Gut, Journal Year: 2023, Volume and Issue: 72(10), P. 1838 - 1847
Published: Feb. 14, 2023
Ulcerative colitis (UC) is a chronic inflammatory disorder of unknown aetiology. Gut virome dysbiosis fundamental in UC progression, although its role the early phases disease far from fully understood. Therefore, we sought to investigate virome-associated protein encoded by
Language: Английский
Hepatology International, Journal Year: 2021, Volume and Issue: 15(5), P. 1031 - 1048
Published: Aug. 24, 2021
Language: Английский
Citations
112
Viruses, Journal Year: 2021, Volume and Issue: 13(8), P. 1463 - 1463
Published: July 27, 2021
Hepatitis B virus (HBV) remains a major medical problem affecting at least 257 million chronically infected patients who are risk of developing serious, frequently fatal liver diseases. HBV is small, partially double-stranded DNA that goes through an intricate replication cycle in its native cellular environment: human hepatocytes. A critical step the viral life-cycle conversion relaxed circular (rcDNA) into covalently closed (cccDNA), latter being template for gene transcription. For this conversion, relies on multiple host factors, as enzymes capable catalyzing relevant reactions not encoded genome. Combinations genetic and biochemical approaches have produced findings provide more holistic picture complex mechanism cccDNA formation. Here, we review some these studies helped to comprehensive rcDNA conversion. Mechanistic insights persistence hold key devising new therapies will lead only suppression but cure.
Language: Английский
Citations
83
Virulence, Journal Year: 2022, Volume and Issue: 13(1), P. 258 - 296
Published: Jan. 31, 2022
Hepatitis B virus (HBV) is a hepatotropic and an important human pathogen. There are estimated 296 million people in the world that chronically infected by this virus, many of them will develop severe liver diseases including hepatitis, cirrhosis hepatocellular carcinoma (HCC). HBV small DNA replicates via reverse transcription pathway. In review, we summarize molecular pathways govern replication its interactions with host cells. We also discuss viral non-viral factors associated HBV-induced carcinogenesis pathogenesis, as well role immune responses persistence pathogenesis.
Language: Английский
Citations
52
Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13
Published: Aug. 12, 2022
Infectious diseases, caused by pathogenic microorganisms, are capable of affecting crises. In addition to persistent infectious diseases such as malaria and dengue fever, the vicious outbreaks Neocon, Ebola SARS-CoV-2 in recent years have prompted search for more efficient convenient means better diagnosis treatment. Antibodies attracted a lot attention due their good structural characteristics applications. Nanobodies smallest functional single-domain antibodies known be able bind stably antigens, with advantages high stability, hydrophilicity, easy expression modification. They can directly target antigen epitopes or constructed multivalent nanobodies nanobody fusion proteins exert therapeutic effects. This paper focuses on construction methods potential functions nanobodies, outlines progress research, highlights various applications human diseases.
Language: Английский
Citations
47
Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 148, P. 112743 - 112743
Published: Feb. 25, 2022
Viral infections are a common cause of morbidity worldwide. The emergence Coronavirus Disease 2019 (COVID-19) has led to more attention viral and finding novel therapeutics. CRISPR-Cas9 system been recently proposed as potential therapeutic tool for the treatment diseases. Here, we review research progress in use CRISPR-Cas technology treating infections, well strategies improving delivery this gene-editing vivo. Key challenges that hinder widespread clinical application also discussed, several possible directions future proposed.
Language: Английский
Citations
44
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
Citations
35
Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13
Published: March 15, 2023
Hepatitis B virus infections have always been associated with high levels of mortality. In 2019, hepatitis (HBV)-related diseases resulted in approximately 555,000 deaths globally. view its lethality, the treatment HBV has presented a huge challenge. The World Health Organization (WHO) came up ambitious targets for elimination as major public health threat by 2030. To accomplish this goal, one WHO’s strategies is to develop curative treatments infections. Current clinical setting included 1 year pegylated interferon alpha (PEG-IFNα) and long-term nucleoside analogues (NAs). Although both demonstrated outstanding antiviral effects, it difficult cure HBV. reason that covalently closed circular DNA (cccDNA), integrated DNA, viral burden, impaired host immune responses all hinder development overcome these problems, there are trials on number molecules being carried out, -showing promising results so far. review, we summarize functions mechanisms action various synthetic molecules, natural products, traditional Chinese herbal medicines, clustered regularly interspaced short palindromic repeats their proteins (CRISPR/Cas)-based systems, zinc finger nucleases (ZFNs), transcription activator-like effector (TALENs), which could destroy stability life cycle. addition, discuss modulators, can enhance or activate system, well some representative products anti-HBV effects.
Language: Английский
Citations
25
Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(1)
Published: Jan. 12, 2024
Abstract Eukaryotic five-methylcytosine (m 5 C) is an important regulator of viral RNA splicing, stability, and translation. However, its role in HBV replication remains largely unknown. In this study, functional m C sites are identified hepatitis B virus (HBV) mRNA. The modification at nt 1291 not only indispensable for Aly/REF export factor (ALYREF) recognition to promote mRNA HBx translation but also the inhibition RIG-I binding suppress interferon-β (IFN-β) production. Moreover, NOP2/Sun methyltransferase 2 (NSUN2) catalyzes addition transcriptionally downregulated by protein HBx, which suppresses EGR1 NSUN2 promoter. Additionally, expression correlates with type I IFN host cells, thus, positively regulating expression. Hence, delicate regulation induces while decreasing levels mRNA, making it a vital component life cycle. These findings provide new molecular insights into mechanism HBV-mediated may inform development IFN-α based therapies.
Language: Английский
Citations
15
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: March 8, 2024
Abstract Liver injury is a core pathological process in the majority of liver diseases, yet genetic factors predisposing individuals to its initiation and progression remain poorly understood. Here we show that asialoglycoprotein receptor 1 (ASGR1), lectin specifically expressed liver, downregulated patients with fibrosis or cirrhosis male mice injury. ASGR1 deficiency exacerbates while overexpression mitigates acetaminophen-induced acute CCl4-induced chronic injuries mice. Mechanistically, binds an endoplasmic reticulum stress mediator GP73 facilitates lysosomal degradation. depletion increases circulating levels promotes interaction between BIP activate stress, leading Neutralization not only attenuates deficiency-induced but also improves survival received lethal dose acetaminophen. Collectively, these findings identify as potential determinant susceptibility propose it therapeutic target for treatment
Language: Английский
Citations
15
Science Advances, Journal Year: 2024, Volume and Issue: 10(2)
Published: Jan. 10, 2024
Nuclear import of the hepatitis B virus (HBV) nucleocapsid is essential for replication that occurs in nucleus. The ~360-angstrom HBV capsid translocates to nuclear pore complex (NPC) as an intact particle, hijacking human importins a reaction stimulated by host kinases. This paper describes mechanisms recognition importins. We found importin α1 binds localization signal (NLS) at far end coat protein Cp183 carboxyl-terminal domain (CTD). NLS exposed surface through icosahedral quasi-sixfold vertex. Phosphorylation serine-155, serine-162, and serine-170 promotes CTD compaction but does not affect affinity α1. binding 30 α1/β1 augments diameter ~620 angstroms, close maximum size trafficable NPC. propose phosphorylation favors externalization prompts its surface, exposing
Language: Английский
Citations
12