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KDM4A-AS1 promotes cell proliferation, migration and invasion via the miR-4306/STX6 axis in hepatocellular carcinoma KDM4A-AS1 通过 miR-4306/STX6 轴促进肝细胞癌细胞的增殖、迁移和侵袭
IF 1.6 4区 医学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1615/critreveukaryotgeneexpr.2024051414
Wei Cao, Yuhan Ren, Ying Liu, Guoshu Cao, Zhen Chen, Fan Wang
Background: As a primary liver malignancy, hepatocellular carcinoma (HCC) is commonly induced by chronic liver disease and cirrhosis. Bioinformatics analysis reveals that long noncoding RNA KDM4A antisense RNA 1 (KDM4A-AS1) may be aberrantly expressed in HCC and its abnormal expression might influence prognosis in patients.Objective: To illustrate the functions and mechanism of KDM4A-AS1 in regulating HCC malignant cell behavior.Methods: KDM4A-AS1, microRNA (miR)-4306 and messenger RNA syntaxin 6 (STX6) expression was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). HCC cell proliferation, apoptosis, migration, and invasion were measured by colony forming assays, flow cytometry, wound healing and Transwell assays. The interaction between genes was verified by RNA immunoprecipitation and luciferase reporter assays. Western blotting was performed to quantify protein expression of STX6 or apoptotic markers.Results: KDM4A-AS1 was highly expressed in HCC cells and tissues. KDM4A-AS1 knockdown led to enhanced HCC cell apoptosis and suppressed HCC cell proliferation, migration, and invasion. MiR-4306 bound to and negatively regulated STX6. KDM4A-AS1 directly bound to miR-4306 and thus upregulated STX6. STX6 overexpression reversed the inhibitory influence of KDM4A-AS1 depletion on HCC malignant behavior.Conclusions: KDM4A-AS1 promotes HCC cell migration, invasion, and growth by upregulating STX6 via miR-4306.
背景:肝细胞癌(HCC)是一种原发性肝脏恶性肿瘤,通常由慢性肝病和肝硬化诱发。生物信息学分析发现,长非编码 RNA KDM4A 反义 RNA 1(KDM4A-AS1)可能在 HCC 中异常表达,其异常表达可能影响患者的预后:阐明 KDM4A-AS1 在调控 HCC 恶性细胞行为中的功能和机制:方法:采用反转录定量聚合酶链反应(RT-qPCR)检测KDM4A-AS1、microRNA(miR)-4306和信使RNA句法蛋白6(STX6)的表达。通过集落形成试验、流式细胞术、伤口愈合和 Transwell 试验测定了 HCC 细胞的增殖、凋亡、迁移和侵袭。通过 RNA 免疫沉淀和荧光素酶报告实验验证了基因之间的相互作用。对 STX6 或凋亡标志物的蛋白表达进行了 Western 印迹定量:结果:KDM4A-AS1在HCC细胞和组织中高表达。结果:KDM4A-AS1在HCC细胞和组织中高表达,敲除KDM4A-AS1可增强HCC细胞凋亡,抑制HCC细胞增殖、迁移和侵袭。MiR-4306 与 STX6 结合并对其进行负调控。KDM4A-AS1 直接与 miR-4306 结合,从而上调 STX6。STX6的过表达逆转了KDM4A-AS1耗竭对HCC恶性行为的抑制作用:结论:KDM4A-AS1通过miR-4306上调STX6,促进了HCC细胞的迁移、侵袭和生长。
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引用次数: 0
Analysis of Transgenic Cotton Plants Containing Universal Stress Protein (GaUSP-1, GaUSP-2) and Zinc Finger Transcriptional Factor (GaZnF) Genes under Drought Stress. 干旱胁迫下含通用胁迫蛋白(GaUSP-1,GaUSP-2)和锌指转录因子(GaZnF)基因的转基因棉花植株的分析。
IF 1.6 4区 医学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1615/CritRevEukaryotGeneExpr.2023048905
Muhammad Hamza Basit, Bushra Rasheed, Kausar Malik, Zoha Masood, Samia Afzal

Water is the most limiting factor for plant growth and crop productivity. Drought stress adversely affects crop yield throughout the world. Up to 50% of crop yield in Pakistan is severely affected by the shortage of water. Cotton is an important cash crop for Pakistan known as "white gold." It accounts for 8.2% of the value added in agriculture and about 3.2% of GDP. Besides, being the world's fourth-largest cotton producer, our yield per acre ranks 13th in the world. If we look at the Pakistan scenario, water deficiency is one of the major yield-limiting factors. Limitations related to conventional breeding and the advancements in plant genomics and biotechnology applications have opened new horizons to plant improvements. Therefore, in the current study, we carry out a comparative analysis to evaluate the morphological, physiological biochemical and molecular parameters in transgenic plants containing GaUSP-1, GaUSP-2 and GaZinc Finger genes under different drought stress conditions. Data showed that transgenic plants showed more tolerance as compared to non-transgenic plants. Transgenic and non-transgenic assist us in our better understanding of the drought-responsive mechanism and its effect on different plant growth traits, so, in this way, we would be able to explore drought tolerance mechanism and this will open the doors for the identification of drought-related genes.

水是限制植物生长和作物生产力的最重要因素。干旱胁迫对世界各地的作物产量产生不利影响。巴基斯坦高达50%的作物产量受到缺水的严重影响。棉花是巴基斯坦重要的经济作物,被称为“白金”。棉花占农业增加值的8.2%,约占国内生产总值的3.2%。此外,作为世界第四大棉花生产国,我们的亩产量位居世界第13位。如果我们看看巴基斯坦的情况,缺水是限制产量的主要因素之一。传统育种的局限性以及植物基因组学和生物技术应用的进步为植物改良开辟了新的视野。因此,在本研究中,我们对含有GaUSP-1、GaUSP-2和GaZinc Finger基因的转基因植物在不同干旱胁迫条件下的形态、生理生化和分子参数进行了比较分析。数据显示,与非转基因植物相比,转基因植物表现出更强的耐受性。转基因和非转基因有助于我们更好地了解干旱反应机制及其对不同植物生长性状的影响,因此,通过这种方式,我们将能够探索耐旱机制,这将为鉴定干旱相关基因打开大门。
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引用次数: 0
Prototype of a salivary assay for quantification of two biomarkers for in vitro diagnosis of endometriosis 用于子宫内膜异位症体外诊断的两种生物标记物定量的唾液测定原型
IF 1.6 4区 医学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1615/critreveukaryotgeneexpr.2023051116
Pietro G Signorile, Sabrina Dominici, Rosa Viceconte, Alfonso Baldi
Endometriosis is a very frequent disease in the female gender and is characterized by the presence of endometrial structures outside the uterine cavity. The lack of a reliable non-invasive diagnostic test together with the fact that the symptoms of this pathology are often very non-specific, are responsible for the delay in the definitive diagnosis of this disease. Recently, through a proteomics approach, our research group has identified two potential diagnostic markers for endometriosis in serum (Zn-alpha2-glycoprotein and complement C3 precursor). In this article, we have defined the experimental conditions of a simple ELISA assay for rapid quantification of these two biomarkers in the saliva of patients with endometriosis. Finally, preliminary experiments on a small cohort of patients and controls have confirmed the potential diagnostic value of this assay.
子宫内膜异位症是一种女性常见病,其特点是子宫内膜结构出现在子宫腔以外。由于缺乏可靠的非侵入性诊断检测方法,加之这种病症的症状往往没有特异性,因此这种疾病迟迟得不到明确诊断。最近,通过蛋白质组学方法,我们的研究小组在血清中发现了两种潜在的子宫内膜异位症诊断标志物(Zn-α2-糖蛋白和补体 C3 前体)。在这篇文章中,我们定义了一种简单的 ELISA 检测方法的实验条件,以快速定量检测子宫内膜异位症患者唾液中的这两种生物标记物。最后,在一小批患者和对照组中进行的初步实验证实了这种检测方法的潜在诊断价值。
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引用次数: 0
Molecular Expression and Prognostic Implications of Krüppel-Like Factor 3 (KLF3) in Clear Cell Renal Cell Carcinoma. 透明细胞肾细胞癌中 Krüppel-Like Factor 3 (KLF3) 的分子表达及其预后意义
IF 1.6 4区 医学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1615/CritRevEukaryotGeneExpr.2023049010
Bin Wan, Wensheng Zhang, Xinxi Deng, Yigang Lu, Zhuo Zhang, Yang Yang

A major subtype of renal cancer is clear cell renal cell carcinoma (ccRCC). Krüppel-like factor 3 (KLF3) dysfunction is also revealed leading to poor prognosis in multiple cancer types. However, dysregulation and molecular dynamics of KLF3 underlying ccRCC progression still remains elusive. Here KLF3 gene and protein expressions in ccRCC were explored using data cohorts from The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), Clinical Proteomic Tumor Analysis Consortium (CPTAC) and verified them in our patient cohort. Correlations of KLF3 expression with clinicopathological features, epigenetic modification, and immune microenvironment characteristics were further investigated. KLF3 was significantly down-regulated expressed in ccRCC tissues compared to adjacent normal controls. Adverse pathological parameters and poor prognosis were associated with lower expression of KLF3. Mechanically, KLF3 regulation was mainly attributed to CpG island methylation. KLF3-high expression subgroup was significantly enriched in cell signaling pathways most associated with EMT markers, angiogenesis, inflammatory response, apoptosis, TGF-β, degradation of ECM, G2M checkpoint, and PI3K-AKT-mTOR. Based on GDSC database, KLF3 upregulation was identified to be associated with higher sensitivities towards PI3K-Akt-mTOR pathway inhibitors such as PI-103, PIK-93, and OSI-027. In addition, patients with down-regulated KLF3 expressions were found more sensitive towards Trametinib, Cetuximab, and Erlotinib. Collectively, our findings suggest that KLF3 may act as a suitable biomarker for prognosis prediction, tumor microenvironment (TME) phenotype identification, thereby helping ccRCC patients to make better therapeutic decisions.

肾癌的一个主要亚型是透明细胞肾细胞癌(ccRCC)。Krüppel样因子3(KLF3)功能障碍也被揭示会导致多种癌症类型的不良预后。然而,ccRCC进展背后的KLF3调控失调和分子动力学仍未确定。本文利用癌症基因组图谱(TCGA)、人类蛋白质图谱(HPA)和临床肿瘤蛋白质组学分析联盟(CPTAC)的数据队列探讨了ccRCC中KLF3基因和蛋白质的表达,并在我们的患者队列中进行了验证。我们还进一步研究了KLF3表达与临床病理特征、表观遗传修饰和免疫微环境特征的相关性。与邻近的正常对照组相比,KLF3在ccRCC组织中的表达明显下调。不良病理参数和不良预后与KLF3的低表达有关。从机制上看,KLF3的调控主要归因于CpG岛甲基化。KLF3高表达亚组明显富集于与EMT标志物、血管生成、炎症反应、细胞凋亡、TGF-β、ECM降解、G2M检查点和PI3K-AKT-mTOR最相关的细胞信号通路中。基于 GDSC 数据库,KLF3 上调被认为与对 PI3K-Akt-mTOR通路抑制剂(如 PI-103、PIK-93 和 OSI-027)更敏感有关。此外,KLF3表达下调的患者对曲美替尼、西妥昔单抗和厄洛替尼更敏感。总之,我们的研究结果表明,KLF3可作为一种合适的生物标记物用于预后预测、肿瘤微环境(TME)表型识别,从而帮助ccRCC患者做出更好的治疗决策。
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引用次数: 0
Transplantation of miR-193b-3p-Transfected BMSCs Improves Neurological Impairment after Traumatic Brain Injury through S1PR3-Mediated Regulation of the PI3K/AKT/mTOR Signaling Pathway 转染 miR-193b-3p 的 BMSCs 移植通过 S1PR3 介导的 PI3K/AKT/mTOR 信号通路调节改善创伤性脑损伤后的神经功能损伤
IF 1.6 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-01 DOI: 10.1615/critreveukaryotgeneexpr.2024053225
Yinghong He, Yuanmou Li, Yan Zhang, Lixia Chen, Juan Luo, Liqiao Bi, Limei Liu, Xuelian Wang, Meifen Lv
The aim of the present study was to explore the molecular mechanisms by which miR-193b-3p-trans-fected bone marrow mesenchymal stem cells (BMSCs) transplantation improves neurological impairment after traumatic brain injury (TBI) through sphingosine-1-phosphate receptor 3 (S1PR3)-mediated regulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway at the cellular and animal levels. BMSCs were transfected with miR-193b-3p. A TBI cell model was established by oxygen−glucose deprivation (OGD)-induced HT22 cells, and a TBI animal model was established by controlled cortical impact (CCI). Cell apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL), and cell activity was detected by a cell counting kit 8 (CCK-8) assay. Western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of related proteins and genes. In this study, transfection of miR-193b-3p into BMSCs significantly enhanced BMSCs proliferation and differentiation. Transfection of miR-193b-3p reduced the levels of the interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-alpha (TNF-α) inflammatory factors in cells and mouse models, and it inhibited neuronal apoptosis, which alleviated OGD-induced HT22 cell damage and neural function damage in TBI mice. Downstream experiments showed that miR-193b-3p targeting negatively regulated the expression of S1PR3, promoted the activation of the PI3K/AKT/mTOR signaling pathway, and inhibited the levels of apoptosis and inflammatory factors, which subsequently improved OGD-induced neuronal cell damage and nerve function damage in TBI mice. However, S1PR3 overexpression or inhibition of the PI3K/AKT/mTOR signaling pathway using the IN-2 inhibitor weakened the protective effect of miR-193b-3p-transfected BMSCs on HT22 cells. Transplantation of miR-193b-3p-transfected BMSCs inhibits neurological injury and improves the progression of TBI in mice through S1PR3-mediated regulation of the PI3K/AKT/mTOR pathway.
本研究旨在探讨经miR-193b-3p转染的骨髓间充质干细胞(BMSCs)移植改善创伤性脑损伤(TBI)后神经功能损伤的分子机制。1-磷酸鞘氨醇受体3(S1PR3)在细胞和动物水平上介导的磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶标(PI3K/AKT/mTOR)通路调节,改善创伤性脑损伤(TBI)后的神经损伤。用 miR-193b-3p 转染 BMSCs。通过氧-葡萄糖剥夺(OGD)诱导的 HT22 细胞建立了创伤性脑损伤细胞模型,通过可控皮质冲击(CCI)建立了创伤性脑损伤动物模型。细胞凋亡通过末端脱氧核苷酸转移酶(TdT)介导的 dUTP缺口末端标记(TUNEL)检测,细胞活性通过细胞计数试剂盒 8(CCK-8)检测。Western 印迹分析和定量实时聚合酶链反应(qRT-PCR)用于检测相关蛋白和基因的表达。在这项研究中,转染 miR-193b-3p 到 BMSCs 能显著增强 BMSCs 的增殖和分化。转染 miR-193b-3p 能降低细胞和小鼠模型中白细胞介素-6(IL-6)、IL-1β 和肿瘤坏死因子-α(TNF-α)等炎症因子的水平,抑制神经细胞凋亡,从而减轻 OGD 诱导的 HT22 细胞损伤和 TBI 小鼠的神经功能损伤。下游实验表明,miR-193b-3p靶向负调控S1PR3的表达,促进PI3K/AKT/mTOR信号通路的激活,抑制细胞凋亡和炎症因子的水平,从而改善OGD诱导的TBI小鼠神经细胞损伤和神经功能损伤。然而,S1PR3过表达或使用IN-2抑制剂抑制PI3K/AKT/mTOR信号通路会削弱miR-193b-3p转染BMSCs对HT22细胞的保护作用。通过 S1PR3 介导的 PI3K/AKT/mTOR 通路调节,移植 miR-193b-3p 转染的 BMSCs 可抑制神经损伤并改善小鼠创伤性脑损伤的进展。
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引用次数: 0
miRNA-27b-3p/TPX2 Axis Regulates Clear Cell Renal Cell Carcinoma Cell Proliferation, Invasion and Migration. miRNA-27b-3p/TPX2轴调节透明细胞肾细胞癌细胞的增殖、侵袭和迁移。
IF 1.6 4区 医学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1615/CritRevEukaryotGeneExpr.2023048827
Nana Liu, Yicheng Jiang, Shiyuan Chen, Fang Pan, Yao Tang, Xingping Tan

There is a wide variety of cancer cells that can be linked to the presence of TPX2. However, there is not a lot of evidence regarding its role in the development and maintenance of clear cell renal cell carcinoma (ccRCC). In our study, bioinformatics analysis was performed to obtain differentially expressed mRNAs and miR-NAs in ccRCC. Survival curves predicted correlation of TPX2 expression with patient survival. The upstream regulatory miRNA of TPX2 was predicted to be miRNA-27b-3p through database, and dual luciferase assay verified the targeted relationship. qRT-PCR and Western blot were employed for examination of TPX2 mRNA and protein expression in ccRCC cells. Proliferation, invasion, migration and cell cycle were detected by CCK-8, colony formation, wound healing, Transwell, and flow cytometry assays. The results showed that TPX2 showed very high expression in ccRCC, and patients with higher TPX2 expression had shorter relative survival. Low miRNA-27b-3p expression was found in ccRCC. Knockdown of TPX2 or forced expression of miRNA-27b-3p in ccRCC cells inhibited cell proliferation, migration, invasion, and arrested cell division in G0/G1 phase. Dual luciferase reporter presented that miRNA-27b-3p targeted TPX2 to inhibit its expression. Rescue experiments demonstrated that the miRNA-27b-3p/ TPX2 axis affected the biological functions of ccRCC cells. Concurrent overexpression of miRNA-27b-3p and TPX2 inhibited the facilitating effect of TPX2 on ccRCC cell growth. The results revealed novel regulatory mechanisms involved in ccRCC progression, hoping that it may spark an insight for later discovery about the new therapeutic targets for ccRCC.

有多种癌症细胞可能与TPX2的存在有关。然而,关于其在透明细胞肾细胞癌(ccRCC)的发展和维持中的作用,还没有很多证据。在我们的研究中,进行了生物信息学分析,以获得ccRCC中差异表达的mRNA和miR NA。生存曲线预测了TPX2表达与患者生存率的相关性。通过数据库预测TPX2的上游调控miRNA为miRNA-27b-3p,双荧光素酶测定验证了靶向关系。采用qRT-PCR和Western blot方法检测TPX2 mRNA和蛋白在ccRCC细胞中的表达。通过CCK-8、集落形成、伤口愈合、Transwell和流式细胞术检测增殖、侵袭、迁移和细胞周期。结果显示,TPX2在ccRCC中表现出非常高的表达,并且TPX2表达较高的患者的相对生存期较短。在ccRCC中发现miRNA-27b-3p的低表达。在ccRCC细胞中敲除TPX2或强制表达miRNA-27b-3p可抑制细胞增殖、迁移、侵袭,并在G0/G1期阻止细胞分裂。双荧光素酶报告基因提示miRNA-27b-3p靶向TPX2以抑制其表达。拯救实验表明,miRNA-27b-3p/TPX2轴影响ccRCC细胞的生物学功能。miRNA-27b-3p和TPX2的同时过表达抑制了TPX2对ccRCC细胞生长的促进作用。研究结果揭示了参与ccRCC进展的新的调控机制,希望它能为以后发现ccRCC的新治疗靶点提供线索。
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引用次数: 0
Oncolytic Virotherapy: An Advanced Microbial Approach for the Management of Cancer. 肿瘤病毒治疗:癌症管理的先进微生物方法。
IF 1.6 4区 医学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1615/CritRevEukaryotGeneExpr.2023048962
Muhammad Farhan Siddiq Rao, Bilal Ahmed, Muhammad Imran Qadir

Destruction of the tumor (cancerous) cells may be caused by live viruses, which have replicative ability and replicate selectively in tumor cells, known as oncolytic virotherapy. In comparison of conservative cancer therapy, tumor-selective replicating viruses have more advantages. These viruses have introduced new methodologies for the human cancer treatment. Numerous strategies are used in development of virotherapeutics. Virotherapy is not unusual concept, but modern advances in technology of genetic modification of oncolytic viruses have improved the ability of targeting tumor cells more specifically, it triggered the development of novel ammunition to fight cancer. An effective virotherapeutic approach with oncolytic viruses exhibits the feasibility and safety under clinical approach. New strategies are being explored to overcome basic obstacles and challenges in virotherapy. Administration of oncolytic viruses, logically, will successfully augment new treatments against many kinds of tumors. Some encouraging antitumor responses shown by combination therapy are provoking strong immunity against established cancer. Chief developments in oncolytic virotherapy have seen in past several years. Significant understandings have been provided by findings on the interface among immune comebacks and viruses, whereas potential results have shown in clinical trials.

肿瘤(癌性)细胞的破坏可能是由活病毒引起的,活病毒具有复制能力并在肿瘤细胞中选择性复制,称为溶瘤病毒疗法。与保守的癌症治疗相比,肿瘤选择性复制病毒具有更大的优势。这些病毒为人类癌症的治疗引入了新的方法。在病毒治疗学的发展中使用了许多策略。病毒疗法并不是一个不寻常的概念,但溶瘤病毒基因修饰技术的现代进步提高了靶向肿瘤细胞的能力,更具体地说,它引发了对抗癌症的新型弹药的开发。一种有效的溶瘤病毒治疗方法在临床上显示出可行性和安全性。正在探索新的策略来克服病毒治疗中的基本障碍和挑战。从逻辑上讲,溶瘤病毒的使用将成功地增强针对多种肿瘤的新治疗方法。联合治疗显示的一些令人鼓舞的抗肿瘤反应正在激发对已确定的癌症的强大免疫力。溶瘤病毒治疗的主要进展已经在过去几年中出现。关于免疫反击和病毒之间的界面的发现已经提供了重要的理解,而临床试验已经显示了潜在的结果。
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引用次数: 0
Arboviruses: Transmission and Host Resistance. 虫媒病毒:传播和宿主抵抗力。
IF 1.6 4区 医学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-01 DOI: 10.1615/CritRevEukaryotGeneExpr.2023049820
Sidra Anwar, Bilal Ahmed, Muhammad Imran Qadir

In this review, there is a complete description of the classes of arboviruses, their evolutionary process, virus characterization, disease transmission methods; it also describes about the vectors involved in transmission and their mood of transmission, both biologically as well as non-biologically and, about host, the resistance mechanism in host, and artificial methods of preventing those viral transmissions. Arboviruses transmitted to hosts by some vectors such as mosquitoes, ticks, etc. The virus replicates in the host can be prevented by some host resistance mechanisms like RNA interference (RNAi), which degrade virus RNA by its antiviral activity, insect repellents, IGRs, and PI technology.

这篇综述全面介绍了虫媒病毒的种类、进化过程、病毒特征、疾病传播方式;还介绍了参与传播的载体及其生物和非生物传播情绪,以及宿主、宿主的抵抗机制和防止病毒传播的人工方法。虫媒病毒通过蚊子、蜱等载体传播给宿主。病毒在宿主体内的复制可以通过一些宿主抵抗机制来阻止,如 RNA 干扰(RNAi)(通过其抗病毒活性降解病毒 RNA)、驱虫剂、IGRs 和 PI 技术。
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引用次数: 0
KRT6A inhibits IL-1β-mediated pyroptosis of keratinocytes via blocking IL-17 signaling KRT6A通过阻断IL-17信号传导抑制il -1β介导的角化细胞焦亡
IF 1.6 4区 医学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-01 DOI: 10.1615/critreveukaryotgeneexpr.2023050039
Yuan Li, Qi Wu
Keratin 6A (KRT6A) is involved in the pathogenesis of various skin diseases. However, the reports on the roles of KRT6A in atopic dermatitis (AD) are limited. This study aimed to investigate the potentials of KRT6A in AD. mRNA levels were detected by RT-PCR. Cytokine release was determined by ELISA. Protein expression was determined using western blot. Cell viability was determined by CCK-8. Cytotoxicity was detected by LDH assay. Cell death was determined by TUNEL. The pyroptosis of keratinocytes was detected using flow cytometry. We found that KRT6A was overexpressed in AD patients. Moreover, KRT6A was stimulated after exposed to proinflammatory cytokines. Overexpressed KRT6A suppressed inflammatory response, while KRT6A knockdown exerted the opposite effects. Overexpressed KRT6A suppressed inflammation-induced pyroptosis of keratinocytes. Additionally, KRT6A negatively regulated IL-17A expression, blocking IL-17 signaling. IL-17a overexpression antagonized the effects of KRT6A and promoted pyroptosis of keratinocytes. In conclusion, KRT6A exerted protective functions in AD via regulating IL-17 signaling. This KRT6A/IL-17 may be a novel target for AD.
角蛋白6A (KRT6A)参与多种皮肤病的发病机制。然而,关于KRT6A在特应性皮炎(AD)中的作用的报道有限。本研究旨在探讨KRT6A在AD中的潜在作用。RT-PCR检测mRNA水平。ELISA法检测细胞因子释放量。western blot检测蛋白表达。CCK-8检测细胞活力。LDH法检测细胞毒性。TUNEL法测定细胞死亡情况。流式细胞术检测角质形成细胞的焦亡。我们发现KRT6A在AD患者中过表达。此外,KRT6A在暴露于促炎细胞因子后受到刺激。KRT6A过表达抑制炎症反应,而KRT6A敲低则发挥相反的作用。过表达KRT6A抑制炎症诱导的角化细胞焦亡。此外,KRT6A负调控IL-17A表达,阻断IL-17信号传导。IL-17a过表达可拮抗KRT6A的作用,促进角质形成细胞的焦亡。综上所述,KRT6A通过调节IL-17信号通路在AD中发挥保护作用。这个KRT6A/IL-17可能是AD的新靶点。
{"title":"KRT6A inhibits IL-1β-mediated pyroptosis of keratinocytes via blocking IL-17 signaling","authors":"Yuan Li, Qi Wu","doi":"10.1615/critreveukaryotgeneexpr.2023050039","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2023050039","url":null,"abstract":"Keratin 6A (KRT6A) is involved in the pathogenesis of various skin diseases. However, the reports on the roles of KRT6A in atopic dermatitis (AD) are limited. This study aimed to investigate the potentials of KRT6A in AD. mRNA levels were detected by RT-PCR. Cytokine release was determined by ELISA. Protein expression was determined using western blot. Cell viability was determined by CCK-8. Cytotoxicity was detected by LDH assay. Cell death was determined by TUNEL. The pyroptosis of keratinocytes was detected using flow cytometry. We found that KRT6A was overexpressed in AD patients. Moreover, KRT6A was stimulated after exposed to proinflammatory cytokines. Overexpressed KRT6A suppressed inflammatory response, while KRT6A knockdown exerted the opposite effects. Overexpressed KRT6A suppressed inflammation-induced pyroptosis of keratinocytes. Additionally, KRT6A negatively regulated IL-17A expression, blocking IL-17 signaling. IL-17a overexpression antagonized the effects of KRT6A and promoted pyroptosis of keratinocytes. In conclusion, KRT6A exerted protective functions in AD via regulating IL-17 signaling. This KRT6A/IL-17 may be a novel target for AD.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138505484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pathogens in Crohn’s Disease: the role of Adherent Invasive Escherichia Coli 克罗恩病的病原体:粘附性侵袭性大肠杆菌的作用
IF 1.6 4区 医学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-12-01 DOI: 10.1615/critreveukaryotgeneexpr.2023050088
Gaetano Iaquinto, Vera Rotondi Aufiero, Giuseppe Mazzarella, Angela Lucariello, Luigi Panico, Raffaele Melina, Salvatore Iaquinto, Antonio De Luca, Carmine Sellitto
In Crohn’s disease (CD) gut dysbiosis is marked by the prevalence of pathogenic bacterial species. Although several microbes have been reported as risk factors or causative agents of CD, it is not yet clear which is the real trigger of the disease. Thirty years ago, a new pathovar of Escherichia Coli (E. coli) strain was isolated in the ileal mucosa of CD patients. This strain, called Adherent Invasive E. coli (AIEC), for its ability to invade the intestinal mucosa, could represent the causative agent of the disease. Several authors studied the mechanisms by which the AIEC penetrate and replicate within mac-rophages, and release inflammatory cytokines sustaining inflammation. In this review we will discuss about the role of AIEC in the pathogenesis of CD, the virulence factors mediating adhesion and invasion of AIEC in mucosal tissue, the environmental conditions improving AIEC survival and replication within macrophages. Finally, we will also give an overview of the new strategies developed to limit AIEC overgrowth.
在克罗恩病(CD)肠道失调的特点是流行的致病菌种类。虽然有几种微生物被报道为乳糜泻的危险因素或病原体,但尚不清楚哪一种是乳糜泻的真正诱因。30年前,在乳糜泻患者的回肠黏膜中分离到了一种新的病原菌大肠杆菌。这种菌株被称为附着性侵袭性大肠杆菌(AIEC),因为它能够侵入肠道粘膜,可能是这种疾病的病原体。几位作者研究了AIEC在巨噬细胞内渗透和复制,并释放炎症细胞因子维持炎症的机制。本文就AIEC在CD发病中的作用、介导AIEC在粘膜组织粘附和侵袭的毒力因子、促进AIEC在巨噬细胞内存活和复制的环境条件等方面进行综述。最后,我们还将概述为限制AIEC过度生长而制定的新策略。
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Critical Reviews in Eukaryotic Gene Expression
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