糖尿病模型大鼠视网膜PGC-1α表达和表观遗传修饰的变化

目的 通过检测糖尿病模型大鼠视网膜过氧化物酶体增生物激活受体γ辅助激活因子1α（PGC-1α）mRNA和蛋白表达以及PPARGC1A启动子区DNA甲基化的改变,探讨糖尿病发生和发展过程中PGC-1α的变化趋势、表观遗传学修饰改变及其在糖尿病视网膜病变（DR）代谢记忆中的作用.方法 取清洁级6～7周龄雄性SD大鼠80只,其中60只采用腹腔内注射链脲佐菌素（STZ）的方法建立糖尿病大鼠模型.将60只糖尿病模型大鼠应用随机数字表法随机分为3个组：血糖控制不佳组大鼠造模后4个月内血糖水平控制不佳;血糖半控制组大鼠造模后2个月内血糖水平控制不佳,2个月后维持正常血糖水平;血糖控制组大鼠造模后4个月内均保持正常血糖水平,每组各20只.对照组为周龄匹配的正常饲养大鼠20只.分离各实验组大鼠视网膜组织,应用实时荧光定量PCR法检测PGC-1α及超氧化物歧化酶2（SOD2） mRNA的表达,应用Western blot法检测PGC-1α及锰超氧化物歧化酶（MnSOD）蛋白的表达,应用亚硫酸氢钠测序法（BSP）检测PPARGC1A启动子区DNA甲基化状态的变化.结果 造模后4个月,对照组大鼠体质量明显高于血糖控制不佳组、血糖半控制组和血糖控制组,血糖控制不佳组血糖水平显著高于对照组,差异均有统计学意义（均P=0.000）.血糖控制组、血糖半控制组和血糖控制不佳组大鼠视网膜组织中PGC-1 αmRNA相对表达量依次下降,均低于对照组,差异均有统计学意义（均P=0.000）;血糖控制组PGC-1αmRNA相对表达量明显高于血糖控制不佳组,差异有统计学意义（P=0.002）.血糖控制组、血糖半控制组和血糖控制不佳组大鼠视网膜组织中SOD2 mRNA表达依次增加,均高于对照组,差异均有统计学意义（P=0.006、0.000、0.000）;血糖控制组与血糖控制不佳组SOD2 mRNA相对表达量比较,差异有统计学意义（P=0.001）.血糖控制不佳组、血糖半控制组和血糖控制组大鼠视网膜中PGC-1α蛋白和MnSOD蛋白相对表达量显著低于对照组,血糖控制组大鼠视网膜PGC-1α蛋白相对表达量显著高于血糖控制不佳组,差异均有统计学意义（均P＜0.05）.糖尿病模型大鼠视网膜组织中PPARGC1A启动子区DNA甲基化水平升高,血糖控制不佳组、血糖半控制组大鼠视网膜组织中PPARGC1A启动子区DNA甲基化的水平较对照组明显升高,差异均有统计学意义（P=0.008、0.031）,血糖半控制组与血糖控制不佳组间比较,差异无统计学意义（P＞0.05）.结论 糖尿病模型大鼠视网膜PGC-1αmRNA及蛋白表达均下降,视网膜SOD2 mRNA表达升高,MnSOD蛋白表达下降,具有代谢记忆的特点.PPARGC1A启动子区DNA甲基化水平的升高可能与PGC-1α表达受到抑制以及代谢记忆相关.

DNA纳米网络修饰碳纤维盘电极及其分子传感应用

DNA immobilization on electrode surfaces has been widely used for fabricating sensors since DNA can interact with a wide variety of biomolecules. Recendy, DNA has been demonstrated as an electronic super conductor and become the most promising biomolecule for application of chemical sensing in biological system. Calf thymus DNA (ct-DNA) is a most popularly used native DNA in many applications. An electrochemical deposition on carbon fiber micro electrode can provide sensitive detection of dopamine in presence of large amount of ascorbic acid.……

应用纳米技术改进骨肉瘤诊治的研究现状

骨肉瘤作为一种恶性肿瘤,其早期诊断与有效治疗是医学界高度关注的焦点之一。随着纳米生物材料技术的发展,纳米技术在骨肉瘤的诊疗方面呈现了不可限量的潜力。本文以简略介绍骨肉瘤和纳米技术为基础,综合纳米材料的多种功能特性,详细探讨了纳米材料在骨肉瘤诊治中的研究现状,包括易修饰性、信号放大、高载药性、光热转换、免疫调节等方面。同时,展望了纳米技术在未来癌症检测和治疗领域的应用前景进,旨在为该领域未来的良好发展提供有益的参考。

Mushroom Pulp Tissue-Based Membrane-Ferrocene-Modified L-Tyrosine Biosensor

A new approach for assembling amperometric mushroom pulp tissue based membrane electrode for determination of L tyrosine analysis is proposed. Ferrocene is used as a mediator of electron transfer between tyrosinase in mushroom tissue and a graphite electrode. The optimal operation conditions are studied. The linear response range of the biosensor is 2 0×10 -4 to 4 5×10 -3 mol·L -1 with response time of less than 5 min and lifetime of at least 30 d. The biosensor can be applied to practical sample analysis.

Transcriptional changes in epigenetic modifiers associated with gene silencing in the intestine of the sea cucumber,Apostichopus japonicus(Selenka),during aestivation

The sea cucumber, Apostichopusjaponicus, undergoes aestivation to improve survival during periods of high-temperature. During aestivation, the metabolic rate is depressed to reduce the consumption of reserved energy. We evaluated the role of epigenetic modification on global gene silencing during metabolic rate depression in the sea cucumber. We compared the expression of epigenetic modifiers in active and aestivating sea cucumbers. The expression of three genes involved in DNA methylation and chromatin remodeling （DNA （cytosine-5）-methyltransferase l, Methyl-CpG-binding domain protein 2）, and Chromodomain-helicase-DNA-binding protein 5） was significantly higher during aestivation （Days 20 and 40）. Similarly, we observed an increase in the expression of genes involved in histone acetylation （Histone deacetylase 3） and Histone-binding protein RBBP4） during the early （Days 5 and 10） and late phases （Days 20 and 40） of aestivation. There was no change in the expression of KAT2B, a histone acetyltransferase. However, the expression of histone methylation associated modifiers （Histone-arginine methyltransferase CARMER and Histone-lysine N-methyltransferase MLL5） was significantly higher after 5 d in the aestivating group. The results suggest that the expression of epigenetic modifiers involved in DNA methylation, chromatin remodeling, histone acetylation, and histone methylation is upregulated during aestivation. We hypothesize that these changes regulate global gene silencing during aestivation in A. japonicus.

DNA methylation and microRNAs in cancer

DNA methylation is a type of epigenetic modification in the human genome,which means that gene expression is regulated without altering the DNA sequence.Methylation and the relationship between methylation and cancer have been the focus of molecular biology researches.Methylation represses gene expression and can influence embryogenesis and tumorigenesis.In different tissues and at different stages of life,the level of methylation of DNA varies,implying a fundamental but distinct role for methylation.When genes are repressed by abnormal methylation,the resulting effects can include instability of that gene and inactivation of a tumor suppressor gene.MicroRNAs have some aspects in common with this regulation of gene expression.Here we reviewed the influence of gene methylation on cancer and analyzed the methods used to profile methylation.We also assessed the correlation between methylation and other epigenetic modifications and microRNAs.About 55 845 research papers have been published about methylation,and one-fifth of these are about the appearance of methylation in cancer.We conclude that methylation does play a role in some cancer types.

Awareness and Perception of Genetic Modification among Science and Technical Vocational Teachers in Guyana： Focusing on Genetically Modified Foods

A study was conducted to determine the awareness and perception of biotechnology focusing on genetically modified foods among public secondary school science and technical vocational teachers in Guyana. A questionnaire was administered to 228 randomly selected teachers of 42 schools in six administrative regions of Guyana, representing about 90% of the population. The results revealed that there was a low level of awareness among the teachers： those who were knowledgeable about the subject were mainly Biology, Agricultural Science and Integrated Science teachers. Most teachers （almost 90%） indicated that the public is not receiving adequate information about genetically-modified foods and opined that the television should be the main medium to provide information. The study also revealed that teachers felt that ethical, religious and social issues should be considered when applying the technology. This view did not vary based on qualifications, years in the profession or subjects taught. Genetic modification was more acceptable to plant-based than animal-based foods, although they seemed ambivalent as to whether genetically modified foods can be harmful to their health. The implications of these findings are that more teachers in various subject areas should be informed about emerging issues in sciences to enable them to better analyze the subject matter, transfer information to the students, and form attitudes and opinions based on facts.

Genomic Imprinting—The Story of the Other Half and the Conflicts of Silencing

G-enomic imprinting is an epigenetic mechanism that produces functional differences between the paternal and mammal genomes and plays an essential role in mammalian development and growth. There are a number of genes in our genomes that are subject to genomic imprinting where one parent＇s copy of the gene is expressed while the other is silent. Silencing of one allele predetermines that any function ascribed to that gene are now dependant on the single active copy. Possession of only a single active allele can lead to deleterious health consequences in humans. If imprinted genes are crucial in mammalian development, one would also expect mutations in these genes to cause diseases. Since imprinting is an epigenetic mechanism, mistakes in maintaining epigenetic mark also cause imprinting disorders. Here we in this review focus on the current understanding of this unique genetic mechanism more than two decades after the first description of the imprinting phenomenon was given by McGrath and Solter. Although the possible molecular mechanisms by which imprinting is imposed and maintained are being identified, we have a long way to go in understanding the molecular mechanisms that regulate the expression of these oddly behaving genes, the function of imprinting and the evolution. Post genomic technologies might ultimately lead to a better understanding of the ＇imprinting effects＇.

Electrocatalytic Oxidation of Calcium Folinate on Carboxyl Graphene Modified CuxO/Cu Electrode

Carboxyl graphene modified CuxO/Cu electrode was fabricated. The bare copper electrode was firstly anodic polarized in 1.0 mol/L NaOH solution in order to get CuxO nanoparticles, then the carboxyl graphene （CG） was electrodeposited on the CuxO/Cu electrode by cyclic potential sweeping. The electrocatalytic oxidation behaviors of calcium folinate （CF） at the graphene modified CuxO/Cu electrode were investigated by cyclic voltammetry. A positive scan polarization reverse catalytic voltammetry was used to obtain the pure catalytic oxidation current. The graphene modified CuxO/Cu electrode was served as the electrochemical sensor of CF, a highly sensitivity of 22.0μA.（μmol/μL）^-1cm^-2 was achieved, and the current response was linear with increasing CF concentration in the range of 2.0×10^-7 mol/L to 2.0×10^-5 mol/L, which crossed three orders of magnitude, and the detection limit was found 7.6×10^-5 mol/L （S/N=3）. In addition, the proposed sensor was successfully applied in determination of CF in drug sample.

Development of Uric Acid Sensor Based on Molecularly Imprinted Polymetl^acrylic Acid-Modified Hanging Mercury Drop Electrode

Development of uric acid sensor based on molecularly imprinted polymer （MIP） was studi ed. The sensor was developed by coating the imprinted polymethacrylic acid on the surface of a hanging mercury drop ele, ctrode （HMDE） at -1 V （vs. Ag/AgCI） during 60 s. Uric acid was accumulated on the modified electrode at -1 V （vs. Ag/AgC1） during 60 s in acetate buffer pH = 5 and stripped at scan rate of 59 mV/s. Oxidation of uric acid on the surface of modified electrode is irreversible through the diffusion controlled process and polymethacrylic acid is a non-electrical conducting polymer. The current signal obtained from Ehe analysis of uric acid by using HMDE is higher than that of the HMD-palymethacrylic acid （polyMAA）, HMD-MIP and HMD-non imprinted polymer （NIP） electrode. The HMD-MIP has demonstrated its performance as a sensitive voltammetric sensor for uric acid. The modified electrode has been tested for the determination of uric acid in the serum sample with recovery percentage of 95.7% （n = 2）. The limit of detection obtained was 6.0 x 10-10 M.

Improvement in Performance of Carbon-based Perovskite Solar Cells through Interface Modification with CTAC

Carbon-based perovskite solar cells have attracted much attention,due to their low cost,simple preparation process and high chemical stability.However,the devices exhibit low photoelectric conversion efficiency,owing to the presence of defects and interface impedance between the perovskite active layer and the contact interface.In order to minimize the interfacial defects and improve the charge transfer performance between the perovskite layer and the contact interface,cetyltrimethylammonium chloride(CTAC)was introduced into the lower interface of HTL-free carbon-based perovskite solar cells,because CTAC can be used as interface modification material to passivate the buried interface of perovskite and promote grain growth.It was found that CTAC can not only passivate the interface defects of perovskite,but also improve the crystalline quality of perovskite.As a result,the photovoltaic conversion efficiency of reaches 17.18%,which is 12.5%higher than that of the control group.After 20 days in air with 60%RH humidity,the cell can still maintain more than 90%of the initial efficiency,which provides a new strategy for interfacial passivation of perovskite solar cells.

DNA methyltransferase inhibitor dramatically alters the secondary metabolism of Pestalotiopsis microspora

5-Azacytidine, a DNA methyltransferase inhibitor, led to significant changes in the secondary metabolism of the plant endophytic fungus, Pestalotiopsis microspora. Analysis of the culture broth extract led to the isolation of a new compound, 4＇-forrnamidophenyl-5-methoxybenzoate （1）, along with seven known polyketides, 4-hydroxybenzoic acid （2）, LL-P880ct （3）, 1＇-hydroxy-4-methoxy-6-pentyl-2H-pyran-2-one （4）, pestalotiollide B （5）, pestalotiopyrone G （6）, endocrocin （7） and 2＇-hydroxy- 6＇-hydroxymethyl-4＇-methylphenyl-2,6-dihydroxy-3-（2-isopentenyl）benzoate （8）. HPLC profiles revealed that all compounds except for 4 belonged to the newly induced secondary metabolites. In addition, all compounds were proved to be devoid of significant antifungal activity in the bioassays.

Contribution of epigenetics in diabetic retinopathy

Diabetes has become the epidemic of the 21 st century, and with over 90% patients with diabetes becoming at a risk of developing retinopathy, diabetic retinopathy has emerged as a major public health concern. In spite of cutting edge research in the field, how retina and its vasculature are damaged by the diabetic milieu remains ambiguous. The environmental factors, life style or disease process can also bring in modifications in the DNA, and these epigenetic modifications either silence or activate a gene without altering the DNA sequence. Diabetic environment up- or downregulates a number of genes in the retina, and emerging research has shown that it also facilitates epigenetic modifications. In the pathogenesis of diabetic retinopathy, the genes associated with important enzymes(e.g., mitochondrial superoxide dismutase, matrix metalloproteinase-9 and thioredoxin interacting protein) and transcriptional factors are epigenetically modified, the enzymes responsible for these epigenetic modifications are either activated or inhibited, and the levels of micro RNAs are altered. With epigenetic modifications taking an important place in diabetic retinopathy, it is now becoming critical to evaluate these modifications, and understand their impact on this slow progressing blinding disease.

Epigenetic reprogramming of embryos derived from sperm frozen at-20℃

Cryopreservation of spermatozoa is a strategy that has been used to conserve the sperm of animal species and animal strains that are valuable for biomedical research. A simple method for preserving spermatozoa after application of intracytoplasmic sperm injection （ICSI） is much needed. It has been shown previously that spermatozoa frozen at -20~C can activate oocytes and support full-term embryo development. However, epigenetic reprogramming could be affected by the environment and by the in vitro manipulation of gametes. Here, we investigated embryo epigenetic reprogramming including DNA methylation and histone modification, in embryos derived from sperm preserved at -20~C without cryoprotectants. The results showed that alt- hough both fertilization and embryo developmental competence were decreased, the dynamic epigenetic reprogramming of embryos derived from frozen sperm was similar to the reprogramrning of embryos derived from fresh sperm. The results re- ported in this study indicate that sperm frozen without cryoprotectant is epigenetically safe for ICSI.

LincRNA1230 inhibits the differentiation of mouse ES cells towards neural progenitors

In vitro, mouse embryonic stem （ES） cells can differentiate into many somatic cell types, including neurons and glial cells. When cultured in serum-free medium, ES cells convert spontaneously and efficiently to a neural fate. Previous studies have shown that the neural conversion of mouse ES cells includes both the participation of neural-specific transcription factors and the regulation of epigenetic modifications. However, the intracellular mechanism underlying this intrinsic transition still re- mains to be further elucidated. Herein, we describe a long intergenic non-coding RNA, LincRNA1230, which participates in the regulation of the neural lineage specification of mouse ES cells. The ectopic forced expression of LincRNAI230 dramatically inhibited mouse ES cells from adopting a neural cell fate, while LincRNA1230 knockdown promoted the conversion of mouse ES cells towards neural progenitors. Mechanistic studies have shown that LincRNA1230 inhibits the activation of early neural genes, such as Pax6 and Soxl, through the modulation of bivalent modifications （tri-methylation of histone3 lysine4 and his- tone3 lysine27） at the promoters of these genes. The interaction of LincRNA1230 with Wdr5 blocked the localization of Wdr5 at the promoters of early neural genes, thereby inhibiting the enrichment of H3K4me3 modifications at these loci. Collectively, these findings revealed a crucial role for LincRNA1230 in the regulation of the neural differentiation of mouse ES cells.

DNA methylation in schizophrenia: progress and challenges

Schizophrenia is a heterogeneous psychiatric disorder broadly accepted being caused by genetic and environmental factors. Although conventional genetic studies have identified some candidate genes for schizophrenia, low odds ratios and penetrance, and a lack of reproducibility have limited their explanatory power. Despite the major efforts made toward identifying environmental factors in schizophrenia, methodological limitations and inconsistent findings of epidemiological reports have obstructed attempts to identify exogenous causal factors. Epigenetic mechanisms, mediating between environment and genes, have recently been proposed to play an important role in the pathogenesis of schizophrenia. DNA methylation is the most stable and well-characterized epigenetic modification. In this paper, we briefly introduce DNA methylation mechanisms, genome-wide DNA methylation studies, and identify specific genomic methylation sites in individuals diagnosed with schizophrenia. The outline candidate genes such as Reelin and COMT, are also outlined before paying attention to the conundrum of recent researches.

Epigenetic and metabolic regulation of breast cancer stem cells

Breast cancer has a relatively high mortality rate in women due to recurrence and metastasis. Increasing evidence has identified a rare population of cells with stem cell-like properties in breast cancer. These cells, termed cancer stem cells （CSCs）, which have the capacity for self-renewal and differentiation, contribute significantly to tumor progression, recurrence, drug resistance and metastasis. Clarifying the mechanisms regulating breast CSCs has important implications for our understanding of breast cancer progression and therapeutics. A strong connection has been found between breast CSCs and epithelial mesenchymal transition （EMT）. In addition, recent studies suggest that the maintenance of the breast CSC phenotype is associated with epigenetic and metabolic regulation. In this review, we focus on recent discoveries about the connection between EMT and CSC, and advances made in under- standing the roles and mechanisms of epigenetic and metabolic reprogramming in controlling breast CSC properties.

Chromodomain protein CDYL is required for transmission/restoration of repressive histone marks

Faithful transmission or restoration of epigenetic information such as repressive histone modifications through generations is crit- ical for the maintenance of cell identity. We report here that chromodomain Y-like protein （CDYL）, a chromodomain-containing transcription corepressor, is physically associated with chromatin assembly factor 1 （CAF-1） and the repiicative heUcase MCM complex. We showed that CDYL bridges CAF-1 and MCM, facilitating histone transfer and deposition during DNA replication. We demonstrated that CDYI. recruits histone-modifying enzymes G9a, SETDB1, and EZH2 to replication forks, leading to the addition of H3Kgme2/3 and H3K27me2/3 on newly deposited histone H3. Significantly, depletion of CDYL impedes early S phase progres- sion and sensitizes cells to DNA damage. Our data indicate that CDYL plays an important role in the transmission/restoration of repressive histone marks, thereby preserving the epigenetic landscape for the maintenance of cell identity.

Study on the Molecular Genetic Alterations in Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma （NPC） was mostly common in Guangdong Province and Guangxi Chuang Autonomous Region. This cancer jeopardized people＇s health in the above areas. In order to understand the mechanisms for NPC, and further promote NPC＇s early diagnosis and therapy, the molecular genetic analysis research of NPC in China and in its outbreak areas becomes an emergent topic. Since NPC is a rare disease in developed countries of Europe and America, the research in this field has not been well-recognized in these countries. Furthermore,