就是看到要给小鼠上机所以截一下（以表吐槽）
还要气管造口和插管
应该说幸好我课题是鼻子而不是肺（？？？）
几个小时过去了我还在看这一页
基因敲除小鼠构建及其相关简写方式
一、 Cre-Lox基本原理
Cre（Cre recombinase 重组酶）：最初在P1噬菌体中被发现，特异性识别 loxP 位点，可以对两个 loxP 位点进行催化重组。
LoxP 位点：34个碱基对构成的回文序列，中间间隔的8个碱基对决定了 LoxP 位点的方向（如图1）。两个 LoxP 位点的位置和方向决定了 Cre 重组的方式，包括敲除、反转和易位。
二、Cre-loxP的应用
携带 loxP 的小鼠被称为 Floxed 小鼠，当它与 Cre 小鼠交配后，Cre-Lox 系统开始工作，可以对两个 loxP 位点以内的基因进行重组，进而实现基因敲除、表达等目的。
1. 组织特异性敲除（conditional knockout, cKO）
当组织特异性 Cre 小鼠（具有组织靶向性的 Cre 小鼠品系很多）与 Floxed 小鼠配繁后，两个 loxP 位点位于同一条染色体上，且方向相同。Cre 重组酶可以介导特定组织中两个同向 loxP 位点发生同源重组。致使“Gene X”处序列被删除，如果该序列的删除使得该基因发生移码突变，则达到基因敲除的效果（如图2）。
2. 组织特异性过表达（conditional knockin, cKI）
Floxed 小鼠转入某个基因的编码序列，并在这段编码序列前面插入“LoxP-STOP-LoxP, LSL”元件。因此，该Floxed小鼠并不表达插入的基因；当存在Cre重组酶时，STOP元件被删除，插入基因才会表达。该体系可用于构建基因条件性敲入小鼠模型（如图3）。
三、基因工程小鼠的一般简写方式
1.基因敲除
可以分别用加、减号上标来表示 wildtype allele 与 mutant allele：
KO 纯合子 Gene-/-
KO 杂合子 Gene+/-
野生型对照 Gene+/+ 或 WT (wildtype)
2.基因敲入
将敲入的元件写在上标里，例如：
Shh 基因 E177A 点突变杂合子：Shh E177A/+
如果 Shh 基因敲入报告基因或Cre重组酶基因，可以写成 Shh EGFP/+，或者也可以直接写成 Shh-EGFP、Shh-Cre。
3.转基因
一般直接写出表达的基因结构，例如：
Villin promoter 驱动 EGFP 报告基因的转基因小鼠就可以表示为 Vil-EGFP。
4.条件性基因敲除
将 flox 作为上标表示，比如：
CKO 纯合子 Gene flox/flox 或 Gene f/f
CKO 杂合子 Gene flox/+ 或 Gene f/+
如果与广泛表达 Cre 或生殖系表达 Cre 工具鼠交配后获得了全身敲除的小鼠，那么可以按 KO 小鼠的规则来简写。
如果与组织特异性 Cre 小鼠交配，那么可以组合写成：Gene flox/flox；Cre。
如果文章中只用到一种组织特异性 Cre 工具鼠，也可以按 KO 的方式简写，即 Gene -/- 可以表示 flox 纯合子且 Cre 阳性小鼠。
如果有多种不同的 Cre，那么就需要分别表示了。
例如：Tlr5 flox 小鼠分别与小肠上皮细胞（IEC）特异性 Cre（Vil-Cre）、 DC 细胞特异性 Cre（CD11c-Cre）交配的子代中发生基因敲除的纯合子小鼠可以分别表示为 Tlr5 flox/flox；Vil-Cre 和 Tlr5 flox/flox；CD11c-Cre。如果觉得这样写太麻烦，也可以这样表示：Tlr5 ΔIEC 和 Tlr5 ΔDC。
KO 杂合子 Gene+/-
CKO 杂合子 Gene flox/+
我还是没搞懂这两个区别，回去问ai吧
我就不应该先问师兄师姐的，因为问了一圈他们都没搞这个所以不知道，到头来还是要问AI
怪不得师姐说这是毫无积累（没有学术资源）的课题组呢
不想看文献
我觉得我总是在某个步骤上卡很久
比如现在，我应该要画一个这篇文献的流程图，但是事实上我还没搞清楚这篇文献各个实验都为了验证什么（逻辑很劝退）
（主要是我真的没法理解逻辑，也很怀疑根本就没有逻辑，我也不是很想要搞这个选题（还没有师姐的选题有搞头
但是如果要搞师姐的选题就要整理一大堆看不懂的数据（从里面筛选出要搞的分子）
而且最卡关的是我在两种思路中摇摆不定
炎症因子究竟是伤害性还是保护性还是两者都有
看了几天这篇文献我还是没搞清楚
A到C B到C都看懂了
但A到B究竟有没有逻辑啊(究竟有没有直接证明啊啊啊啊啊啊啊)
这种思路其实是挺垃圾的
我真的不想搞这个
又到了传统想死之看文献环节
肿瘤的文章就是好发啊
这篇比上篇好读很多，不知道是不是因为上一篇作者英语不好，句子都很绕
（到现在看的全都是中国发的论文，也没办法）
primary culture 原代培养
formalin-fixed paraffin embedded
福尔马林固定石蜡包埋
看了一会儿就昏昏欲睡，下午要搞执医报名然后运动一下就要去吃饭了
玩嗨了，差点都忘了明天要和师姐去实验室跑电泳
好emo，我自己的课题还是没有着落，很快就花粉季了，又一直拖延不看文献，导师对科研一窍不通
心态belike：人生不在工作，临床不在科研
已经一个月没碰课题嘟串了
FSTL1-knockdown improves neural oscillation via decreasing neuronal-inflammation regulating apoptosis in Aβ1–42 induced AD model mice
好烦啊，学校账号也没买这篇文献
scihub和librarygenesis都没有搜到
要学学怎么用AI hack吗
师姐在一个付费群里面，那个群用AI hack出来赚中间价
To determine if a long noncoding RNA (lncRNA) has cis-regulatory functions, several criteria are typically considered:
Proximity to Target Gene: The lncRNA should be located near the target gene on the same chromosome.
Expression Correlation: There should be a correlation between the expression of the lncRNA and the target gene.
Functional Evidence: Experimental evidence, such as loss-of-function or gain-of-function studies, should show that the lncRNA can regulate the target gene’s expression.
Physical Interaction: The lncRNA should physically interact with the target gene’s DNA or associated chromatin.
Conservation: The regulatory function of the lncRNA should be conserved across different species or cell types, if applicable.
瞅了瞅这234不就是师姐的主要的实验嘛
表达相关性、敲低之后再看、再来个荧光素酶之类的确定是有结合的
Testing the proximity of a long noncoding RNA (lncRNA) to its target gene involves several methods:
Genomic Location Analysis: By examining the genomic coordinates of lncRNAs and potential target genes, researchers can determine physical proximity within the genome.
Expression Studies: Correlating the expression levels of lncRNAs and nearby genes can suggest regulatory relationships, especially when changes in lncRNA expression affect the gene’s expression.
Chromatin Conformation Capture (3C): Techniques like 3C or Hi-C can be used to detect physical interactions between the lncRNA and the target gene’s DNA, indicating proximity within the three-dimensional structure of the genome.
Computational Prediction: Databases like LncRNA2Target provide information on experimentally validated lncRNA-target interactions, which can be used to predict potential cis-regulatory relationships.
Experimental Validation: Techniques such as RNA immunoprecipitation or RNA pull-down assays can confirm the physical interaction between the lncRNA and the target gene’s DNA or RNA1.
These methods collectively help in establishing the cis-regulatory role of lncRNAs by confirming their proximity to target genes.
what the whole shitty thing is exactly?
ceRNA stands for competing endogenous RNA. In molecular biology, ceRNAs are transcripts that regulate other RNA molecules by competing for shared microRNAs (miRNAs). This interaction is part of a complex regulatory network where ceRNAs can influence the levels and activity of miRNAs, thereby affecting the expression of miRNA targets.
The ceRNA network includes various types of RNAs such as long noncoding RNAs (lncRNAs), pseudogenes, and circular RNAs (circRNAs), all of which can act as molecular sponges. They bind to miRNAs through miRNA response elements (MREs), reducing the miRNAs’ ability to target other RNAs. This mechanism is crucial for maintaining the balance of gene expression and has implications in various biological processes and diseases, including cancer
[摘自公众号文章]
因此这种模式来预测靶基因的原理就是预测lncRNA序列与mRNA序列结合的自由能，自由能越小，越容易结合。
说来变态反应的炎症和一些其他炎症的分子机制一样吗？
FSTL1 flox/+ 和 FSTL1 +/- 小鼠之间的区别在于它们的基因构成和由此产生的生理效应：
FSTL1 flox/+ 小鼠：这个称呼通常指的是小鼠中有一个FSTL1基因被loxP位点包围（flox），这允许在特定组织或特定时间通过Cre重组酶的结合来有条件地删除该基因。"+"表示存在一个正常的、非flox的FSTL1基因的等位基因。
FSTL1 +/- 小鼠：这些是杂合子小鼠，其中一个FSTL1基因被敲除（因此是"-“），另一个是正常的基因（因此是”+"）。这些小鼠可以用来研究FSTL1基因表达减少的效果。
神td暗示，怪不得我读不懂
The flox and Cre systems are integral parts of genetic engineering, particularly in creating genetically modified organisms like mice for research purposes. Here’s a more detailed explanation:
Flox: The term “flox” refers to a DNA sequence that has been flanked by loxP sites. These loxP sites are specific 34-base pair sequences that are recognized by the Cre recombinase enzyme1. When a gene is “floxed,” it means that it can be conditionally removed or altered by the action of Cre recombinase, which allows researchers to study the function of the gene in a controlled manner.
Cre: Cre is an enzyme called Cre recombinase that comes from bacteriophage P1. It recognizes loxP sites in the DNA and can cut and rejoin the DNA at these sites1. This allows for precise manipulation of the genome, such as the deletion, insertion, or inversion of DNA segments. The activity of Cre recombinase can be controlled so that it only acts in specific cell types or in response to certain stimuli, making it a powerful tool for studying gene function and creating models of human disease2.
The Cre-Lox system is widely used in neuroscience and other fields of biology to study complex systems and diseases. For example, it can be used to delete a gene in only certain types of neurons, which helps scientists understand the role of that gene in brain function1. It’s also used in creating models for diseases like cancer, where researchers can activate or deactivate cancer-related genes in specific tissues1.
This system provides a high level of control over gene expression and is invaluable for research that requires the study of gene function in living organisms. It’s one of the most precise tools available for genetic manipulation and has revolutionized the field of genetics.
感觉这里的小破实验室应该不具备这项技术
1. 定义研究目标
- 探索 circ_0002111 在甲状腺乳头状癌（PTC）进展中的调控机制
2. 提出假设
- circ_0002111 在 PTC 中上调并影响细胞增殖、迁移和糖酵解
3. 设计实验
a. RT-qPCR 测量 circ_0002111 表达水平
b. MTT 实验检测细胞增殖
c. EdU 掺入实验检测 DNA 合成
d. 集落形成实验检测长期增殖
e. Transwell 实验检测细胞迁移
f. Seahorse 分析进行代谢剖析
g. 西方印迹法分析蛋白表达
h. 小鼠体内移植瘤实验检测体内肿瘤形成能力
i. RNA 拉下实验确定 circ_0002111 的相互作用
j. 双荧光素酶报告基因表达调控实验
4. 进行实验
- 执行上述实验并记录观察结果
5. 数据分析
- 与对照组比较结果，确定 circ_0002111 的效果
6. 得出结论
- 评估数据是否支持假设
7. 报告发现
- circ_0002111 通过海绵 miR-134-5p 和调节 FSTL1 促进 PTC 进展
Here’s a summary of the key experiments and their conclusions from the article:
Circ_0002111 Expression Analysis: The study found that circ_0002111 was significantly upregulated in PTC tissues and cells, suggesting its role in PTC progression1.
Functional Assays: Silencing circ_0002111 inhibited PTC cell proliferation, migration, and glycolytic metabolism, indicating its oncogenic function23.
In Vivo Tumorigenesis: Knockdown of circ_0002111 reduced tumor growth in a xenograft model, further confirming its role in promoting PTC4.
miR-134-5p Interaction: Circ_0002111 was shown to act as a sponge for miR-134-5p, affecting its expression and PTC cell behavior.
FSTL1 Regulation: The study demonstrated that miR-134-5p targets FSTL1, and circ_0002111 can regulate FSTL1 levels by sponging miR-134-5p.
反转录定量聚合酶链反应 (RT-qPCR)
用于检测circ_0002111、miR-134-5p和FSTL1的水平。1
通过SYBR™ Green Master Mix和TaqMan™ Fast Advanced Master Mix进行定量反应。
细胞增殖评估
使用MTT试剂、EdU试剂和克隆形成试验来评估细胞增殖。
通过显微镜观察和图像分析软件计数。
细胞迁移能力测定
通过Transwell试验来确定细胞迁移能力。2
使用结晶紫染色并通过倒置显微镜观察。
糖酵解分析
通过外部酸化率(ECAR)、氧消耗率(OCR)、葡萄糖消耗和乳酸产生来分析糖酵解。
使用Seahorse XFe 96 Extracellular Flux Analyzer进行检测。
1. Define Research Objective
- Explore regulatory mechanism of circ_0002111 in PTC progression
2. Formulate Hypothesis
- circ_0002111 upregulates in PTC and affects cell proliferation, migration, and glycolysis
3. Design Experiments
a. RT-qPCR to measure circ_0002111 expression levels
b. MTT assay for cell proliferation
c. EdU incorporation assay for DNA synthesis
d. Colony formation assay for long-term proliferation
e. Transwell assay for cell migration
f. Seahorse analysis for metabolic profiling
g. Western blot for protein expression analysis
h. Xenograft tumor assay in mice for in vivo tumorigenicity
i. RNA pull-down to identify circ_0002111 interactions
j. Dual-luciferase reporter assay for gene expression regulation
4. Conduct Experiments
- Perform the above assays and record observations
5. Analyze Data
- Compare results with control groups to determine the effect of circ_0002111
6. Draw Conclusions
- Assess whether the data supports the hypothesis
7. Report Findings
- circ_0002111 promotes PTC progression by sponging miR-134-5p and regulating FSTL1
TPC1 and IHH4 are cell lines used in scientific research, particularly in the study of thyroid cancer.
TPC1 is a cell line that has the RET/PTC rearrangement, which is associated with papillary thyroid cancer (PTC). This genetic alteration is often studied because it can provide insights into the development and progression of PTC1.
IHH4 is another cell line that is mutated for BRAFV600E, also used in the context of PTC research. The BRAFV600E mutation is one of the most common mutations found in PTC and is a significant area of focus for understanding the disease and developing targeted therapies1.
The article details several experiments conducted to explore the role of circular RNA (circ_0002111) in the progression of papillary thyroid carcinoma (PTC). Here’s a detailed one-to-one list of the experiments and their demonstrations:
RT-qPCR: Used to detect the levels of circ_0002111, miR-134-5p, and FSTL1, demonstrating that circ_0002111 is upregulated in PTC samples and cells1.
Cell Proliferation Assays (MTT, EdU, Colony Formation): Showed that downregulation of circ_0002111 suppresses PTC cell proliferation.
Transwell Assay: Indicated that circ_0002111 knockdown reduces PTC cell migration ability2.
Glycolysis Analysis (ECAR, OCR, Glucose Consumption, Lactate Production): Demonstrated that circ_0002111 downregulation leads to decreased glycolytic metabolism in PTC cells.
Western Blot: Confirmed that silencing circ_0002111 reduces the levels of proteins associated with proliferation, migration, and glycolysis.
Xenograft Tumor Assay: Revealed that circ_0002111 promotes tumorigenesis in vivo34.
Dual-Luciferase Reporter and RNA Pull-Down Assays: Validated that circ_0002111 acts as a sponge for miR-134-5p and regulates FSTL1 expression.
虽然快要下班了一篇文献都没做好PPT但是终于找到了个合适的prompt，等着晚上量产了
The term “PCD5-ciR” refers to a fifth-generation circular RNA (circRNA) expression vector. It is designed with a specialized circRNA expression framework that includes carefully modified Alu elements, binding sites for RNA-binding proteins (RBPs) like QKI, and a newly designed circularization mediating sequence to ensure accurate and efficient circularization of the inserted circRNA. The expression framework has reserved EcoRI and BamHI restriction sites for direct enzyme digestion and insertion of the target circRNA fragment1.
This vector is used in molecular biology and genetic research to overexpress specific circRNAs, which are a novel class of RNA molecules formed by back-splicing of pre-mRNAs produced by host genes. CircRNAs have been increasingly associated with various biological processes, including tumorigenesis and progression2. In the context of cancer research, vectors like PCD5-ciR are valuable tools for studying the function and regulatory mechanisms of circRNAs
完球了我的prompt没存下来，虽然记得但是重写一遍有点麻烦
The article discusses experiments conducted to explore the role and mechanism of circular RNA circ_HECTD1 in cell injury after cerebral infarction12. Here’s a breakdown of the key experiments and their purposes:
Expression Analysis: RT-qPCR was used to detect the levels of circ_HECTD1, miR-27a-3p, and FSTL13. This helped establish the relationship between these molecules in the context of cerebral infarction.
Subcellular Localization: A subcellular fractionation assay determined the localization of circ_HECTD1 within cells, suggesting its potential regulatory mechanisms4.
Cell Proliferation and Apoptosis Assays: EdU, MTT, and flow cytometry assays assessed the effects of circ_HECTD1 on cell proliferation and apoptosis, indicating its impact on cell survival after injury.
Protein Level Analysis: Western blot assays measured the protein levels of PCNA, Bcl-2, Bax, PARP, and FSTL1, providing insights into the molecular changes associated with circ_HECTD1 activity5.
Luciferase Reporter Assay: This experiment confirmed the direct interaction between miR-27a-3p and circ_HECTD1 or FSTL1, elucidating the regulatory pathway involved in cell injury.
Each experiment contributed to understanding how circ_HECTD1, through the miR-27a-3p/FSTL1 axis, can affect cell injury mechanisms relevant to cerebral infarction, offering potential therapeutic targets
Subcellular Fractionation & RNase R Treatment: 3
Purpose: To determine the localization and stability of circ_HECTD1.
Result: Circ_HECTD1 was found mainly in the cytoplasm and resistant to RNase R, indicating its circular nature.
Cell Transfection:
Purpose: To knock down circ_HECTD1 and observe the effects on cell proliferation and apoptosis4.
Result: Knockdown of circ_HECTD1 enhanced cell proliferation and reduced apoptosis in OGD/R-treated HT22 cells5.
EdU & MTT Assays:
Purpose: To assess cell proliferative ability6.
Result: Circ_HECTD1 knockdown increased the number of EdU-positive cells and cell viability, indicating improved cell proliferation.
Flow Cytometry:
Purpose: To analyze cell apoptosis.
Result: Circ_HECTD1 knockdown decreased the apoptosis rate in OGD/R-treated HT22 cells5.
Western Blot:
Purpose: To measure the protein levels related to cell proliferation and apoptosis.
Result: Circ_HECTD1 deficiency led to increased levels of PCNA (a proliferation marker) and Bcl-2 (an anti-apoptotic marker), and decreased levels of Bax and Cleaved PARP (pro-apoptotic markers).
Dual-Luciferase Reporter Assay:1
Purpose: To verify the binding relationship between miR-27a-3p and circ_HECTD1 or FSTL17.
Result: Confirmed that circ_HECTD1 directly interacts with miR-27a-3p and that miR-27a-3p targets FSTL1
RT-qPCR (Reverse Transcription Quantitative Polymerase Chain Reaction):
Purpose: To quantify the expression levels of circ_HECTD1, miR-27a-3p, and FSTL1 mRNA in cells affected by cerebral infarction.
Result: The RT-qPCR results would typically show the relative expression levels of these genes. An increase or decrease in the Ct (Cycle threshold) values would indicate changes in gene expression. For instance, a lower Ct value for circ_HECTD1 might suggest higher expression in cells post-infarction, which could be associated with the cellular response to injury
The article describes several experiments to investigate the role of FSTL1 and miR-125a-3p in adipogenic differentiation and inflammation1. Here’s a summary of the experiments and their results:
Isolation and Differentiation of Preadipocytes: Mouse subcutaneous preadipocytes were isolated and induced to differentiate in vitro2. The study observed morphological changes and lipid accumulation, confirming the suitability of these cells for further experiments.
Plasmid Construction and Luciferase Reporter Assay: A plasmid containing the FSTL1 gene was constructed, and a luciferase reporter assay was performed to validate miR-125a-3p targeting the 3′ UTR region of FSTL134. The assay confirmed that miR-125a-3p could bind to the 3′ UTR of FSTL1, reducing luciferase activity.
Transfection of Plasmids, siRNAs, and miRNAs: The study used transfection techniques to overexpress or silence FSTL1 and miR-125a-3p in preadipocytes5. The results showed that overexpression of FSTL1 inhibited adipogenesis and promoted inflammation, while silencing FSTL1 had the opposite effect67.
Oil Red O Staining and Triglyceride Assay: These assays were used to visualize and quantify lipid accumulation in differentiated adipocytes. Overexpression of FSTL1 reduced lipid droplets, whereas miR-125a-3p promoted lipid accumulation8.
Quantitative Real-Time PCR and Western Blotting: These methods were employed to measure the expression levels of adipogenic and inflammatory genes. The results supported the findings that FSTL1 negatively regulates adipogenesis and promotes inflammation, while miR-125a-3p has the opposite effects6.
Overall, the experiments demonstrated that FSTL1 acts as a pro-inflammatory factor inhibiting adipogenesis, and miR-125a-3p can reverse these effects by targeting FSTL1. This suggests potential therapeutic targets for obesity-related inflammatory diseases.
The article details several experiments conducted to investigate the role of circATP8A1 in gastric cancer progression1. Here’s a summary of the key experiments and their implications:
Exosome Isolation and Characterization: Exosomes were isolated from plasma and characterized to confirm their size and presence of specific markers. This established the foundation for studying the role of exosomal circRNAs in gastric cancer2.
circRNA Microarray Analysis: A microarray was used to identify differentially expressed circRNAs in exosomes from gastric cancer patients compared to healthy individuals. This led to the discovery of circATP8A1 as a novel oncogenic circRNA.
Functional Assays: Various in vitro assays (CCK-8, colony formation, and transwell migration/invasion) were performed to assess the effects of circATP8A1 on gastric cancer cell proliferation, colony formation, and invasiveness. The results indicated that circATP8A1 promotes these malignant behaviors.
Macrophage Polarization: The study explored how exosomal circATP8A1 affects macrophage polarization, finding that it induces M2 polarization through the STAT6 pathway, which is associated with tumor progression3.
Molecular Interactions: The interaction between circATP8A1 and miR-1-3p was investigated using FISH, RIP, RNA pull-down, and luciferase reporter assays5. These experiments confirmed that circATP8A1 acts as a sponge for miR-1-3p, affecting the STAT6 pathway and macrophage polarization4.
Animal Models: In vivo experiments with mice models were conducted to study the effects of circATP8A1 on tumor growth and macrophage polarization, further confirming the oncogenic role of circATP8A1 in gastric cancer progression.
The article describes several experiments conducted to investigate the role of circS100A11 in childhood asthma. Here’s a summary of the key experiments and their implications:
Microarray Analysis:
Purpose: To identify differentially expressed circRNAs in PBMCs of children with asthma compared to healthy controls.
Result: 372 circRNAs were found to be differentially expressed, with circS100A11 being significantly upregulated in asthmatic children.
Macrophage Activation Assays:
Purpose: To determine the effect of circS100A11 on M2a macrophage activation.
Result: circS100A11 facilitated M2a macrophage activation by enhancing the translation of its host gene, S100A11.
Murine Asthma Model:
Purpose: To test the role of circS100A11 in lung inflammation in a cockroach allergen extract (CRE)-induced asthma model.
Result: Overexpression of circS100A11 in macrophages exacerbated lung inflammation, while macrophage-specific knockdown of S100A11 alleviated it.
RNA Immunoprecipitation and Chromatin Immunoprecipitation Assays:
Purpose: To explore the mechanism by which circS100A11 promotes S100A11 translation and affects STAT6 expression.
Result: circS100A11 was found to bind competitively to CAPRIN1, reducing its suppression of S100A11 translation, which in turn enhanced STAT6 expression and M2a macrophage activation.
These experiments collectively suggest that circS100A11 and S100A11 play a significant role in promoting M2a macrophage activation and lung inflammation in asthma, making them potential therapeutic and diagnostic targets.
The article discusses a study on the role of circS100A11 in childhood asthma. Here’s a summary of the experiments and their logic:
Expression Analysis: Researchers identified 372 circRNAs differentially expressed in PBMCs of children with asthma. circS100A11 was notably upregulated and mainly expressed in monocytes.
M2a Macrophage Activation: circS100A11 was shown to facilitate M2a macrophage activation by enhancing the translation of its host gene, S100A11, which worsened lung inflammation in a murine asthma model12.
Mechanistic Insights: The study revealed that circS100A11 competitively binds to CAPRIN1, reducing its suppression on S100A11 translation34. S100A11 then promotes SP3 binding to the STAT6 promoter, enhancing STAT6 expression and M2a macrophage activation56.
Therapeutic Potential: Macrophage-specific knockdown of S100A11 alleviated lung inflammation in the murine model, suggesting circS100A11 and S100A11 as potential therapeutic targets for childhood asthma.
The logic connecting these experiments is to demonstrate how circS100A11 contributes to asthma pathogenesis by regulating macrophage activation and to explore potential therapeutic interventions. The study progresses from identifying a key circRNA to understanding its function, mechanism, and therapeutic implications.
我佛了，AI越来越懒了
相比之下，除非使用Cre重组酶特异性地删除flox的FSTL1基因，否则FSTL1 flox/+ 小鼠不会表现出这些效应。提到的研究没有直接提供未经Cre介导的重组的FSTL1 flox/+ 小鼠的信息，但暗示如果没有基因删除，它们不会表现出与FSTL1 +/- 小鼠相同的抵抗力1。