Expression

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  • 文章类型: Journal Article
    Polycystic ovarian syndrome (PCOS) is a common heterogeneous reproductive endocrine metabolic disorder in women of reproductive age characterized by clinical and biochemical hyperandrogenemia, ovulation disorders, and polycystic ovarian morphology. Ferroptosis is a novel type of cell death driven by iron accumulation and lipid peroxidation. Ferroptosis plays a role in maintaining redox balance, iron metabolism, lipid metabolism, amino acid metabolism, mitochondrial activity, and many other signaling pathways linked to diseases. Iron overload is closely related to insulin resistance, decreased glucose tolerance, and the occurrence of diabetes mellitus. There is limited research on the role of ferroptosis in PCOS. Patients with PCOS have elevated levels of ferritin and increased reactive oxygen species in ovarian GCs. Studying ferroptosis in PCOS patients is highly important for achieving personalized treatment. This article reviews the progress of research on ferroptosis in PCOS, introduces the potential connections between iron metabolism abnormalities and oxidative stress-mediated PCOS, and provides a theoretical basis for diagnosing and treating PCOS.
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  • 文章类型: Journal Article
    hsa-miR-520a is derived from MIR520A located at 19q13.42 and has a significant part in the development of various disorders, including different types of cancers, recurrent pregnancy loss, cerebral ischemia/reperfusion injury, and sciatica. In relation to cancer, numerous studies have presented diverse findings regarding the function of this particular miRNA. To summarize, it has been observed to be down-regulated in pancreatic cancer, glioma, ovarian cancer, cervical cancer, uterine corpus endometrial carcinoma, lung cancer, and acute myeloid leukemia. The purpose of this review is to offer an inclusive overview of the role of has-miR-520a in these disorders, with a specific focus on its target mRNAs in each setting and the deregulated signaling pathways involved. Additionally, we aimed to summarize the implication of miR-520a as a prognostic factor in malignancies. Finally, we performed comprehensive in-silico analyses to uncover the biological roles of this miRNA and introducing innovative concepts for future research endeavors.
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  • 文章类型: Journal Article
    X连锁隐性肌萎缩蛋白病是人和狗中最常见的肌营养不良(MD)。迄今为止,在犬肌营养不良蛋白基因(DMD)中描述了20种特定的MD相关变体,包括边境牧羊犬混合品种中肌营养不良蛋白缺乏的MD。这里,我们报告了5个月大的男性边境牧羊犬的轻度肌营养不良蛋白缺乏症MD的诊断和随访,与新型DMD变体相关。诊断基于神经学检查和实验室评估,包括肌酸激酶活性,肌电图和肌肉活检免疫荧光染色。对受影响的肌肉活检的RNA-seq数据的Sashimi图的检查导致在DMD内含子63中发现了162bp的L1假外显子,引入了移码和过早终止密码子(NM_001003343.1:c.9271_9272insN[162]p。(Ala3091fs*21))。在受影响的肌肉中,非假外显子(50倍以下)和假外显子(3倍以下)的转录本都检测到DMDmRNA水平降低,与对照肌肉中含有非伪外显子的转录物的水平相比,导致非常低的肌营养不良蛋白水平和上调的乌托邦蛋白。因为变异只在受影响的狗身上发现,不是健康的母亲和祖母,或来自比利时人口的108名无关的边境牧羊犬(46名男性和62名女性),它被认为是从头变种。尽管肌萎缩蛋白病的预后通常被认为较差,狗在6个月大时稳定,在2岁时临床上仍然稳定。
    X-linked recessive dystrophinopathies are the most common muscular dystrophies (MDs) in humans and dogs. To date, 20 breed-specific MD-associated variants are described in the canine dystrophin gene (DMD), including one associated with dystrophin-deficient MD in the Border Collie mixed breed. Here, we report the diagnosis and follow-up of mild dystrophin-deficient MD in a 5-month-old male Border Collie, associated with a novel DMD variant. Diagnosis was based on neurological examination and laboratory evaluations including creatine kinase activity, electromyography and muscle biopsies with immunofluorescent staining. Inspection of the Sashimi plots of the RNA-seq data from the affected muscle biopsy led to the discovery of a 162-bp L1 pseudoexon in DMD intron 63, introducing a frameshift and a premature stop codon (NM_001003343.1: c.9271_9272insN[162] p.(Ala3091fs*21)). Reduced DMD mRNA levels were detected for both the non-pseudoexon (50× less) and pseudoexon (3× less) containing transcripts in the affected muscle, compared with the level of the non-pseudoexon containing transcript in a control muscle, resulting in very low dystrophin protein levels and the upregulation of utrophin. Because the variant was only found in the affected dog, not in the healthy mother and grandmother, or in 108 unrelated Border Collies from the Belgian population (46 males and 62 females), it was considered a de novo variant. Although the prognosis for dystrophinopathy is generally regarded as poor, the dog stabilised at the age of 6 months and is still clinically stable at the age of 2 years.
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  • 文章类型: Journal Article
    节食夜蛾是一种远距离迁徙的害虫,具有很强的传播能力,快速的繁殖速度和破坏性的喂养,所以很难预防和控制。拟除虫菊酯杀虫剂通常用于害虫防治,由于电压门控钠通道(VGSC)是拟除虫菊酯的主要靶标,研究该基因对害虫防治具有重要意义。VGSC是一种完整的跨膜蛋白,由神经元中发现的约2,000个氨基酸残基组成。肌细胞,内分泌细胞,和卵巢细胞,并参与可兴奋细胞动作电位的启动和传播。在这项研究中,通过快速扩增cDNA末端(RACE)从S.frugiperda中鉴定出VGSC的cDNA序列,该cDNA末端包含6,261bp的开放阅读框,编码2,086个氨基酸的蛋白质。该蛋白的分子量预计为236kDa,理论等电点为5.21。基于鳞翅目昆虫构建的系统发育树表明,frugiperda的VGSC与斜纹夜蛾的VGSC最接近。VGSC是一种高度保守的蛋白质,具有跨膜蛋白的离子通道保守结构域。qPCR显示VGSC基因在2龄幼虫表皮中高表达,其在其他组织中的表达水平较低,例如前肠和马尔皮根小管。此外,在pu前阶段也检测到VGSC,然后在进入成年阶段后逐渐增加,成年雄性在第4天达到顶峰,后来减少了。构建pSumo-mut-VGSC的重组质粒并诱导表达His标签融合的VGSC蛋白。从纯化的重组VGSC蛋白制备多克隆抗体。抗体是ELISA滴定的,免疫印迹结果显示它能特异性识别VGSC,无论是重组蛋白还是内源蛋白。这些研究结果为今后研究该基因在草本生长发育中的生理功能奠定了基础。
    Spodoptera frugiperda is a long-distance migratory pest with strong dispersal ability, fast reproduction speed and destructive feeding, so it is difficult to prevent and control. Pyrethroid insecticides are commonly used in pest insects control, And since the voltage-gated sodium channel (VGSC) serves as a major target of pyrethroids, it is important to study this gene for pest control. VGSC is an integral transmembrane protein consisting of approximately 2,000 amino acid residues found in neurons, myocytes, endocrine cells, and ovarian cells and involved in the initiation and propagation of excitable cellular action potentials. In this study, the cDNA sequence of the VGSC was identified from S. frugiperda by rapid amplification of cDNA ends (RACE) which contained an open reading frame of 6,261 bp encoding a protein of 2,086 amino acids. The molecular weight of this protein was predicted to be 236 kDa, and the theoretical isoelectric point was 5.21. A phylogenetic tree constructed based on lepidopteran insects showed that the VGSC of S. frugiperda was most closely relative to that of Spodoptera litura. VGSC is a highly conserved protein with Ion channel conserved structural domains of transmembrane proteins. qPCR showed that the VGSC gene was highly expressed in the epidermis of 2nd instar larvae, and its expression level was low in other tissues, such as the foregut and Malpighian tubules. In addition, VGSC was also detected in the prepupal stage, then gradually increased in abundance after entering the adult stage, peaked at the adult males on the 4th day of pupal stage, and decreased afterwards. The recombinant plasmid of pSumo-mut-VGSC was constructed and induced to express a His tag fused VGSC protein. Polyclonal antibodies were prepared from purified recombinant VGSC protein. The antibody was ELISA-titered, and the western blotting results showed that it specifically recognized VGSC, whether it was recombinant or endogenous protein. These results have laid the foundation for future studies on the physiological function of this gene in the growth and development of S. frugiperda.
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  • 文章类型: Journal Article
    小辅助RNA(SAURs),最大的早期生长素反应基因家族,在多个过程中起着至关重要的作用,包括细胞扩增,叶片生长和衰老,生长素运输,热带生长等等。虽然水稻SAUR基因家族在2006年就已被鉴定出来,但由于其分析方法的不完善,对水稻SAUR基因的鉴定十分必要。在这项研究中,在水稻(Oryzasativa)中,共有60个OsSAUR(包括两个假基因)分布在10条染色体上。生物信息学工具用于系统分析理化性质,亚细胞定位,主题组成,染色体位置,基因复制,进化关系,OsSAURs的生长素响应顺式元素。此外,基因芯片数据分析得到的表达谱显示,OsSAUR基因在不同组织中具有不同的表达模式,表明OsSAUR基因家族成员之间的功能差异。一句话,本研究为水稻SAUR基因家族提供了基础资料,为进一步研究SAUR在水稻生长发育中的作用奠定了基础。
    SMALL AUXIN UP RNAs (SAURs), the largest family of early auxin response genes, plays crucial roles in multiple processes, including cell expansion, leaf growth and senescence, auxin transport, tropic growth and so on. Although the rice SAUR gene family was identified in 2006, it is necessary to identify the rice SAUR gene due to the imperfection of its analysis methods. In this study, a total of 60 OsSAURs (including two pseudogenes) distributed on 10 chromosomes were identified in rice (Oryza sativa). Bioinformatics tools were used to systematically analyze the physicochemical properties, subcellular localization, motif compositions, chromosomal location, gene duplication, evolutionary relationships, auxin-responsive cis-elements of the OsSAURs. In addition, the expression profiles obtained from microarray data analysis showed that OsSAUR genes had different expression patterns in different tissues and responded to auxin treatment, indicating functional differences among members of OsSAUR gene family. In a word, this study provides basic information for SAUR gene family of rice and lays a foundation for further study on the role of SAUR in rice growth and development.
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  • 文章类型: Journal Article
    引言本研究的目的是通过实时聚合酶链反应(PCR)技术在肺癌患者中鉴定外周血中的基因表达。材料和方法收集非小细胞和小细胞肺癌患者的外周血样本。靶基因包括生存素,CK7,ASH1,HMGB3,L587S,CLCA2β-肌动蛋白是参考基因。如果靶基因的平均CT(阈值循环)值≥40,则认为基因表达不可检测。结果纳入50例肺癌患者和30例健康对照者。在六个基因中,survivin与对照组相比显示26.8倍的倍数变化;ASH1和L587S分别为0.54和0.06;与对照组相比,HMGB3、CLCA2和CK7的倍数变化不显著.检测的6个靶基因在肺癌中的总检出率为84%,50名患者中有42名检测呈阳性。较高的阶段和ASH1(p=0.031),CK7(p=<0.001),与HMGB3,p=0.011有显著相关性。CLCA2在无肾上腺转移患者中表达较高(p=0.044)。结论与其他研究相比,生活方式和地理差异可能是可变基因表达的可能原因。然而,需要进一步的研究来确定这些标志物的临床意义,尤其是在更大的早期患者群体中。
    Introduction The objective of the present study was to identify gene expression in peripheral blood by a real-time polymerase chain reaction (PCR) technique in patients who have lung carcinoma. Material and methods Peripheral blood samples of patients with non-small cell and small cell lung cancer were collected. Target genes included survivin, CK7, ASH1, HMGB3, L587S, and CLCA2. β-Actin was the reference gene. If the mean CT (threshold cycle) value for a target gene is ≥40, the gene expression is considered undetectable. Results Fifty patients with lung carcinoma were included and 30 healthy controls. Out of the six genes, survivin showed 26.8 times fold change as compared to controls; ASH1 and L587S were 0.54 and 0.06, respectively; and HMGB3, CLCA2, and CK7 had non-significant fold change in comparison to controls. The overall detection rate of the six target genes examined in lung cancer was 84%, with 42 out of 50 patients testing positive. Higher stages and ASH1 (p = 0.031), CK7 (p = <0.001), and HMGB3, p = 0.011 were associated significantly. CLCA2 had higher expression in patients without adrenal metastases (p = 0.044). Conclusions Lifestyle and geographical variation might be a probable cause of variable gene expression as compared to other studies. However, further research is needed to determine the clinical implication of these markers, especially in larger groups of early-stage patients.
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  • 文章类型: Journal Article
    目的:探讨核糖体S6激酶4(RSK4)蛋白在非小细胞肺癌(NSCLC)组织及癌旁组织中的表达。并阐明其与NSCLC临床病理特征的相关性。
    方法:我们分析了2020年6月至2022年6月在浙江大学医学院附属第二医院接受治疗的100例NSCLC患者。患者人口统计学和临床数据,包括性别,年龄,糖尿病史,肿瘤位置,肿瘤分化程度,淋巴结转移,和临床分期,被收集。通过免疫组织化学染色评估组织样品中的RSK4蛋白表达。
    结果:RSK4蛋白在35.00%的癌组织中阳性表达,69.00%显著低于癌旁非肿瘤组织(P<0.05)。肿瘤分化程度较低的患者,晚期肿瘤淋巴结转移(TNM)分期,和淋巴结转移显示RSK4表达显著降低,与高分化者相比,早期TNM阶段,无淋巴结转移(均P<0.05)。Cox回归分析表明,TNM阶段,低分化,淋巴结转移对RSK4表达有显著影响(均P<0.05)。生存分析显示,在RSK4表达阳性的患者中,阳性预后生存率更高,为74.29%(26/35)。阴性表达者为53.85%(35/65)(P<0.05)。Spearman相关分析显示RSK4表达与TNM分期呈显著正相关,淋巴结转移,和患者预后(均P<0.05)。
    结论:NSCLC组织中RSK4阳性表达与晚期癌症分期显著相关。分化差,淋巴结转移,提示RSK4在非小细胞肺癌中的潜在抑癌作用。这种关联强调了其在NSCLC患者中的预后相关性。
    OBJECTIVE: To evaluate the expression of Ribosomal S6 kinase 4 (RSK4) protein in non-small cell lung cancer (NSCLC) tissues and adjacent non-tumor tissues, and to elucidate its correlation with clinicopathological features of NSCLC.
    METHODS: We analyzed 100 NSCLC patients treated at the Second Affiliated Hospital of Zhejiang University School of Medicine from June 2020 to June 2022. Patient demographics and clinical data, including gender, age, history of diabetes, tumor location, degree of tumor differentiation, lymph node metastasis, and clinical stage, were collected. RSK4 protein expression was assessed in tissue samples via immunohistochemical staining.
    RESULTS: RSK4 protein was positively expressed in 35.00% of cancerous tissues, significantly lower than the 69.00% observed in adjacent non-tumor tissues (P < 0.05). Patients with lower tumor differentiation, advanced Tumor Node Metastasis (TNM) stages, and lymph node metastases showed significantly reduced RSK4 expression compared to those with higher differentiation, earlier TNM stages, and no lymph node metastases (all P < 0.05). Cox regression analysis indicated that TNM stage, low differentiation, and lymph node metastases significantly influenced RSK4 expression (all P < 0.05). Survival analysis revealed a higher positive prognosis survival rate of 74.29% (26/35) among patients with positive RSK4 expression, versus 53.85% (35/65) in those with negative expression (P < 0.05). Spearman correlation analysis demonstrated a significant positive correlation of RSK4 expression with TNM stage, lymph node metastasis, and patient prognosis (all P < 0.05).
    CONCLUSIONS: Positive RSK4 expression in NSCLC tissues is significantly correlated with advanced cancer stage, poor differentiation, and presence of lymph node metastasis, suggesting a potential tumor suppressor role for RSK4 in NSCLC. This association underscores its prognostic relevance in NSCLC patients.
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  • 文章类型: Journal Article
    长链非编码RNA(lncRNA),定义为长度超过200个核苷酸的RNA分子,与各种生物过程的调节和肿瘤的进展有关。其中,LINC00518是一种最近鉴定的由位于染色体6p24.3上的基因编码的lncRNA,由三个外显子组成,预计会正向调节特定基因的表达。LINC00518已成为多种癌症类型中的关键致癌lncRNA。它通过调节几个靶基因的表达发挥其肿瘤促进作用,主要通过充当microRNAs(miRNAs)的海绵。此外,LINC00518影响关键信号通路,包括Wnt/β-catenin,JAK/STAT,和整合素β3/FAK途径。肿瘤组织中LINC00518的水平升高与肿瘤大小增加有关,晚期临床阶段,转移,生存预后差。这篇综述提供了遗传特征的全面总结,表达模式,生物学功能,以及LINC00518在人类疾病中的潜在机制。
    Long non-coding RNAs (lncRNAs), defined as RNA molecules exceeding 200 nucleotides in length, have been implicated in the regulation of various biological processes and the progression of tumors. Among them, LINC00518, a recently identified lncRNA encoded by a gene located on chromosome 6p24.3, consists of three exons and is predicted to positively regulate the expression of specific genes. LINC00518 has emerged as a key oncogenic lncRNA in multiple cancer types. It exerts its tumor-promoting effects by modulating the expression of several target genes, primarily through acting as a sponge for microRNAs (miRNAs). Additionally, LINC00518 influences critical signaling pathways, including the Wnt/β-catenin, JAK/STAT, and integrin β3/FAK pathways. Elevated levels of LINC00518 in tumor tissues are associated with increased tumor size, advanced clinical stage, metastasis, and poor survival prognosis. This review provides a comprehensive summary of the genetic characteristics, expression patterns, biological functions, and underlying mechanisms of LINC00518 in human diseases.
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  • 文章类型: Journal Article
    大麻二酚(CBD)是从大麻中提取的非精神活性药物。众所周知,CBD减弱了滥用药物的增强作用,虽然其作用机制尚未完全了解。当前的研究试图阐明腹侧被盖区(VTA)中D1样多巴胺受体(D1R)在CBD对甲基苯丙胺(METH)条件位置偏爱(CPP)的获取和表达的抑制作用中的作用。在CPP培训中,成年雄性Wistar大鼠皮下施用METH(1mg/kg)5天。三组动物在VTA中接受多剂量的SCH23390(作为D1R拮抗剂;0.25、1和4μg/0.3μl盐水)治疗,分别,在采集阶段的脑室内(ICV)注射CBD(10μg/5μlDMSO)之前。在研究的第二个实验中,大鼠在VTA中接受SCH23390,然后在ICV中给予CBD(50μg/5μlDMSO)表达METHCPP。这里,目前的研究表明,CBD抑制METHCPP的获得和表达,而将D1R拮抗剂(1和4μg)显微注射到VTA中显着降低了CBD对METH位置偏好的获得和表达的抑制作用。此外,这项研究表明,SCH23390或CBD单独并不会导致CPP范式中的位置偏好.基于这些数据,这项研究表明,D1R的药理学操作可能会改变CBD对METH条件偏好的影响。
    Cannabidiol (CBD) is a non-psychoactive drug extracted from marijuana. It is well established that CBD attenuates the reinforcing effects of drugs of abuse, although its mechanism of action is not fully understood. The current study tries to clarify the role of D1-like dopamine receptors (D1R) in the ventral tegmental area (VTA) in the inhibitory effects of the CBD on the acquisition and expression of methamphetamine (METH)-conditioned place preference (CPP). In the CPP training, adult male Wistar rats were conditioned with subcutaneous administration of METH (1mg/kg) for five days. Three groups of animals were treated with multiple doses of SCH23390 (as a D1R antagonist; 0.25, 1, and 4μg/0.3μl saline) in the VTA, respectively, before intracerebroventricular (ICV) injection of CBD (10μg/5μl DMSO) in the acquisition phase. In the second experiment of the study, rats received SCH23390 in the VTA before ICV administration of CBD (50μg/5μl DMSO) in the expression of METH CPP. Here, the current study demonstrated that CBD inhibits the acquisition and expression of METH CPP, while microinjection of D1R antagonists (1 and 4μg) into the VTA significantly reduced CBD\'s suppressive effect on the acquisition and expression of METH place preference. Furthermore, this research demonstrated that either SCH23390 or CBD alone does not lead to place preference in the CPP paradigm. Based on these data, this study suggests that pharmacological manipulations of D1R may alter the CBD\'s effect on METH-conditioned preference.
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  • 文章类型: Journal Article
    为了开发多瘤病毒VP1重组蛋白免疫测定,两种多瘤病毒的表达(卡罗林斯卡研究所多瘤病毒;KIPyV,和华盛顿大学多瘤病毒;WUPyV)使用改进的杆状病毒系统(BacMagic)研究了昆虫细胞中的VP1s。通过建立酶联免疫吸附测定(ELISA),证实了纯化的VP1在血清学测试中作为抗原的可靠性。使用了两组血清样本,第一组包含60份血清(20KIPyV阳性,20WUPyV阳性,和20个阴性)和第II组,由134个状态未知的血清组成。研究人群中KIPyV和WUPyV的血清阳性率分别为62%和50%,分别。抗体阴性血清在两种ELISA中均表现出低反应性,而抗体阳性血清在KIPyV和WUPyVELISA中显示出高反应性,中位光密度值为1.37和1.47,分别。每种病毒的抗体阳性和阴性之间的血清反应性差异具有统计学意义(p<0.0001;95%置信区间)。研究表明,KIPyV和WUPyV的血清转化发生在儿童时期,5岁后,KIPyV血清阳性达到70%,WUPyV血清阳性达到60%。多瘤病毒的成人血清阳性率很高,超过64%和51%的成人KIPyV和WUPyV血清呈阳性,分别。在年龄组中,KIPyV和WUPyV抗体的持续流行表明该抗体终生存在。抗体滴度通常随时间稳定的事实揭示了人类群体中多瘤病毒的持续感染。已证明基于昆虫细胞的重组VP1的ELISA作为血清学测定是有价值的,提供有效的,可靠,快,不费力,和经济的程序。
    To develop polyomavirus VP1 recombinant protein-based immunoassay, the expression of two polyomavirus (Karolinska Institute Polyomavirus; KIPyV, and Washington University Polyomavirus; WUPyV) VP1s in insect cells was investigated using an improved baculovirus system (BacMagic). The reliability of the purified VP1 to serve as antigens in serological tests was confirmed by the establishment of an enzyme-linked immunosorbent assay (ELISA). Two panels of serum samples were used, with Panel I comprising 60 sera (20 KIPyV-positive, 20 WUPyV-positive, and 20 negative) and Panel II consisting of 134 sera with unknown status. The seroprevalence of KIPyV and WUPyV in the study population was determined to be 62% and 50%, respectively. Antibody-negative sera exhibited low reactivities in both ELISAs, whereas antibody-positive sera displayed high reactivity with median optical density values of 1.37 and 1.47 in the KIPyV and WUPyV ELISAs, respectively. The differences in seroreactivities between antibody positive and negative for each virus were statistically significant (p < 0.0001; with 95% confidence interval). The study suggests that seroconversion for KIPyV and WUPyV occurs in childhood, with KIPyV seropositivity reaching 70% and WUPyV seropositivity reaching 60% after the age of 5 years. Adult seroprevalence for polyomaviruses was high, with more than 64% and 51% of the adult population being seropositive for KIPyV and WUPyV, respectively. The constant prevalence of KIPyV and WUPyV antibody in the age groups suggested that this antibody persists for life. The fact that antibody titers were generally stable over time revealed a persistent infection of polyomaviruses in the human population. The insect cell-derived recombinant VP1-based ELISA has been demonstrated to be valuable as a serological assay, offering a valid, reliable, fast, nonlaborious, and economical procedure.
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