Successful reproduction of adenoviral gizzard erosion in 20-week-old SPF layer-type chickens and efficacious prophylaxis due to live vaccination with an apathogenic fowl adenovirus serotype 1 strain (CELO)

Recently, outbreaks of adenoviral gizzard erosion (AGE) have been documented in pullets and layers housed free range and in enriched cage systems characterized by increased mortality and a negative impact on egg production. In the present study the pathogenicity of a fowl adenovirus serotype 1 (FAdV-1) field strain as well as the aetiological role of a FAdV-8a strain, both isolated from AGE affected pullets, were investigated in vivo in 20-week-old specific-pathogen-free (SPF) layer-type chickens. Furthermore, the efficacy of a single (week 17) and double (week 14 and 17) application of a live vaccine consisting of an apathogenic FAdV-1 (CELO strain) against challenge with virulent FAdV-1 was investigated.For the first time, AGE was successfully reproduced in adult birds after oral infection of 20-week-old SPF birds with a virulent FAdV-1 field isolate, characterized by pathological changes of the gizzard from 7 days post challenge onwards. In addition, a negative impact of the FAdV-1 infection on the development of the reproductive tract was observed. Thus, confirming the pathogenicity and aetiological role of FAdV-1 in the development of AGE and economic losses due to AGE in layers. In contrast, no pathological changes were observed in birds infected with FAdV-8a.Independent of a single or double application of the live FAdV-1 vaccine strain CELO, no gross pathological changes were observed in gizzards post challenge with the virulent FAdV-1, indicating that complete protection of layers against horizontal induction of AGE was achieved. Nonetheless, virulent FAdV-1 was detected in cloacal swabs and gizzards in both vaccinated groups post challenge determined by the application of an amplification refractory mutation system quantitative PCR used to differentiate between vaccine and challenge strains.     

Combined therapies to treat complex diseases: The role of the gut microbiota in multiple sclerosis

The commensal microbiota has emerged as an environmental risk factor for multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE) models have shown that the commensal microbiota is an essential player in triggering autoimmune demyelination. Likewise, the commensal microbiota modulates the host immune system, alters the integrity and function of biological barriers and has a direct effect on several types of central nervous system (CNS)-resident cells. Moreover, a characteristic gut dysbiosis has been recognized as a consistent feature during the clinical course of MS, and the MS-related microbiota is gradually being elucidated. This review highlights animal studies in which commensal microbiota modulation was tested in EAE, as well as the mechanisms of action and influence of the commensal microbiota not only in the local milieu but also in the innate and adaptive immune system and the CNS. Regarding human research, this review focuses on studies that show how the commensal microbiota might act as a pathogenic environmental risk factor by directing immune responses towards characteristic pathogenic profiles of MS. We speculate how specific microbiome signatures could be obtained and used as potential pathogenic events and biomarkers for the clinical course of MS. Finally, we review recently published and ongoing clinical trials in MS patients regarding the immunomodulatory properties exerted by some microorganisms. Because MS is a complex disease with a large variety of associated environmental risk factors, we suggest that current treatments combined with strategies that modulate the commensal microbiota would constitute a broader immunotherapeutic approach and improve the clinical outcome for MS patients.     

Efficacy of novel recombinant fowlpox vaccine against recent Mexican H7N3 highly pathogenic avian influenza virus

Since 2012, H7N3 highly pathogenic avian influenza (HPAI) has produced negative economic and animal welfare impacts on poultry in central Mexico. In the present study, chickens were vaccinated with two different recombinant fowlpox virus vaccines (rFPV-H7/3002 with 2015 H7 hemagglutinin [HA] gene insert, and rFPV-H7/2155 with 2002 H7 HA gene insert), and were then challenged three weeks later with H7N3 HPAI virus (A/chicken/Jalisco/CPA-37905/2015). The rFPV-H7/3002 vaccine conferred 100% protection against mortality and morbidity, and significantly reduced virus shed titers from the respiratory and gastrointestinal tracts. In contrast, 100% of sham and rFPV-H7/2155 vaccinated birds shed virus at higher titers and died within 4?days. Pre- (15/20) and post- (20/20) challenge serum of birds vaccinated with rFPV-H7/3002 had antibodies detectable by hemagglutination inhibition (HI) assay using challenge virus antigen. However, only a few birds (3/20) in the rFPV-H7/2155 vaccinated group had antibodies that reacted against the challenge strain but all birds had antibodies that reacted against the homologous vaccine antigen (A/turkey/Virginia/SEP-66/2002) (20/20). One possible explanation for differences in vaccines efficacy is the antigenic drift between circulating viruses and vaccines. Molecular analysis demonstrated that the Mexican H7N3 strains have continued to rapidly evolve since 2012. In addition, we identified in silico three potential new N-glycosylation sites on the globular head of the H7 HA of A/chicken/Jalisco/CPA-37905/2015 challenge virus, which were absent in 2012 H7N3 outbreak virus. Our results suggested that mutations in the HA antigenic sites including increased glycosylation sites, accumulated in the new circulating Mexican H7 HPAIV strains, altered the recognition of neutralizing antibodies from the older vaccine strain rFPV-H7/2155. Therefore, the protective efficacy of novel rFPV-H7/3002 against recent outbreak Mexican H7N3 HPAIV confirms the importance of frequent updating of vaccines seed strains for long-term effective control of H7 HPAI virus.     

食蟹猴SPF种群建立过程中病毒抗体的动态监测

目的 调查研究从老挝引种的食蟹猴BV、SRV、SIV和STLV-1四项病毒抗体阳性、可疑的比例,并对SPF种群建立过程中四项病毒的动态变化进行了监测,进而比较普通种群和SPF种群幼猴病毒抗体的阳性率。 方法 采用专用试剂盒对四项病毒进行连续监测并进行比较分析。 结果 引种的1998只食蟹猴,BV抗体阳性比例高达52.35%,可疑比例为8.31%,抗体阴性的比例仅为39.34%;SRV和STLV-1抗体阳性率分别为7.45%和8.56%;未检测出SIV抗体阳性或可疑的食蟹猴。经过筛选后组建的SPF种群,2010年监测的BV、SRV和STLV-1三项病毒抗体阳性率分别为5.24%、1.01%和0.4%,经过连续5年的不断筛选和淘汰,截至2014年年底三种病毒抗体阳性率分别下降至0.82%、0.27%和0.27%,未监测出SIV抗体阳性或可疑的食蟹猴。普通群繁殖幼猴B病毒抗体阳性的比例为9.71%,可疑率为1.85%;而SPF繁殖种群B病毒抗体阳性率仅为0.22%。 结论 连续监测病毒抗体并不断淘汰抗体阳性和可疑的动物对组建SPF食蟹猴种群具有重要的生产意义。     

SPF级新西兰兔脏器参数、血液指标、颈动脉血压、心率、心室压的测定与比较

目的 准确测定SPF新西兰兔生物学特性尤其是疾病相关的指标,并进行性别间比较。 方法 取70-80日龄左右SPF新西兰兔30只,饲养一周后,精确称量体重及主要脏器重量;采集动脉血测定血液生理、生化、血气指标;颈动脉插管测定动脉压,呼吸支持情况下进行开胸测定心室压。 结果 雄性与雌性新西兰兔比较： 甲状腺、肾上腺、肝的质量差异有显著性意义（P＜0.05或P＜0.01）;脑、脑垂体、甲状腺的脏器系数差异有显著性意义（P＜0.05或P＜0.01）;甲状腺、肾上腺、肝的脏脑比系数差异有显著性意义（P＜0.05或P＜0.01）。红细胞平均体积、平均血红蛋白量的差异有显著性意义（P＜0.05或P＜0.01）;谷氨酰转肽酶、淀粉酶的差异有显著性意义（P＜0.05或P＜0.01）;血气分析、心率、颈动脉收缩/舒张压,左心室收缩/舒张压,右心室收缩/舒张压不存在性别间差异。 结论 性别对新西兰兔脏器重量及血液生理生化指标有一定影响,而血气、血压、心率及心室压等不存在性别间差异。     

1,25(OH)2D3干预糖尿病肾病模型大鼠肾脏组织MicroRNA-130b及转化生长因子β1的变化

文题释义： 1,25(OH)₂D3：维生素D3是胆固醇的衍生物,其活性形式有25-羟维生素D3[25(OH)D3]和1,25-二羟维生素D3[1,25(OH)₂D3]两种,其中1,25-二羟维生素D3活性更高。体内的维生素D3无生物活性,它首先在肝脏被25-羟化酶催化为具有一定生物活性的25(OH)D3,然后在肾近端小管1α-羟化酶的催化下生成活性更高的1,25(OH)₂D3,1,25(OH)₂D3在肾脏具有促进肾小管对钙、磷的重吸收,尿钙、磷排出量减少等方面作用。MicroRNA-130b：microRNA(miRNA)是一种内源性小分子RNA,由21-25个核苷酸组成,可通过与靶基因mRNA的3’UTR或者CDS序列配对,促进mRNA的降解或抑制其翻译,从而抑制靶基因的表达,其中MicroRNA-130b与多脏器的多种病变有关,在糖尿病的进程中MicroRNA-130b与早期肾脏损伤具有一定的关系,可能成为糖尿病患者早期肾脏损害以及肾脏损害严重程度的新的生物学标志。 背景：1,25(OH)₂D3在糖尿病肾病的发展过程中发挥着重要调节作用。 目的：探索1,25(OH)₂D3对糖尿病肾病大鼠肾脏组织MicroRNA-130b及转化生长因子β1表达的影响作用。 方法：实验方案经新疆医科大学动物实验中心动物实验伦理委员会批准。将25只清洁级SD大鼠随机分为正常对照组、糖尿病肾病+1,25(OH)₂D3组、糖尿病肾病+花生油组,后2组分别给予骨化三醇(即1,25(OH)₂D3,活性维生素D3) 0.03 μg/(kg • d)治疗、花生油对照处理。37 d后采集标本,以实时聚合酶链式反应(RT-PCR)、Western blot及免疫组织化学方法检测大鼠肾脏组织转化生长因子β1的表达;RT-PCR检测MicroRNA-130b的表达;采用苏木精-伊红及Masson染色对大鼠肾脏形态结构及纤维化程度进行分析。 结果与结论：①RT-PCR结果显示,糖尿病肾病+1,25(OH)₂D3组及糖尿病肾病+花生油组MicroRNA-130b的表达明显低于正常对照组(P < 0.01),糖尿病肾病+1,25(OH)₂D3组明显高于糖尿病肾病+花生油组(P < 0.01);②RT-PCR、Western blot、免疫组织化学及病理结果显示,糖尿病肾病+1,25(OH)₂D3组及糖尿病肾病+花生油组转化生长因子β1 mRNA和蛋白的表达、大鼠肾脏组织结构紊乱及纤维化程度明显高于正常对照组(P < 0.01),糖尿病肾病+1,25(OH)₂D3组明显低于糖尿病肾病+花生油组(P < 0.01);③结果说明,糖尿病肾病大鼠肾脏MicroRNA-130b表达水平下降,转化生长因子β1 mRNA及蛋白表达水平升高,肾脏组织结构紊乱及纤维化程度严重;1,25(OH)₂D3可上调糖尿病肾病大鼠肾脏MicroRNA-130b的表达水平,同时还可下调糖尿病肾病大鼠肾脏转化生长因子β1的表达水平,改善肾脏组织结构紊乱及纤维化程度。ORCID: 0000-0002-5676-5016(刘玥彤) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

The recovery of bladder epithelial hyperplasia caused by a melamine diet-induced bladder calculus in mice

Applying a model of bladder epithelial hyperplasia (BEH) caused by melamine-induced bladder calculus (BC), the recovery of BEH after melamine withdrawal was investigated. One experiment, comprising untreated, melamine and recovery groups, was conducted in Balb/c mice. Each group included 4 subgroups. Mice were fed normal-diet in untreated or a melamine-diet in other groups. The melamine-diet was then substituted with normal-diet in recovery group. Both of BC and BEH were observed after 14 and 56 days of melamine-diet. The BC is relatively uniform at the same melamine-diet durations. The BEH was diffuse with many mitotic figures, 4–7 rows of nuclei, and well-defined umbrella/intermediate cells. No marked differences in BEH degree were observed in the two different melamine-diet durations. On 4–42 days after melamine withdrawal, BC was not found, as the progressive regression with complete regression of BEH was observed, along with well-defined ageing/apoptotic cells in the superficial regions of BEH regression tissue. Conclusion, the melamine-induced BEH is relatively uniform, may be self-limiting in rows of nuclei, and can return to normal. Melamine withdrawal duration is critical for the BEH regression. Tissue of the BEH and its regression is ideal for exploring the renewal as well as growth biology of mammalian urothelium.