表观遗传生物标志物在人类疾病早期诊治中的研究进展

表观遗传修饰异常见于人类的多种疾病(如肿瘤、老年性疾病、发育源性疾病等),影响着这些疾病的发生发展。已有的研究表明,异常表观遗传改变可以作为疾病状态和疾病预测的生物标志物。表观遗传修饰改变的可逆性和可控性也为疾病早期的预防和治疗提供了新策略。本文对DNA甲基化修饰、组蛋白共价修饰、非编码RNA等三种表观遗传方式在肿瘤、老年性疾病和发育源性疾病的研究,以及三者作为表遗传生物标志物在疾病早期诊断和治疗的应用展开介绍,以期为肿瘤、老年性和发育源性相关疾病的诊断与治疗提供借鉴和 参考。     

转基因动物与医学及生物医药研究进展

转基因动物与医学及生物医药研究的关系越来越密切。近年来,各种人类疾病转基因动物模型不断建立。本文介绍了转基因动物在遗传病、心血管疾病、肿瘤、高血压病、病毒性疾病、异种移植、输血医学、药理学研究中的应用概况。     

拮抗人和动物病毒的细菌及其作用机制研究进展

目前病毒性疾病对人类、动物健康的危害以及对国民经济各领域的影响,突出了研发有效、安全防控病毒性疾病新产品的重要意义.某些细菌如益生乳酸菌和芽胞杆菌、放线菌等具有良好的抗病毒作用,可作为病毒性疾病防控新产品研制基料.本文综述了细菌抗人和动物病毒作用及机制方面的国内外研究现状,以期为细菌尤其是益生菌在病毒性疾病防控上的应用提供科学参考.     

综述与专论: 灵长类动物在人类神经系统疾病动物模型中的应用

灵长类动物遗传、行为、认知、生理、生化和解剖结构等生物学特性更接近人类,具有其他实验动物无法替代的高级脑功能结构及神经活动的优势,是研究人类神经系统疾病理想的模式动物,研究的结果更容易推广应用到人类。常被用来建立神经退行性疾病、精神性疾病等疾病的动物模型,研究其发病机制、病程的发生发展及治疗药物等,为人类神经科学及相关医学研究做出了不可替代的贡献。本文综述了近年来国内外灵长类动物在人类神经系统疾病动物模型研究中的应用进展,分析了该领域目前存在的困难和问题,探讨了未来的一些研究方向,以期为神系统经疾病的深入研究提供思路。     

基因编辑动物模型在人类疾病研究中的应用

近年来,随着以CRISPR/Cas9为代表的多种CRISPR系统的开发和不断改进,基因编辑技术逐渐完善,并广泛应用于人类疾病动物模型的制备。基因编辑动物模型为人类疾病的发病机理、病理过程以及预防和治疗等方面的研究提供了重要的素材。目前,用于人类疾病研究的基因编辑动物模型主要有小鼠、大鼠为代表的啮齿类动物模型和以猪为代表的大动物模型。其中啮齿类动物在机体各方面与人类差别较大,且寿命短,无法对人类疾病的研究和治疗提供有效评估和长期追踪;而猪在生理学、解剖学、营养学和遗传学等各方面与人类更接近,是器官移植和人类疾病研究领域重要的动物模型。文中主要介绍了基因编辑动物模型在神经退行性疾病、肥厚心肌病、癌症、免疫缺陷类疾病和代谢性疾病等5种人类疾病研究中的应用情况,以期为人类疾病研究及相关动物模型的制备提供参考。     

科研快讯

<正>《人类分子遗传》:帕金森病研究取得进展帕金森病(PD)是仅次于老年痴呆的世界第二大神经退行性疾病,对中老年人的健康造成严重威胁。PD的发现、确诊往往是在病程的中后期,以至治疗效果不理想。由于研究PD的早期病理机制过程中缺少理想的动物模型,目前对于该病的早期发病机理和针对性治疗知之甚少。猕猴与人类在神经生理结构及行为学方面具有高度相似性,是研究神经疾病的理想实验动物。中国科学院遗传与发育生物学研究所李晓江等人曾在美国Emory大学于2008年用转基因方法建立了首例神经退行性疾病(享廷顿病)猕猴模型。采用相类似的转基因方法,李晓江研究组与     

灵长类实验动物疾病模型研究团队简介

广东蓝岛生物技术有限公司(华南灵长类动物研究开发中心)下属的灵长类实验动物疾病模型研究团队,目前研究领域主要有三个方面:代谢性疾病灵长类模型与疾病机理研究;重大传染病灵长类动物模型及分子免疫学研究;退行性神经疾病(PD、AD等)灵长类模型及机理研究;在致病性微生物研究、疾病     

非编码RNA研究进展

非编码RNA是指不具备蛋白质编码能力的RNA,包括转运RNA、核糖体RNA、小核仁RNA(small nucleolar RNA, snoRNA)以及长非编码RNA(long noncoding RNA, lncRNA)等.非编码RNA广泛参与生命活动中重要的生物功能,如生物个体的发育与分化、生殖、细胞凋亡和细胞重编程等,并且与人类疾病密切相关.近年来,随着我国经济的发展和人口老龄化,心血管疾病、肿瘤、代谢性疾病等疾病已成为威胁中国居民健康的重大慢性非传染性疾病,一些罕见病,例如小胖威利综合征(Prader-Willi syndrome, PWS)也随着人口基数的不断增大逐渐影响我国居民的身体健康.随着对这些慢性疾病及罕见疾病发生发展的相关机制研究,我国科学家发现非编码RNA与这些疾病密切相关.非编码RNA参与调控一系列的心血管疾病、肿瘤、代谢性疾病、感染免疫性疾病和PWS等疾病过程.本文对我国学者在非编码RNA领域的贡献进行综述,详细阐述了非编码RNA的加工形成和功能研究等主要进展,并对探究这些非编码RNA与PWS、心血管疾病、肿瘤、代谢性疾病和感染免疫性疾病等发生发展中的重要调控作用,以及我国科学家对该领域的贡献进行了详细的综述和总结.     

黑叶猴个体识别的新方法：基于腹股沟白斑斑纹观测

<正>动物个体识别是进行种群数量监测、动物行为学和生态学研究的基础。通过区分个体特征差异,可收集个体行为、社会联属行为和迁移行为等重要数据(Cronin,2012;Crouse et al.,2017),为动物种群数量评估和制定有效保护策略提供关键基础数据。濒危野生动物个体识别方法目前有足迹识别、条纹识别(顾佳音等,2013)、DNA识别(张保卫,2005)、基于卷积神经网络(Convolutional Neural Network,CNN)进行个体面部图像识别(王革伟,2018;Qi et al.,2020)等。     

人类疾病猫模型的制作与应用

猫作为实验动物在医学研究中占有越来越重要的地位,尤其是对于神经学、生理学和毒理学的研究。与啮齿类动物相比,猫的生理学特性、解剖学特点、病理及生化反应,更接近于人类;与灵长类动物相比,具有经济、资源丰富等优点。因此,猫在人类疾病动物模型方面有广泛的应用前景。本文主要回顾和总结了近年来猫在眼科、神经系统、肿瘤等领域作为人类疾病动物模型的制作方法与研究概况。     

Expression and Localization of Lung Surfactant Proteins in Human Testis

Background

Surfactant proteins (SPs) have been described in various tissues and fluids including tissues of the nasolacrimal apparatus, airways and digestive tract. Human testis have a glandular function as a part of the reproductive and the endocrine system, but no data are available on SPs in human testis and prostate under healthy and pathologic conditions.

Objective

The aim of the study was the detection and characterization of the surfactant proteins A, B, C and D (SP-A, SP-B, SP-C, SP-D) in human testis. Additionally tissue samples affected by testicular cancer were investigated.

Results

Surfactant proteins A, B, C and D were detected using RT-PCR in healthy testis. By means of Western blot analysis, these SPs were detected at the protein level in normal testis, seminoma and seminal fluid, but not in spermatozoa. Expression of SPs was weaker in seminoma compared to normal testicular tissue. SPs were localized in combination with vimentin immunohistochemically in cells of Sertoli and Leydig.

Conclusion

Surfactant proteins seem to be inherent part of the human testis. By means of physicochemical properties the proteins appear to play a role during immunological and rheological process of the testicular tissue. The presence of SP-B and SP-C in cells of Sertoli correlates with their function of fluid secretion and may support transportation of spermatozoa. In seminoma the expression of all SP''s was generally weaker compared to normal germ cells. This could lead to a reduction of immunomodulatory and rheology processes in the germ cell tumor.     

Is the Testis a Chemo-Privileged Site? Is There a Blood-Testis Barrier?

The incidence of testicular cancer, primarily seminoma, has been increasing in many countries, including the United States. The testis is often the site of residual cancer after adequate treatment with systemic chemotherapy. The blood-testis barrier is commonly cited as the explanation for residual tumor within the gonad after chemotherapy and as the indication for delayed orchiectomy. Conversely, complete eradication of viable tumor from the primary site is common and argues against the testis as a "tumor sanctuary." Residual tumor is also demonstrated within metastatic foci, and the disparity between the histopathologic response of the primary tumor and metastatic sites may be best explained by tumor heterogeneity and multiple tumor clones. Regardless of the scientific and academic arguments, delayed radical orchiectomy remains an important part of treatment for patients undergoing primary chemotherapy.     

First report of fatal baylisascariasis-induced acute pancreatitis in a giant panda

A wild adult male giant panda that was rescued from a nature reserve in Sichuan Province, China, has died. The panda had been in poor physical condition: it was wheezing and had increased serum amylase. A pathological examination was performed in order to determine the cause of death. Gross examination revealed 1380 mL of yellowish fluid in the abdominal cavity, 356 nematodes in the digestive tract and one filling the pancreatic duct, contractions and variably-sized dark purple areas in the spleen, a collapsed right lung and consolidation of the left lung. Acute pancreatitis was confirmed histopathologically via edema, focal necrosis and hemorrhage with inflammatory cell infiltration. Other major histopathological changes included serous-hemorrhagic pneumonia, lymphocytic necrosis and depletion in the spleen, and degeneration and necrosis of renal tubular epithelial cells. The nematodes were identified as Baylisascaris schroederi via molecular assays. In conclusion, the cause of death of the giant panda was determined to be multiple organ dysfunction syndrome caused by baylisascariasis-induced acute pancreatitis. To our knowledge, this is the first report of fatal baylisascariasis-induced acute pancreatitis in the giant panda.     

An oestrogen-producing seminoma responsible for gynaecomastia.

In feminising testicular tumours, oestrogens can be either secreted by the tumour itself or produced by normal Leydig cells in response to paracrine and/or endocrine stimulation by hCG. Typical hormonal Leydig cell tumour patterns include: plasma oestradiol levels > 300 pmol/l on day 3 following an hCG injection, reduced plasma testosterone, and normal plasma hCG and gonadotrophin levels. Except for elevated plasma oestradiol levels, opposite results are observed in seminomas. We report a case of oestrogen-secreting seminoma mimicking a Leydig cell tumour. A 24-year-old Caucasian patient had complained of gynaecomastia for 6 months before admission. Hormonal pattern was typical of Leydig cell tumour. A 1.4 cm tumour was found in the left testis and confirmed on sonography. Considering the likely diagnosis of Leydig cell tumour, the patient was treated by tumourectomy. Surprisingly, pathological examination revealed a pure seminoma. Perifusion experiments showed that the tumour was able to secrete significant amounts of oestradiol. In addition, hCG induced a two-fold increase in oestradiol production from perifused tumour explants. Immunohistochemistry revealed that the tumour was composed of nests of seminoma cells intermingled with lymphoid infiltrates. Tumour cells also expressed aromatase, the hCG/LH receptor and the Leydig cell marker relaxin-like factor, but were betahCG-negative. These results demonstrate that a pure seminoma of the testis is able to synthesise and secrete oestrogens. They also illustrate that the body of proof favouring the diagnosis of feminising Leydig cell tumour of the testis is not rigorously specific.     

基于高分辨率网络的大熊猫姿态估计方法

对圈养大熊猫 (Ailuropoda melanoleuca) 开展长期行为监测能及时了解其所处生理周期和健康状况,有助于繁殖饲养机构迅速采取相应繁育保护措施提高饲养管理水平,但目前无法对大熊猫进行24 h监控并及时地获得相应的行为信息。准确的动物姿态估计是动物行为研究的关键,也是诸多下游应用的基础。了解大熊猫的姿态可以促进大熊猫行为研究并提升保护管理水平。为了提高复杂环境下大熊猫姿态估计的准确率,本文以高分辨率网络 (High resolution net, HRNet) 为基础网络架构提出了一种大熊猫姿态估计方法：针对大熊猫不同部位尺度差异较大的问题,在HRNet-32中引入了空洞空间金字塔池化 (Atrous spatial pyramid pooling, ASPP) 模块,在提升特征感受野的同时捕获多尺度信息;同时对大熊猫身体关键点进行分组,引入基于部位的多分支结构来学习特定于每个部位组的表征。多次对比实验结果表明本文所用模型具有较高的检测精度：在PCK@0.05中所用模型精度达到了81.51%。本文提出的方法可为大熊猫的行为分析和健康评估提供技术支撑。     

Expression of Connexin 43 in normal canine testes and canine testicular tumors

In human testis, gap junctions containing connexin(Cx)43 are located within the seminiferous epithelium between Sertoli cells and between Sertoli and germ cells. Cx43 is known to play a role in the differentiation and proliferation of these cell types. It can further be associated with human seminoma development. The dog has been proposed as a model for studies of the male reproductive system, because of the frequent occurrence of testicular neoplasms. Thus, we investigated Cx43-mRNA and -protein expression in testes of normal prepubertal dogs, adult dogs, and in canine testicular tumors. Sertoli cells in prepubertal cords express Cx43 mRNA, but do synthesize only less Cx43 protein. Within the seminiferous tubules, Cx43 mRNA was detected in Sertoli cells, spermatogonia, and spermatocytes. Cx43 protein was mainly present in the basal compartment. In canine testicular tumors Cx43 mRNA was detectable in both seminoma and neoplastic Sertoli cells, whereas Cx43 protein was only found in neoplastic Sertoli cells. Our data indicate that Cx43 is regulated differentially in testicular tumors and that alterations of Cx43 expression may be involved in the pathogenesis of canine testicular malignancies. This study represents the first morphological work on the spatiotemporal expression pattern of Cx43 in normal and neoplastic canine testis.     

基于发育网络识别模型的大熊猫面部识别

个体识别是动物行为学与生态学研究工作的基础,也是制定珍稀野生动物保护政策的重要依据。为了丰富大熊猫个体识别和种群数量调查的方法,我们于2017年7月分别在四川省雅安市碧峰峡大熊猫基地和四川省汶川县耿达镇的中华大熊猫苑共计拍摄18只大熊猫个体,每只大熊猫拍摄6~13张高质量面部照片（共计131张）,利用发育网络（Developmental Network）建立大熊猫面部识别模型。利用此模型对存在部分背景的大熊猫面部照片进行识别检测,得到的个体识别率为79.41%,对完全去除背景的大熊猫面部照片进行识别检测,得到的个体识别率为58.82%。研究表明,发育网络具有足够的大熊猫个体识别能力,不同背景比例的照片对大熊猫个体识别的实际结果具有较大的影响。随着发育网络识别模型的发展,我们建议更多的野生动物保护研究者结合这一技术深入地开展珍稀野生动物（如大熊猫）个体识别研究,逐步提高识别准确度,并应用到关键区域大规模的动物调查中。     

Establishment and characterization of human choriocarcinoma cell line derived from a metastatic focus of a testicular mixed germ cell tumor

A human testicular choriocarcinoma cell line HKRT-II was established by the single-cell cloning method from a mixed cell culture system derived from a retroperitoneal metastatic germ cell tumor composed of a yolk-sac tumor, a choriocarcinoma, and an immature teratoma. Its primary tumor rose from the testis and was comprised of a seminoma, a yolk-sac tumor, a choriocarcinoma and an immature teratoma. The HKRT-II cells were spindle or polygonal in shape and contained multi-nucleated giant cells showing neoplasticity and pleomorphism. The cells proliferated in a stable manner, and the population doubling time was 42 hours. The chromosome numbers showed a wide distribution of aneuploidy, while the mode was in the hypertetraploid range. Double minute chromosomes and homogeneously staining regions were recognized in about 5% to 10% of the metaphase plates, respectively. Heterotransplantation was not difficult. Subcutaneous transplantation of 1 x 10(7) cells into nude mice formed a tumor composed of only a choriocarcinoma. The most noteworthy characteristics of the cell line were that it produced human chorionic gonadotropin (hCG) in an in vitro culture system and in in vivo grafted cells, and that the N-myc gene was amplified about 10 times.     

Clonal analysis of a transplantable rat seminoma]

The study of rat testis seminoma by the method of clonal analysis and ectopic transplantations has shown that typical and anaplastic types are different stages of tumor progression in the course of which atypical and anaplastic features of the seminoma cell elements increase. It does not seem inconceivable that the spermacytic form, never encountered during our investigation of 400 tumors, may be an independent seminoma form incapable of transforming into a typical one. A spindle-cell form of seminoma has been described most frequently occurring during transplantation of a typical seminoma into testis and during cloning. The obtained evidence permits to consider the small dark cells of the seminoma as being cambial cells of the tumor which occur abundantly in growing tumors, and are absent in tumors with ceased proloferating. At later stages of the seminoma development, the small dark cells may be absent, their function being performed practically by all tumor cells. Acinar structures found in part of clones from lungs and in the majority of transplants from eye anterior chamber suggest a histogenetic relationship between the typical seminoma and embryocarcinoma, and thus enable us to regard the latter as the most differentiated variants of the seminoma.     

Osteoclastomalike giant cell tumor of the parotid gland: report of a case with fine needle aspiration diagnosis

BACKGROUND: Osteoclastomalike giant cell tumor of the parotid gland has been reported rarely. The tumor has occurred rarely at many sites, such as thyroid, pancreas, soft tissue, breast, skin, heart, colon, lung, kidney, ovary and bladder. The exact origin of the tumor is unclear. However, osteoclastlike giant cells have been considered either part of a stromal process reactive to a neoplasm or a component of a primary neoplasm. CASE: A 35-year-old female presented with a mass in the left parotid gland clinically diagnosed as a pleomorphic adenoma. Fine needle aspiration (FNA) was advised before surgical excision. FNA smears revealed numerous osteoclastlike, multinucleated giant cells and many malignant-looking mononuclear cells. The smears were diagnosed as positive for malignancy, suggestive of osteoclastomalike giant cell tumor. The tumor was excised, and histopathologic study confirmed the cytologic diagnosis. CONCLUSION: The cytologic findings of osteoclastomalike giant cell tumor of the parotid gland have not been previously reported. FNA aided the diagnosis and planning of treatment. FNA is important in the diagnosis of parotid tumors.