Epigenetic regulation in antiviral innate immunity

Emerging life-threatening viruses have posed great challenges to public health. It is now increasingly clear that epigenetics plays a role in shaping host-virus interactions and there is a great need for a more thorough understanding of these intricate interactions through the epigenetic lens, which may represent potential therapeutic opportunities in the clinic. In this review, we highlight the current understanding of the roles of key epigenetic regulators — chromatin remodeling and histone modification — in modulating chromatin openness during host defense against virus. We also discuss how the RNA modification m6A (N6-methyladenosine) affects fundamental aspects of host-virus interactions. We conclude with future directions for uncovering more detailed functions that epigenetic regulation exerts on both host cells and viruses during infection.     

Revised Korean Antiviral Guideline Reduces the Hepatitis B-related Hepatocellular Carcinoma Risk in Cirrhotic Patients

BackgroundSince September 2015, the initiation of antiviral therapy (AVT) for patients with chronic hepatitis B (CHB)-related cirrhosis has been reimbursed according to the revised Korean Association for the Study of Liver (KASL) guideline, if the patient had hepatitis B virus DNA level ≥ 2,000 IU/L, regardless of aminotransferase or alanine aminotransferase levels. This study investigated whether the KASL guideline implementation reduced the risk of CHB-related hepatocellular carcinoma (HCC) in patients with cirrhosis in South Korea.MethodsA total of 429 patients with CHB-related cirrhosis who initiated AVT between 2014 and 2016 were recruited. The risk of HCC development was compared between patients who initiated AVT before and after September 2015 (pre-guideline [n = 196, 45.7%] vs. post-guideline implementation [n = 233, 54.3%]).ResultsUnivariate analysis showed that AVT initiation before guideline implementation, older age, male gender, and diabetes significantly predicted increased risk of HCC development (all P < 0.05). Subsequent multivariate analysis showed that AVT initiation before guideline implementation (HR = 1.941), older age (HR = 5.762), male gender (HR = 2.555), and diabetes (HR = 1.568) independently predicted increased risk of HCC development (all P < 0.05). Additionally, multivariate analysis showed that AVT initiation before guideline implementation (HR = 2.309), male gender (HR = 3.058), and lower platelet count (HR = 0.989) independently predicted mortality (P < 0.05). The cumulative incidences of HCC and mortality were significantly higher in patients who initiated AVT before guideline implementation than in those who initiated AVT after guideline implementation (all P < 0.05, log-rank test).ConclusionThe prognosis of patients with CHB-related cirrhosis who initiated AVT improved after guideline implementation according to the revised KASL guideline.     

CMV-, EBV- and ADV-Specific T Cell Immunity: Screening and Monitoring of Potential Third-Party Donors to Improve Post-Transplantation Outcome

Adoptive immunotherapy with virus-specific T lymphocytes can efficiently reconstitute antiviral immunity against cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (ADV) without causing acute toxicity or increasing the risk of graft-versus-host disease. To gain insight into antiviral T cell repertoires and to identify the most efficient antigens for immunotherapy, the frequencies of CMV-, EBV- and ADV-specific T cells in 204 HLA-typed healthy donors were assessed using viral peptides and peptide pools. Confirmatory testing for CMV serology by Western blot technique revealed 19 of 143 (13%) false-positive results. We observed highly significant individual and overall differences in T cell frequencies against CMV, EBV, and ADV antigens, whereas antigen-specific T cells were detected in 100% of CMV- seropositive donors, 73% of EBV- seropositive donors, and 73% of ADV-seropositive donors. At least 124 (61%) potential T cell donors were identified for each virus. Among the tested antigens, frequencies for CMVpp65 and EBVBZLF1 peptide pools were highest. Short-term in vitro peptide stimulation revealed that a donor response to a certain ADV- and EBV-derived peptide may not be determined without prior stimulation. A modified granzyme B ELISpot was used to detect T cell specificity and alloreactivity. Treatment with allogeneic virus-specific cytotoxic T lymphocytes from seropositive third-party donors may be a feasible therapeutic option for infections following cord-blood stem cell transplantation or hematopoietic stem cell transplantation from virus-seronegative donors.     

干扰素诱导的跨膜蛋白在肿瘤中的研究进展

干扰素诱导的跨膜蛋白(IFITM)是一种近来发现的细胞内抗病毒蛋白家族,它能抑制多种有或者无胞膜病毒的复制而起到抗病毒作用;同时近期有研究显示IFITM3对人类多种肿瘤细胞及干细胞的迁移等起重要作用,但IFITM3在人类肿瘤发生、发展和扩散转移的作用机制尚不明确.本文主要对IFITM3蛋白在人类肿瘤的研究进展及未来的研究方向作一综述.     

复方白芍颗粒质量控制研究

目的 建立复方白芍颗粒的质量标准.方法 采用薄层色谱法对制剂中的白芍、泽泻进行定性鉴别,采用高效液相色谱法测定制剂中芍药苷含量.结果 薄层色谱斑点清晰,且阴性对照无干扰;芍药苷浓度在33.35～333.50μg/mL范围内与峰面积的线性关系良好,平均回收率为97.39％(RSD=1.35％,n=6).结论 所建立的方法操作简单,重复性好,可有效控制复方白芍颗粒质量.     

芪归糖痛宁颗粒调节炎性因子预防糖尿病周围神经病变的机制研究

目的 通过观察芪归糖痛宁颗粒预防性给药对相关炎性因子的影响,探究其改善糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)的机制。方法 将120只SD大鼠分为正常组,模型组,芪归糖痛宁颗粒高、中、低剂量组和甲钴胺组,采用链脲佐菌素腹腔注射联合高脂饲料喂养法复制糖尿病大鼠模型,预防性给予相应药物8周,以运动神经传导速度（motor nerve conduction velocity,MNCV）和摆尾温度阈值评价DPN的改善情况,采用酶联免疫吸附法测定大鼠血清基质金属蛋白酶-1 (matrix metalloproteinase 1,MMP-1)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1（interleukin 1,IL-1）、单核细胞趋化蛋白-1（monocyte chemotactic protein 1,MCP-1)含量。结果 与正常组比较,模型组大鼠摆尾温度阈值显著升高（P<0.05）,MNCV显著下降（P<0.05）,血清MMP-1、TNF-α、IL-1和MCP-1均显著升高（P<0.05）。芪归糖痛宁颗粒对DPN大鼠的MNCV、摆尾温度阈值及血清MMP-1、TNF-α、IL-1和MCP-1的效应具有明显的剂量依赖性（P<0.05）,不同剂量对不同指标的效应呈现不同的量效关系;不同剂量芪归糖痛宁颗粒与甲钴胺对DPN大鼠的MNCV、摆尾温度阈值及血清MMP-1、TNF-α和IL-1的效应相比较,差异均具有统计学意义（P<0.05）。结论 芪归糖痛宁颗粒能预防DPN,其机制与调控复杂的炎性因子网络有关,其效应具有明显的剂量依赖性。     

肝移植术后乙肝主动免疫重建受体停用乙肝免疫球蛋白和(或)抗病毒药物的可行性

目的 探讨乙肝肝移植术后乙肝主动免疫重建成功受体停用乙肝免疫球蛋白(HBIG)和(或)抗病毒药物的可行性及临床指征.方法 检测乙肝主动免疫重建成功受体体内的HBV DNA和ccc DNA的水平,并监测其停用HBIG和(或)抗病毒药物后的乙肝复发情况.结果 共20例乙肝主动免疫重建成功受体纳入本研究.所有受体血浆均未检测到HBV DNA,1例受体的外周血单个核细胞中检测出微量HBV DNA (0.023 6 copies/cell),另1例受体的肝组织中检测出微量HBV DNA,但均未检测到ccc DNA.随访期间,所有受体均停用HBIG,13例停用抗病毒药物.1例外周血单个核细胞中检测到HBV DNA的受体有乙肝复发,并检测出HBV变异(变异位点G145R).结论 乙肝肝移植术后乙肝主动免疫重建成功受体停用HBIG和(或)抗病毒药物是安全可行的,但必须在停药前检测体内的HBV和病毒变异情况.     

神经阻滞联合抗病毒药物对带状疱疹患者疼痛及睡眠质量影响

目的 探究神经阻滞联合抗病毒药物对带状疱疹患者治疗效果,为临床疼痛缓解和改善睡眠质量提供依据.方法 选用来我院神经内科就诊带状疱疹患者90例,随机分为甲30例、乙30例、丙30例,甲组采用单纯抗病毒治疗,乙组采用抗病毒联合镇痛消炎药治疗,丙组采用神经阻滞联合抗病毒治疗,记录三组视觉评分(VAS)和睡眠质量评分(QS),分析三组疼痛和睡眠质量改善情况.结果 疼痛评分上,甲组治疗前后未见明显好转,2w后,才出现明显差异(t=4.329、5.424,P＜0.05);乙、丙两组在治疗后1w存在统计学差异(P＜0.05).在睡眠质量上,甲组睡眠质量没有明显改善(P＞0.05),1周后,睡眠质量改善(P＜0.05),乙、丙两组治疗前后存在显著统计学差异(P＜0.05),乙丙两组之间无明显差异(P＞0.05).结论 神经阻滞联合抗病毒药物对带状疱疹患者具有很好缓解疼痛和改善睡眠的作用,可以用于临床治疗.     

养阴退热颗粒提取物中用高效液相色谱法测芍药苷含量

目的:建立一个采用高效液相色谱法测定养阴退热颗粒提取物中芍药苷含量的方法。方法:Odshypersil色谱柱(4.6 mm×250 mm,5μm),乙腈-0.1%磷酸溶液洗脱,柱温度32℃,流量0.8 m L/min,检测波长230 nm。结果:芍药苷在在5~200μg/m L范围内线性关系良好,平均回收率为99.83%,RSD为0.76%,A类不确定度Ua=0.003417.结论:3批样品的抽检结果显示,该方法准确、方便、重复性好,可用于测定芍药苷在养阴退热颗粒提取物中的含量。     

Elastography for Longitudinal Assessment of Liver Fibrosis after Antiviral Therapy: A Review

Chronic hepatitis B or C viral infection is a common cause of liver cirrhosis and hepatocellular carcinoma. Fibrosis regression can be achieved after long-term antiviral therapy (AVT). Monitoring of dynamic changes in liver fibrosis after treatment is essential for establishing prognosis and formulation of a follow-up surveillance program. Routine surveillance of fibrosis after AVT by liver biopsy, the gold standard for fibrosis assessment, is hindered by its invasive nature, sampling error and observer variability. Elastography is a noninvasive quantitative alternative that has been widely used and validated for the staging of liver fibrosis prior to treatment. Recently, increasing research interest has been focused on the role of elastography in longitudinal assessment of liver fibrosis after AVT. In this review, the basic principles, acquisition techniques, diagnostic performances, and strengths and limitations of ultrasound elastography and magnetic resonance elastography are presented. Emerging evidence regarding the use of elastography techniques for the monitoring of liver fibrosis after AVT is summarized. Current challenges and future directions are also discussed, designed to optimize the application of these techniques in clinical practice.