prognostic, diagnostic, and therapeutic tools, especially for chronic hepatitis viruses (HBV and HCV), as well as how they could be used as new biomarkers during infection and advanced treatment.

Monocyte locomotion inhibitory factor (MLIF) is a heat-stable pentapeptide from Entamoeba histolytica. Our previous study found that MLIF protects against ischemic stroke in rats and mice and exerts a neuroprotection effect in human neuroblastoma SH-SY5Y cells. Microglia/macrophage polarization has been proven to be vital in the pathology of ischemic stroke. Nevertheless, whether MLIF is able to modulate microglia/macrophage polarization remains unclear. We performed middle cerebral artery occlusion (MCAO) on C57BL/6J male mice and induced cultured BV2 microglia by oxygen-glucose deprivation (OGD), respectively. Immunfluorescence was utilized to detect the M1/2 markers, such as CD206 and CD16/32. qPCR and ELISA were used to detect the signature gene change of M1/2. The MAPK and NF-κB pathway associated proteins were measured by Western blot. To identify the protein target of MLIF, a pull-down assay was performed. We found that MLIF promoted microglia transferring from a “sick” M1 phenotype to a “healthy” M2 phenotype in vivo or in vitro. Furthermore, we proved that eukaryotic elongation factor 1A1 (eEF1A1) was involved in the modulation of microglia/macrophage polarization. Knocking down eEF1A1 by siRNA exhibited the M1 promotion effect and M2 inhibition effect. Taken together, our results demonstrated MLIF modulated microglia/macrophage polarization by targeting eEF1A1 in ischemic stroke.

OBJECTIVES:The aim of the present research is to elucidate the anti-oxidant and anti-tumor activities of the mucin extracted from Ereminia desertorum snails´ mucus against two types of tumor cell lines; human colon adenocarcinoma (CACO-2) cells and human hepatoma (HepG-2) cells.METHODS:Both cell lines were treated with Ereminia desertorum snails´ mucin and the oxidative markers were measured in culture media and cells by biochemical and gene expression analysis using RT-PCR. The tumor suppressor gene expression was also evaluated using RT-PCR.RESULTS:The culture media of HepG-2 or CACO-2 cells treated with the extract have high significant increased levels of catalase, SOD, GSH and total antioxidants. Apart from SOD in CACO-2 cells that didn't differ from untreated cells. Also, Gene expression levels (2^-ddct) of the antioxidant markers in HepG-2 cells; GSTA-1, catalase, SOD, and GPx increased in mucin- treated cells. Also, these antioxidant genetic markers were up-regulated in CACO-2 cells by treatment with mucin extract. Gene expression levels (2^-ddct) of tumor suppression genes (p53, Rb, APC, and PTEN) in both HepG-2 and CaCO-2 cells were increased in mucin extract-treated cells.CONCLUSION:The present study highlighted the anti-oxidant and the anti-cancer activities of the mucin extracted from E. desertorum snails´ mucus that could attract attention to such natural product as a possible source of therapeutic compounds against liver and colon cancers.

HBV mainly infects human hepatocytes, but it has also been found to infect extrahepatic tissues such as kidney and testis. Nonetheless, cell-based HBV models are limited to hepatoma cell lines (such as HepG2 and Huh7) overexpressing a functional HBV receptor, sodium taurocholate co-transporting polypeptide (NTCP). Here, we used 293T-NE-3NRs (293T overexpressing human NTCP, HNF4α, RXRα and PPARα) and HepG2-NE (HepG2 overexpressing NTCP) as model cell lines. HBV infection in these cell lines was performed either by using concentrated HBV virus particles from HepG2.2.15 or co-culturing HepG2.2.15 with the target cell lines. HBcAg immunofluorescence for HBcAg was performed to confirm HBV infection. The two methods presented here will help us study HBV infection in non-hepatic cell lines.

Hepatitis B virus (HBV) infection affects ~350 million people and poses a major public health problem worldwide. HBV is a major cause of cirrhosis and hepatocellular carcinoma. Fewer than 5% of HBV-infected adults (but up to 90% of HBV-infected infants and children) develop chronic HBV infection as indicated by continued, detectable expression of hepatitis B surface antigen (HBsAg) for at least 6 months after the initial infection. Increasing evidence indicates that HBV interacts with innate immunity signaling pathways of hepatocytes to suppress innate immunity. However, it is still not clear how HBV avoids monitoring by the innate immunity of hepatocytes and whether the innate immunity of hepatocytes can be effective against HBV if re-triggered. Moreover, a deep understanding of virus–host interactions is important in developing new therapeutic strategies for the treatment of HBV infection. In this review, we summarize the current knowledge regarding how HBV represses innate immune recognition, as well as recent progress with respect to in vitro models for studying HBV infection and innate immunity.

Comparison of biochemical tests for liver disease (alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin and albumin) results between the HBV occult and non-occult groups showed that each of serum AST, ALT, albumin and bilirubin level was significantly higher in non-occult group (P=0.033, 0.042, 0.010 and 0.002), respectively. HBV serology (hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), Total hepatitis B core antibody (anti-HBC), hepatitis B core antibody IgM (anti-HBC IgM), hepatitis B envelope antigen (HBeAg) and hepatitis B envelope antibody (anti-HBe) assays revealed that all occult patients were negative HBsAg and the number of positive cases for total anti-HBc was higher in occults and HBV DNA titres were lower in occults (mean (SD) of 4.31x10(2) (4.98x10(2))) than non-occults (mean (SD) of 8.91x10(4) (2.67x10(2))). Moreover, after cutting the HBV polymerase fragments of 274 bp by restriction enzyme FokI, 181 bp by Alw441 and 138 bp by SspI, the results of RFLP analysis showed that the frequency of M522V, M522I mutations and mixed YMDD wild type/M522V or M522I/M522V mutations at codon 552 in YMDD motif of the gene was higher in occult group (35%, 25% and 10%, respectively) than non-occult group (13.33%, 13.33 and 6.66, respectively). Conclusion: These results indicated that there is aHBsAg-escape mutant(s) which is a source of infection especially for blood units. Therefore, the prevalent genotypes, genome sequences and different antigen variants of HBV in the world must be updated for production of corresponding vaccines and polyclonal antibodies.