Hedgehogs

刺猬
  • DOI:
    文章类型: Case Reports
    该病例描述了一名58岁的妇女,她出现在皮肤科门诊诊所,手上有进行性皮肤病变。体格检查显示红斑鳞状斑块。根据真菌培养物诊断人畜共患皮肤真菌病,显示了毛癣菌。这种皮肤癣菌特别通过刺猬传播。患者似乎已经照顾了受感染的刺猬。
    This case describes a 58-year-old woman who presented to the dermatology outpatient clinic with progressive skin lesions on the hands. Physical examination showed erythematosquamous plaques. The diagnosis zoonotic dermatomycosis was made based on fungal cultures, which showed a Trichophyton erinacei. This dermatophyte is particularly transmitted through hedgehogs. The patient appeared to have taken care of an infected hedgehog.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    蜱传病原体对人类很重要,兽医,和野生动物的健康。伯氏柯西氏菌是一个例子,它广泛分布在各种宿主中,可以跨越物种边界。在巴基斯坦,在野生动物和牲畜的交汇处,关于C.burnetii的数据很少。蜱虫是从卡苏尔地区的反刍动物和野生动物中收集的,竹藤,还有巴基斯坦的Okara.共收集了5种蜱虫,共571只蜱,分布如下:56.4%anatolicum,22.4%微小根孢,10.5%Hyalommamarginatum,7.9%血象,和2.8%的水曲柳。使用实时PCR测定筛选50个蜱池的伯氏梭菌以扩增IS1111的片段。从绵羊和山羊收集的蜱对C.burnetii有更高的阳性率(40%和38%,分别)与印度长耳刺猬相比,患病率为2%。伯氏柯西氏菌在微触毛(92.3%)和anatolicum(88.9%)中突出,其次是水曲柳(66.6%),血根虫(33.3%),和边缘卫生学(25.0%)。来自Pakpattan地区的蜱虫显示出最高的C.burnetii患病率(88.9%),而最低的是Kasur区的蜱(77.3%)。蜱性别与C.burnetii感染之间没有显着关联。雌性寄主动物更有可能藏有含有B.burnetii的蜱,患病率为81.8%。该研究强调迫切需要对巴基斯坦的C.burnetii进行全面研究,尤其是在野生动物和牲畜的交界处。在某些蜱类和地理区域观察到的高患病率强调了有针对性的公共卫生干预措施的重要性。未来的研究应集中在阐明传播动力学和实施有效的控制措施,以减轻这些病原体对人类的影响,兽医,以及该地区的野生动物健康。
    Tick-borne pathogens are significant for human, veterinary, and wildlife health. Coxiella burnetii is an example that is widely distributed across various hosts and can cross species boundaries. In Pakistan, there is a scarcity of data regarding C. burnetii at the intersection of wildlife and livestock. Ticks were collected from ruminants and wildlife from the districts of Kasur, Pakpattan, and Okara in Pakistan. Five tick species totaling 571 ticks were collected, with the following distribution: 56.4% Hyalomma anatolicum, 22.4% Rhipicephalus microplus, 10.5% Hyalomma marginatum, 7.9% Rhipicephalus sanguineus, and 2.8% Rhipicephalus turanicus. Fifty tick pools were screened for C. burnetii to amplify a segment of the IS1111 using real-time PCR assays. Ticks collected from sheep and goats had a greater rate of positivity for C. burnetii (40% and 38%, respectively) compared to Indian long-eared hedgehogs with a prevalence of 2%. Coxiella burnetii was prominent in Rhipicephalus microplus (92.3%) and Hyalomma anatolicum (88.9%), followed by Rhipicephalus turanicus (66.6%), Rhipicephalus sanguineus (33.3%), and Hyalomma marginatum (25.0%). Ticks from Pakpattan district displayed the highest prevalence of C. burnetii (88.9%), whereas the lowest was observed in ticks from Kasur district (77.3%). There was no significant association between tick gender and C. burnetii infection. Female host animals were more likely to harbor ticks containing C. burnetii, with a prevalence rate of 81.8%. The research underscores the urgent need for comprehensive studies on C. burnetii in Pakistan, especially at the interface of wildlife and livestock. The high prevalence rates observed in certain tick species and geographic regions emphasize the importance of targeted public health interventions. Future research should focus on elucidating the transmission dynamics and implementing effective control measures to mitigate the impact of these pathogens on human, veterinary, and wildlife health in the region.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    肠胞虫双子小孢子虫是感染多种脊椎动物和无脊椎动物宿主的新兴病原体,已知具有人畜共患特征,因为它们感染野生动物和家养动物,和人类。尽管意义重大,关于刺猬微孢子虫的流行病学数据非常有限,尤其是欧洲刺猬(Erinaceuseuropaeus)和长耳刺猬(Hemiechinusauritus),前者被称为同向刺猬,后者适合作为宠物。因此,本研究旨在评估葡萄牙刺猬中E.bieneusi的存在。为此,来自三个物种的110只刺猬的粪便样本-E.europaeus(n=106),H.auritus(n=1),和Atelerixalbiventris(n=3)-被收集并通过PCR靶向ITS区域和rRNA的侧翼小亚基和大亚基来测试E.bieneusi。我们发现总体发生率为22.7%(25/110;95%[CI]:15.28-31.70),在E.europaeus中,22.6%(24/106;95%[CI]:15.08-31.79),100%(1/1)在金丝雀,和0%在阿比文特里斯。有趣的是,确定了三种新的基因型,全部属于潜在的人畜共患组1。我们的发现强调了刺猬作为E.bieneusi潜在水库的重要性,并强调需要进一步研究以了解它们在传播动力学中的作用并评估对公共和兽医健康的相关风险。
    对Synthropic刺猬进行了肠孢子虫bieneusi测试,人类微孢子虫病的主要病因。结果显示22.7%的刺猬脱落E.bieneusi孢子,具有来自人畜共患组1的三种新基因型。刺猬可能会传播给人类/动物,保证更多的研究。
    Enterocytozoon bieneusi microsporidia are emerging pathogens infecting a wide range of vertebrate and invertebrate hosts, known to have zoonotic features since they infect both wild and domestic animals, and humans. Despite their significance, there is very limited epidemiological data on microsporidia in hedgehogs, especially European hedgehogs (Erinaceus europaeus) and long-eared hedgehogs (Hemiechinus auritus), the former known as synantropic hedgehogs, and the latter suited as pets. As such, the present study aimed to assess the presence of E. bieneusi in hedgehogs from Portugal. For this purpose, fecal samples from 110 hedgehogs of three species-E. europaeus (n = 106), H. auritus (n = 1), and Atelerix albiventris (n = 3)-were collected and tested for E. bieneusi by PCR targeting the internal transcribed spacer region and the flanking small and large subunits of the rRNA. We found an overall occurrence of 22.7% (25/110; 95% confidence interval [CI]: 15.28-31.70), with 22.6% (24/106; 95% [CI]: 15.08-31.79) in E. europaeus, 100% (1/1) in H. auritus, and 0% in A. albiventris. Interestingly, three novel genotypes were identified, all belonging to the potentially zoonotic Group 1. Our findings highlight the importance of hedgehogs as potential reservoirs for E. bieneusi and emphasize the need for further research to understand their role in transmission dynamics and assess the associated risks to public and veterinary health.
    Synanthropic hedgehogs were tested for Enterocytozoon bieneusi, the main cause of human microsporidiosis. Results showed 22.7% of hedgehogs were shedding E. bieneusi spores, with three new genotypes from the zoonotic Group 1. Hedgehogs may transmit to humans/animals, warranting more research.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    北非刺猬(Atelerixalgirus)是来自西北非洲的引进物种,目前分布在加那利群岛。这种刺猬已被研究为肠道病原体的储库,包括隐孢子虫。然而,没有物种层面的数据。因此,本研究的目的是确定加那利群岛刺猬种群(n=36)中存在的隐孢子虫物种。使用针对隐孢子虫小亚基核糖体RNA(18SrRNA)基因的常规聚合酶链反应(PCR)进行分子筛选。36个粪便样品中的7个(19.45%)是阳性的,并通过靶向18SrRNA基因的巢式PCR和Sanger测序得到证实。在11.1%(4/36)和5.6%(2/36)的样品中鉴定出微小隐孢子虫和细胞隐孢子虫,分别,而一个样本只能在属水平上鉴定。人畜共患亚型IIdA15G1(n=1),IIdA16G1b(n=1),通过巢式PCR鉴定C.parvum的IIdA22G1(n=1),然后分析60kDa糖蛋白(gp60)基因序列。这项研究是隐孢子虫的第一个遗传表征。在A.algirus,确定寄生虫的人畜共患物种和亚型。
    The North African hedgehog (Atelerix algirus) is an introduced species from Northwest Africa and is currently distributed in the Canary Islands. This species of hedgehog has been studied as a reservoir of enteropathogens, including Cryptosporidium spp. However, there are no data at species level. Therefore, the aim of the present study was to identify the Cryptosporidium species present in a population of hedgehogs (n = 36) in the Canary Islands. Molecular screening was performed using conventional polymerase chain reaction (PCR) targeting the small subunit ribosomal RNA (18S rRNA) gene of Cryptosporidium spp. Seven of the 36 fecal samples (19.45%) were positive and confirmed by nested PCR targeting the 18S rRNA gene and Sanger sequencing. Cryptosporidium parvum and Cryptosporidium muris were identified in 11.1% (4/36) and 5.6% (2/36) of the samples, respectively, while one sample could only be identified at the genus level. The zoonotic subtypes IIdA15G1 (n = 1), IIdA16G1b (n = 1), and IIdA22G1 (n = 1) of C. parvum were identified by nested PCR followed by analysis of the 60 kDa glycoprotein (gp60) gene sequence. This study is the first genetic characterization of Cryptosporidium spp. in A. algirus, identifying zoonotic species and subtypes of the parasite.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    背景:欧洲刺猬(Erinaceuseuropaeus)在欧洲广泛分布。它们可能通过在环境中以及向人类和动物传播人畜共患病细菌而发挥重要作用。我们工作的目的是研究野生刺猬中最重要的食源性细菌病原体的患病率和特征。
    结果:研究了来自芬兰南部赫尔辛基地区的148只住院野生刺猬的粪便样本。通过PCR在60%的刺猬中检测到食源性病原体。李斯特菌(26%)和STEC(26%)是最常见的食源性病原体。沙门氏菌,耶尔森氏菌,弯曲杆菌的检出率为18%,16%,和7%的刺猬,分别。沙门氏菌和耶尔森氏菌对所测试的抗菌剂高度敏感。肠炎沙门氏菌和单核细胞增生李斯特菌2a是刺猬中最常见的类型。所有肠炎沙门氏菌都属于一种序列类型(ST11),形成四个密切相关的分离株簇。单核细胞增生李斯特菌在基因上比沙门氏菌更多样化,属于11个STS。还发现了空肠杆菌ST45和ST677、ST9和ST42的假结核Y.O:1和ST139的小肠结肠炎Y.O:9。
    结论:我们的研究表明,野生欧洲刺猬应被视为食源性病原体的重要来源,因此,与刺猬接触后采取适当的卫生措施以及农场周围严格的生物安全至关重要。
    BACKGROUND: European hedgehogs (Erinaceus europaeus) are widely distributed across Europe. They may play an important role by spreading zoonotic bacteria in the environment and to humans and animals. The aim of our work was to study the prevalence and characteristics of the most important foodborne bacterial pathogens in wild hedgehogs.
    RESULTS: Faecal samples from 148 hospitalised wild hedgehogs originating from the Helsinki region in southern Finland were studied. Foodborne pathogens were detected in 60% of the hedgehogs by PCR. Listeria (26%) and STEC (26%) were the most common foodborne pathogens. Salmonella, Yersinia, and Campylobacter were detected in 18%, 16%, and 7% of hedgehogs, respectively. Salmonella and Yersinia were highly susceptible to the tested antimicrobials. Salmonella Enteritidis and Listeria monocytogenes 2a were the most common types found in hedgehogs. All S. Enteritidis belonged to one sequence type (ST11), forming four clusters of closely related isolates. L. monocytogenes was genetically more diverse than Salmonella, belonging to 11 STs. C. jejuni ST45 and ST677, Y. pseudotuberculosis O:1 of ST9 and ST42, and Y. enterocolitica O:9 of ST139 were also found.
    CONCLUSIONS: Our study shows that wild European hedgehogs should be considered an important source of foodborne pathogens, and appropriate hygiene measures after any contact with hedgehogs and strict biosecurity around farms are therefore important.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    背景为了更好地为新兴的野生动物动物共患病做好准备,我们需要加强野生动物疾病监测。目的这项研究的目的是创建野生动物物种中人畜共患病原体的局部概述,以确定知识差距和改善野生动物疾病监测的机会。方法我们创建了一个数据库,这是基于Embase的系统文献综述,重点是欧洲10种常见的城市野生动物哺乳动物中的人畜共患病原体,即棕色老鼠,家鼠,木鼠,普通田鼠,红松鼠,欧洲兔子欧洲刺猬,欧洲痣,石马和红狐狸.总的来说,我们检索了6,305篇独特文章,其中882篇被收录.结果总的来说,描述了186种人畜共患病原体,包括90种细菌,42个蠕虫,19原生动物,22种病毒和15种真菌。这些病原体中的大多数仅在一种动物物种中进行研究。即使考虑到一些病原体是相对特定的物种,许多欧洲国家没有(可访问的)有关这些相关动物物种中人畜共患病原体的数据。我们以荷兰为例,展示了其他国家如何使用该数据库来确定国家层面的野生动植物疾病监测差距。在荷兰,仅研究了所有潜在宿主-病原体组合的4%。结论该数据库包含一个全面的概述,可以指导欧洲和国家范围内野生动物传播的人畜共患疾病的未来研究。共享和扩展该数据库为未来在欧洲范围内开展合作以改善野生动植物疾病监测提供了坚实的起点。
    BackgroundTo be better prepared for emerging wildlife-borne zoonoses, we need to strengthen wildlife disease surveillance.AimThe aim of this study was to create a topical overview of zoonotic pathogens in wildlife species to identify knowledge gaps and opportunities for improvement of wildlife disease surveillance.MethodsWe created a database, which is based on a systematic literature review in Embase focused on zoonotic pathogens in 10 common urban wildlife mammals in Europe, namely brown rats, house mice, wood mice, common voles, red squirrels, European rabbits, European hedgehogs, European moles, stone martens and red foxes. In total, we retrieved 6,305 unique articles of which 882 were included.ResultsIn total, 186 zoonotic pathogen species were described, including 90 bacteria, 42 helminths, 19 protozoa, 22 viruses and 15 fungi. Most of these pathogens were only studied in one single animal species. Even considering that some pathogens are relatively species-specific, many European countries have no (accessible) data on zoonotic pathogens in these relevant animal species. We used the Netherlands as an example to show how this database can be used by other countries to identify wildlife disease surveillance gaps on a national level. Only 4% of all potential host-pathogen combinations have been studied in the Netherlands.ConclusionsThis database comprises a comprehensive overview that can guide future research on wildlife-borne zoonotic diseases both on a European and national scale. Sharing and expanding this database provides a solid starting point for future European-wide collaborations to improve wildlife disease surveillance.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    众所周知,非洲侏儒刺猬(Atelerixalbiventris)的肿瘤发病率很高。然而,研究该物种的肿瘤一直受到有限的研究材料,如细胞系和基因组信息的限制。在这项研究中,我们成功地从非洲侏儒刺猬的组织细胞肉瘤(HS)中建立了一个新的细胞系,允许我们进行药物筛选.我们使用FDA批准的药物库筛选进行调查,以确定该肿瘤细胞系对哪种抗癌药物敏感,作为细胞凋亡实验的结果,发现三种蛋白酶体抑制剂中的硼替佐米通过显着增加caspase-3的裂解而诱导癌细胞死亡(P<0.01)。因此,我们阐明了蛋白酶体抑制剂,尤其是硼替佐米,通过与人类肿瘤中描述的机制相当的机制,对非洲侏儒刺猬中HS衍生的细胞系表现出抗肿瘤作用。这项研究报告了来自非洲侏儒刺猬的第一个特征细胞系,并强调了硼替佐米作为该物种HS抗肿瘤治疗的潜在用途。
    The African pygmy hedgehog (Atelerix albiventris) is known to have a high incidence of tumor. However, investigating the tumors of this species has been constrained by the limited availability of research materials such as cell lines and genome information. In this study, we successfully established a novel cell line from a histiocytic sarcoma (HS) of an African pygmy hedgehog, allowing us to conduct a drug screening. We investigated using FDA-approved drug library screening to determine which anticancer drug this tumor cell line is sensitive to, and as a result of apoptosis experiments, bortezomib among the three proteasome inhibitors was found to induce cell death of cancer cells by significantly increasing caspase-3 cleavage (P<0.01). Thus, we elucidated that the proteasome inhibitors, particularly bortezomib, exhibit anti-tumor effects on a cell line derived from an HS in an African pygmy hedgehog through a mechanism comparable to that described in human tumors. This study reports the first characterized cell line from the African pygmy hedgehog and also highlights the potential utility of bortezomib as an anti-tumor treatment for HS in this species.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    光学系统的一个关键组件是睫状体(CB)。这个身体分泌房水,这对于保持内部眼压以及晶状体和角膜的清晰度至关重要。组织学研究旨在提供以下脊椎动物类别的前眼房中CB和虹膜的形态差异:鱼(草鱼),两栖动物(阿拉伯蟾蜍),爬行动物(半水龟,扇脚壁虎,带牙的石龙子,埃及刺尾蜥蜴,阿拉伯有角毒蛇),鸟类(普通鸽子,普通鹌鹑,普通凯斯特尔),和哺乳动物(BALB/c小鼠,兔子,金色仓鼠,沙漠刺猬,较小的埃及人,埃及水果蝙蝠)。结果表明,每个物种的CB和虹膜的形态特征不同,从鱼类到哺乳动物。本比较研究得出的结论是,CB和虹膜的形态结构是物种对其生活方式或在特定栖息地中生存的适应。
    One crucial component of the optical system is the ciliary body (CB). This body secretes the aqueous humour, which is essential to maintain the internal eye pressure as well as the clearness of the lens and cornea. The histological study was designed to provide the morphological differences of CB and iris in the anterior eye chambers of the following vertebrate classes: fish (grass carp), amphibians (Arabian toad), reptiles (semiaquatic turtle, fan-footed gecko, ocellated skink, Egyptian spiny-tailed lizard, Arabian horned viper), birds (common pigeon, common quail, common kestrel), and mammals (BALB/c mouse, rabbit, golden hamster, desert hedgehog, lesser Egyptian jerboa, Egyptian fruit bat). The results showed distinct morphological appearances of the CB and iris in each species, ranging from fish to mammals. The present comparative study concluded that the morphological structure of the CB and iris is the adaptation of species to either their lifestyle or survival in specific habitats.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    通过磁性纳米粒子(MN)高效分离脱氧核糖核酸(DNA)是一种广泛使用的生物技术。刺猬启发的MNs(HMN)由于刺猬具有明显的毛刺状结构而具有高表面积,但是没有关于HMN用于DNA提取的报道。在这里,为了改善MN的选择并说明HMN用于DNA分离的性能,制备了HMN和二氧化硅包覆的Fe3O4纳米颗粒(Fe3O4@SiO2),并对其高效分离病原菌的DNA进行了比较。大肠杆菌(E.大肠杆菌)和金黄色葡萄球菌(S.金黄色葡萄球菌)是典型的革兰氏阴性菌和革兰氏阳性菌,被选为模式致病菌。为了提高两种MNs的提取效率,各种参数,包括预处理,裂解,结合和洗脱条件,已经详细优化了。在大多数分离实验中,HMN的DNA产率高于Fe3O4@SiO2。因此,将基于HMN的磁性固相微萃取(MSPE)和定量实时PCR(qPCR)集成在一起,用于检测实际样品中的病原菌。有趣的是,基于HMN的MSPE联合qPCR策略表现出高灵敏度,橙汁中大肠杆菌的检出限为2.0×101CFUmL-1,金黄色葡萄球菌的检出限为4.0×101CFUmL-1,牛奶中大肠杆菌为2.8×102CFUmL-1,金黄色葡萄球菌为1.1×102CFUmL-1,分别。所提出的策略的性能明显优于商业套件。这项工作可以证明,新型HMN可用于从复杂的生物样品中有效分离DNA。
    Efficient separation of deoxyribonucleic acid (DNA) through magnetic nanoparticles (MN) is a widely used biotechnology. Hedgehog-inspired MNs (HMN) possess a high-surface-area due to the distinct burr-like structure of hedgehog, but there is no report about the usage of HMN for DNA extraction. Herein, to improve the selection of MN and illustrate the performance of HMN for DNA separation, HMN and silica-coated Fe3O4 nanoparticles (Fe3O4@SiO2) were fabricated and compared for the high-efficient separation of pathogenic bacteria of DNA. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are typical Gram-negative and Gram-positive bacteria and are selected as model pathogenic bacteria. To enhance the extraction efficiency of two kinds of MNs, various parameters, including pretreatment, lysis, binding and elution conditions, have been optimized in detail. In most separation experiments, the DNA yield of HMN was higher than that of Fe3O4@SiO2. Therefore, a HMN-based magnetic solid-phase microextraction (MSPE) and quantitative real-time PCR (qPCR) were integrated and used to detect pathogenic bacteria in real samples. Interestingly, the HMN-based MSPE combined qPCR strategy exhibited high sensitivity with a limit of detection of 2.0 × 101 CFU mL-1 for E. coli and 4.0 × 101 CFU mL-1 for S. aureus in orange juice, and 2.8 × 102 CFU mL-1 for E. coli and 1.1 × 102 CFU mL-1 for S. aureus in milk, respectively. The performance of the proposed strategy was significantly better than that of commercial kit. This work could prove that the novel HMN could be applicable for the efficient separation of DNA from complex biological samples.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    致癌信号通路之间的串扰在驱动癌症发展中起着至关重要的作用。我们之前证明了膳食多酚,特别是白藜芦醇(RSV)和其他芪类,在乳腺癌中通过DNA超甲基化沉默的表观遗传靶癌基因。在本研究中,我们确定了RSV高甲基化靶标中的信号转导调节因子,并研究了RSV介导的DNA高甲基化在Hedgehog和Wnt信号调节中的功能作用。非侵入性ER阳性MCF-7和高侵入性三阴性MCF10CA1a人乳腺癌细胞系用作实验模型。暴露于15µMRSV9天后,进行焦磷酸测序和qRT-PCR以评估GLI2和WNT4的DNA甲基化和表达,GLI2和WNT4是Hedgehog和Wnt途径的上游调节因子,分别。我们的结果表明,RSV导致GLI2和WNT4增强子内DNA甲基化增加,伴随着基因表达的减少。始终如一,我们观察到Hedgehog和Wnt信号下游基因的下调,包括两种途径共有的共同目标,CCND1和CYR61。进一步分析使用染色质免疫沉淀鉴定增加H3K27三甲基化和减少H3K9和H3K27乙酰化,随着OCT1转录因子结合的废除。这些变化表明GLI2和WNT4增强子的转录沉默染色质状态。使用磷酸抗体阵列证实了对Wnt信号转导的抑制,所述磷酸抗体阵列证明了对Wnt调节因子的阳性抑制和对阴性Wnt调节因子的刺激。总之,我们的研究结果为膳食多酚作为表观遗传学调节剂提供了科学证据,可以使癌基因重新甲基化和沉默,减少致癌信号转导。靶向这种作用可能是乳腺癌预防和/或辅助治疗的有效策略。
    The crosstalk between oncogenic signaling pathways plays a crucial role in driving cancer development. We previously demonstrated that dietary polyphenols, specifically resveratrol (RSV) and other stilbenoids, epigenetically target oncogenes for silencing via DNA hypermethylation in breast cancer. In the present study, we identify signal transduction regulators among RSV-hypermethylated targets and investigate the functional role of RSV-mediated DNA hypermethylation in the regulation of Hedgehog and Wnt signaling. Non-invasive ER-positive MCF-7 and highly invasive triple-negative MCF10CA1a human breast cancer cell lines were used as experimental models. Upon 9-day exposure to 15 µM RSV, pyrosequencing and qRT-PCR were performed to assess DNA methylation and expression of GLI2 and WNT4, which are upstream regulators of the Hedgehog and Wnt pathways, respectively. Our results showed that RSV led to a DNA methylation increase within GLI2 and WNT4 enhancers, which was accompanied by decreases in gene expression. Consistently, we observed the downregulation of genes downstream of the Hedgehog and Wnt signaling, including common targets shared by both pathways, CCND1 and CYR61. Further analysis using chromatin immunoprecipitation identified increased H3K27 trimethylation and decreased H3K9 and H3K27 acetylation, along with abolishing OCT1 transcription factor binding. Those changes indicate a transcriptionally silent chromatin state at GLI2 and WNT4 enhancers. The inhibition of the Wnt signal transduction was confirmed using a phospho-antibody array that demonstrated suppression of positive and stimulation of negative Wnt regulators. In conclusion, our results provide scientific evidence for dietary polyphenols as epigenetics-modulating agents that act to re-methylate and silence oncogenes, reducing the oncogenic signal transduction. Targeting such an action could be an effective strategy in breast cancer prevention and/or adjuvant therapy.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

公众号