Function, Detection and Alteration of Acylcarnitine Metabolism in Hepatocellular Carcinoma

Metabolites, Journal Year: 2019, Volume and Issue: 9(2), P. 36 - 36

Published: Feb. 21, 2019

Acylcarnitines play an essential role in regulating the balance of intracellular sugar and lipid metabolism. They serve as carriers to transport activated long-chain fatty acids into mitochondria for β-oxidation a major source energy cell activities. The liver is most important organ endogenous carnitine synthesis Hepatocellular carcinoma (HCC), primary malignancy live with poor prognosis, may strongly influence level acylcarnitines. In this paper, function, detection alteration acylcarnitine metabolism HCC were briefly reviewed. An overview was provided introduce metabolic roles acylcarnitines involved acid β-oxidation. Then different analytical platforms methodologies also summarised. relationship between described. Many studies reported that short, medium altered patients. These findings presented current evidence support new candidate biomarkers on pathogenesis development HCC. Finally we discussed challenges perspectives exploiting its related pathways target diagnosis prognosis.

Language: Английский

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Hepatitis B Virus Entry into Cells

Cells, Journal Year: 2020, Volume and Issue: 9(6), P. 1486 - 1486

Published: June 18, 2020

Hepatitis B virus (HBV), an enveloped partially double-stranded DNA virus, is a widespread human pathogen responsible for more than 250 million chronic infections worldwide. Current therapeutic strategies cannot eradicate HBV due to the persistence of viral genome in special structure (covalently closed circular DNA, cccDNA). The identification sodium taurocholate co-transporting polypeptide (NTCP) as entry receptor both and its satellite hepatitis delta (HDV) has led great advances our understanding life cycle HBV, including early steps infection particular. However, mechanisms internalization host factors involved this uptake remain unclear. Improvements would facilitate design new approaches targeting stage preventing de novo naïve hepatocytes. In review, we provide overview current knowledge about process into cells.

Language: Английский

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Revisiting Hepatitis B Virus: Challenges of Curative Therapies

Journal of Virology, Journal Year: 2019, Volume and Issue: 93(20)

Published: July 26, 2019

With a yearly death toll of 880,000, hepatitis B virus (HBV) remains major health problem worldwide, despite an effective prophylactic vaccine and well-tolerated, antivirals. HBV causes chronic hepatitis, fibrosis, cirrhosis, hepatocellular carcinoma. The viral genome persists in infected hepatocytes even after long-term antiviral therapy, its integration, though no longer able to support replication, destabilizes the host genome. is DNA that utilizes virus-encoded reverse transcriptase convert RNA intermediate, termed pregenomic RNA, into relaxed circular genome, which subsequently converted covalently closed (cccDNA) cell nucleus. cccDNA maintained nucleus hepatocyte as stable minichromosome functions transcriptional template for production all gene products, thus, it molecular basis persistence. nuclear pool can be replenished through recycling newly synthesized, DNA-containing capsids. Licensed antivirals target activity but fail eliminate cccDNA, would required cure infection. Elimination so far only achieved by immune responses. Thus, this review will focus on possible curative strategies aimed at eliminating or crippling cccDNA. Newer insights life cycle response provide novel, potentially therapeutic opportunities targets.

Language: Английский

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Application of human liver organoids as a patient-derived primary model for HBV infection and related hepatocellular carcinoma

eLife, Journal Year: 2021, Volume and Issue: 10

Published: July 30, 2021

The molecular events that drive hepatitis B virus (HBV)-mediated transformation and tumorigenesis have remained largely unclear, due to the absence of a relevant primary model system. Here we propose use human liver organoids as platform for modeling HBV infection related tumorigenesis. We first describe ex vivo HBV-infection derived from healthy donor after challenge with recombinant or HBV-infected patient serum. produced covalently closed circular DNA (cccDNA) early antigen (HBeAg), expressed intracellular RNA proteins, infectious HBV. This differentiated hepatocyte organoid was amenable drug screening both anti-HBV activity drug-induced toxicity. also studied replication in transgenically modified organoids; exogenously overexpressing receptor sodium taurocholate co-transporting polypeptide (NTCP) lentiviral transduction were not more susceptible HBV, suggesting necessity additional host factors efficient infection. generated transgenic harboring integrated representing long-term culture system suitable viral production study transcription. Finally, patient-derived non-tumor cirrhotic tissue explants transplant patients. Interestingly, transcriptomic analysis indicated presence an aberrant cancer gene signature, which clustered hepatocellular carcinoma (HCC) cohort on Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset away tissue, may provide invaluable novel biomarkers development HCC surveillance

Language: Английский

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iPSC-Derived Liver Organoids: A Journey from Drug Screening, to Disease Modeling, Arriving to Regenerative Medicine

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(17), P. 6215 - 6215

Published: Aug. 27, 2020

Liver transplantation is the most common treatment for patients suffering from liver failure that caused by congenital diseases, infectious agents, and environmental factors. Despite a high rate of patient survival following transplantation, organ availability remains key limiting factor. As such, research has focused on different cell types are capable repopulating restoring function. The best cellular mix engrafting proliferating over long-term, as well optimal immunosuppression regimens, remain to be clearly well-defined. Hence, alternative strategies in field regenerative medicine have been explored. Since discovery induced pluripotent stem cells (iPSC) potential differentiating into broad spectrum types, many studies reported achievement iPSCs differentiation cells, such hepatocytes, cholangiocytes, endothelial Kupffer cells. In parallel, an increasing interest study self-assemble or matrix-guided three-dimensional (3D) organoids paved way functional bioartificial livers. this review, we will focus recent breakthroughs development iPSCs-based major drawbacks challenges need overcome future applications.

Language: Английский

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Regulation and functional roles of chemokines in liver diseases

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2021, Volume and Issue: 18(9), P. 630 - 647

Published: May 11, 2021

Language: Английский

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The Functions of Hepatitis B Virus Encoding Proteins: Viral Persistence and Liver Pathogenesis

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Aug. 12, 2021

About 250 million people worldwide are chronically infected with Hepatitis B virus (HBV), contributing to a large burden on public health. Despite the existence of vaccines and antiviral drugs prevent infection suppress viral replication respectively, chronic hepatitis (CHB) cure remains remote treatment goal. The persistence caused by HBV is account for which increases risk developing liver cirrhosis hepatocellular carcinoma (HCC). virion utilizes various strategies escape surveillance host immune system therefore enhancing its replication, while precise mechanisms involved remain elusive. Accumulating evidence suggests that proteins encoded (hepatitis surface antigen, core envelope HBx polymerase) play an important role in pathogenesis. This review summarizes major findings functions encoding proteins, illustrating how these affect hepatocytes system, may open new venues CHB therapies.

Language: Английский

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Interferon and interferon-stimulated genes in HBV treatment

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Dec. 1, 2022

Human hepatitis B virus (HBV) is a small enveloped DNA with complex life cycle. It the causative agent of acute and chronic hepatitis. HBV can resist immune system responses often causes persistent infections. leading cause liver cancer cirrhosis. Interferons (IFNs) are cytokines antiviral, immunomodulatory, antitumor properties. IFNs glycoproteins strong antiviral activity that plays an important role in adaptive innate responses. They classified into three categories (type I, II, III) based on structure their cell-surface receptors. As effective drug for controlling viral infections, Type I approved to be clinically used treatment infection. The therapeutic effect interferon will enhanced when combined other drugs. play biological function by inducing expression hundreds IFN-stimulated genes (ISGs) host cells, which responsible inhibiting replication, transcription, processes. Animal models HBV, such as chimpanzees, also tools studying IFN ISG regulation. In present review, we summarized recent progress IFN-HBV focused its mechanism through interaction between ISGs.

Language: Английский

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Choosing a cellular model to study SARS-CoV-2

Frontiers in Cellular and Infection Microbiology, Journal Year: 2022, Volume and Issue: 12

Published: Oct. 21, 2022

As new pathogens emerge, challenges must be faced. This is no different in infectious disease research, where identifying the best tools available laboratories to conduct an investigation can, at least initially, particularly complicated. However, context of emerging virus, such as SARS-CoV-2, which was recently detected China and has become a global threat healthcare systems, developing models infection pathogenesis urgently required. Cell-based approaches are crucial understanding coronavirus biology, growth kinetics, tropism. Usually, laboratory cell lines first line experimental study viral pathogenicity perform assays aimed screening antiviral compounds efficient blocking replication viruses, saving time resources, reducing use animals. determining ideal type can challenging, especially when several researchers have adapt their studies specific requirements. review strives guide scientists who venturing into studying SARS-CoV-2 help them choose right cellular models. It revisits basic concepts virology presents currently

Language: Английский

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Relevance of HBx for Hepatitis B Virus-Associated Pathogenesis

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4964 - 4964

Published: March 4, 2023

The hepatitis B virus (HBV) counts as a major global health problem, it presents significant causative factor for liver-related morbidity and mortality. development of hepatocellular carcinomas (HCC) characteristic persistent, chronic infection could be caused, among others, by the pleiotropic function viral regulatory protein HBx. latter is known to modulate an onset cellular signaling processes with emerging influence in liver pathogenesis. However, flexible multifunctional nature HBx impedes fundamental understanding related mechanisms associated diseases, has even led partial controversial results past. Based on distribution HBx—nuclear-, cytoplasmic- or mitochondria-associated—this review encompasses current knowledge previous investigations context pathways HBV-associated In addition, particular focus set clinical relevance potential novel therapeutic applications

Language: Английский

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