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马明仁;焦丕奇;刘明浩;王昱喆;王菲;马凌 《病毒学报》2024,(5):1137-1150
新型冠状病毒感染疫情对全球医疗救治体系提出了前所未有的严峻考验,尽管当前疫情传播得到有效控制,但是新型冠状病毒感染相关并发症以及“长新冠综合征”给健康带来的负面效应仍不容忽视,尤其是心血管循环系统更是严重急性呼吸综合征冠状病毒2易感的靶器官。微小RNA是调节重要生物学进程的内源性小分子单链非编码RNA,已证实微小RNA在心血管疾病的发生发展进程中扮演重要角色,并且循环微小RNA差异表达与新型冠状病毒感染并发心血管系统疾病密切相关,然而循环微小RNA在疾病病理进展中的作用机制尚不明确。因此,本文综述了循环微小RNA在新型冠状病毒感染并发心血管系统疾病中的作用及相关机制,同时对基于循环微小RNA为靶点的诊疗策略进行展望,以期为新型冠状病毒感染并发心血管系统疾病的防治提供新思路。 相似文献
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长链非编码RNA(long non-coding RNA,lncRNA),是一种长度大于200个核苷酸的调控性非编码RNA,能在转录水平、转录后水平及表观遗传水平等多个层面影响基因的表达。脂肪生成是一个复杂而有序的过程。大量研究表明,lncRNA在脂肪生成过程中扮演着重要角色,它可以影响脂质代谢及成脂分化等多种生物过程,从而间接影响肉品质。这对于提高畜禽肉品质、避免养殖业饲料过多转化成脂肪所导致的浪费以及对预防和治疗与脂肪代谢相关的疾病都具有重要意义。对lncRNA的基本特征、在动物脂肪沉积中的作用进展进行了综述,以期为培育优质畜禽,预防和治疗与脂肪代谢相关的疾病提供理论依据。 相似文献
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为研究无量山乌骨鸡(Gallus gallus)肝组织脂代谢相关miRNA (microRNA)在不同发育阶段的表达特征,本研究采集出壳当日(D1)和168日龄(D168)母鸡肝组织样品作为试验材料,利用DNBSEQ平台进行测序,采用DEGseq筛选差异表达的miRNA及其靶基因,随机选取9个差异表达miRNA进行RT-qPCR验证,KEGG通路分类筛选出脂代谢相关miRNA并进行聚类分析,预测脂代谢相关miRNA靶基因并进行GO和KEGG通路功能富集,构建脂代谢相关miRNA和靶基因关联网络。分析结果表明,筛选出106个差异表达miRNAs,包括54个上调miRNA和52个下调miRNA;聚类得到41个脂代谢相关的miRNAs;预测到38个靶基因,对靶基因的功能注释确定主要富集于甘油磷脂代谢、脂肪酸代谢和鞘脂代谢等脂质代谢相关通路,novel-gga-miR2311-5p-DGKZ、 novel-gga-miR2047-3p-ACACA、 novel-gga-miR866-3p-DGKH是脂代谢相关候选miRNA-mRNA关系对。研究提示无量山乌骨鸡肝组织miRNA在不同发育阶段的表... 相似文献
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鼻咽癌(nasopharyngeal carcinoma, NPC)是一种多基因遗传性疾病,好发生于我国华南、东南亚及部分非洲地区。近年来随着分子生物学及其技术的迅速发展,人们对鼻咽癌发生、发展及其生物学行为的研究已进入基因水平。microRNA(miRNA)是一类广泛存在于动植物体内的非编码小RNA,主要参与基因转录后水平调控。随着对miRNA研究的深入,发现肿瘤的细胞分化障碍、增殖失控、细胞永生化与miRNA密切相关。人类肿瘤组织与正常细胞组织间的miRNA表达水平和类型存在明显差异,提示miRNA可能是一类新的参与肿瘤发生的重要分子。本文就鼻咽癌与miRNA相关的研究进展作一综述。 相似文献
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鼻咽癌(nasopharyngeal carcinoma,NPC)是一种多基因遗传性疾病,好发生于我国华南、东南亚及部分非洲地区。近年来随着分子生物学及其技术的迅速发展,人们对鼻咽癌发生、发展及其生物学行为的研究已进入基因水平。microRNA(miRNA)是一类广泛存在于动植物体内的非编码小RNA,主要参与基因转录后水平调控。随着对miRNA研究的深入,发现肿瘤的细胞分化障碍、增殖失控、细胞永生化与miRNA密切相关。人类肿瘤组织与正常细胞组织间的miRNA表达水平和类型存在明显差异,提示miRNA可能是一类新的参与肿瘤发生的重要分子。本文就鼻咽癌与miRNA相关的研究进展作一综述。 相似文献
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姜黄素(curcumin)是近年来发现的一种具有多种生物学活性的中药单体,研究表明姜黄素能够杀伤多种肿瘤细胞,显示出良好的防癌和抗癌作用,美国国立卫生(nationalinstituteofhealth,N/H)已将姜黄素列为第三代化学预防药,相关的临床试验已经展开。微小RNA(micmRNA,miRNA)是细胞内高度保守的非编码RNA,参与了包括肿瘤在内的多个病理生理过程。最新研究表明姜黄素通过调控miRNA机制发挥抗癌作用,我们的研究亦证实姜黄素影响肺癌细胞特异性miRNA表达引起肿瘤细胞凋亡和逆转耐药。总结最新研究进展,本文就姜黄素在不同系统肿瘤细胞中通过调控特异性miRNA发挥抗癌作用的机制作一综述。 相似文献
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脂代谢是心肌能量代谢网络的重要环节,其稳态的调控是心肌适应不同病理、生理状态的关键.运动是心肌脂代谢稳态的重要调节手段,大量研究发现miRNAs参与其中.该文将综述细胞内与脂代谢相关miRNAs的作用机制,阐释循环miRNAs对一次性运动的反应和对长期规律性运动的适应,以及心肌miRNAs表达对不同运动方式的适应,并探... 相似文献
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Daniel E. Cooper Trisha J. Grevengoed Eric L. Klett Rosalind A. Coleman 《The Journal of biological chemistry》2015,290(24):15112-15120
Glycerol-3-phosphate acyltransferase-4 (GPAT4) null pups grew poorly during the suckling period and, as adults, were protected from high fat diet-induced obesity. To determine why Gpat4−/− mice failed to gain weight during these two periods of high fat feeding, we examined energy metabolism. Compared with controls, the metabolic rate of Gpat4−/− mice fed a 45% fat diet was 12% higher. Core body temperature was 1 ºC higher after high fat feeding. Food intake, fat absorption, and activity were similar in both genotypes. Impaired weight gain in Gpat4−/− mice did not result from increased heat loss, because both cold tolerance and response to a β3-adrenergic agonist were similar in both genotypes. Because GPAT4 comprises 65% of the total GPAT activity in brown adipose tissue (BAT), we characterized BAT function. A 45% fat diet increased the Gpat4−/− BAT expression of peroxisome proliferator-activated receptor α (PPAR) target genes, Cpt1α, Pgc1α, and Ucp1, and BAT mitochondria oxidized oleate and pyruvate at higher rates than controls, suggesting that fatty acid signaling and flux through the TCA cycle were enhanced. To assess the role of GPAT4 directly, neonatal BAT preadipocytes were differentiated to adipocytes. Compared with controls, Gpat4−/− brown adipocytes incorporated 33% less fatty acid into triacylglycerol and 46% more into the pathway of β-oxidation. The increased oxidation rate was due solely to an increase in the oxidation of exogenous fatty acids. These data suggest that in the absence of cold exposure, GPAT4 limits excessive fatty acid oxidation and the detrimental induction of a hypermetabolic state. 相似文献
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Nina M. Pollak Martina Schweiger Doris Jaeger Dagmar Kolb Manju Kumari Renate Schreiber Stephanie Kolleritsch Philipp Markolin Gernot F. Grabner Christoph Heier Kathrin A. Zierler Thomas Rülicke Robert Zimmermann Achim Lass Rudolf Zechner Guenter Haemmerle 《Journal of lipid research》2013,54(4):1092-1102
Cardiac triacylglycerol (TG) catabolism critically depends on the TG hydrolytic activity of adipose triglyceride lipase (ATGL). Perilipin 5 (Plin5) is expressed in cardiac muscle (CM) and has been shown to interact with ATGL and its coactivator comparative gene identification-58 (CGI-58). Furthermore, ectopic Plin5 expression increases cellular TG content and Plin5-deficient mice exhibit reduced cardiac TG levels. In this study we show that mice with cardiac muscle-specific overexpression of perilipin 5 (CM-Plin5) massively accumulate TG in CM, which is accompanied by moderately reduced fatty acid (FA) oxidizing gene expression levels. Cardiac lipid droplet (LD) preparations from CM of CM-Plin5 mice showed reduced ATGL- and hormone-sensitive lipase-mediated TG mobilization implying that Plin5 overexpression restricts cardiac lipolysis via the formation of a lipolytic barrier. To test this hypothesis, we analyzed TG hydrolytic activities in preparations of Plin5-, ATGL-, and CGI-58-transfected cells. In vitro ATGL-mediated TG hydrolysis of an artificial micellar TG substrate was not inhibited by the presence of Plin5, whereas Plin5-coated LDs were resistant toward ATGL-mediated TG catabolism. These findings strongly suggest that Plin5 functions as a lipolytic barrier to protect the cardiac TG pool from uncontrolled TG mobilization and the excessive release of free FAs. 相似文献
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Anna Foryst-Ludwig Michael C. Kreissl Verena Benz Sarah Brix Elia Smeir Zsofia Ban El?bieta Januszewicz Janek Salatzki Jana Grune Anne-Kathrin Schwanstecher Annelie Blumrich Andreas Schirbel Robert Klopfleisch Michael Rothe Katharina Blume Martin Halle Bernd Wolfarth Erin E. Kershaw Ulrich Kintscher 《The Journal of biological chemistry》2015,290(39):23603-23615
Endurance exercise training induces substantial adaptive cardiac modifications such as left ventricular hypertrophy (LVH). Simultaneously to the development of LVH, adipose tissue (AT) lipolysis becomes elevated upon endurance training to cope with enhanced energy demands. In this study, we investigated the impact of adipose tissue lipolysis on the development of exercise-induced cardiac hypertrophy. Mice deficient for adipose triglyceride lipase (Atgl) in AT (atATGL-KO) were challenged with chronic treadmill running. Exercise-induced AT lipolytic activity was significantly reduced in atATGL-KO mice accompanied by the absence of a plasma fatty acid (FA) increase. These processes were directly associated with a prominent attenuation of myocardial FA uptake in atATGL-KO and a significant reduction of the cardiac hypertrophic response to exercise. FA serum profiling revealed palmitoleic acid (C16:1n7) as a new molecular co-mediator of exercise-induced cardiac hypertrophy by inducing nonproliferative cardiomyocyte growth. In parallel, serum FA analysis and echocardiography were performed in 25 endurance athletes. In consonance, the serum C16:1n7 palmitoleate level exhibited a significantly positive correlation with diastolic interventricular septum thickness in those athletes. No correlation existed between linoleic acid (18:2n6) and diastolic interventricular septum thickness. Collectively, our data provide the first evidence that adipose tissue lipolysis directly promotes the development of exercise-induced cardiac hypertrophy involving the lipokine C16:1n7 palmitoleate as a molecular co-mediator. The identification of a lipokine involved in physiological cardiac growth may help to develop future lipid-based therapies for pathological LVH or heart failure. 相似文献
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Bonnet M Cassar-Malek I Chilliard Y Picard B 《Animal : an international journal of animal bioscience》2010,4(7):1093-1109
The lean-to-fat ratio, that is, the relative masses of muscle and adipose tissue, is a criterion for the yield and quality of bovine carcasses and meat. This review describes the interactions between muscle and adipose tissue (AT) that may regulate the dynamic balance between the number and size of muscle v. adipose cells. Muscle and adipose tissue in cattle grow by an increase in the number of cells (hyperplasia), mainly during foetal life. The total number of muscle fibres is set by the end of the second trimester of gestation. By contrast, the number of adipocytes is never set. Number of adipocytes increases mainly before birth until 1 year of age, depending on the anatomical location of the adipose tissue. Hyperplasia concerns brown pre-adipocytes during foetal life and white pre-adipocytes from a few weeks after birth. A decrease in the number of secondary myofibres and an increase in adiposity in lambs born from mothers severely underfed during early pregnancy suggest a balance in the commitment of a common progenitor into the myogenic or adipogenic lineages, or a reciprocal regulation of the commitment of two distinct progenitors. The developmental origin of white adipocytes is a subject of debate. Molecular and histological data suggested a possible transdifferentiation of brown into white adipocytes, but this hypothesis has now been challenged by the characterization of distinct precursor cells for brown and white adipocytes in mice. Increased nutrient storage in fully differentiated muscle fibres and adipocytes, resulting in cell enlargement (hypertrophy), is thought to be the main mechanism, whereby muscle and fat masses increase in growing cattle. Competition or prioritization between adipose and muscle cells for the uptake and metabolism of nutrients is suggested, besides the successive waves of growth of muscle v. adipose tissue, by the inhibited or delayed adipose tissue growth in bovine genotypes exhibiting strong muscular development. This competition or prioritization occurs through cellular signalling pathways and the secretion of proteins by adipose tissue (adipokines) and muscle (myokines), putatively regulating their hypertrophy in a reciprocal manner. Further work on the mechanisms underlying cross-talk between brown or white adipocytes and muscle fibres will help to achieve better understanding as a prerequisite to improving the control of body growth and composition in cattle. 相似文献
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ABSTRACTCitrus plants are rich in flavonoids and beneficial for lipid metabolism. However, the mechanism has not been fully elucidated. Both citrus peel flavonoid extracts (CPFE) and a mixture of their primary flavonoid compounds, namely, nobiletin, tangeretin and hesperidin, citrus flavonoid purity mixture (CFPM), were found to have lipid-lowering effects on oleic acid-induced lipid accumulation in HepG2 cells. The carnitine palmitoyltransferase 1α (CPT1α) gene was markedly increased, while the fatty acid synthase (FAS) gene was significantly decreased by both CPFE and CFPM in oleic acid-treated HepG2 cells. Flavonoid compounds from citrus peel suppressed miR-122 and miR-33 expression, which were induced by oleic acid. Changes in miR-122 and miR-33 expression, which subsequently affect the expression of their target mRNAs FAS and CPT1α, are most likely the principal mechanisms leading to decreased lipid accumulation in HepG2 cells. Citrus flavonoids likely regulate lipid metabolism by modulating the expression levels of miR-122 and miR-33. 相似文献
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Joaquín López-Soriano Josep M. Argilés Francisco J. López-Soriano 《Molecular and cellular biochemistry》1995,143(2):113-118
Intravenous administration of a single dose (100 g/kg bw) of recombinant tumour necrosis factor- (TNF, cachectin) to rats increased the rate ofin vitro fatty acid synthesis in interscapular brown adipose tissue (IBAT) from both glucose and alanine, without changes in the oxidation of these substrates to14CO2. Lactate production and glycerol release were also unaffected by treatment with the cytokine. Additionally, the presence of TNF in the incubation media did not affect fatty acid synthesis, suggesting an indirect effect of the cytokine. The activities of different enzymes of glucose and alanine metabolism such as hexokinase, phosphofructokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase and alanine transaminase, did not suffer changes as a consequence of TNF administration. The same applied to the enzymatic activities involved in fatty acid synthesis such as fatty acid synthase, acetyl-CoA carboxylase and ATP-citrate lyase. Conversely, citrate levels in IBAT were increased in animals treated with TNF, suggesting that it could be the cause for the increased fatty acid synthesis in this tissue. 相似文献
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Joona Tapio Riikka Halmetoja Elitsa Y. Dimova Joni M. Mki Anu Laitala Gail Walkinshaw Johanna Myllyharju Raisa Serpi Peppi Koivunen 《The Journal of biological chemistry》2022,298(8)
Hypoxia-inducible factor (HIF) prolyl 4-hydroxylases (HIF-P4Hs 1–3) are druggable targets in renal anemia, where pan-HIF-P4H inhibitors induce an erythropoietic response. Preclinical data suggest that HIF-P4Hs could also be therapeutic targets for treating metabolic dysfunction, although the contributions of HIF-P4H isoenzymes in various tissues to the metabolic phenotype are inadequately understood. Here, we used mouse lines that were gene-deficient for HIF-P4Hs 1 to 3 and two preclinical pan-HIF-P4H inhibitors to study the contributions of these isoenzymes to the anthropometric and metabolic outcome and HIF response. We show both inhibitors induced a HIF response in wildtype white adipose tissue (WAT), liver, and skeletal muscle and alleviated metabolic dysfunction during a 6-week treatment period, but they did not alter healthy metabolism. Our data indicate that HIF-P4H-1 contributed especially to skeletal muscle and WAT metabolism and that its loss lowered body weight and serum cholesterol levels upon aging. In addition, we found HIF-P4H-3 had effects on the liver and WAT and its loss increased body weight, adiposity, liver weight and triglyceride levels, WAT inflammation, and cholesterol levels and resulted in hyperglycemia and insulin resistance, especially during aging. Finally, we demonstrate HIF-P4H-2 affected all tissues studied; its inhibition lowered body and liver weight and serum cholesterol levels and improved glucose tolerance. We found very few HIF target metabolic mRNAs were regulated by the inhibition of three isoenzymes, thus suggesting a potential for selective therapeutic tractability. Altogether, these data provide specifications for the future development of HIF-P4H inhibitors for the treatment of metabolic diseases. 相似文献