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排序方式: 共有1786条查询结果,搜索用时 15 毫秒
1.
Xiaoyan Lu Isabelle R. Miousse Sandra V. Pirela Jodene K. Moore Stepan Melnyk 《Nanotoxicology》2016,10(5):629-639
Evidence continues to grow on potential environmental health hazards associated with engineered nanomaterials (ENMs). While the geno- and cytotoxic effects of ENMs have been investigated, their potential to target the epigenome remains largely unknown. The aim of this study is two-fold: 1) determining whether or not industry relevant ENMs can affect the epigenome in vivo and 2) validating a recently developed in vitro epigenetic screening platform for inhaled ENMs. Laser printer-emitted engineered nanoparticles (PEPs) released from nano-enabled toners during consumer use and copper oxide (CuO) were chosen since these particles induced significant epigenetic changes in a recent in vitro companion study. In this study, the epigenetic alterations in lung tissue, alveolar macrophages and peripheral blood from intratracheally instilled mice were evaluated. The methylation of global DNA and transposable elements (TEs), the expression of the DNA methylation machinery and TEs, in addition to general toxicological effects in the lung were assessed. CuO exhibited higher cell-damaging potential to the lung, while PEPs showed a greater ability to target the epigenome. Alterations in the methylation status of global DNA and TEs, and expression of TEs and DNA machinery in mouse lung were observed after exposure to CuO and PEPs. Additionally, epigenetic changes were detected in the peripheral blood after PEPs exposure. Altogether, CuO and PEPs can induce epigenetic alterations in a mouse experimental model, which in turn confirms that the recently developed in vitro epigenetic platform using macrophage and epithelial cell lines can be successfully utilized in the epigenetic screening of ENMs. 相似文献
2.
Anne?W.?Higgins Karen?M.?Gustashaw Huntington?F.?WillardEmail author 《Chromosome research》2005,13(8):745-762
The centromere is essential for the faithful distribution of a cell's genetic material to subsequent generations. Despite
intense scrutiny, the precise genetic and epigenetic basis for centromere function is still unknown. Here, we have used engineered
dicentric human chromosomes to investigate mammalian centromere structure and function. We describe three classes of dicentric
chromosomes isolated in different cell lines: functionally monocentric chromosomes, in which one of the two genetically identical
centromeres is consistently inactivated; functionally dicentric chromosomes, in which both centromeres are consistently active;
and dicentric chromosomes heterogeneous with respect to centromere activity. A study of serial single cell clones from heterogeneous
cell lines revealed that while centromere activity is usually clonal, the centromere state (i.e. functionally monocentric
or dicentric) in some lines can switch within a growing population of cells. Because pulsed field gel analysis indicated that
the DNA at the centromeres of these chromosomes did not change detectably, this switching of the centromere state is most
likely due to epigenetic changes. Inactivation of one of the two active centromeres in a functionally dicentric chromosome
was observed in a percentage of cells after treatment with Trichostatin A, an inhibitor of histone deacetylation. This study
provides evidence that the activity of human centromeres, while largely stable, can be subject to dynamic change, most likely
due to epigenetic modification. 相似文献
3.
Shanlee M. Davis Mitchell E. Geffner 《American journal of medical genetics. Part C, Seminars in medical genetics》2019,181(1):60-66
Individuals with Turner syndrome (TS) have a higher morbidity and mortality compared to the general population. Diabetes and cardiovascular disease are the major contributors to this burden. Precursors to diabetes and cardiovascular disease make up what is known as metabolic syndrome, including abdominal obesity, hypertension, dyslipidemia, and elevated fasting glucose. These features of poor cardiometabolic health are also prevalent among women with TS. Youth with TS also exhibit many of these features, indicating that the pathogenesis of these cardiometabolic conditions may begin early in life. The etiology of the increased risk of cardiometabolic conditions in TS is likely multifactorial, involving genetics, epigenetics, hypogonadism, medical comorbidities, medications, and lifestyle. Counseling for the increased risk of cardiometabolic diseases as well as efforts to prevent or lower this risk should be routinely provided in the care of all patients with TS. Clinical practice guidelines are now available to guide screening and treatment of cardiometabolic conditions in girls and women with TS. 相似文献
4.
5.
Epigenetics refers to covalent modifications of DNA and core histones that regulate gene activity without altering DNA sequence. To date, the best-characterized DNA modification associated with the modulation of gene activity is methylation of cytosine residues within CpG dinucleotides. Human disorders associated with epigenetic abnormalities include rare imprinting diseases, molar pregnancies, and childhood cancers. Germ cell development and early embryo development are critical times when epigenetic patterns are initiated or maintained. This review focuses on the epigenetic modification DNA methylation and discusses recent progress that has been made in understanding when and how epigenetic patterns are differentially established in the male and female germlines, the mouse, and human disorders associated with abnormalities in epigenetic programming in germ cells and early embryos, as well as genetic and other modulators (e.g. nutrition and drugs) of reproductive epigenetic events. 相似文献
6.
Wojciech Czogaa Magorzata Czogaa Wojciech Strojny Gracjan Wtor Pawe Wokow Magorzata Wjcik Mirosaw Bik Multanowski Przemysaw Tomasik Andrzej Wdrychowicz Wojciech Kowalczyk Karol Miklusiak Agnieszka azarczyk Przemysaw Haubiec Szymon Skocze 《Nutrients》2021,13(5)
The occurrence of childhood obesity is influenced by both genetic and epigenetic factors. FTO (FTO alpha-ketoglutarate dependent dioxygenase) is a gene of well-established connection with adiposity, while a protooncogene PLAG1 (PLAG1 zinc finger) has been only recently linked to this condition. We performed a cross-sectional study on a cohort of 16 obese (aged 6.6–17.7) and 10 healthy (aged 11.4–16.9) children. The aim was to evaluate the relationship between methylation and expression of the aforementioned genes and the presence of obesity as well as alterations in anthropometric measurements (including waist circumference (WC), body fat (BF_kg) and body fat percent (BF_%)), metabolic parameters (lipid profile, blood glucose and insulin levels, presence of insulin resistance) and blood pressure. Expression and methylation were measured in peripheral blood mononuclear cells using a microarray technique and a method based on restriction enzymes, respectively. Multiple regression models were constructed to adjust for the possible influence of age and sex on the investigated associations. We showed significantly increased expression of the FTO gene in obese children and in patients with documented insulin resistance. Higher FTO expression was also associated with an increase in WC, BF_kg, and BF_% as well as higher fasting concentration of free fatty acids (FFA). FTO methylation correlated positively with WC and BF_kg. Increase in PLAG1 expression was associated with higher BF%. Our results indicate that the FTO gene is likely to play an important role in the development of childhood adiposity together with coexisting impairment of glucose-lipid metabolism. 相似文献
7.
This study investigated the impact of the administration of HAART and anti-Koch's, singly and in combination, on sexual competence and birth statistics. Adult male Wistar rats were randomised into distilled water-treated control, HAART-treated, anti-Koch's-treated and HAART + anti-Koch's-treated groups. The 56-day oral treatment led to impaired sexual competence evident by significantly reduced motivation to mate, prolonged latencies of mount, intromissions, ejaculations and post-ejaculatory interval, as well as reduced frequencies of mount, intromissions and ejaculations. This was accompanied by significant reductions in penile erection reflex and penile grooming. HAART and anti-Koch's, when administered singly or in combination, also led to significant reductions in the circulatory follicle-stimulating hormone, luteinizing hormone, testosterone and intratesticular testosterone, but a significant rise in prolactin. Also, HAART and/or anti-Koch's significantly reduced sperm count, sperm motility, sperm viability and spermatozoa with normal morphology. Furthermore, HAART and anti-Koch's, separately or in combination, significantly lowered fertility capacity, litter size and litter weight and offspring survival. The deleterious effects of these drugs were more pronounced when combined. Findings of the present study revealed that HAART and/or anti-Koch's impair sexual competence via a testosterone-dependent hyperprolactinemia-mediated mechanism. These events are associated with reduced fertility capacity, poor sperm quality and lowered offspring survival. 相似文献
8.
目的:探讨Wnt3a通过Jumonji C结构域6( Jumonji C domain 6,JMJD6)的表观遗传修饰在神经病理性疼痛
中发挥作用的机制。方法:将SD大鼠分为4组:Sham组,慢性缩窄性损伤(chronic constriction injury,CCI)组,CCI+阴性慢病毒表达载体(LV-NC)组;CCI+慢病毒过表达载体(LV-JMJD6)组。构建SD大鼠坐骨神经CCI模型和JMJD6慢病毒
表达载体。CCI术后第3天通过鞘内导管给药,按照分组分别给予生理盐水和含慢病毒的试剂(病毒滴度1×108 TU/mL)
各20 μL。监测大鼠的机械缩足阈值(paw withdrawal mechanical threshold,PWMT)和热缩足潜伏期(paw withdrawal thermal latency,PWTL),并运用蛋白质印迹法检测脊髓水平Wnt3a及NR2B蛋白的表达变化,免疫共沉淀检测JMJD6与Wnt3a之间是否存在直接相互作用。结果:与Sham组相比,CCI术后各组大鼠的PWMT明显降低和PWTL明显缩短(P<0.05)。与CCI组和CCI+LV-NC组相比,CCI+LV-JMJD6组的PWMT在术后第10和14天明显升高,PWTL在术后第14
天明显延长(P<0.05)。CCI术后第14天,CCI组及CCI+LV-NC组Wnt3a和NR2B蛋白表达水平较Sham组明显升高,鞘内注
射慢病毒载体后, CCI+LV-JMJD6组的Wnt3a和NR2B蛋白表达水平较CCI+LV-NC组降低(P<0.05)。免疫共沉淀结果显示Wnt3a与JMJD6之间无直接相互作用。结论:Wnt3a参与调节神经病理性疼痛,其作用可能与JMJD6的表观遗传修饰相关,两者可能通过间接相互作用进行调节。 相似文献
9.
Benjamin Lebeau Maïka Jangal Tiejun Zhao Cheng Kit Wong Nolan Wong Eduardo Cepeda Caedo Steven Hbert Adriana Aguilar-Mahecha Catherine Chabot Marguerite Buchanan Rachel Catterall Luke McCaffrey Genevive Deblois Claudia Kleinman Morag Park Mark Basik Michael Witcher 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(36)