Hepatitis B virus infection

乙型肝炎病毒感染
  • 文章类型: Journal Article
    乙型肝炎病毒(HBV)感染与结直肠癌肝转移(CRLM)之间的关联在当前基于人群的证据中仍然模棱两可。为了澄清这一点,我们对5871例结直肠癌(CRC)患者进行了回顾性分析.倾向评分匹配(PSM)用于协调HBV+(n=1696)和HBV-(n=4175)组中的年龄和性别差异,并进一步在HBV+慢性亚组(CHB,n=474)和隐匿性(OHB,n=1222)感染。我们的初步结果表明HBV感染和同步结直肠肝转移(SYN-CRLM)之间的显着关联;然而,这种关联在PSM用于校正混杂变量后消失.在PSM之前和之后,HBV感染与异时性结直肠癌肝转移(MET-CRLM)之间均未观察到显着关联。进一步分析表明,HBV复制状态不影响CRLM的发生率。然而,HBV+参与者表现出异时肝外转移的发生率增加,尤其是肺部。我们的发现暗示,无论是过去还是现在的HBV感染都与SYN-CRLM或MET-CRLM的发生显着相关。HBV复制状态与CRLM发病率之间没有关联,突出了在HBV感染状态之外的CRLM临床管理中纳入更广泛因素的重要性。
    The association between Hepatitis B virus (HBV) infection and colorectal liver metastases (CRLM) remains ambiguous in current population-based evidence. To clarify this, we present a retrospective analysis of 5871 colorectal cancer (CRC) patients. Propensity score matching (PSM) was applied to harmonize age and sex disparities within HBV+ (n = 1696) and HBV- (n = 4175) groups and further within HBV+ subgroups of chronic (CHB, n = 474) and occult (OHB, n = 1222) infections. Our initial results indicated a significant association between HBV infection and synchronous colorectal liver metastasis (SYN-CRLM); however, this association dissipated after PSM was employed to adjust for confounding variables. No significant association was observed between HBV infection and metachronous colorectal liver metastases (MET-CRLM) both before and after PSM. Further analysis revealed that HBV replication status did not influence the incidence of CRLM. However, HBV+ participants demonstrated an increased incidence of metachronous extrahepatic metastases, particularly to the lungs. Our findings imply that neither past nor present HBV infection is significantly correlated with the occurrence of SYN-CRLM or MET-CRLM. The absence of an association between HBV replication status and CRLM incidence highlights the importance of incorporating a broader range of factors in the clinical management of CRLM beyond the status of HBV infection.
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  • 文章类型: Journal Article
    牛磺胆酸钠共转运多肽(NTCP),胆汁酸转运蛋白,在调节胆汁酸水平和影响HBV感染风险中起着至关重要的作用。SLC10A1基因的遗传变异,编码NTCP,影响这些功能。然而,SLC10A1基因变异对代谢和生化性状的影响尚不清楚.我们的目的是调查SLC10A1基因变异与临床和生化参数的关联,以及台湾人群中不同HBV感染状态和胆结石疾病的风险。使用Axiom全基因组CHB阵列分析了来自117,679台湾生物库参与者的基因分型数据。区域图关联分析显示SLC10A1rs2296651基因型与血脂谱之间的全基因组显著关联,γ谷氨酰转移酶(γGT)水平和抗HBc阳性。基因型-表型关联分析显示总胆固醇显著降低,低密度脂蛋白(LDL)胆固醇和尿酸水平,在罕见的rs2296651-A等位基因携带者中,较高的γGT水平和较高的胆结石发生率。具有rs2296651AA基因型的参与者表现出抗HBc阳性率和HBsAg阳性率显着降低。与GG基因型相比,非GG基因型的个体降低了各种HBV感染状态的风险:AA基因型显示出大大降低的风险,而GA基因型显示风险较低。预测工具还表明,rs2296651变体可能会诱导蛋白质损伤和致病作用。总之,我们的数据揭示了SLC10A1rs2296651基因型对生化性状水平以及HBV感染和胆结石疾病风险的多效性作用.这证实了SLC10A1的多功能性,并暗示其基因型在预测生化性状和疾病易感性方面。
    Sodium taurocholate co-transporting polypeptide (NTCP), a bile acid transporter, plays a crucial role in regulating bile acid levels and influencing the risk of HBV infection. Genetic variations in the SLC10A1 gene, which encodes NTCP, affect these functions. However, the impact of SLC10A1 gene variants on the metabolic and biochemical traits remained unclear. We aimed to investigate the association of SLC10A1 gene variants with the clinical and biochemical parameters, and the risk of different HBV infection statuses and gallstone disease in the Taiwanese population. Genotyping data from 117,679 Taiwan Biobank participants were analyzed using the Axiom genome-wide CHB arrays. Regional-plot association analysis demonstrated genome-wide significant association between the SLC10A1 rs2296651 genotypes and lipid profile, gamma glutamyl transferase (γGT) level and anti-HBc-positivity. Genotype-phenotype association analyses revealed significantly lower total cholesterol, low-density lipoprotein (LDL) cholesterol and uric acid levels, a higher γGT level and a higher gallstone incidence in rare rs2296651-A allele carrier. Participants with the rs2296651 AA-genotype exhibited significantly lower rates of anti-HBc-positivity and HBsAg-positivity. Compared to those with the GG-genotype, individuals with non-GG-genotypes had reduced risks for various HBV infection statuses: the AA-genotype showed substantially lower risks, while the GA-genotype demonstrated modestly lower risks. Predictive tools also suggested that the rs2296651 variant potentially induced protein damage and pathogenic effects. In conclusion, our data revealed pleiotropic effects of the SLC10A1 rs2296651 genotypes on the levels of biochemical traits and the risk of HBV infection and gallstone disease. This confirms SLC10A1\'s versatility and implicates its genotypes in predicting both biochemical traits and disease susceptibility.
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  • 文章类型: Journal Article
    目的:探讨妊娠期乙型肝炎病毒(HBV)感染的关系,抗病毒治疗,和妊娠结局。
    方法:回顾性选择2016年10月1日至2020年10月1日在福建医科大学附属医院住院分娩的乙肝表面抗原(HBsAg)阳性孕妇。对照组为随机选取同期住院分娩的健康孕妇。
    结果:总体而言,1115名参与者被纳入并分组为对照组(n=380)和HBsAg阳性组(n=735),进一步分为I组(n=407;低病毒载量),II(n=207;无抗病毒治疗的高病毒载量),和III(n=121;抗病毒治疗的高病毒载量)。HBV孕妇与妊娠肝内胆汁淤积症(ICP)的发生率呈正相关(调整比值比[aOR]5.1,95%置信区间[CI]2.62-9.92,P<0.001),新生儿黄疸(aOR10.56,95%CI4.49-24.83,P<0.001),和新生儿窒息(aOR5.03,95%CI1.46-17.27,P=0.01)。天冬氨酸转氨酶(AST)高于正常值上限(ULN)是ICP发生率升高的独立危险因素(aOR3.49,95%CI1.26~9.67,P=0.019)。抗病毒治疗显着降低HBVDNA和改善肝功能。高病毒载量和抗病毒治疗与不良妊娠结局无显著相关性(P<0.05)。
    结论:HBV孕妇的ICP发病率显著升高,新生儿黄疸,新生儿窒息与病毒载量无显著相关性。AST大于ULN独立地增加ICP的风险。抗病毒治疗可有效减少病毒复制并改善肝功能,而不会增加不良后果的风险。
    OBJECTIVE: To explore the relationships between gestational hepatitis B virus (HBV) infection, antiviral therapy, and pregnancy outcomes.
    METHODS: We retrospectively selected hepatitis B surface antigen (HBsAg)-positive pregnant women hospitalized for delivery at Fujian Medical University Affiliated Hospital from October 1, 2016 to October 1, 2020. The control group included randomly selected healthy pregnant women hospitalized for delivery during the same time.
    RESULTS: Overall, 1115 participants were enrolled and grouped into control (n = 380) and HBsAg-positive groups (n = 735), which were further divided into groups I (n = 407; low viral load), II (n = 207; high viral load without antiviral therapy), and III (n = 121; high viral load with antiviral therapy). Pregnant women with HBV were positively correlated with the incidence of intrahepatic cholestasis of pregnancy (ICP) (adjusted odds ratio [aOR] 5.1, 95% confidence interval [CI] 2.62-9.92, P < 0.001), neonatal jaundice (aOR 10.56, 95% CI 4.49-24.83, P < 0.001), and neonatal asphyxia (aOR 5.03, 95% CI 1.46-17.27, P = 0.01). Aspartate aminotransferase (AST) greater than the upper limit of normal (ULN) was an independent risk factor for increased ICP incidence (aOR 3.49, 95% CI 1.26-9.67, P = 0.019). Antiviral therapy considerably reduced HBV DNA and improved liver function. High viral load and antiviral therapy did not correlate significantly with adverse pregnancy outcomes (P < 0.05).
    CONCLUSIONS: Pregnant women with HBV have significantly elevated incidence of ICP, neonatal jaundice, and neonatal asphyxia not significantly correlated with viral load. AST greater than ULN independently increases the risk of ICP. Antiviral therapy effectively reduces viral replication and improves liver function without increasing the risk of adverse outcomes.
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  • 文章类型: Journal Article
    乙型肝炎病毒(HBV)感染是肝细胞癌(HCC)的主要危险因素。程序性细胞死亡(PCD)是抑制肿瘤生长的关键过程,PCD相关基因的改变可能有助于HBV-HCC的进展。这项研究旨在开发一种基于PCD相关基因的整合基因组和临床信息的预后模型,通过生物信息学分析和实验验证,为HBV-HCC的分子异质性提供新的见解。
    在这项研究中,我们分析了来自癌症基因组图谱(TCGA)的139个HBV-HCC样本,并使用来自基因表达综合(GEO)数据库的30个样本进行了验证。各种生物信息学工具,包括差异表达分析,基因集变异分析,和机器学习算法用于从HBV-HCC患者的RNA测序数据的综合分析。此外,在PCD相关基因中,我们最终选择DLAT进行组织芯片和患者队列的进一步研究.此外,免疫组织化学,进行qRT-PCR和Western印迹分析。
    聚类分析确定了三个不同的HBV-HCC患者亚组。其中,簇2在DNA复制相关途径和肿瘤相关过程中显示出显著的激活。对PCD相关基因的拷贝数变异(CNVs)的分析也揭示了三个亚组中的不同模式,这可能与通路激活和生存结局的差异有关。HBV-HCC患者肿瘤组织中的DLAT上调。
    基于PCD相关基因,我们开发了一个结合了基因组和临床信息的预后模型,并为HBV-HCC的分子异质性提供了新的见解。在我们的研究中,我们强调了PCD相关基因的重要性,特别是DLAT,对其进行了体外检查,以探索其潜在的临床意义。
    UNASSIGNED: Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Programmed cell death (PCD) is a critical process in suppressing tumor growth, and alterations in PCD-related genes may contribute to the progression of HBV-HCC. This study aims to develop a prognostic model that incorporates genomic and clinical information based on PCD-related genes, providing novel insights into the molecular heterogeneity of HBV-HCC through bioinformatics analysis and experimental validation.
    UNASSIGNED: In this study, we analyzed 139 HBV-HCC samples from The Cancer Genome Atlas (TCGA) and validated them with 30 samples from the Gene Expression Omnibus (GEO) database. Various bioinformatics tools, including differential expression analysis, gene set variation analysis, and machine learning algorithms were used for comprehensive analysis of RNA sequencing data from HBV-HCC patients. Furthermore, among the PCD-related genes, we ultimately chose DLAT for further research on tissue chips and patient cohorts. Besides, immunohistochemistry, qRT-PCR and Western blot analysis were conducted.
    UNASSIGNED: The cluster analysis identified three distinct subgroups of HBV-HCC patients. Among them, Cluster 2 demonstrated significant activation in DNA replication-related pathways and tumor-related processes. Analysis of copy number variations (CNVs) of PCD-related genes also revealed distinct patterns in the three subgroups, which may be associated with differences in pathway activation and survival outcomes. DLAT in tumor tissues of HBV-HCC patients is upregulated.
    UNASSIGNED: Based on the PCD-related genes, we developed a prognostic model that incorporates genomic and clinical information and provided novel insights into the molecular heterogeneity of HBV-HCC. In our study, we emphasized the significance of PCD-related genes, particularly DLAT, which was examined in vitro to explore its potential clinical implications.
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  • 文章类型: Journal Article
    本文的目的是建立和研究慢性乙型肝炎病毒感染动力学行为的新型数学模型。该模型包括暴露的感染肝细胞,含HBVDNA的细胞内衣壳,使用病毒感染的一般发生率函数,涵盖文献中提供的各种特殊病例,并描述了杀死受感染肝细胞的细胞毒性T淋巴细胞与发送抗体免疫防御以中和游离病毒体的B细胞的相互作用。Further,一个时间延迟被纳入考虑实际衣壳生产。其他时间延迟用于解释衣壳和游离病毒的成熟。我们从分析所提出的模型开始,通过建立局部和全局的存在,独特性,解的非负性和有界性。定义阈值参数后,我们通过使用狡猾的Lyapunov泛函讨论了所有可能的稳态常数的稳定性。拉萨尔不变性原理和线性化方法。通过对基本繁殖数量和感染状态类别的局部和全球敏感性分析,讨论了三个时间延迟对HBV感染传播的影响。最后,提供了一个应用程序,并进行了数值模拟来说明和解释所获得的理论结果。有人建议,根除或控制宿主体内HBV感染的良好策略应集中在任何可能延长这三种延迟值的药物上.
    The aim of this paper is to develop and investigate a novel mathematical model of the dynamical behaviors of chronic hepatitis B virus infection. The model includes exposed infected hepatocytes, intracellular HBV DNA-containing capsids, uses a general incidence function for viral infection covering a variety of special cases available in the literature, and describes the interaction of cytotoxic T lymphocytes that kill the infected hepatocytes and the magnitude of B-cells that send antibody immune defense to neutralize free virions. Further, one time delay is incorporated to account for actual capsids production. The other time delays are used to account for maturation of capsids and free viruses. We start with the analysis of the proposed model by establishing the local and global existence, uniqueness, non-negativity and boundedness of solutions. After defined the threshold parameters, we discuss the stability properties of all possible steady state constants by using the crafty Lyapunov functionals, the LaSalle\'s invariance principle and linearization methods. The impacts of the three time delays on the HBV infection transmission are discussed through local and global sensitivity analysis of the basic reproduction number and of the classes of infected states. Finally, an application is provided and numerical simulations are performed to illustrate and interpret the theoretical results obtained. It is suggested that, a good strategy to eradicate or to control HBV infection within a host should concentrate on any drugs that may prolong the values of the three delays.
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  • 文章类型: Case Reports
    背景:乙型肝炎很少导致脱髓鞘性神经病,尽管周围神经病变是乙型肝炎感染的首发症状。
    方法:一名64岁的男性患者表现为多个周围神经的感觉运动症状。血清学测试表明,这些症状是由于乙肝后接受治疗包括静脉注射免疫球蛋白和抗病毒药物,他的症状有了显著的改善。
    结论:尽管已知乙型肝炎病毒(HBV)感染会影响肝细胞,认识到与这种感染有关的其他表现的范围至关重要。长期HBV感染和脱髓鞘神经病之间的联系很少被记录;因此,及时的诊断和治疗至关重要。患者对免疫球蛋白的阳性反应似乎与抗原-抗体免疫复合物的产生有关。
    BACKGROUND: Hepatitis B rarely leads to demyelinating neuropathy, despite peripheral neuropathy being the first symptom of hepatitis B infection.
    METHODS: A 64-year-old man presented with sensorimotor symptoms in multiple peripheral nerves. Serological testing showed that these symptoms were due to hepatitis B. After undergoing treatment involving intravenous immunoglobulin and an antiviral agent, there was a notable improvement in his symptoms.
    CONCLUSIONS: Although hepatitis B virus (HBV) infection is known to affect hepatocytes, it is crucial to recognize the range of additional manifestations linked to this infection. The connection between long-term HBV infection and demyelinating neuropathy has seldom been documented; hence, prompt diagnostic and treatment are essential. The patient\'s positive reaction to immunoglobulin seems to be associated with production of the antigen-antibody immune complex.
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  • 文章类型: Journal Article
    乙型肝炎病毒(HBV)衣壳组装调节剂(CAM)代表了治疗HBV感染的有希望的治疗方法。在这项研究中,通过筛选内部化合物文库鉴定命中的化合物CDI(IC50=2.46±0.33μM)。然后设计并合成了新型有效的苯并咪唑衍生物作为核心组装调节剂,并在体外和体内生物学实验中评估了它们的抗病毒作用。结果表明,化合物26f显示出HBV衣壳组装的最优化调节剂(IC50=0.51±0.20μM,EC50=2.24±0.43μM,CC50=84.29μM)和高选择性指数。此外,在流体动力学注射(HDI)小鼠模型中,用化合物26f治疗14天显著降低血清HBVDNA水平。因此,化合物26f可以被认为是进一步开发具有所需效力和安全性的新型HBVCAM的有希望的候选药物。
    Hepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a promising therapeutic approach for the treatment of HBV infection. In this study, the hit compound CDI (IC50 = 2.46 ± 0.33 μM) was identified by screening of an in-house compound library. And then novel potent benzimidazole derivatives were designed and synthesized as core assembly modulators, and their antiviral effects were evaluated in vitro and in vivo biological experiments. The results indicated that compound 26f displayed the most optimized modulator of HBV capsid assembly (IC50 = 0.51 ± 0.20 μM, EC50 = 2.24 ± 0.43 μM, CC50 = 84.29 μM) and high selectivity index. Moreover, treatment with compound 26f for 14 days significantly decreased serum levels of HBV DNA levels in the Hydrodynamic-Injection (HDI) mouse model. Therefore, compound 26f could be considered as a promising candidate drug for further development of novel HBV CAMs with the desired potency and safety.
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  • 文章类型: Journal Article
    乙型肝炎病毒(HBV)感染是肝细胞癌(HCC)的主要病因。一个有趣的问题是如何不同的HBV感染(HBV+)和非HBV感染(HBV-)肝癌之间的分子和表型谱?包括批量和单细胞数据,我们收集和测序的数据,我们对HBV+和HBV-HCC的分子和表型特征进行了全面比较.我们的分析表明,与HBV-HCC相比,HBV+HCC有明显更好的临床结果,更高的基因组不稳定性,更富集的DNA修复和免疫相关途径,基质和致癌信号通路的富集度较低,和更好的免疫疗法反应。此外,体外实验证实,HBV+HCC具有较高的免疫力,PD-L1表达和DNA损伤应答途径的激活。这项研究可以提供对HBV+和HBV-HCC的概况的见解,并指导肝癌患者的合理治疗干预。
    Hepatitis B virus (HBV) infection is a major etiology of hepatocellular carcinoma (HCC). An interesting question is how different are the molecular and phenotypic profiles between HBV-infected (HBV+) and non-HBV-infected (HBV-) HCCs? Based on the publicly available multi-omics data for HCC, including bulk and single-cell data, and the data we collected and sequenced, we performed a comprehensive comparison of molecular and phenotypic features between HBV+ and HBV- HCCs. Our analysis showed that compared to HBV- HCCs, HBV+ HCCs had significantly better clinical outcomes, higher degree of genomic instability, higher enrichment of DNA repair and immune-related pathways, lower enrichment of stromal and oncogenic signaling pathways, and better response to immunotherapy. Furthermore, in vitro experiments confirmed that HBV+ HCCs had higher immunity, PD-L1 expression and activation of DNA damage response pathways. This study may provide insights into the profiles of HBV+ and HBV- HCCs, and guide rational therapeutic interventions for HCC patients.
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  • 文章类型: Journal Article
    多项观察性研究表明2型糖尿病(T2DM)与慢性肝病(CLD)之间存在关联。然而,T2DM对CLDs的因果关系在不同种族中仍然未知.
    我们获得了T2DM的工具变量,并进行了双样本孟德尔随机化(MR)研究,以检查非酒精性脂肪肝(NAFLD)的因果关系。肝细胞癌(HCC),病毒性肝炎,乙型肝炎病毒(HBV)感染,欧洲人和东亚人的丙型肝炎病毒(HCV)感染风险。主要分析使用逆方差加权(IVW)技术来评估T2DM和CLD之间的因果关系。此外,我们进行了一系列严格的分析,以增强MR结果的可靠性.
    在欧洲人中,我们发现,T2DM的遗传倾向与NAFLD的风险增加有关(IVW:OR=1.3654,95%置信区间[CI],1.2250-1.5219,p=1.85e-8),病毒性肝炎(IVW:OR=1.1173,95CI,1.0271-1.2154,p=0.0098),T2DM和HCC之间存在暗示性正相关(IVW:OR=1.2671,95CI,1.0471-1.5333,p=0.0150),HBV(IVW:OR=1.1908,95%CI,1.0368-1.3677,p=0.0134)。未发现T2DM和HCV之间的因果关系。在东亚人中,然而,T2DM与NAFLD的代理之间存在显着负相关(ALT:IVWOR=0.9752,95CI0.9597-0.9909,p=0.0021;AST:IVWOR=0.9673,95CI,0.9528-0.9821,p=1.67e-5),和HCV(IVW:OR=0.9289,95CI,0.8852-0.9747,p=0.0027)。值得注意的是,T2DM和HCC之间没有因果关系,病毒性肝炎,或HBV。
    我们的MR分析揭示了东亚人和欧洲人的T2DM和CLDs之间不同的因果关系。需要进一步研究,以调查各个种族群体的潜在机制,这可能会对T2DM患者CLDs的早期筛查和预防策略产生新的见解。
    Multiple observational studies have demonstrated an association between type 2 diabetes mellitus (T2DM) and chronic liver diseases (CLDs). However, the causality of T2DM on CLDs remained unknown in various ethnic groups.
    We obtained instrumental variables for T2DM and conducted a two-sample mendelian randomization (MR) study to examine the causal effect on nonalcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC), viral hepatitis, hepatitis B virus (HBV) infection, and hepatitis C virus (HCV) infection risk in Europeans and East Asians. The primary analysis utilized the inverse variance weighting (IVW) technique to evaluate the causal relationship between T2DM and CLDs. In addition, we conducted a series of rigorous analyses to bolster the reliability of our MR results.
    In Europeans, we found that genetic liability to T2DM has been linked with increased risk of NAFLD (IVW : OR =1.3654, 95% confidence interval [CI], 1.2250-1.5219, p=1.85e-8), viral hepatitis (IVW : OR =1.1173, 95%CI, 1.0271-1.2154, p=0.0098), and a suggestive positive association between T2DM and HCC (IVW : OR=1.2671, 95%CI, 1.0471-1.5333, p=0.0150), HBV (IVW : OR=1.1908, 95% CI, 1.0368-1.3677, p=0.0134). No causal association between T2DM and HCV was discovered. Among East Asians, however, there was a significant inverse association between T2DM and the proxies of NAFLD (ALT: IVW OR=0.9752, 95%CI 0.9597-0.9909, p=0.0021; AST: IVW OR=0.9673, 95%CI, 0.9528-0.9821, p=1.67e-5), and HCV (IVW: OR=0.9289, 95%CI, 0.8852-0.9747, p=0.0027). Notably, no causal association was found between T2DM and HCC, viral hepatitis, or HBV.
    Our MR analysis revealed varying causal associations between T2DM and CLDs in East Asians and Europeans. Further research is required to investigate the potential mechanisms in various ethnic groups, which could yield new insights into early screening and prevention strategies for CLDs in T2DM patients.
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  • 文章类型: Journal Article
    髓系来源的抑制细胞(MDSC)作为癌症发生和发展中的突出决定因素进化,并且在功能上发现抑制癌症中的T细胞。关于其参与病毒感染的研究并不多。这项研究旨在研究MDSCs在乙型肝炎病毒(HBV)感染中的作用,以及如何用我们的新型全反式维甲酸包封的脂质体制剂靶向这些细胞可以改善C57BL/6小鼠的免疫治疗。
    通过C57BL/6小鼠的尾静脉以流体动力学方式注射10微克(10μg)的质粒腺相关病毒(pAAV/HBV1.2,基因型A)。具有缓释特性的全反式维甲酸包封的脂质体制剂(L-ATRA)与富马酸替诺福韦酯(TDF)联合使用,核苷酸类似物逆转录酶抑制剂(nRTI)治疗HBV感染。L-ATRA制剂以5mg/kg的剂量静脉内(IV)给予,每周两次。TDF以每天30mg/kg口服给药。
    我们的结果表明,L-ATRA抑制HBV感染小鼠的MDSCs,并在体外增强T细胞增殖。体内研究显示,与接受单一疗法的组相比,同时接受L-ATRA和TDF的小鼠具有更高和改善的免疫治疗作用。较低的HBVDNA拷贝,较低浓度的HBsAg和HBeAg,在接受L-ATRA+TDF联合治疗的小鼠中观察到较低水平的ALT和AST以及较少的肝损伤。
    实际上,靶向MDSCs与L-ATRA和TDF的组合有效降低mMDSC和改善在HBV感染小鼠的免疫治疗。靶向MDSCs可以在对抗乙型肝炎病毒感染方面提供突破。
    UNASSIGNED: Myeloid-derived suppressor cells (MDSCs) are evolving as a prominent determinant in cancer occurrence and development and are functionally found to suppress T cells in cancer. Not much research is done regarding its involvement in viral infections. This research was designed to investigate the role of MDSCs in hepatitis B virus (HBV) infection and how targeting these cells with our novel all-trans retinoic acid encapsulated liposomal formulation could improve immunotherapy in C57BL/6 mice.
    UNASSIGNED: Ten micrograms (10 μg) of plasmid adeno-associated virus (pAAV/HBV 1.2, genotype A) was injected hydrodynamically via the tail vein of C57BL/6 mice. An all-trans retinoic acid encapsulated liposomal formulation (L-ATRA) with sustained release properties was used in combination with tenofovir disoproxil fumarate (TDF), a nucleotide analog reverse transcriptase inhibitor (nRTI) to treat the HBV infection. The L-ATRA formulation was given at a dose of 5 mg/kg intravenously (IV) twice a week. The TDF was given orally at 30 mg/kg daily.
    UNASSIGNED: Our results revealed that L-ATRA suppresses MDSCs in HBV infected mice and enhanced T-cell proliferation in vitro. In vivo studies showed higher and improved immunotherapeutic effect in mice that received L-ATRA and TDF concurrently in comparison with the groups that received monotherapy. Lower HBV DNA copies, lower concentrations of HBsAg and HBeAg, lower levels of ALT and AST and less liver damage were seen in the mice that received the combination therapy of L-ATRA + TDF.
    UNASSIGNED: In effect, targeting MDSCs with the combination of L-ATRA and TDF effectively reduced mMDSC and improved immunotherapy in the HBV infected mice. Targeting MDSCs could provide a breakthrough in the fight against hepatitis B virus infection.
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