Wip1基因对动物繁殖及免疫的调节作用

野生型p53诱导的磷酸酶1（wild-type p53-induced phosphatase 1,Wip1）是蛋白磷酸酶2C （protein phosphatase type 2C,PP2C）家族中的一员,可以靶向调控机体内多种重要的信号分子,如p53、MAPK和Chk1/Chk2等,在动物细胞周期、增殖、分化、凋亡、衰老、自噬及DNA损伤修复等生理过程中发挥重要作用。Wip1基因缺失会使小鼠生殖激素水平失衡,且该基因通过ATM、Wnt、凋亡和炎症等信号通路影响精子生成过程,导致雄性动物繁殖力下降。此外,Wip1基因还可通过动态平衡调节DNA损伤反应和去磷酸化作用来影响卵母细胞和胚胎发育,从而调控雌性动物的生殖。免疫系统是机体执行免疫应答及免疫功能的重要系统,其与炎症反应和肿瘤发生有着紧密的联系。Wip1基因缺失会使病原体敏感性增强,影响T细胞、B细胞和中性粒细胞迁移及凋亡,进而导致炎症反应。作为原癌基因,Wip1基因通过调控各种信号分子影响DNA损伤修复、细胞周期进程及细胞凋亡等,参与肿瘤发生。因此,Wip1基因在动物繁殖调控和免疫调节中扮演着重要角色。目前,Wip1基因受到越来越多学者的关注,特别是其调控动物疾病发生发展的机制已成为研究热点。本研究主要综述了Wip1基因对动物繁殖及免疫的调节作用,以期为家畜育种、疾病防治及靶向治疗提供新思路。     

Wnt信号通路及其在动物生长发育过程中的作用

Wnt途径是重要的细胞信号转导途径,该途径参与了从胚胎到成体的一系列控制胚胎早期的发育、决定细胞分化、细胞增殖及生长的调控,异常表达或激活该途径会导致各种疾病甚至肿瘤发生。本文重点阐述了Wnt信号通路在胚胎发育、细胞分化及其在肿瘤发生过程中的作用,同时揭示深入研究Wnt信号通路,设计出阻断Wnt通路的物质,可为将来肿瘤的治疗开辟一条新的途径。     

Molecular approaches to equine sarcoids

Sarcoids are the most commonly diagnosed skin tumours in equines. Bovine papillomaviruses (BPVs) are the primary causative agent of sarcoids. There has been intensive research to discover the molecular mechanisms that may contribute to the aetiopathogenesis of this disease and tumour suppressors and proto-oncogenes known to play a role in human neoplastic conditions have been investigated in equine sarcoids. Current approaches include the identification of gene expression profiles, characterising sarcoid and normal skin tissues, and an assessment of epigenetic alterations such as microRNA differential expression and DNA methylation status. This review focuses on selected groups of genes that contribute to the molecular mechanisms of sarcoid formation. These genes have the potential to complement current clinical examinations of equine sarcoid disease in diagnosis, prognosis, therapeutic response and screening.     

WW 结构域及相关蛋白在肿瘤发生中的作用

WW结构域由35～40个氨基酸残基组成,存在两个高度保守的色氨酸残基,能特异地与富含脯氨酸的蛋白基序结合。WW结构域存在于多种蛋白中,广泛参与细胞内各种生化过程和信号通路。WW结构域及其参与构成的蛋白与包括癌症在内的多种人类疾病存在密切联系,成为疾病诊断、治疗和药物开发的新靶标。本论文中,我们综述了WW结构域及其参与构成的蛋白在肿瘤和癌症发生中的重要作用和研究进展。     

I. Immunosurveillance and tumorigenesis in BALB/c mice—1. Early reactive state in mesenteric granulomas

The cellular immune response in BALB/c mice mesenteric granulomas (MG) was analysed by the means of functional ultrastructure and the assessment of the presence or absence of asynchronous plasma cells in situ.

Results from this study establish: (a) the sequential events involved in the genesis of the oil-induced granulomas, (b) the weak T-cellular immune response and the almost absence of these cells in mitosis, (c) the presence of asynchronous plasma cells of type II was found in mice Nos. 8, 9, 10 and 11 and they were considered to be plasma cell mutants of temporary type, to indicate the first step of this cell alienation in tumorigenesis, (d) the high ratio of peritoneal macrophages was found and connected with what is known about it in the literature. It was speculated that the supraoptimal presence of peritoneal macrophages could have been responsible for the appearance of plasma cell mutants and (e) four morphological types of macrophages have been found in this animal's oil-induced MG, representing different stages of the monocyte transformation in situ.     

Mechanisms of Mycotoxin-induced Dermal Toxicity and Tumorigenesis Through Oxidative Stress-related Pathways

Among the many mycotoxins, T-2 toxin, citrinin (CTN), patulin (PAT), aflatoxin B1 (AFB1) and ochratoxin A (OTA) are known to have the potential to induce dermal toxicity and/or tumorigenesis in rodent models. T-2 toxin, CTN, PAT and OTA induce apoptosis in mouse or rat skin. PAT, AFB1 and OTA have tumor initiating properties, and OTA is also a tumor promoter in mouse skin. This paper reviews the molecular mechanisms of dermal toxicity and tumorigenesis induced in rodent models by these mycotoxins especially from the viewpoint of oxidative stress-mediated pathways.