Tissue-specific and reversible RNA interference in transgenic mice

肝纤维化的英文名词解释Liver Fibrosis: An In-depth ExplorationIntroduction:Liver fibrosis, also known as hepatic fibrosis, refers to the excessive accumulation of extracellular matrix proteins—particularly collagen—in the liver, resulting in the progressive scarring and stiffening of the organ. It develops as a response to chronic liver injury and can eventually lead to cirrhosis if left untreated. In this article, we aim to provide a comprehensive understanding of liver fibrosis, its causes, progression, and potential treatments.Causes of Liver Fibrosis:Liver fibrosis can be caused by various factors, including chronic viral hepatitis B and C, excessive alcohol consumption, non-alcoholic fatty liver disease (NAFLD), autoimmunity disorders, and drug-induced liver injury. These conditions trigger an immune response, leading to inflammation and the activation of hepatic stellate cells—the primary cells involved in fibrogenesis.Progression of Liver Fibrosis:Liver fibrosis typically progresses through several stages, characterized by the accumulation of connective tissue and architectural changes in the liver. These stages are usually assessed using a scoring system known as the METAVIR or Ishak scoring system, which grades fibrosis from F0 (no fibrosis) to F4 (cirrhosis).Stage 1 (F1): Portal Fibrosis with Few SeptaAt this early stage, there is minimal scarring and fibrosis, mainly around the portal tracts in the liver. The condition is usually reversible at this point with appropriate treatment and lifestyle changes.Stage 2 (F2): Portal Fibrosis with Occasional SeptaProgressing from the first stage, the liver shows increased fibrosis, with occasional bridging septa formation between the portal tracts. Early intervention is crucial at this stage to prevent further advancement.Stage 3 (F3): Numerous Septa without CirrhosisThe liver now exhibits multiple bridging septa, potentially leading to the distortion of the liver architecture. Timely medical intervention is vital to slow down or halt the progression of liver fibrosis.Stage 4 (F4): CirrhosisIn the final stage of liver fibrosis, extensive scarring and the formation of regenerative nodules disrupt the normal liver structure and function. Cirrhosis can lead to severe complications, and liver transplantation may be the only viable treatment option.Potential Treatments for Liver Fibrosis:1. Lifestyle Changes: Adopting a healthy lifestyle is crucial in managing liver fibrosis. This includes maintaining a balanced diet, exercising regularly, avoiding excessive alcohol consumption, and reducing exposure to toxins.2. Antiviral Therapy: In cases where viral hepatitis is the underlying cause, antiviral medications can help suppress the replication of the virus, reduce inflammation, and slow down fibrosis progression.3. Pharmacological Interventions: Various pharmaceutical agents are being researched for their potential anti-fibrotic effects. These include drugs that target specific signaling pathways involved in fibrogenesis, such as transforming growth factor-beta (TGF-β) inhibitors and angiotensin receptor blockers (ARBs).4. Liver Transplantation: In severe cases of cirrhosis, where liver function is severely compromised, a liver transplant may be the only viable option. However, the availability of suitable donor organs limits the widespread use of this treatment.Conclusion:Liver fibrosis is a complex and progressive condition that can have significant implications for an individual's health. Timely diagnosis, understanding the underlying causes, and implementing appropriate treatments are crucial in managing and potentially halting the progression of this disease. Ongoing research and advancements in medical interventions hold promise for more effective treatments for liver fibrosis in the future.。

星形胶质细胞rna提取 ## English Response: ##。

Materials.Brain tissue.Sterile dissecting instruments.RNAlater (Sigma-Aldrich)。

QIAzol Lysis Reagent (Qiagen)。

Chloroform.Isopropanol (cold)。

75% Ethanol (cold)。

RNase-Free Water.Microcentrifuge and tubes.Procedure.1. Harvest the brain tissue. Euthanize the animal and remove the brain. Carefully dissect the brain tissue of interest (e.g., hippocampus, cortex).2. Immerse the tissue in RNAlater. Transfer the dissected tissue to a tube containing RNAlater. Incubate overnight at 4°C.3. Lyse the tissue. Centrifuge the RNAlater-treated tissue at 12,000 x g for 10 minutes at 4°C. Remove the supernatant and resuspend the pellet in QIAzol Lysis Reagent. Homogenize the tissue using a tissue homogenizer or sonication.4. Extract the RNA. Add chloroform to the homogenized tissue and mix vigorously. Centrifuge at 12,000 x g for 15 minutes at 4°C. Transfer the upper aqueous phase to a newtube.5. Precipitate the RNA. Add isopropanol to the aqueous phase and mix. Centrifuge at 12,000 x g for 10 minutes at 4°C. Wash the RNA pellet with cold 75% ethanol.6. Resuspend the RNA. Centrifuge the RNA pellet at12,000 x g for 5 minutes at 4°C. Remove the ethanol andair-dry the pellet. Resuspend the RNA in RNase-Free Water.Quantification and Quality Assessment.Quantify the RNA concentration using a spectrophotometer (e.g., Nanodrop).Assess the RNA quality using an Agilent Bioanalyzer or similar platform.## 中文回答，##。

Epigenetic Regulation of Development Epigenetic regulation of development is a complex process that involves the modification of gene expression without altering the DNA sequence. It plays a crucial role in various stages of development, including embryonic development, cell differentiation, and tissue-specific gene expression. Epigenetic modifications are heritable and reversible, making them an essential mechanism for regulating gene expression during development. In this essay, we will discuss the role of epigenetic regulation in development from different perspectives.From a biological perspective, epigenetic regulation is a fundamental mechanism that ensures the proper development of an organism. During embryonic development, cells undergo a series of epigenetic modifications that determine their fate and function. For example, DNA methylation, histone modification, and non-coding RNA regulation are essential epigenetic mechanisms that regulate gene expression during development. These modifications ensure that genes are expressed at the right time and in the right place, which is critical for proper development.From a medical perspective, epigenetic regulation plays a significant role in the development of various diseases. Epigenetic changes can alter gene expression and contribute to the development of cancer, neurological disorders, and other diseases. For example, aberrant DNA methylation patterns have been linked to the development of cancer. Understanding the epigenetic mechanisms that contribute to disease development can help in the development of new treatments and therapies.From an ethical perspective, epigenetic regulation raises ethical concerns about the manipulation of gene expression. Advances in epigenetic research have made it possible to manipulate gene expression and alter the development of an organism. This raises concerns about the potential misuse of this technology, such as the creation of designer babies. It is essential to consider the ethical implications of epigenetic research and ensure that it is used for the benefit of society.From a social perspective, epigenetic regulation has the potential to impact society in various ways. For example, epigenetic research can provide insights into the effects of environmental factors on gene expression and development. This can help in the development of public health policies and interventions that promote healthy development. Additionally, epigenetic research can help in the development of personalized medicine, which can lead to better health outcomes for individuals.From a personal perspective, epigenetic regulation is a fascinating area of research that has the potential to impact individuals' lives. Understanding the epigenetic mechanisms that regulate gene expression can provide insights into the development of diseases and potential treatments. Additionally, epigenetic research can help individuals make lifestyle choices that promote healthy development. For example, research has shown that environmental factors, such as diet and stress, can impact epigenetic modifications and alter gene expression. By understanding these mechanisms, individuals can make informed decisions about their health.In conclusion, epigenetic regulation plays a crucial role in development from various perspectives, including biological, medical, ethical, social, and personal. Understanding the epigenetic mechanisms that regulate gene expression can provide insights into the development of diseases and potential treatments. Additionally, epigenetic research can help in the development of public health policies and interventions that promote healthy development. However, it is essential to consider the ethical implications of epigenetic research and ensure that it is used for the benefit of society. Overall, epigenetic regulation is a fascinating area of research that has the potential to impact individuals' lives significantly.。

520203962021403[摘要]急性大血管闭塞性缺血性卒中（AIS-LVO ）的早期血管内治疗，在过去几年取得了较大的发展。

静脉溶栓和机械取栓成为急性缺血性卒中治疗的标准方案。

对于颅内动脉粥样硬化性狭窄（ICAS ）导致的AIS-LVO ，多见于亚洲人群，目前尚无大型随机对照研究证实血管内治疗方案的有效性。

由于其发病机制不同，单纯机械取栓效果不如心源性栓塞（CE ），除支架取栓外往往需要局部动脉内抗血小板药物应用以及球囊扩张、支架置入等更为复杂的操作。

另一方面，由于其慢性狭窄导致的缺血耐受，这类患者的术前评估和术后处理也不同于CE ，组织窗评估可能更为重要。

因此本文拟将ICAS 导致的AIS-LVO 血管内治疗进展作一总结。

[关键词]急性缺血性卒中颅内动脉粥样硬化性狭窄血管内治疗Advances in endovascular treatment of acute ischemic stroke with large vessel occlusion caused by intracranial atherosclerotic stenosisLI Yulin,PAN Haizhou,GAO Yuhai,CHEN Yan,WAN Shu.Department of Neurology,Pinghu Branchof Zhejiang Hospital Affiliated to Zhejiang University School of Medicine,Jiaxing 314200,China Corresponding author:WAN Shu,[Abstract]The endovascular treatment of acute ischemic stroke with large vessel occlusion(AIS-LVO)has madeepoch-making progress in the past few years.Intravenous thrombolysis and mechanical thrombectomy have become the standard treatment for acute ischemic stroke(AIS).AIS-LVO caused by intracranial atherosclerotic stenosis (ICAS)is common in Asia,and there is no large RCT study to confirm the effectiveness of mechanical thrombectomy.Because of the different pathogenesis,mechanical thrombectomy which was designed primarily for embolic occlusion,may not be an effective treatment for acute ischemic stroke caused by ICAS.Besides stent retriever thrombectomy,more complex techniques and operations such as local intra-arterial antiplatelet drugs,angioplasty,and rescue stenting are often needed in ICAS patients.On the other hand,due to the ischemic tolerance caused by chronic stenosis,the preoperative evaluation and postoperative management of these patients are different from those of CE,and the reversible ischemic tissue evaluation may be more important.Therefore,this article will summarize the progress of endovascular treatment related to AIS-LVO caused by ICAS.[Key words]Acute ischemic stroke Intracranial atherosclerotic stenosisEndovascular treatment颅内动脉粥样硬化性狭窄导致的急性大血管闭塞性缺血性卒中血管内治疗进展李玉林潘海洲高宇海陈岩万曙DOI ：10.12124/j.issn.2095-3933.2021.3.2021-4389作者单位：314200嘉兴，浙江大学医学院附属浙江医院平湖分院神经内科（李玉林），神经外科（潘海洲）；浙江大学医学院附属浙江医院脑科中心（高宇海、陈岩、万曙）通信作者：万曙，E-mail ：万曙，教授，主任医师，硕士研究生导师。

天然mRNA竟作为⾼效“miRNA海绵”发挥⾮编码功能,调控肿瘤⽣长Nature⼦刊天然mRNA竟作为⾼效“miRNA海绵”发挥⾮编码功能，调控肿瘤⽣长Nature⼦刊订阅号APExBIO近⽇，来⾃法国国家科学研究中⼼（CNRS）的研究团队发现， TYRP1 mRNA，除了编码TYRP1，还可以有效地扣留（sequestering）miR-16。

miR-16被扣留后不能够抑制其mRNA靶标，例如RAB17 mRNA。

由于RAB17促进⿊素瘤细胞的增殖和肿瘤⽣长，因此miR-16⽆法再发挥肿瘤抑制活性。

通过沉默TYRP1或增加miR-16的表达，可以在体外恢复miR-16的肿瘤抑制功能。

重要的是，利⽤⼩寡核苷酸掩蔽TYRP1 mRNA上的miR-16结合位点也可以阻碍TYRP1对miR-16的扣留。

miRNA 异位成为⿊⾊素瘤新的靶向治疗⽅向。

该结果发表于《Nature Cell Biology》。

MicroRNA（miRNA）是⼀类⼩的（?22个核苷酸）的⾮编码RNA，在许多⽣物过程和疾病中起关键作⽤，包括瘤形成。

miRNA指导沉默Argonaute蛋⽩复合体到信使RNA靶标以引发转录后抑制。

当编码蛋⽩质的基因在细胞内处于活性状态时，其信息会从DNA形式转录为信使RNA(mRNA)。

如果⼀切顺利，这些编码的mRNA信号会通向细胞的蛋⽩质制造⼯⼚，在那⾥⽤它作为模板合成新的蛋⽩质。

miRNA通常靶向⼀个或者多个mRNA，通过抑制翻译或降解靶标mRNA来调节基因的表达。

图1▲来源于⽹络miRNA种⼦序列（核苷酸2⾄7）与mRNA的miRNA反应元件（MREs，miRNA response elements）之间的完美碱基配对可抑制mRNA翻译并介导mRNA衰减。

不完美的种⼦配对也是有效的。

除了导致转录后抑制的这些miRNA-mRNA相互作⽤之外，很多研究已经鉴定了⼤量⾮典型结合位点，这⾥称为⾮典型MREs。

泛素特异性蛋白酶7（USP7）在非小细胞肺癌中的研究进展发布时间：2021-11-17T03:43:04.112Z 来源：《健康世界》2021年19期作者：李芝瑜1，何敏诗2，鲁蓝艺2，吴金晓2，郑锦花2[导读] 泛素特异性蛋白酶7 (ubiquitin-specific protease，USP7) 是一种去泛素化酶，可调节众多蛋白的活性，包括肿瘤抑制因子，DNA修复蛋白，免疫应答，病毒蛋白和表观遗传调节剂李芝瑜1，何敏诗2，鲁蓝艺2，吴金晓2，郑锦花2桂林医学院，桂林市 541199；2.桂林医学院附属医院，桂林市 541001摘要：泛素特异性蛋白酶7 (ubiquitin-specific protease，USP7) 是一种去泛素化酶，可调节众多蛋白的活性，包括肿瘤抑制因子，DNA 修复蛋白，免疫应答，病毒蛋白和表观遗传调节剂。

USP7通过去泛素化作用，调控蛋白质的表达，参与肿瘤的多种信号通路的调节，促进肿瘤的发生和发展，是当前癌症治疗研究中人们广泛关注的几种去泛素化酶之一。

本篇综述，总结了对 USP7 研究的进展，重点关注其在非小细胞肺癌中的作用。

关键词：USP7；非小细胞肺癌Research progress of ubiquitin-specific protease 7 (USP7) in non-small cell lung cancerZhiYu Li1，MinShi He2，LanYi Lu2，JinXiao Wu2，JinHua Zheng2（1.Guangxi Key Laboratory of Tumor Immunity and Microenvironment Regulation, Guilin Medical College, 541000, China; 2. Affiliated Hospital of Guilin Medical College, 541000, China）Abstract: Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that can regulate the activity of many proteins, including tumor suppressor factors, DNA repair proteins, immune responses, viral proteins, and epigenetics Modifier. USP7 regulates protein expression through deubiquitination, participates in the regulation of multiple signal pathways in tumors, and promotes the occurrence and development of tumors. It is one of several deubiquitinating enzymes that have been widely concerned in current cancer treatment research. This review summarizes the research progress of USP7, focusing on its role in non-small cell lung cancer.Keywords: USP7; non-small cell lung cancer现如今肺癌已经成为全球发病率和死亡率最高的恶性肿瘤之一，5年生存率＜16%[1]，已成为影响生存率的第一大致死原因，尽管广大医务工作者为应对这种恶性疾病付出了数十年的努力，但肺癌的预后仍然不乐观，尤其是晚期非小细胞肺癌 (NSCLC)。

内皮素受体拮抗剂对肝硬化大鼠转化生长因子β1和Ⅰ型胶原mRNA表达的影响陈汇;许冰【摘要】Aim; To investigate the effects of ET receptor antagonist on the expression of collagen type I and TGFpl mRNA in carbon tetrachloride-induced cirrhosis rats. Methods: A total of 40 male SD rats were allocated into carbon tetra-chloride group, normal group,endothelin A receptor antagonist group, endothelin B receptor antagonist group,and combined treatment group. The posterior 3 groups were injected with BQ-123( 12.5 μg/kg) ,BQ-788(15 μg/kg) ,and BQ-123 + BQ-788 .respectively,besides carbon tetrachloride treatment. The expressions of collagen type I and TGF(31 mRNA were determined by RT-PCR. And a specific portion of liver tissue in every group was took for routine pathology testing. Results:The expression of TGF|31 mRNA in 5 groups had no significant difference( F = 1. 857 ,P = 0. 765 ) , but that of collagen type I mRNA in 5 groups[ (0.437 ±0.082) ,(0.623 ±0.142) , (0.655 ±0. 124) , (0.558 ±0.183), and (0.874 ±0. 170)] had significant differences ( F = 11. 235 ,P =0. 023) . Microscopic image showed that inflammatory reaction decreased in the cirrhotic rats with injection of both ET receptor antagonists or combination administration. Conclusion: Endothelin receptor antagonists could inhibit the expression of hepatic collagen typelin cirrhotic rats effectively, and reduce inflammation reaction and liver fibrosis.%目的:探讨内皮素受体拮抗剂对肝硬化大鼠转化生长因子β1和I型胶原mRNA表达的影响.方法:40只雄性SD大鼠,随机分成四氯化碳组、正常对照组、内皮素A受体拮抗剂治疗组、内皮素B 受体拮抗剂治疗组和联合治疗组5组,每组8只.后3组在四氯化碳灌胃的基础上2次/d(间隔10 h)分别皮下注射BQ-123(12.5μg/kg)和BQ-788(15μg/kg)以及BQ-123+ BQ-788(12.5 μg/kg+ 15 μg/kg).取部分肝组织进行常规病理学检测,部分采用RT-PCR测定大鼠肝组织转化生长因子β1和I型胶原mRNA表达水平.结果:常规病理结果显示内皮素受体拮抗剂处理组肝脏炎症反应及纤维化明显减轻.5组大鼠肝组织转化生长因子β1 mRNA表达水平比较,差异无统计学意义(F=2.857,P=0.765);Ⅰ型胶原mRNA表达水平比较[(0.437±0.082)、(0.623±0.142)、(0.655±0.124)、(0.558±0.183)和(0.874±0.170)],差异有统计学意义(F=11.235,P=0.023).结论:内皮素受体拮抗剂能有效抑制肝硬化大鼠I型胶原mRNA的表达,缓解肝脏炎症反应和肝纤维化.【期刊名称】《郑州大学学报（医学版）》【年(卷),期】2011(046)005【总页数】3页(P745-747)【关键词】内皮素受体拮抗荆;肝硬化;I型胶原;转化生长因子β1;大鼠【作者】陈汇;许冰【作者单位】郑州大学第一附属医院肝胆胰外科郑州450052;郑州大学第一附属医院肝胆胰外科郑州450052【正文语种】中文【中图分类】R657.3内皮素是一种多肽，在体内广泛存在，具有强烈的缩血管作用。