[go: up one dir, main page]

CN116819094A - Igfbp5基因在隐睾症诊断中的应用 - Google Patents

Igfbp5基因在隐睾症诊断中的应用 Download PDF

Info

Publication number
CN116819094A
CN116819094A CN202310719326.9A CN202310719326A CN116819094A CN 116819094 A CN116819094 A CN 116819094A CN 202310719326 A CN202310719326 A CN 202310719326A CN 116819094 A CN116819094 A CN 116819094A
Authority
CN
China
Prior art keywords
cryptorchidism
gene
igfbp5
cells
diagnosis
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
CN202310719326.9A
Other languages
English (en)
Inventor
杨世华
袁靖丽
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
South China Agricultural University
Original Assignee
South China Agricultural University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by South China Agricultural University filed Critical South China Agricultural University
Priority to CN202310719326.9A priority Critical patent/CN116819094A/zh
Publication of CN116819094A publication Critical patent/CN116819094A/zh
Withdrawn legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54393—Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/581—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with enzyme label (including co-enzymes, co-factors, enzyme inhibitors or substrates)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
    • G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/36—Gynecology or obstetrics
    • G01N2800/367—Infertility, e.g. sperm disorder, ovulatory dysfunction

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Analytical Chemistry (AREA)
  • Biotechnology (AREA)
  • Pathology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Food Science & Technology (AREA)
  • General Physics & Mathematics (AREA)
  • Cell Biology (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biophysics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

本发明属于隐睾研究技术领域，公开了IGFBP5基因在隐睾症诊断中的应用。本研究采用隐睾症食蟹猴模型，隐睾睾丸中显著变化的细胞有Leydig。在Leydig细胞中表达的基因表达量增加特别明显的是基因IGFBP5，同时RPS16和ANXA6的表达量也显著增加(P<0.05)。但其他几个基因RPS2、RPL27A、EEF1B2、RPS20等的表达量则为显著下调。因此，可以通过检测待测样本单细胞中基因IGFBP5的表达量，来作为诊断隐睾的手段。从而为隐睾症所致男性不育的研究奠定基础，为临床诊疗方案的研究提供新思路。

Description

IGFBP5基因在隐睾症诊断中的应用
技术领域
本发明涉及隐睾研究技术领域，更具体的，涉及IGFBP5基因在隐睾症诊断中的应用。
背景技术
隐睾症是男性中最常见的生殖系统先天性异常之一，男性中约有1％～9％在出生时表现为至少有一个隐睾睾丸。隐睾症增加了男性不育、睾丸癌、生殖细胞丢失和精子发生受损的风险。30.8％的单侧隐睾患者存在少精子症；25％～89％双侧隐睾患者存在无精子症，不育者高达60％～100％。有32％的药物治疗者和46％的外科手术者发展为无精症，单方面隐睾症的无精症发生率为13％，而与患者是否接受治疗无关。目前使用腹腔镜辅助隐睾切除术或者睾丸固定术治疗隐睾。
目前有研究发现，紧密连接(TJ)相关分子的表达在人工隐睾或睾丸热处理后24～48h显著降低，而血-睾丸屏障(BTB)的通透性增加且在10d后恢复。该过程还伴随着TGF-β2和TGF-β3的表达增高，p38 MAPK和ERK/MAPK信号通路的激活。在隐睾生精过程的相关生物信息学鉴定中发现花生四烯酸途径和mTOR途径被认为是生精的重要途径，而RICTOR和GPX8被认为是参与隐睾症患者生精过程中的关键基因。但是，隐睾症的自身机制和分子通路等尚不清楚。
发明内容
本发明所要解决的技术问题是克服现有技术中存在的上述问题，首先提供基因IGFBP5的应用。
本发明的目的通过以下技术方案实现：
物质A在制备诊断隐睾症的功能产品中的应用，所述物质A用于检测细胞中基因IGFBP5的表达量。
优选的，所述物质A为IGFBP-5抗体。
研究发现单细胞测序中，同正常侧的睾丸组织相比，IGFBP5在隐睾侧睾丸组织Leydig细胞中高表达，这一点在RT-PCR检测中也得到了验证。因此该基因适用于鉴定是否患有隐睾症。
与现有技术相比，本发明具有以下有益效果：
本研究采用隐睾症食蟹猴模型，隐睾睾丸中显著变化的细胞有Leydig。在Leydig细胞中表达的基因表达量增加特别明显的是基因IGFBP5，同时RPS16和ANXA6的表达量也显著增加(P<0.05)。但其他几个基因RPS2、RPL27A、EEF1B2、RPS20等的表达量则为显著下调。
因此，可以通过检测待测样本单细胞中基因IGFBP5的表达量，来作为诊断隐睾的手段。从而为隐睾症所致男性不育的研究奠定基础，为临床诊疗方案的研究提供新思路。
附图说明
图1为食蟹猴隐睾的单细胞转录组分析；其中，图a:单细胞RNA测序数据质控图；b:单细胞RNA测序数据同转录组测序数据对比分析图；c:两只实验猴隐睾侧睾丸单细胞测序结果无监督聚类分析图；d:两只实验猴阴囊侧睾丸单细胞测序结果无监督聚类分析图；
图2为Leydig细胞中上调基因的RT-qPCR验证。
具体实施方式
下面对本发明的具体实施方式作进一步说明。在此需要说明的是，对于这些实施方式的说明用于帮助理解本发明，但并不构成对本发明的限定。此外，下面所描述的本发明各个实施方式中所涉及的技术特征只要彼此之间未构成冲突就可以相互组合。
一、实验动物的选择
本研究使用两只普通级生理状态良好的雄性食蟹猴，年龄为9岁和13岁。两只猴子均被单笼饲养在广东蓝岛生物技术有限公司，于每天早上十点及下午三点给予正餐，中午十二点和下午五点投喂瓜果蔬菜，自由饮水，并处于适宜温湿度控制下连续12小时交替明暗循环。在每个猴笼里都单独放置一些玩具，供实验猴消遣玩乐。所有动物程序均经广东蓝岛生物技术有限公司动物护理与使用专业委员会批准(IACUA审批同意书编号：LDACU20210310-01HE)。
二、外科手术
2只食蟹猴单侧隐睾手术均由一位经验丰富的临床兽医师完成。整个手术过程均为无菌操作。首先按0.02～0.04mL/kg的剂量肌注静灵(盐酸右美托咪定)(Dexmedetomidine HCl,Krasiv Russia Pharmaceuticals)对实验猴进行镇静处理，15min后，按5mg/kg的剂量肌注舒泰-50(#HC-DWYY-ST50，Virbac)做诱导麻醉，气管插管后使用呼吸麻醉机(#EZ-7000，E-Z Systems)进行呼吸麻醉，手术过程中异氟烷(Baxter HealthcareCorp,#153107015，GSY BIOTECHNOLOGY)浓度维持在2.5％。手术区域剃毛并用碘酒消毒，75％酒精脱碘。腹中线左侧1.5cm处开口，将左侧睾丸提至腹腔中，剪断韧带，使用5-0肠道可吸收线(Ethicon Inc,Somerville,NJ)缝合腹股沟及腹部切口，左侧睾丸为手术性隐睾，右侧睾丸保持不变用作对照。术后连续七天每天20mg/kg的剂量肌注头孢曲松钠。
三、睾丸组织取材、存储
在手术4周后，摘除隐睾和对侧正常睾丸，去除周围附属组织和脂肪，用生理盐水冲洗干净后用纱布擦干并称取睾丸的净重。之后放于加入2％双抗(#SV30010，Hyclone)的DMEM/F-12(#11330032，Gibco)培养液中，置于冰上，于15min紫外线照射过的超净台内进行睾丸组织分离和样本取材。
四、人工单侧隐睾模型睾丸组织单细胞RNA测序样本制备
用于单细胞测序实验的睾丸组织样本，PBS缓冲液冲洗睾丸3次后，用无菌剪刀剪碎组织(每个组织块重量为500mg～1g)，放入组织保存液(Tissue StorageSolution，#130-100-008，Miltenyi)中，手术取样后48h内，使用组织解离试剂盒(Multi Tissue Dissociation Kit，#130-110-201，Miltenyi)对睾丸组织进行解离。解离时，首先离心去除组织保存液，并用DMEM/F-12(#11330032，Gibco)清洗3次，用剪刀快速将其剪成2～3mm的组织块。向gentleMACS C管中加入4.7mL DMEM、200μL Enzyme D、100μLEnzyme R和25μL Enzyme A，配置成酶解液后，加入剪碎后的组织，拧紧C管，置于组织处理器中37℃消化50min，显微镜下每5min检查一次消化进度，直到消化为单细胞悬浮液。结束后40μm过滤收集细胞悬液。清洗重悬并做裂红处理。再次清洗重悬，使用Dead CellRemoval Kit(#130-090-101，Miltenyi)去除死细胞和碎片，使用1×PBS(#70011-004，Gibco)清洗并用适量1×PBS重悬细胞，使用Cellometer Auto 2000instrument(#SD-100,Nexcelom Bioscience)对重悬的细胞进行计数观察。最终细胞结团率小于10％且细胞活率大于80％时，准备进行单细胞RNA测序。
五、RT-PCR验证
1、NA抽提(枪头和离心管均经过湿热灭菌，无RNA酶)
1)取匀浆管，加入1mL的RNA提取液，置冰上预冷。
2)取100mg组织，加入到匀浆管中。
3)研磨仪充分研磨直至无可见组织块，12000rpm离心10min取上清。
4)加入250μL三氯甲烷，颠倒离心管15s，充分混匀，静置3min。
5)4℃下12000rpm离心10min。
6)将400mL上清转移到一个新的离心管中，加0.8倍体积的异丙醇，颠倒混匀。
7)-20℃放置15min。
8)4℃下12000rpm离心10min，管底的白色沉淀即为RNA。
9)吸除液体，加入75％乙醇1.5mL洗涤沉淀。
10)4℃下12000rpm离心5min。
11)将液体吸除干净，将离心管置于超净台上吹3min。
12)加入15μL无RNA酶的水溶解RNA，55℃孵育5min。
13)使用Nanodrop 2000检测RNA浓度及纯度：仪器空白调零后取2.5μL待测RNA溶液于检测基座上，放下样品臂，使用电脑上的软件开始吸光值检测。
14)将浓度过高的RNA进行适当比例的稀释，使其终浓度为100～500ng/μL。
2、转录(枪头和PCR均经过湿热灭菌，无RNA酶)
1)逆转录反应体系配制(推荐20μL反应体系)，见表6.1。
2)轻轻混匀并离心。
3)逆转录程序设置，见表6.2。
表1逆转录反应体系
表2逆转录程序
3、定量PCR
1)取0.2mL PCR管，配制如下反应体系，每个反转录产物配制3管。
表3定量PCR反应体系
2)PCR扩增
表4PCR反应体系
4、结果处理
ΔΔCT法：
A＝CT(目的基因，待测样本)-CT(内标基因，待测样本)
B＝CT(目的基因，对照样本)-CT(内标基因，对照样本)
K＝A-B
表达倍数＝2-K。
实施例1单侧隐睾食蟹猴睾丸单细胞转录组测序分析
为分析食蟹猴单侧隐睾睾丸中的细胞类型，对单细胞RNA测序数据进行分析。其中，两只实验猴的阴囊侧睾丸命名为CST#1和CST#2，单独消化后制备单细胞悬液，取等量细胞数的单细胞悬液混样后上机测序。隐睾侧睾丸命名为UAT#1和UAT#2，同样在单独消化后制备单细胞悬液，取等量细胞数的单细胞悬液混样后上机测序。通过10×Genomics平台获取单细胞RNA测序数据。质控后共获取到21457个细胞(CST有10560个细胞，UAT有10897个细胞)(图1a)。为验证单细胞RNA测序数据集的准确性，将单细胞测序数据同转录组测序数据进行对比分析，两份数据高度一致(UAT的r＝0.7564和CST的r＝0.8008)，表明单细胞RNA-seq测序数据的准确性(图1b)。无监督聚类分析显示，UAT#1和UAT#2样本中所含有的细胞类型及各类细胞的分布结果相似(图1c)，CST#1和CST#2样本中所含有的细胞类型及各类细胞的分布结果也相似(图1d)，因此，对两个样本的组合数据进行后续分析是可行的。
实施例2UAT vs CST差异基因RT-PCR验证
通过RT-PCR对隐睾模型中差异表达基因的表达量进行验证，其中Leydig细胞有11个。
在Leydig细胞中表现为上调的11个基因中，有3个(IGFBP5、RPS16和ANXA6)基因的表达量显著增加，2个(RPL13A和RPS3A)无差异，6个(RPS2、RPL27A、EEF1B2、RPS20、HSPB1和RPL1)显著减少(图2)。结果显示：在Leydig细胞中表达的基因表达量增加特别明显的是基因IGFBP5，同时RPS16和ANXA6的表达量也显著增加(P<0.05)。但其他几个基因RPS2、RPL27A、EEF1B2、RPS20等的表达量则为显著下调。
因此，可以通过检测待测样本单细胞中基因IGFBP5的表达量，来作为诊断隐睾的手段。
例如，用ELISA方法测定细胞中IGFBP5蛋白的表达量，具体为：用抗人IGFBP-5抗体包被于酶标板上，实验时样品(或标准品)及生物素化的抗人IGFBP-5抗体同时加入酶标板中，样本(或标准品)中的人IGFBP-5会与包被抗体结合，同时抗人IGFBP-5抗体与结合在包被抗体上的人IGFBP-5结合，游离的成分被洗去。再加入辣根过氧化物酶标记的亲和素，生物素与亲和素特异性结合而形成免疫复合物，游离的成分被洗去。加入显色底物(TMB)，TMB在辣根过氧化物酶的催化下呈现蓝色，加终止液后变成黄色。用酶标仪在450nm波长处测OD值，IGFBP-5浓度与OD450值之间呈正比，通过绘制标准曲线计算出样品中IGFBP-5的浓度。
以上对本发明的实施方式作了详细说明，但本发明不限于所描述的实施方式。对于本领域的技术人员而言，在不脱离本发明原理和精神的情况下，对这些实施方式进行多种变化、修改、替换和变型，仍落入本发明的保护范围内。

Claims (2)

1.物质A在制备诊断隐睾症的功能产品中的应用，其特征在于，所述物质A用于检测细胞中基因IGFBP5的表达量。
2.根据权利要求1所述的应用，其特征在于，所述物质A为IGFBP-5抗体。
CN202310719326.9A 2023-06-16 2023-06-16 Igfbp5基因在隐睾症诊断中的应用 Withdrawn CN116819094A (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202310719326.9A CN116819094A (zh) 2023-06-16 2023-06-16 Igfbp5基因在隐睾症诊断中的应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202310719326.9A CN116819094A (zh) 2023-06-16 2023-06-16 Igfbp5基因在隐睾症诊断中的应用

Publications (1)

Publication Number Publication Date
CN116819094A true CN116819094A (zh) 2023-09-29

Family

ID=88115095

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202310719326.9A Withdrawn CN116819094A (zh) 2023-06-16 2023-06-16 Igfbp5基因在隐睾症诊断中的应用

Country Status (1)

Country Link
CN (1) CN116819094A (zh)

Similar Documents

Publication Publication Date Title
Zhang et al. Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice
Feng et al. Infection-induced thrombin production: a potential novel mechanism for preterm premature rupture of membranes (PPROM)
Zhao et al. Motility-related microRNAs identified in pig seminal plasma exosomes by high-throughput small RNA sequencing
Crotwell et al. Advances in whole-genome genetic testing: from chromosomes to microarrays
Wang et al. ATP5D is a potential biomarker for male fertility
Galley et al. Urine-derived extracellular vesicle miRNAs as possible biomarkers for and mediators of necrotizing enterocolitis: A proof of concept study
Chang et al. A novel homozygous nonsense variant of AK7 is associated with multiple morphological abnormalities of the sperm flagella
Wang et al. The effect of sperm DNA fragmentation on in vitro fertilization outcomes for women with polycystic ovary syndrome
CN116773824A (zh) Des基因作为特异性标记基因在鉴别睾丸组织细胞类型中的应用
CN111593116A (zh) 一种复发性流产生物标志物及其应用
RU2474823C1 (ru) Способ прогнозирования качества эмбрионов в программе экстракорпорального оплодотворения
CN116819094A (zh) Igfbp5基因在隐睾症诊断中的应用
CN107312865B (zh) Loc100130111在制备骨肉瘤诊断产品、治疗药物中的用途
Watson et al. RNA-Seq analysis in an avian model of maternal phenylketonuria
CN107475386A (zh) 用于诊治骨肉瘤的长链非编码rna标志物
CN105349652B (zh) 类固醇生成因子1sf-1启动子区高甲基化作为宫内发育迟缓的分子标记及其应用
CN108165627B (zh) 一种诊治盆腔脱垂的分子标志物
Ren et al. TIGAR attenuates intervertebral disc degeneration via autophagy-mediated Keap1 degradation and Nrf2 nuclear translocation to suppress nucleus pulposus pyroptosis
Ma et al. Adenovirus-mediated Sirt1 and Tgfbr2 gene therapy improves fertility in natural ovarian aging and doxorubicin-induced premature ovarian insufficiency mice
CN111514167A (zh) 阿胶在用于缓解细胞氧化应激损伤产品中的应用
Weng et al. Decreased glycolysis due to LDHA m6A methylation in endometrium of endometriosis impairs its decidualization and contributes to related infertility
Ling et al. HE4 overexpression in mice leads to leydig cell hyperplasia and spermatogensis impairment: Pathological implications for oligospermia
LU508003B1 (en) Application of shikonin in preparing medicine for promoting tissue regeneration
Yuan et al. IGFBP1 stabilizes Umod expression through m6A modification to inhibit the occurrence and development of cystitis by blocking NF-κB and ERK signaling pathways
CN120586061A (zh) Plac8启动子甲基化促进剂在制备促进猪胎盘血管生成的产品中的应用

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
WW01 Invention patent application withdrawn after publication

Application publication date: 20230929

WW01 Invention patent application withdrawn after publication