In silico epitope-based vaccine design against influenza a neuraminidase protein: Computational analysis established on B- and T-cell epitope predictions

ObjectiveInfluenza A virus belongs to the most studied virus and its mutant initiates epidemic and pandemics outbreaks. Inoculation is the significant foundation to diminish the risk of infection. To prevent an incidence of influenza from the transmission, various practical approaches require more advancement and progress. More efforts and research must take in front to enhance vaccine efficacy.MethodsThe present research emphasizes the development and expansion of a universal vaccine for the influenza virus. Research focuses on vaccine design with high efficacy. In this study, numerous computational approaches were used, covering a wide range of elements and ideas in bioinformatics methodology. Various B and T-cell epitopic peptides derived from the Neuraminidase protein N1 are recognized by these approaches. With the implementation of numerous obtained databases and bioinformatics tools, the different immune framework methods of the conserved sequences of N1 neuraminidase were analyzed. NCBI databases were employed to retrieve amino acid sequences. The antigenic nature of the neuraminidase sequence was achieved by the VaxiJen server and Kolaskar and Tongaonkar method. After screening of various B and T cell epitopes, one efficient peptide each from B cell epitope and T cell epitopes was assessed for their antigenic determinant vaccine efficacy. Identical two B cell epitopes were recognized from the N1 protein when analyzed using B-cell epitope prediction servers. The detailed examination of amino acid sequences for interpretation of B and T cell epitopes was achieved with the help of the ABCPred and Immune Epitope Database.ResultsComputational immunology via immunoinformatic study exhibited RPNDKTG as having its high conservancy efficiency and demonstrated as a good antigenic, accessible surface hydrophilic B-cell epitope. Among T cell epitope analysis, YVNISNTNF was selected for being a conserved epitope. T cell epitope was also analyzed for its allergenicity and cytotoxicity evaluation. YVNISNTNF epitope was found to be a non-allergen and not toxic for cells as well. This T-cell epitope with maximum world populace coverages was scrutinized for its association with the HLA-DRB1*0401 molecule. Results from docking simulation analyses showed YVNISNTNF having lower binding energy, the radius of gyration (Rg), RMSD values, and RMSE values which make the protein structure more stable and increase its ability to become an epitopic peptide for influenza virus vaccination.ConclusionsWe propose that this epitope analysis may be successfully used as a measurement tool for the robustness of an antigen–antibody reaction between mutant strains in the annual design of the influenza vaccine.     

Polymorphisms of interferon-inducible genes OAS-1 and MxA associated with SARS in the Vietnamese population

We hypothesized that host antiviral genes induced by type I interferons might affect the natural course of severe acute respiratory syndrome (SARS). We analyzed single nucleotide polymorphisms (SNPs) of 2',5'-oligoadenylate synthetase 1 (OAS-1), myxovirus resistance-A (MxA), and double-stranded RNA-dependent protein kinase in 44 Vietnamese SARS patients with 103 controls. The G-allele of non-synonymous A/G SNP in exon 3 of OAS-1 gene showed association with SARS (p=0.0090). The G-allele in exon 3 of OAS-1 and the one in exon 6 were in strong linkage disequilibrium and both of them were associated with SARS infection. The GG genotype and G-allele of G/T SNP at position -88 in the MxA gene promoter were found more frequently in hypoxemic group than in non-hypoxemic group of SARS (p=0.0195). Our findings suggest that polymorphisms of two IFN-inducible genes OAS-1 and MxA might affect susceptibility to the disease and progression of SARS at each level.     

新型冠状病毒的动物源性和传染源控制

根据现有的数据,新型冠状病毒(2019 novel coronavirus,2019-nCoV)比严重急性呼吸综合征冠状病毒(severe acute respiratory syndrome coronavirus,SARS-CoV)的传染性强、传播速度快、疫情规模大、病死率低。其传染性、传播速度和疫情规模似乎具有甲型流感病毒(influenza A virus)的特点。尽管2019-nCoV来源于何种动物尚无定论,但它与SARS-CoV同属冠状病毒,具有共同之处。如果流行过后 2019-nCoV没能在人群中持续传播和存在(如同SARS-CoV一样),则控制野生动物传染源乃重中之重;如果2019-nCoV获得了能在人群中持续传播的能力,预防控制策略将与SARS-CoV明显不同,疫苗便成为至关重要的手段。     

MicroRNA-363-3p/sphingosine-1-phosphate receptor 1 axis inhibits sepsis-induced acute lung injury via the inactivation of nuclear factor kappa-B ligand signaling

Infection-associated inflammation and coagulation are critical pathologies in sepsis-induced acute lung injury (ALI). This study aimed to investigate the effects of microRNA-363-3p (miR-363-3p) on sepsis-induced ALI and explore the underlying mechanisms. A cecal ligation and puncture-induced septic mouse model was established. The results of this study suggested that miR-363-3p was highly expressed in lung tissues of septic mice. Knockdown of miR-363-3p attenuated sepsis-induced histopathological damage, the inflammation response and oxidative stress in lung tissues. Furthermore, knockdown of miR-363-3p reduced the formation of platelet-derived microparticles and thrombin generation in blood samples of septic mice. Downregulation of miR-363-3p suppressed sphingosine-1-phosphate receptor 1 (S1PR1) expression in lung tissues and subsequently inactivated the nuclear factor kappa-B ligand (NF-κB) signaling. A luciferase reporter assay confirmed that miR-363-3p directly targeted the 3’-untranslated region of the mouse S1pr1 mRNA. Collectively, our study suggests that inactivation of NF-κB signaling is involved in the miR-363-3p/S1PR1 axis-mediated protective effect on septic ALI.     

重症急性胰腺炎患者早期肠内营养治疗的作用及价值探讨

目的:探讨经鼻空肠管早期行肠内营养(EN)在重症急性胰腺炎(S AP)治疗中的作用。方法:40例SAP患者随机分为治疗组和对照组,每组各20例,对照组给予常规治疗,治疗组在常规治疗的基础上加用肠内营养。观察两组治疗前后血清白蛋白和淀粉酶水平、血浆内毒素及肿瘤坏死因子TNF-α水平的变化情况。考察治愈率症、感染率、病死率、平均住院时间及费用。结果:治疗组患者行肠内营养后,血浆内毒素、TNF-α下降速度明显快于对照组P<0.05,感染率、平均住院时间与费用明显降低。结论:EN能改善ASP患者的营养状况,改善肠道黏膜屏障及降低炎性细胞因子分泌来加强治疗效果,是SAP重要治疗手段。     

血必净注射液联合比阿培南对重症肺炎患者肺功能的影响

摘要 目的：研究血必净注射液联合比阿培南对重症肺炎患者肺功能的影响。方法：选择2017年1月～2019年12月我院的103例重症肺炎患者,随机分为两组。对照组静脉滴注比阿培南0.3 g ,每 8 h给药1次;观察组联合静脉滴注血必净50 mL,每天两次。检测两组的炎症因子：白介素-1（Interleukin-1, IL-1）、肿瘤坏死因子-α（Tumor necrosis factor-α, TNF-α）和IL-6水平,应激激素：皮质醇（Cortisol, Cor）、人血管紧张素Ⅰ（Human angiotensin I, AngⅠ）、去甲肾上腺素（Noradrenaline, NE）和人血管紧张素Ⅱ（Human angiotensinⅡ, AngⅡ）水平,肺功能：第一秒最大呼气量（Maximum expiratory volume in the first second, FEV₁）、FEV₁%pred、用力肺活量（Forced vital capacity, FVC）。结果：观察组的有效率明显高于对照组（P<0.05）。治疗后,两组的血清IL-1、TNF-α、IL-6、Cor、AngⅠ、NE和AngⅡ水平水平均明显降低,FEV₁、FEV₁%pred和FEV₁/FVC明显升高（P<0.05）,且观察组的上述指标明显优于对照组（P<0.05）。结论：血必净注射液联合比阿培南对重症肺炎有显著的疗效,不但能明显改善肺功能,还能有效抑制患者的应激反应和炎症反应,值得推广。     

Oxygenation dynamics of sepsis patients undergoing far‐infrared intervention based on near‐infrared spectroscopy

Near‐infrared spectroscopy (NIRS; continuous wave type) is a noninvasive tool for detecting the relative change of oxyhemoglobin and deoxyhemoglobin. To make this change, intervention methods must be applied. This study determined the hemodynamics of 44 healthy participants and 35 patients with sepsis during exposure to FIR as a novel physical intervention approach. Local microcirculation of their brachioradialis was monitored during exposure and recovery through NIRS. The variations in blood flow and microvascular reaction were determined by conducting paired and unpaired t tests. The oxyhemoglobin levels of the healthy participants increased continuously, even during recovery. In contrast to expextations, the oxyhemoglobin levels of the patients plateaued after only 5 min of FIR illumination. The proposed method has potential applications for ensuring efficient treatment and facilitating doctors in diagnosing the functions of vessels in intensive care units.

Mapping diagrams of HbO₂ in healthy males and males with sepsis illustrated unique scenarios during the process.     

SARS冠状病毒感染Lewis大鼠模型的建立

目的通过观察SARS-CoV感染Lewis大鼠后,病理学、免疫学以及病毒的复制与外排情况变化,探讨其能否作为有效的SARS动物模型。方法SARS病毒感染9只Lewis大鼠,在感染后不同时间安乐死动物,应用光镜对动物的各脏器进行病理观察研究;用病毒分离和RT-PCR方法检测病毒外排与复制的情况;用ELISA法检测动物产生特异性抗体情况。结果在SARS-CoV感染Lewis大鼠后,肺组织出现一定的与人类SARS疾病相似的病理改变,在动物体内可检测到活病毒或病毒核酸,并可检测到特异性IgG抗体的存在。结论Lewis大鼠出现了特异的免疫反应及特征性病理改变,可做为灵长类SARS动物模型的有益补充用于SARS发病机理及疫苗的研发等。     

加味射干麻黄汤对重度支气管哮喘患者血清ECP、LPO、FeNO及肺功能的影响

目的:探讨加味射干麻黄汤对重度支气管哮喘患者血清嗜酸性粒细胞阳离子蛋白(ECP)、脂质过氧化物(LPO)、呼出气一氧化氮(FeNO)及肺功能的影响。方法:选择2015年9月至2017年9月我院接诊的96例重度支气管哮喘患者进行研究,通过随机数表法分为观察组(n=48)和对照组(n=48),在常规治疗基础上,对照组给予异丙托溴铵溶液、甲泼尼龙琥珀酸钠治疗,观察组联合加味射干麻黄汤治疗,均连续治疗4周。比较两组临床疗效、治疗前后中医证候积分、肺功能、血清ECP、LPO及FeNO的变化和不良反应。结果:治疗后,观察组临床疗效总有效率为91.67%(44/48),明显高于对照组的72.92%(35/48)(P0.05);治疗后,两组各中医证候积分、肺功能、血清ECP、LPO及FeNO较治疗前均显著改善(P0.05);中医证候积分中,观察组治疗后喘息、咳嗽、咳痰、胸闷、哮鸣音积分均明显低于对照组,肺功能中,观察组第1秒用力呼出量(FEV1)、FEV1/用力肺活量(FEV1/FVC)均明显高于对照组,呼气峰值流速(PEF)昼夜变异率明显低于对照组,且观察组血清ECP、LPO及FeNO明显比低于对照组,差异均具有统计学意义(P0.05);两组治疗期间不良反应比较无显著差异(P0.05)。结论:在重度支气管哮喘患者中应用加味射干麻黄汤效果显著,可有效改善肺功能及临床症状,其内在机制可能和调节气道慢性炎症反应、氧化应激反应,降低血清ECP、LOP及FeNO的表达相关,且用药安全性高,值得应用推广。