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转录组相关研究(三)

RNA专题

英文题目:Obesity-induced insulin resistance via changes in the DNA methylation profile of  insulin pathway genes.

中文题目:肥胖通过改变胰岛素途径基因的DNA甲基化谱诱导胰岛素抵抗。

作者:Małodobra-Mazur M

作者单位:Molecular Techniques Unit, Department of Forensic Medicine, Wroclaw Medical University, Poland.波兰弗罗茨瓦夫大学法医学系分子技术室

期刊:Adv Clin Exp Med.  发表时间;2019-11    IF = 1.127

DOI: 10.17219/acem/110321

英文摘要:

BACKGROUND: Obesity has been shown to play a key role in the development of insulin resistance (IR). Abundant data implicate obesity in DNA hypermethylation  at global and site-specific levels, including genes regulating insulin sensitivity. Deregulation of epigenetic marks implicates gene expression and changes in cell metabolism.OBJECTIVES: Our previous reports demonstrated that the strongest risk factor in the development of IR is BMI; accordingly, the objective of this study was to investigate the effect of obesity on DNA methylation and insulin sensitivity. MATERIAL AND METHODS: A study was carried out on lymphocytes (N-34) and visceral  adipose tissue (VAT; N-35) of insulin-resistant subjects and healthy controls.Genetic material (DNA and RNA) was extracted from cells. Global and site-specific DNA methylation was analyzed with the use of restriction enzymes followed by real-time polymerase chain reaction (PCR). Gene expression was analyzed as relative mRNA level normalized to a housekeeping gene. RESULTS: Global DNA methylation increased in both types of tissue in obese and insulin-resistant individuals and correlated positively with IR. Two of the 3 investigated promoters of insulin pathway genes were hypermethylated, which correlated negatively with gene expression and positively with IR. The DNMT3a gene was upregulated in obese insulin-resistant individuals in both types of tissues and correlated positively with global DNA methylation. CONCLUSIONS: DNA methylation profile changed depending on body mass index (BMI) and influenced glucose metabolism and insulin sensitivity in VAT.

中文摘要:

背景:肥胖在胰岛素抵抗(IR)的发生发展中起着关键作用。大量的数据表明肥胖与DNA甲基化有关,包括调节胰岛素敏感性的基因。表观遗传标记的解除与基因表达和细胞代谢的改变有关。目的:我们以前的报告表明,IR的发生最危险的因素是BMI;因此,本研究的目的是研究肥胖对DNA甲基化和胰岛素敏感性的影响。材料和方法:对胰岛素抵抗者和健康对照者的淋巴细胞(N-34)和内脏脂肪组织(VATN-35)进行了研究,从细胞中提取了遗传物质(DNARNA)。用限制性内切酶和实时聚合酶链反应(PCR)分析DNA甲基化。结果:肥胖者和胰岛素抵抗者两种组织DNA甲基化水平均升高,且与胰岛素抵抗呈正相关。3个胰岛素途径基因启动子中有2个高甲基化,与基因表达呈负相关,与IR呈正相关。DNMT3a基因在肥胖胰岛素抵抗者两种组织中均上调,并与DNA甲基化呈正相关。结论:DNA甲基化谱随体重指数(BMI)的变化而改变,并影响血糖代谢和胰岛素敏感性。

 

 

英文题目:MicroRNA-124 regulates lactate transportation in the muscle of largemouth bass (micropterus salmoides) under hypoxia by targeting MCT1.

中文题目:MyrON-124McT1为靶点,在低氧条件下调节大口黑鲈肌肉中的乳酸转运。

作者:Zhao LL

作者单位:College of Animal Science and Technology, Sichuan Agricultural University, Wenjiang, Chengdu, Sichuan, 611130, China. Electronic address: zhaoliulan2007@163.com.四川农业大学动物科学与技术学院

期刊:AQUATIC TOXICOLOGY 发表时间2019-11 IF = 3.451

DOI: 10.1016/j.aquatox.2019.105359

英文摘要:

Carbohydrate metabolism switches from aerobic to anaerobic (glycolysis) to supply energy in response to acute hypoxic stress. Acute hypoxic stress with dissolvedoxygen (DO) levels of 1.2 ± 0.1 mg/L for 24 h and 12 h re-oxygenation was used to investigate the response of the anaerobic glycolytic pathway in Micropterus salmoides muscle. The results showed that the glucose concentration was significantly lower in muscle, while the lactic acid and pyruvic acid concentrations tended to increase during hypoxic stress. No significant difference was observed in muscle glycogen, and ATP content fluctuated significantly. The activities of gluconeogenesis-related enzymes were slightly elevated, such as phosphoenolpyruvate carboxykinase (PEPCK). The activities of the glycolytic enzymes increased after the induction of hypoxia, such as hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase (LDH). Curiously, phosphofructokinase (PFK) activity was significantly down-regulated within 4 h during hypoxia, although these effects were transient, and most indices returned to control levels after 12 h of re-oxygenation. Upregulated hif-1α, ampkα, hk, glut1, and ldh mRNA expression suggested that carbohydrate metabolism was reprogrammed under hypoxia. Lactate transport was regulated by miR-124-5p according to quantitative polymerase chain reaction and dualluciferase reporter assays. Our findings provide new insight into the molecular regulatory mechanism of hypoxia in Micropterus salmoides muscle.

中文摘要:

碳水化合物代谢从需氧到无氧(糖酵解)转变为急性低氧应激反应。以1.2×0.1±0.1 mgL的氧(DO)水平为研究对象,对急性缺氧应激进行了24 h12 h的复氧研究。结果表明,低氧应激时肌肉中葡萄糖浓度显著降低,乳酸和丙酮酸浓度趋于升高。肌糖原无显著性差异,ATP含量波动显著。糖异生相关酶活性略有升高,如磷酸烯醇丙酮酸羧激酶(PEPCK)。糖酵解酶的活性在缺氧诱导后增加,如己糖激酶(HK)、丙酮酸激酶(PK)和乳酸脱氢酶(LDH)。奇怪的是,磷酸果糖激酶(PFK)活性在缺氧4小时内显著下调,虽然这些作用是暂时的,大多数指标在复氧12小时后恢复到对照水平。HIF-1αAMPKαHKGLUT1LDH mRNA的表达提示缺氧条件下碳水化合物代谢被重新编程。根据定量聚合酶链反应和双荧光素酶报告分析,miR-124-5p调节乳酸转运。本研究结果为沙门氏菌低氧的分子调控机制提供了新的线索。

 

 

英文题目:Granulocyte colony stimulating factor (G-CSF) regulates neutrophils infiltration  and periodontal tissue destruction in an experimental periodontitis.

中文题目: 粒细胞集落刺激因子(G-CSF)调节实验性牙周炎中性粒细胞浸润和牙周组织破坏。

作者:Zhang Z

作者单位:Department of Stomatology, Beijing Chao-Yang Hospital, Capital Medical

University, 8th Gongti South Road, Beijing, 100020, China; Department of

Periodontology, Tianjin Stomatological Hospital, Hospital of Stomatology, Nankai

University, 75th Dagu North Road, Tianjin, 300000, China.首都医科大学朝阳医院口腔科

期刊:MOL IMMUNOL    发表时间:2019-11   IF  = 2.973

DOI: 10.1016/j.molimm.2019.11.003

英文摘要:

Although granulocyte colony-stimulating factor(G-CSF) has pathogenic roles in several immune inflammatory diseases, its role in periodontitis has not been investigated. Here we detected local expression of G-CSF using public datasets in the Gene Expression Omnibus (GEO) database, and immune cell infiltration into gingival tissue was estimated based on single-sample gene set enrichment analysis (ssGSEA). G-CSF expression and neutrophil infiltration were also confirmed by human gingival biopsies analysis. Moreover, anti-G-CSF neutralizing antibody was  locally administrated to investigate the effects of G-CSF neutralization on neutrophils infiltration and periodontal tissue destruction in periodontitis mice model. Two public datasets (GSE10334 and GSE16134), which included 424 patients with periodontitis and 133 health controls, were used in the analysis. Markedly increased immune cell infiltration and G-CSF expression in gingival tissues were  found in the periodontitis group as compared to the control group. The higher expression of G-CSF was correlated with higher infiltration of immune cells, especially with neutrophil infiltration. Analysis of gingival biopsies further confirmed high neutrophil infiltration and G-CSF expression. In addition, anti-G-CSF antibody-treated mice with periodontitis showed significantly reduced  alveolar bone resorption and neutrophil infiltration when compared with periodontitis mice treated with isotype control antibody. Also, anti-G-CSF antibody treatment significantly reduced mRNA expression of CXC chemokines(CXCL1, CXCL2 and CXCL3), interleukin 1β (IL-1β), IL-6, matrix metalloproteinases 9, receptor activator of nuclear factor κB ligand/osteoprotegerin (RANKL/OPG) ratio and osteoclasts number in periodontal tissues. In summary, neutrophil infiltration and G-CSF expression levels were significantly increased in inflamed gingival tissues. G-CSF neutralization in periodontal inflammation could alleviate neutrophil infiltration and periodontal tissue destruction in experimental periodontitis.

中文摘要:

虽然粒细胞集落刺激因子(G-CSF)在多种免疫性炎症疾病中具有致病作用,但其在牙周炎中的作用尚未被研究。利用基因表达综合数据库(GEO)中的公共数据集检测G-CSF的局部表达,并基于单样本基因集富集分析(ssGSEA)估计免疫细胞对牙龈组织的浸润。G-CSF表达和中性粒细胞浸润也被牙龈活检证实。局部应用抗G-CSF中和抗体,观察G-CSF中和对牙周炎小鼠中性粒细胞浸润和牙周组织破坏的影响。采用两个公共数据集(GSE10334GSE16134)进行分析,其中包括424名牙周炎患者和133名健康对照者。牙周炎组牙龈组织免疫细胞浸润和G-CSF表达较对照组明显增强。G-CSF的高表达与免疫细胞浸润程度有关,尤其与中性粒细胞浸润有关。牙龈活检进一步分析。证实中性粒细胞浸润和G-CSF表达增高。此外,抗G-CSF抗体治疗的牙周炎小鼠牙槽骨吸收和中性粒细胞浸润均明显低于同型抗体治疗的牙周炎小鼠。抗G-CSF抗体治疗可显著降低牙周组织CXC趋化因子(CXCL1CXCL2CXCL3)、白细胞介素IL-1β)、白细胞介素6、基质金属蛋白酶的mRNA表达;9、核因子-κB配体受体激活剂/骨保护素(RANKL/OPG)、比值及破骨细胞数。总之,炎症牙龈组织中性粒细胞浸润和G-CSF表达水平显著升高。G-CSF中和可减轻实验性牙周炎中性粒细胞浸润和牙周组织破坏。

 

 

英文题目:Genome-wide identification, evolution, and mRNA expression of complement genes in common carp (Cyprinus carpio).

中文题目:鲤鱼补体基因的全基因组鉴定、进化和mRNA表达。

作者:Lv H

作者单位:College of Fisheries, Henan Normal University, Xinxiang, Henan, 453007, China; State Key Laboratory of Marine Environmental Science, College of Ocean and Earth  Sciences, Xiamen University, Xiamen, 361102, China.河南师范大学渔业学院,河南新乡

期刊:Fish Shellfish Immunol. 发表时间:2019-11     IF = 2.674

DOI: 10.1016/j.fsi.2019.11.032

英文摘要:

Complement is a complex component of innate immune system, playing an important role in defense against pathogens and host homeostasis. The complement system has been comprehensively studied in mammals, however less is known about complement in teleost, especially in tetraploid common carp (Cyprinus carpio). In this study, a total of 110 complement genes were identified and characterized in common carp, which include almost all the homologs of mammalian complement genes. These genes were classified into three pathways (alternative pathways, lectin pathways and classical pathways), similar to those in mammals. Phylogenetic and selection pressure analysis showed that the complement genes were evolving-constrained and the function was conserved. Most of the complement genes were highly expressed in spleen, liver, brain and skin among the tested 12 health tissues of common carp. After Aeromonas hydrophila infection in the common carp,  many members of complement genes were activated to bring about an immune response and expressed to against any pathogenic encroachment. Gene expression divergences which were found between two homoeologous genes suggested the functional divergences of the homoeologous genes after the 4R WGD event, revealing the evolutionary fate of the tetraploid common carp after the recent WGD.

中文摘要:

补体是先天免疫系统的一个复杂组成部分,在抵抗病原体和宿主内环境稳定方面发挥着重要作用。哺乳动物补体系统的研究已较为全面,但对硬骨鱼类补体系统的研究较少,特别是四倍体鲤。在本研究中,共有110个补体基因在鲤鱼中被鉴定和鉴定,其中包括哺乳动物补体基因的几乎所有同源基因。这些基因被分为三种途径(替代途径、凝集素途径和经典途径),与哺乳动物相似。系统发育和选择压力分析表明,补体基因具有进化限制性,功能保守。在12个健康鲤鱼组织中,大部分补体基因在脾、肝、脑和皮肤中高表达。鲤鱼嗜水气单胞菌感染后,许多补体基因成员被激活,产生免疫应答,并被表达以抵抗任何致病性侵害。两个同源基因的基因表达差异表明同源基因在4R-WGD事件后的功能差异,揭示了四倍体鲤鱼在最近WGD事件后的进化命运。

 

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英文题目:Prenatal Opioid Exposure: The Next Neonatal Neuroinflammatory Disease.

中文题目:前阿片类药物暴露:下一个新生儿神经炎症疾病。

作者:Jantzie LL

作者单位:Department of Pediatrics, Johns Hopkins University School of Medicine,

Baltimore, MD, United States; 美国巴尔的摩约翰霍普金斯大学医学院儿科

期刊:Brain Behav Immun. 发表时间:2019-11  IF =6.128 

DOI: 10.1016/j.bbi.2019.11.007

英文摘要:

The rates of opioid use disorder during pregnancy have more than quadrupled in the last decade, resulting in numerous infants suffering exposure to opioids during the perinatal period, a critical period of central nervous system (CNS) development. Despite increasing use, the characterization and definition of the molecular and cellular mechanisms of the long-term neurodevelopmental impacts of  opioid exposure commencing in utero remains incomplete. Thus, in consideration of the looming public health crisis stemming from the multitude of infants with prenatal opioid exposure entering school age, we undertook an investigation of the effects of perinatal methadone exposure in a novel preclinical model. Specifically, we examined the effects of opioids on the developing brain to elucidate mechanisms of putative neural cell injury, to identify diagnostic biomarkers and to guide clinical studies of outcome and follow-up. We hypothesized that methadone would induce a pronounced inflammatory profile in both dams and their pups, and be associated with immune system dysfunction, sustained CNS injury, and altered cognition and executive function into adulthood. This investigation was conducted using a combination of cellular, molecular, biochemical, and clinically translatable biomarker, imaging and cognitive assessment platforms. Data reveal that perinatal methadone exposure increases inflammatory cytokines in the neonatal peripheral circulation, and reprograms and primes the immune system through sustained peripheral immune hyperactivity. In the brain, perinatal methadone exposure not only increases chemokines and cytokines throughout a crucial developmental period, but alsoalters microglia morphology consistent with activation, and upregulates TLR4 and MyD88 mRNA. This increase in neuroinflammation coincides with reduced myelin basic protein and altered neurofilament expression, as well as reduced structural coherence and significantly decreased fractional anisotropy on diffusion tensor imaging. In addition to this microstructural brain injury, adult rats exposed to  methadone in the perinatal period have significant impairment in associative learning and executive control as assessed using touchscreen technology. Collectively, these data reveal a distinct systemic and neuroinflammatory signature associated with prenatal methadone exposure, suggestive of an altered CNS microenvironment, dysregulated developmental homeostasis, complex concurrent neural injury, and imaging and cognitive findings consistent with clinical literature. Further investigation is required to define appropriate therapies targeted at the neural injury and improve the long-term outcomes for this exceedingly vulnerable patient population.

中文摘要:

在过去的十年中,怀孕期间阿片类药物使用障碍的发生率增加了四倍多,导致许多婴儿在围产期,即中枢神经系统(CNS)发育的关键时期暴露于阿片类药物。尽管使用越来越多,但从子宫开始暴露阿片类药物对神经发育的长期影响的分子和细胞机制的特征和定义仍不完整。因此,考虑到由于大量产前阿片类药物暴露的婴儿进入学龄期而引起的迫在眉睫的公共卫生危机,我们在一个新的临床前模型中对围产期美沙酮暴露的影响进行了调查,我们研究了阿片类药物对发育中大脑的影响,以阐明假定的神经细胞损伤的机制,鉴定诊断性生物标记物,并指导预后和随访的临床研究。我们假设美沙酮会在母鼠和幼鼠体内引起明显的炎症反应,并与免疫系统功能障碍、持续的中枢神经系统损伤以及成年后认知和执行功能的改变有关。本研究使用细胞、分子、生化和临床可翻译生物标记物、成像和认知评估平台进行。数据显示,围产期美沙酮暴露会增加新生儿外周循环中的炎性细胞因子,并通过持续的外周免疫多动重新编程和启动免疫系统。在大脑中,围产期美沙酮的暴露不仅在关键发育期增加了趋化因子和细胞因子,而且改变了与活化相一致的小胶质细胞形态,上调了TLR4MyD88 mRNA。神经炎症的增加与髓鞘、碱性蛋白和神经丝表达的改变,以及结构一致性的降低和扩散张量成像的分数各向异性的显著降低相一致。除了这种微结构脑损伤外,围产期暴露于美沙酮的成年大鼠在使用触摸屏技术评估的联想、学习和执行控制方面也有明显的损伤,这些数据揭示了与产前美沙酮暴露相关的明显的全身和神经炎症特征,提示中枢神经系统微环境改变,发育稳态失调,复杂的并发神经损伤,以及与临床文献一致的影像学和认知学发现。需要进一步的研究来确定合适的治疗方法。针对神经损伤并改善其长期预后。极易受伤害的患者群体。

 

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