M344_HNMR_08541_MedChemExpress
BLU-554_SDS_MedChemExpress
Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:May-24-2017Print Date:May-24-20171. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :BLU-554Catalog No. :HY-100492CAS No. :1707289-21-11.2 Relevant identified uses of the substance or mixture and uses advised againstIdentified uses :Laboratory chemicals, manufacture of substances.1.3 Details of the supplier of the safety data sheetCompany:MedChemExpress USATel:609-228-6898Fax:609-228-5909E-mail:sales@1.4 Emergency telephone numberEmergency Phone #:609-228-68982. HAZARDS IDENTIFICATION2.1 Classification of the substance or mixtureNot a hazardous substance or mixture.2.2 GHS Label elements, including precautionary statementsNot a hazardous substance or mixture.2.3 Other hazardsNone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms:NoneFormula:C24H24Cl2N4O4Molecular Weight:503.38CAS No. :1707289-21-14. FIRST AID MEASURES4.1 Description of first aid measuresEye contactRemove any contact lenses, locate eye-wash station, and flush eyes immediately with large amounts of water. Separate eyelids with fingers to ensure adequate flushing. Promptly call a physician.Skin contactRinse skin thoroughly with large amounts of water. Remove contaminated clothing and shoes and call a physician.InhalationImmediately relocate self or casualty to fresh air. If breathing is difficult, give cardiopulmonary resuscitation (CPR). Avoid mouth-to-mouth resuscitation.IngestionWash out mouth with water; Do NOT induce vomiting; call a physician.4.2 Most important symptoms and effects, both acute and delayedThe most important known symptoms and effects are described in the labelling (see section 2.2).4.3 Indication of any immediate medical attention and special treatment neededTreat symptomatically.5. FIRE FIGHTING MEASURES5.1 Extinguishing mediaSuitable extinguishing mediaUse water spray, dry chemical, foam, and carbon dioxide fire extinguisher.5.2 Special hazards arising from the substance or mixtureDuring combustion, may emit irritant fumes.5.3 Advice for firefightersWear self-contained breathing apparatus and protective clothing.6. ACCIDENTAL RELEASE MEASURES6.1 Personal precautions, protective equipment and emergency proceduresUse full personal protective equipment. Avoid breathing vapors, mist, dust or gas. Ensure adequate ventilation. Evacuate personnel to safe areas.Refer to protective measures listed in sections 8.6.2 Environmental precautionsTry to prevent further leakage or spillage. Keep the product away from drains or water courses.6.3 Methods and materials for containment and cleaning upAbsorb solutions with finely-powdered liquid-binding material (diatomite, universal binders); Decontaminate surfaces and equipment by scrubbing with alcohol; Dispose of contaminated material according to Section 13.7. HANDLING AND STORAGE7.1 Precautions for safe handlingAvoid inhalation, contact with eyes and skin. Avoid dust and aerosol formation. Use only in areas with appropriate exhaust ventilation.7.2 Conditions for safe storage, including any incompatibilitiesKeep container tightly sealed in cool, well-ventilated area. Keep away from direct sunlight and sources of ignition.Recommended storage temperature:Powder-20°C 3 years4°C 2 yearsIn solvent-80°C 6 months-20°C 1 monthShipping at room temperature if less than 2 weeks.7.3 Specific end use(s)No data available.8. EXPOSURE CONTROLS/PERSONAL PROTECTION8.1 Control parametersComponents with workplace control parametersThis product contains no substances with occupational exposure limit values.8.2 Exposure controlsEngineering controlsEnsure adequate ventilation. Provide accessible safety shower and eye wash station.Personal protective equipmentEye protection Safety goggles with side-shields.Hand protection Protective gloves.Skin and body protection Impervious clothing.Respiratory protection Suitable respirator.Environmental exposure controls Keep the product away from drains, water courses or the soil. Cleanspillages in a safe way as soon as possible.9. PHYSICAL AND CHEMICAL PROPERTIES9.1 Information on basic physical and chemical propertiesAppearance White to light yellow (Solid)Odor No data availableOdor threshold No data availablepH No data availableMelting/freezing point No data availableBoiling point/range No data availableFlash point No data availableEvaporation rate No data availableFlammability (solid, gas)No data availableUpper/lower flammability or explosive limits No data availableVapor pressure No data availableVapor density No data availableRelative density No data availableWater Solubility No data availablePartition coefficient No data availableAuto-ignition temperature No data availableDecomposition temperature No data availableViscosity No data availableExplosive properties No data availableOxidizing properties No data available9.2 Other safety informationNo data available.10. STABILITY AND REACTIVITY10.1 ReactivityNo data available.10.2 Chemical stabilityStable under recommended storage conditions.10.3 Possibility of hazardous reactionsNo data available.10.4 Conditions to avoidNo data available.10.5 Incompatible materialsStrong acids/alkalis, strong oxidising/reducing agents.10.6 Hazardous decomposition productsUnder fire conditions, may decompose and emit toxic fumes.Other decomposition products - no data available.11.TOXICOLOGICAL INFORMATION11.1 Information on toxicological effectsAcute toxicityClassified based on available data. For more details, see section 2Skin corrosion/irritationClassified based on available data. For more details, see section 2Serious eye damage/irritationClassified based on available data. For more details, see section 2Respiratory or skin sensitizationClassified based on available data. For more details, see section 2Germ cell mutagenicityClassified based on available data. For more details, see section 2CarcinogenicityIARC: No component of this product present at a level equal to or greater than 0.1% is identified as probable, possible or confirmed human carcinogen by IARC.ACGIH: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by ACGIH.NTP: No component of this product present at a level equal to or greater than 0.1% is identified as a anticipated or confirmed carcinogen by NTP.OSHA: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by OSHA.Reproductive toxicityClassified based on available data. For more details, see section 2Specific target organ toxicity - single exposureClassified based on available data. For more details, see section 2Specific target organ toxicity - repeated exposureClassified based on available data. For more details, see section 2Aspiration hazardClassified based on available data. For more details, see section 212. ECOLOGICAL INFORMATION12.1 ToxicityNo data available.12.2 Persistence and degradabilityNo data available.12.3 Bioaccumlative potentialNo data available.12.4 Mobility in soilNo data available.12.5 Results of PBT and vPvB assessmentPBT/vPvB assessment unavailable as chemical safety assessment not required or not conducted.12.6 Other adverse effectsNo data available.13. DISPOSAL CONSIDERATIONS13.1 Waste treatment methodsProductDispose substance in accordance with prevailing country, federal, state and local regulations.Contaminated packagingConduct recycling or disposal in accordance with prevailing country, federal, state and local regulations.14. TRANSPORT INFORMATIONDOT (US)This substance is considered to be non-hazardous for transport.IMDGThis substance is considered to be non-hazardous for transport.IATAThis substance is considered to be non-hazardous for transport.15. REGULATORY INFORMATIONSARA 302 Components:No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302.SARA 313 Components:This material does not contain any chemical components with known CAS numbers that exceed the threshold (De Minimis) reporting levels established by SARA Title III, Section 313.SARA 311/312 Hazards:No SARA Hazards.Massachusetts Right To Know Components:No components are subject to the Massachusetts Right to Know Act.Pennsylvania Right To Know Components:No components are subject to the Pennsylvania Right to Know Act.New Jersey Right To Know Components:No components are subject to the New Jersey Right to Know Act.California Prop. 65 Components:This product does not contain any chemicals known to State of California to cause cancer, birth defects, or anyother reproductive harm.16. OTHER INFORMATIONCopyright 2017 MedChemExpress. The above information is correct to the best of our present knowledge but does not purport to be all inclusive and should be used only as a guide. The product is for research use only and for experienced personnel. It must only be handled by suitably qualified experienced scientists in appropriately equipped and authorized facilities. The burden of safe use of this material rests entirely with the user. MedChemExpress disclaims all liability for any damage resulting from handling or from contact with this product.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
组蛋白去乙酰化酶及去甲基化酶抑制剂在胃肠道肿瘤的研究进展
现代消化及介入诊疗 ２０２１年第２６卷第１期ＭｏｄｅｒｎＤｉｇｅｓｔｉｏｎ＆Ｉｎｔｅｒｖｅｎｔｉｏｎ２０２１牞Ｖｏｌ．２６牞Ｎｏ．１ ·综述·组蛋白去乙酰化酶及去甲基化酶抑制剂在胃肠道肿瘤的研究进展陈俊豪１，２，丁杰１，２，李显２，岑祥莹２，张林２，吴明２，樊斐２，曾家兴２ 【提要】 组蛋白甲基化及乙酰化修饰的平衡失调与多种肿瘤的发生、发展、侵袭、转移密切相关，多种胃肠道肿瘤中发现组蛋白去乙酰化酶（ＨＤＡＣ）及组蛋白赖氨酸特异性去甲基酶１（ＬＳＤ１）异常增高。
相应的，一些组蛋白去乙酰化酶抑制剂（ＨＤＡＣｉ）和ＬＳＤ１抑制剂已在胃肠道肿瘤的研究中取得进展，如异羟肟酸类ＨＤＡＣｉ在胃肠道抗肿瘤研究中取得良好疗效，但因其特异选择性低，易产生耐药性和严重副作用，在临床的进一步研究中受到限制；苯甲酰胺类ＨＤＡＣｉ在特异选择性有所提高，并且能够通过抑制肿瘤细胞分化、诱导免疫自噬、抑制细胞周期蛋白产生抑瘤作用，但其由于活性低而受到限制；环肽类ＨＤＡＣｉ特异性进一步增加，但只是出于研究的基础阶段。
相应的，ＬＳＤ１抑制剂，如苯环丙胺类、多肽类、小分子化合物抑制剂均在细胞层面有着良好的抑瘤作用，也在后期的整体实验均显示出耐药性和严重副作用。
这提示着单一的ＨＤＡＣｉ和ＬＳＤ１抑制剂的抑瘤效应均不佳，由于ＨＤＡＣ常和ＬＳＤ１形成复合体发挥转录调节作用，因此，双靶点抑制剂可能是有效的，后期的双靶点抑制剂，比如ＤｕａｎＹＣ等人报道了ＴＣＰ和ＳＡＨＡ的组合产生的环戊二烯衍生物，ＡｎａｓｔａｓＪＮ报道的Ｃｏｒｉｎ，的确呈现出更加显著的抑瘤成效，本文就ＨＤＡＣ、ＬＳＤ１抑制剂及二者的双重抑制剂在胃肠道肿瘤的研究进展进行综述。
【关键词】 组蛋白去甲基化酶；组蛋白去乙酰化酶；组蛋白去甲基化酶抑制剂；组蛋白去乙酰化酶抑制剂；双重抑制剂；胃癌与结肠癌中图分类号：Ｒ７３５．２；Ｒ５７ 文献标志码：Ａ ＤＯＩ：１０．３９６９／ｊ．ｉｓｓｎ．１６７２－２１５９．２０２１．０１．０２８作者单位：１５６３００３遵义医科大学研究生院；２５５００００贵州省人民医院胃肠外科通信作者：丁杰，Ｅ ｍａｉｌ：ｄｉｎｇｊｉｅｂｏｙ＠１２６．ｃｏｍ基金项目：国家自然科学基金（８１３６０３６６，８１３０２１６９）；贵州省社会发展攻关项目（黔科合ＳＹ字［２０１４］３０２３号）；贵州省优秀青年科技人才培养对象（黔科合平台人才［２０１７］５６０２）；贵州省高层次创新型人才培养对象（ＧＺＳＹＱＣＣ［２０１４］００１）；贵州省科技计划项目（黔科合基础［２０１９］１１９８号，黔科合基础［２０２０］１Ｚ０６４）；贵州省高层次留学人才创新创业项目（留学人才择优资助合同［２０１８］０４号） 胃癌新发病例排在恶性肿瘤的第５位［１］，而结直肠癌是世界第三大恶性肿瘤和第四大癌症死亡原因，且无论是发病例数还是死亡率均呈上升趋势［２］。
Gelucire-14-44-SDS-MedChemExpress
Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:Nov.-23-2018Print Date:Nov.-23-20181. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :Gelucire 14/44Catalog No. :HY-Y1892CAS No. :121548-04-71.2 Relevant identified uses of the substance or mixture and uses advised againstIdentified uses :Laboratory chemicals, manufacture of substances.1.3 Details of the supplier of the safety data sheetCompany:MedChemExpress USATel:609-228-6898Fax:609-228-5909E-mail:sales@1.4 Emergency telephone numberEmergency Phone #:609-228-68982. HAZARDS IDENTIFICATION2.1 Classification of the substance or mixtureNot a hazardous substance or mixture.2.2 GHS Label elements, including precautionary statementsNot a hazardous substance or mixture.2.3 Other hazardsNone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms:NoneFormula:N/AMolecular Weight:N/ACAS No. :121548-04-74. FIRST AID MEASURES4.1 Description of first aid measuresEye contactRemove any contact lenses, locate eye-wash station, and flush eyes immediately with large amounts of water. Separate eyelids with fingers to ensure adequate flushing. Promptly call a physician.Skin contactRinse skin thoroughly with large amounts of water. Remove contaminated clothing and shoes and call a physician.InhalationImmediately relocate self or casualty to fresh air. If breathing is difficult, give cardiopulmonary resuscitation (CPR). Avoid mouth-to-mouth resuscitation.IngestionWash out mouth with water; Do NOT induce vomiting; call a physician.4.2 Most important symptoms and effects, both acute and delayedThe most important known symptoms and effects are described in the labelling (see section 2.2).4.3 Indication of any immediate medical attention and special treatment neededTreat symptomatically.5. FIRE FIGHTING MEASURES5.1 Extinguishing mediaSuitable extinguishing mediaUse water spray, dry chemical, foam, and carbon dioxide fire extinguisher.5.2 Special hazards arising from the substance or mixtureDuring combustion, may emit irritant fumes.5.3 Advice for firefightersWear self-contained breathing apparatus and protective clothing.6. ACCIDENTAL RELEASE MEASURES6.1 Personal precautions, protective equipment and emergency proceduresUse full personal protective equipment. Avoid breathing vapors, mist, dust or gas. Ensure adequate ventilation. Evacuate personnel to safe areas.Refer to protective measures listed in sections 8.6.2 Environmental precautionsTry to prevent further leakage or spillage. Keep the product away from drains or water courses.6.3 Methods and materials for containment and cleaning upAbsorb solutions with finely-powdered liquid-binding material (diatomite, universal binders); Decontaminate surfaces and equipment by scrubbing with alcohol; Dispose of contaminated material according to Section 13.7. HANDLING AND STORAGE7.1 Precautions for safe handlingAvoid inhalation, contact with eyes and skin. Avoid dust and aerosol formation. Use only in areas with appropriate exhaust ventilation.7.2 Conditions for safe storage, including any incompatibilitiesKeep container tightly sealed in cool, well-ventilated area. Keep away from direct sunlight and sources of ignition.Recommended storage temperature:Pure form-20°C 3 years4°C 2 yearsIn solvent-80°C 6 months-20°C 1 monthShipping at room temperature if less than 2 weeks.7.3 Specific end use(s)No data available.8. EXPOSURE CONTROLS/PERSONAL PROTECTION8.1 Control parametersComponents with workplace control parametersThis product contains no substances with occupational exposure limit values.8.2 Exposure controlsEngineering controlsEnsure adequate ventilation. Provide accessible safety shower and eye wash station.Personal protective equipmentEye protection Safety goggles with side-shields.Hand protection Protective gloves.Skin and body protection Impervious clothing.Respiratory protection Suitable respirator.Environmental exposure controls Keep the product away from drains, water courses or the soil. Cleanspillages in a safe way as soon as possible.9. PHYSICAL AND CHEMICAL PROPERTIES9.1 Information on basic physical and chemical propertiesAppearance White to off-white (Oil)Odor No data availableOdor threshold No data availablepH No data availableMelting/freezing point No data availableBoiling point/range No data availableFlash point No data availableEvaporation rate No data availableFlammability (solid, gas)No data availableUpper/lower flammability or explosive limits No data availableVapor pressure No data availableVapor density No data availableRelative density No data availableWater Solubility No data availablePartition coefficient No data availableAuto-ignition temperature No data availableDecomposition temperature No data availableViscosity No data availableExplosive properties No data availableOxidizing properties No data available9.2 Other safety informationNo data available.10. STABILITY AND REACTIVITY10.1 ReactivityNo data available.10.2 Chemical stabilityStable under recommended storage conditions.10.3 Possibility of hazardous reactionsNo data available.10.4 Conditions to avoidNo data available.10.5 Incompatible materialsStrong acids/alkalis, strong oxidising/reducing agents.10.6 Hazardous decomposition productsUnder fire conditions, may decompose and emit toxic fumes.Other decomposition products - no data available.11.TOXICOLOGICAL INFORMATION11.1 Information on toxicological effectsAcute toxicityClassified based on available data. For more details, see section 2Skin corrosion/irritationClassified based on available data. For more details, see section 2Serious eye damage/irritationClassified based on available data. For more details, see section 2Respiratory or skin sensitizationClassified based on available data. For more details, see section 2Germ cell mutagenicityClassified based on available data. For more details, see section 2CarcinogenicityIARC: No component of this product present at a level equal to or greater than 0.1% is identified as probable, possible or confirmed human carcinogen by IARC.ACGIH: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by ACGIH.NTP: No component of this product present at a level equal to or greater than 0.1% is identified as a anticipated or confirmed carcinogen by NTP.OSHA: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by OSHA.Reproductive toxicityClassified based on available data. For more details, see section 2Specific target organ toxicity - single exposureClassified based on available data. For more details, see section 2Specific target organ toxicity - repeated exposureClassified based on available data. For more details, see section 2Aspiration hazardClassified based on available data. For more details, see section 212. ECOLOGICAL INFORMATION12.1 ToxicityNo data available.12.2 Persistence and degradabilityNo data available.12.3 Bioaccumlative potentialNo data available.12.4 Mobility in soilNo data available.12.5 Results of PBT and vPvB assessmentPBT/vPvB assessment unavailable as chemical safety assessment not required or not conducted.12.6 Other adverse effectsNo data available.13. DISPOSAL CONSIDERATIONS13.1 Waste treatment methodsProductDispose substance in accordance with prevailing country, federal, state and local regulations.Contaminated packagingConduct recycling or disposal in accordance with prevailing country, federal, state and local regulations.14. TRANSPORT INFORMATIONDOT (US)This substance is considered to be non-hazardous for transport.IMDGThis substance is considered to be non-hazardous for transport.IATAThis substance is considered to be non-hazardous for transport.15. REGULATORY INFORMATIONSARA 302 Components:No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302.SARA 313 Components:This material does not contain any chemical components with known CAS numbers that exceed the threshold (De Minimis) reporting levels established by SARA Title III, Section 313.SARA 311/312 Hazards:No SARA Hazards.Massachusetts Right To Know Components:No components are subject to the Massachusetts Right to Know Act.Pennsylvania Right To Know Components:No components are subject to the Pennsylvania Right to Know Act.New Jersey Right To Know Components:No components are subject to the New Jersey Right to Know Act.California Prop. 65 Components:This product does not contain any chemicals known to State of California to cause cancer, birth defects, or anyother reproductive harm.16. OTHER INFORMATIONCopyright 2018 MedChemExpress. The above information is correct to the best of our present knowledge but does not purport to be all inclusive and should be used only as a guide. The product is for research use only and for experienced personnel. It must only be handled by suitably qualified experienced scientists in appropriately equipped and authorized facilities. The burden of safe use of this material rests entirely with the user. MedChemExpress disclaims all liability for any damage resulting from handling or from contact with this product.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
非编码RNA_调控铁死亡在肝细胞癌中作用的研究进展
㊃消化专栏㊃[收稿日期]2023-03-02[基金项目]内蒙古自然科学基金(2022M S 08032);北京市海淀区卫生健康发展科研培育计划(H P 2021-19-50701);航天中心医院院级课题(Y N 202104);中国航天科工集团课题(2020-L C Y L -009)[作者简介]李林林(1981-),男,内蒙古赤峰人,赤峰学院附属医院副主任检验技师,医学硕士,从事肿瘤生物标志物研究㊂*通信作者㊂E -m a i l :h d d 2011yx @163.c o m 非编码R N A 调控铁死亡在肝细胞癌中作用的研究进展李林林1(综述),郝丹丹2*,王玉敏3(审校)(1.赤峰学院附属医院检验科,内蒙古赤峰024000;2.赤峰学院医学部基础医学院生理学教研室,内蒙古赤峰024000;3.航天中心医院,北京大学航天临床医学院呼吸与危重症医学科,北京100049) [摘要] 铁死亡是一种铁依赖介导的脂质过氧化诱导的调节细胞死亡形式,与肿瘤发生密切相关㊂越来越多证据表明,非编码R N A (n o n c o d i n g R N A s ,n c R N A )能够调节肝细胞癌(h e p a t o c e l l u l a r c a r c i n o m a ,H C C )中的铁死亡,进而参与H C C 恶性生物学表型㊂本文我们总结了铁死亡关的n c R N A 与肝癌进展之间的关系㊂本文将有助于我们理解n c R N A 在肝细胞铁死亡和肝细胞癌进展中的作用,并可能为未来探索新的肝细胞癌诊断和治疗生物标志物提供新的思路㊂[关键词] 肝肿瘤;铁死亡;R N A ,未翻译 d o i :10.3969/j.i s s n .1007-3205.2024.02.012 [中图分类号] R 735.7 [文献标志码] A [文章编号] 1007-3205(2024)02-0191-05肝细胞癌(h e pa t o c e l l u l a rc a r c i n o m a ,H C C )是最常见的原发性肝癌,是一种病死率极高的消化系统恶性肿瘤,全球发病率位居所有恶性肿瘤的前5位㊁病死率位列前3位[1]㊂中国是肝癌的高发区,发病率与病死率均位居世界首位,发病率呈逐年上升趋势[2]㊂H C C 发生发展机制仍有待于深入研究㊂尽管最近在治疗等方面取得了一些进展,肝癌的预后仍然很差[3]㊂2020年肝癌死亡例数为830180例,在癌症相关死亡例数中排名第3[1]㊂尽管在治疗病毒性肝炎(H C C 的最大病因)方面取得了显著进展,但随着脂肪性肝炎发病率的增加,肝细胞癌的发病率和病死率仍在增加㊂然而,肝癌复杂的病理生理学限制了有效诊断和治疗干预的发展,促使人们全面了解肝癌的发生机制[4]㊂铁死亡可通过介导耐药㊁放疗抵抗和调控免疫治疗抑制参与H C C[5-10]㊂非编码R N A (n o n -c o d i n g RN A s ,n c R N A s )通过调节铁死亡,在H C C 的发生和发展中起着重要作用[11-13]㊂因此,阐明n c R N A s 对铁死亡的调控作用有助于加深铁死亡在H C C 中的作用的理解㊂本文首先简要介绍了铁死亡,然后重点介绍了n c R N A s 调节铁死亡参与H C C 的分子机制最新进展,进而从n c R N A 角度阐述铁死亡参与H C C 提供理解和思路,并可能为未来探索新的肝细胞癌诊断和治疗生物标志物提供新的思路㊂1 铁死亡铁死亡是2012年提出的一种由铁依赖性㊁脂质过氧化引起的调节性细胞死亡形式[14]㊂生物化学上,细胞内谷胱甘肽(g l u t a t h i o n e ,G S H )的耗尽和谷胱甘肽过氧化物酶4(gl u t a t h i o n e p e r o x i d a s e4,G P X 4)的活性失活导致细胞铁死亡,因为G P X 4催化的还原反应不能消除过量产生的脂质过氧化物[15]㊂铁死亡的关键特征包括膜脂质过氧化(l i pi d pe r o x i d a t i o n ,L P O )㊁细胞内铁稳态失衡和抗氧化防御体系的丧失[5-6]㊂铁死亡的发生需要两个关键启动信号,即抑制抗氧化系统溶质载体家族7成员11(s o l u t e c a r r i e r f a m i l y 7m e m b e r 11,S L C 7A 11)/谷胱甘肽G S H /G P X 4通路受到抑制和游离铁的积累(图1)㊂在铁死亡过程中,多不饱和脂肪酸(p o l y u n s a t u r a t e d f a t t y a c i d ,P U F A )极易发生过氧化,从而破坏脂质双层,破坏膜功能㊂将P U F A 掺入细胞磷脂(尤其是磷脂酰乙醇胺)需要参与脂肪酸合成的特定酶即酯酰辅酶A 合成酶长链家族成员4(A c y l -C o As y n t h e t a s e l o n g -c h a i nf a m i l ym e m b e r 4,A C S L 4)的作用㊂A C S L 4使P U F A 酯化生成P U F A -C o A ,随后通过溶血磷脂酰胆碱酰基转移酶3㊃191㊃第45卷第2期2024年2月河北医科大学学报J O U R N A L O F H E B E I M E D I C A L U N I V E R S I T YV o l .45 N o .2F e b . 2024(l y s o p h o s p h a t i d y l c h o l i n e a c y l t r a n s f e r a s e3, L P C A T3)将P U F A-C o A掺入磷脂膜㊂铁死亡的最后一步是脂质过氧化或其次级产物(如4-H N E和M D A)直接或间接诱导血浆或细胞器膜上的孔隙形成,最终引发细胞死亡(图1)㊂目前研究显示,铁死亡的发生与以下三个因素密切相关[15-16]:①脂质过氧化物的过度产生:F e2+又可以与N A D P H氧化酶激活产生的过氧化氢通过芬顿反应产生脂质过氧化物的前体羟自由基㊂②细胞内二价铁离子(F e2+)的升高:铁在铁死亡中起着核心作用㊂与运输和结合铁相关的转铁蛋白受体1(t r a n s f e r r i n r e c e p t o r1,T f R1)的增加以及铁蛋白和铁转运蛋白(t r a n s f e r r i n,T f)的减少均会导致F e2+的增加从而诱发铁死亡㊂③脂质过氧化损伤修复机制的抑制:G P X4和胱氨酸/谷氨酸逆向转运体(s y s t e m X c-)对铁死亡过程中脂质过氧化损伤的修复具有重要的作用㊂s y s t e m X c-是细胞膜上的一种氨基酸转运体,由S L C7A11(又叫x C T)和S L C3A22组成,它负责细胞胱氨酸的输入和谷氨酸的输出,导致G S H的合成㊂x C T可将细胞外的胱氨酸转运到细胞内与谷氨酸合成G S H,进而G P X4利用产生的G S H将脂质过氧化物还原为相应的醇或水,对抗细胞的氧化应激完成脂质过氧化的修复㊂铁死亡激活剂e r a s t i n或R S L3可以通过抑制x C T 中G P X4活性,最终导致细胞铁死亡㊂2n c R N A调控铁死亡在H C C发病中作用n c R N A s是无蛋白编码功能的一类功能性转录本,其可分为二大类:即小于200个核苷酸的s m a l l n c R N A s和大于200核苷酸的l o n g n c R N A s[17]㊂n c R N A s作为调节分子在转录水平㊁翻译水平和翻译后水平改变基因表达,介导一系列细胞过程,如染色质重塑㊁转录以及转录后修饰等[17]㊂因此,某些n c R N A s能够作为癌基因或肿瘤抑制因子发挥作用㊂在肿瘤中发挥重要作用的主要调节性n c R N A s 包括小R N A(m i c r o R N A s,m i R N A s)㊁长链非编码R N A(l o n g n o n-c o d i n g R N A s,L n c R N A s)以及环状R N A s(c i r c u l a rR N A s,c i r c R N A s)㊂越来越多的研究表明,n c R N A s通过调节铁死亡,在H C C的发生和发展中起着重要作用(图1)㊂图1n c R N A通过调控铁死亡在肝细胞癌中作用2.1 m i R N A调控铁死亡参与H C C耐药和进展转录因子E T S原癌基因1(E T S p r o t o-o n c o g e n e1,E T S1)转录激活m i R-23a-3p,m i R-23a-3p在H C C 中表达增高介导索拉菲尼耐药,并与不良预后相关㊂㊃291㊃河北医科大学学报第45卷第2期索拉菲尼耐药的H C C细胞系中m i R-23a-3p增加,体内外研究显示敲低m i R-23a-3p后增加H C C对索拉菲尼的敏感性㊂m i R-23a-3p通过靶向抑制A C S L4进而抑制铁死亡发生,而m i R-23a-3p敲低后上调A C S L4,增强索拉菲尼诱导的H C C细胞铁死亡发生㊂A C S L4敲低后逆转m i R-23a-3p m i R-23a-3p敲低后索拉菲尼诱导的H C C细胞铁死亡发生,表明在H C C中E T S1上调m i R-23a-3p,m i R-23a-3p通过靶向抑制A C S L4进而抑制铁死亡发生,从而介导H C C对索拉菲尼耐药[18]㊂M i c r o R N A-214-3p在肝癌发生中起调节作用㊂在肝癌细胞系中m i R-214过表达增加细胞对铁死亡诱导剂e r a s t i n诱导细胞死亡的敏感性,这与其增加了e r a s t i n诱导的丙二醛和活性氧水平㊁上调了F e2+浓度和降低G S H水平有关,即表明m i R-214增强H C C细胞对铁死亡的敏感性㊂M i c r o R N A-214-3p通过抑制转录因子4(t r a n s c r i p t i o n f a c t o r4, A T F4)的激活,进而诱导铁死亡发生㊂进一步体内移植瘤研究显示,M i c r o R N A-214-3p过表达抑制了A T F4的表达,进而促进e r a s t i n的抗肿瘤效果,表明M i c r o R N A-214-3p在H C C中通过抑制A T F4进而诱导铁死亡,从而增强e r a s t i n的抗肿瘤效果[19]㊂乙型肝炎病毒(h e p a t i t i sB,H B V)诱导M1巨噬细胞铁死亡,而m i R-142-3p通过抑制,进而促进M1巨噬细胞铁死亡,加速H C C的侵袭和迁移[20]㊂H B V阳性肝细胞癌患者来源的外泌体中m i R-142-3p表达增加,通过上调转铁蛋白受体1(t r a n s f e r r i n r e c e p t o r1,T f R1),下调铁蛋白重链1(f e r r i t i n h e a v y c h a i n1,F T H1)㊁G P X4和A T F4诱导M1巨噬细胞铁死亡,进而促进H C C肿瘤发生,m i R-142-3p靶向抑制S L C3A2促进M1巨噬细胞铁死亡,进而在体内外抑制H C C肿瘤发生[21]㊂2.2 L n c R N A调控铁死亡参与H C C发生发展L n c R N A H E P F A L在肝癌组织中的表达减少,其通过降低S L C7A11表达,增加脂质活性氧和铁的水平来促进铁死亡发生㊂同时l n c R N A H E P F A L 增加了e r a s t i n诱导H C C细胞对铁死亡的敏感性,这可能与m T O R C1有关,并且l n c R N A H E P F A L 可以促进S L C7A11的泛素化并降低S L C7A1蛋白的稳定性,从而导致表达降低㊂表明,L n c R N A H E P F A L在H C C中通过促进S L C7A11泛素化降解,进而诱导H C C铁死亡,发挥其对肿瘤的抑制作用[22]㊂L I N C01134在H C C中表达增加进而促进肿瘤发生,并与不良临床预后相关㊂L I N C01134敲低后升高H C C细胞内R O S㊁脂质R O S㊁M D A水平和降低G S H/G S S G,进而增强对奥沙利铂(O x a l i p l a t i n)的化疗敏感性,表明敲低L I N C01134通过诱导铁死亡增加化疗敏感性[23]㊂机制研究发现,L I N C01134可以促进N r f2募集到G P X4启动子区,从而对G P X4进行转录调控,从抑制铁死亡发生㊂因此在H C C中L I N C01134作为癌基因,通过激活N r f2/ G P X4通路抑制铁死亡发生,进而促进肿瘤发生[23]㊂在H C C中,L n c R N A N E A T1能够通过诱导肌醇加氧酶(m y o-i n o s i t o l o x y g e n a s e,M I O X)的表达,促进H C C对铁死亡诱导剂e r a s t i n和R S L3的敏感性,从而增强它们的抗肿瘤效果[24]㊂铁死亡诱导剂e r a s t i n和R S L3通过促进p53与N E A T1启动子的结合来增加L n c R N A N E A T1的表达㊂诱导的L n c R N A N E A T1通过竞争性结合m i R-362-3p促进肌醇加氧酶M I O X的表达㊂M I O X是一种非血红素铁蛋白,M I O X的上调促进了R O S的产生,减少了烟酰胺腺嘌呤二核苷酸磷酸(n i c o t i n a m i d e a d e n i n ed i n u c l e o t i d e p h o s p h a t e,N A D P H)和G S H,导致细胞抗氧化能力下降㊂M I O X增加了R O S的产生,降低了细胞内N A D P H和G S H的水平,导致了e r a s t i n和R S L3诱导的铁死亡增强㊂L n c R N A N E A T1过表达促进铁死亡,提高了e r a s t i n和R S L3的抗肿瘤活性㊂总之,L n c R N A N E A T1通过调节m i R-362-3p和M I O X在铁死亡㊂因此,诱导铁死亡可能是L n c R N A N E A T1高表达的H C C患者的一种有前途的治疗策略[24]㊂L n c R N A HU L C在H C C中高表达,作为癌基因促进肿瘤发生[25]㊂敲低L n c R N A HU L C增加H C C细胞中的铁死亡和氧化应激㊂L n c R N A HU L C作为m i R-3200-5p的c e R N A发挥作用,并且m i R-3200-5p通过靶向A T F4调节铁死亡,从而抑制H C C细胞内的增殖和转移,表明下调L n c R N A HU L C能够通过靶向m i R-3200-5p/ A T F4轴来诱导H C C细胞铁死亡,抑制肿瘤进展[25]㊂在H C C中L n c R N A G A B P B1-A S1表达增高, L n c R N A-G A B P B1-A S1与G A B P B1m R N A形成R N A双链,然后抑制G A B P B1翻译,导致P R D X5表达减少,最终导致铁死亡[26]㊂E r a s t i n上调l n c R N A G A B P B1-A S1,l n c R N A G A B P B1-A S1通过阻断G A结合蛋白转录因子β1(G A b i n d i n g p r o t e i n t r a n s c r i p t i o n f a c t o r s u b u n i t b e t a1,㊃391㊃河北医科大学学报第45卷第2期G A B P B1)翻译下调G A B P B1蛋白水平,从而导致编码过氧化物酶原5(p e r o x i r e d o x i n-5,P R D X5)过氧化物酶的基因下调,并最终抑制细胞抗氧化能力㊂G A B P B1的高表达水平与H C C患者的不良预后相关,而H C C患者的高G A B P B1-A S1水平与总体生存率的提高相关㊂总之,这些数据证明了G A B P B1及其反义l n c R N A G A B P B1-A S1在e r a s t i n诱导的铁细胞凋亡中的机制联系,并将G A B P B1和G A B P B1-A S1确立为H C C有吸引力的治疗靶点㊂2.3 C i r c R N A调控铁死亡参与H C C发生和耐药c i r c0097009在H C C癌组织和细胞系中高表达,敲低c i r c0097009抑制H C C细胞增殖和侵袭,进一步发现c i r c0097009通过虹吸抑制m i R-1261进而上调S L C7A11从而抑制铁死亡发生,促进H C C发生[27]㊂C i r c I L4R在H C C组织和细胞中异常过表达,C i r c I L4R敲低后铁死亡增加,抑制H C C细胞增殖㊂C i r c I L4R可直接海绵虹吸抑制m i R-541-3p, m i R-541-3p抑制可减轻C i r c I L4R敲低对H C C细胞的影响㊂C i r c I L4R作为m i R-541-3p海绵调节其靶点G P X4㊂G P X4上调减轻了m i R-541-3p诱导的肿瘤抑制和铁死亡㊂表明,C i r c I L4R通过虹吸抑制m i R541-3p进而上调G P X4从而抑制铁死亡发生,促进H C C发生[28]㊂H s a_c i r c_0008367(c I A R S)在索拉非尼治疗后H C C细胞中表达最高,敲低c I A R S后显著抑制细胞对索拉非尼或E r a s t i n的敏感性㊂c I A R S与R N A结合蛋白A L K B H5相互作用,后者是H C C自噬的负调节因子㊂A L K B H5沉默介导的B C L-2/B E C N1复合物的解离被干扰c I A R S有效阻断㊂此外,A L K B H5下调显著地抑制干扰c I A R S引起的铁死亡㊁自噬和铁自噬㊂总之, c I A R S通过抑制A L K B H5介导的自噬抑制,积极调节索拉非尼诱导的铁死亡[29]㊂3问题与展望n c R N A在H C C的多个过程中扮演着重要角色,参与H C C的发生发展㊂近年来n c R N A在调控铁死亡进而在调控肿瘤恶性生物学中发挥着重要作用㊂从本文可以看出n c R N A可以调控铁死亡多个靶点进而参与H C C的发生发展和耐药等㊂然而对于n c R N A在H C C中调控铁死亡的研究目前处于起步阶段,探索其他n c R N A在H C C中调控铁死亡仍值得深入探索㊂因此,深入研究其他n c R N A在调控H C C中铁死亡进程也是未来的重要研究方向,值得我们进一步深入关注㊂另外部分n c R N A 通过铁死亡介导耐药等调控H C C恶性生物学作用,那么能否实现n c R N A的靶向输运在肿瘤部位精准积聚实现对肿瘤的抑制作用,值得思考㊂[参考文献][1]S u n g H,F e r l a y J,S i e g e lR L,e ta l.G l o b a lc a n c e rs t a t i s t i c s2020:G L O B O C A N e s t i m a t e s o fi n c i d e n c e a n d m o r t a l i t yw o r l d w i d e f o r36c a n c e r s i n185c o u n t r i e s[J].C A C a n c e rJC l i n,2021,71(3):209-249.[2]S u nH C,Z h o u J,W a n g Z,e t a l.C h i n e s ee x p e r t c o n s e n s u so nc o n v e r s i o n t h e r a p y f o r h e p a t o c e l l u l a r c a r c i n o m a(2021e d i t i o n)[J].H e p a t o b i l i a r y S u r g N u t r,2022,11(2):227-252.[3]翟来慧,陆海波.晚期原发性肝细胞癌的药物治疗[J].现代肿瘤医学,2020,28(2):326-329.[4] A l q a h t a n i A,K h a n Z,A l l o g h b i A,e t a l.H e p a t o c e l l u l a rc a r c i n o m a:m o l e c u l a rm e c h a n i s m s a nd t a r ge t e d t h e r a p i e s[J].M e d i c i n a(K a u n a s),2019,55(9):526.[5] Y u a nJ,L v T,Y a n g J,e t a l.H D L B P-s t a b i l i z e d l n c F A Li n h i b i t s f e r r o p t o s i s v u l n e r a b i l i t y b y d i m i n i s h i n g T r i m69-d e p e n d e n tF S P1d e g r a d a t i o n i nh e p a t o c e l l u l a rc a r c i n o m a[J].R e d o xB i o l,2022,58:102546.[6] H uX,H eY,H a nZ,e t a l.P N O1i n h i b i t s a u t o p h a g y-m e d i a t e df e r r o p t o s i s b y G S H m e t a b o l i c r e p r og r a mm i n g i nh e p a t o c e l l u l a r c a r c i n o m a[J].C e l lD e a t h D i s,2022,13(11):1010.[7] D u X,Q i Z,X u J,e ta l.L o s s o f G A B A R A P L1c o n f e r sf e r r o p t o s i s r e s i s t a n c e t o c a n c e r s t e m-l i k e c e l l s i nh e p a t o c e l l u l a rc a r c i n o m a[J].M o l O n c o l,2022,16(20):3703-3719.[8] C h e n Q,Z h e n g W,G u a n J,e t a l.S O C S2-e n h a n c e du b i q u i t i n a t i o n o f S L C7A11p r o m o t e s f e r r o p t o s i s a n dr a d i o s e n s i t i z a t i o n i nh e p a t o c e l l u l a rc a r c i n o m a[J].C e l lD e a t hD i f f e r,2023,30(1):137-151.[9] C a s i n iA,L e o n eS,V a c c a r o R,e ta l.T h ee m e r g i n g r o l eo ff e r r o p t o s i s i n l i v e r c a n c e r s[J].L i f e(B a s e l),2022,12(12):[10] A j o o l a b a d y A,T a n g D,K r o e m e r G,e ta l.F e r r o p t o s i si nh e p a t o c e l l u l a rc a r c i n o m a:m e c h a n i s m sa n dt a r g e t e dt h e r a p y[J].B r JC a n c e r,2023,128(2):190-205.[11] B a l i h o d z i cA,P r i n zF,D e n g l e r MA,e ta l.N o n-c o d i n g R N A sa n d f e r r o p t o s i s:p o t e n t i a l i m p l i c a t i o n s f o r c a n c e r t h e r a p y[J].C e l lD e a t hD i f f e r,2022,29(6):1094-1106.[12] H s i e hP L,C h a oS C,C h uP M,e t a l.R e g u l a t i o no f f e r r o p t o s i sb y n o n-c od i n g R N A s i nhe a d a n dn e c kc a n c e r s[J].I n t J M o lS c i,2022,23(6):3142.[13] Z u oY B,Z h a n g Y F,Z h a n g R,e ta l.F e r r o p t o s i si nc a n c e rp r o g r e s s i o n:r o l e o f n o n c o d i n g R N A s[J].I n t J B i o l S c i,2022,18(5):1829-1843.[14] W a n g Y,W u X,R e n Z,e t a l.O v e r c o m i n g c a n c e rc h e m o t h e r a p y r e s i s t a n c eb y t h e i nd u c t i o no f fe r r o p t o s i s[J].D r u g R e s i s tU p d a t,2023,66:100916.[15] Y u Y,Y a n Y,N i u F,e t a l.F e r r o p t o s i s:a c e l l d e a t hc o n n e c t i n g o x id a t i v es t re s s,i nf l a mm a t i o na n dc a r d i o v a s c u l a rd i se a s e s[J].C e l lD e a t hD i s c o v,2021,7(1):193.[16] Z h e n g K,D o n g Y,Y a n g R,e t a l.R e g u l a t i o no f f e r r o p t o s i sb y㊃491㊃河北医科大学学报第45卷第2期b i o ac t i v e p h y t o c h e m i c a l s:I m p l i c a t i o n s f o rm ed i c a l n u t r i t i o n a lt h e r a p y[J].P h a r m a c o lR e s,2021,168:105580. [17] B o l t o nE M,T u z o v aA V,W a l s hA L,e t a l.N o n c o d i n g R N A s i np r o s t a t e c a n c e r:t h e l o n g a n d t h e s h o r t o f i t[J].C l i nC a n c e rR e s,2014,20(1):35-43.[18] L u Y,C h a n Y T,T a n H Y,e ta l.E p i g e n e t i cr e g u l a t i o n o ff e r r o p t o s i s v i a E T S1/m i R-23a-3p/A C S L4a x i s m e d i a t e ss o r a f e n i b r e s i s t a n c e i nh u m a nh e p a t o c e l l u l a r c a r c i n o m a[J].JE x p C l i nC a n c e rR e s,2022,41(1):3.[19] B a iT,L i a n g R,Z h u R,e ta l.M i c r o R N A-214-3p e n h a n c e se r a s t i n-i n d u c e df e r r o p t o s i sb y t a rg e t i n g A T F4i nh e p a t o m ac e l l s[J].JC e l l P h y s i o l,2020,235(7/8):5637-5648.[20] H uZ,Y i nY,J i a n g J,e t a l.E x o s o m a lm i R-142-3p s e c r e t e db yh e p a t i t i sB v i r u s(H B V)-h e p a t o c e l l u l a rc a r c i n o m a(H C C)c e l l s p r o m o t e sf e r r o p t o s i so f M1-t y p e m a c r o p h a g e st h r o u g hS L C3A2a n d t h e m e c h a n i s m o f H C C p r o g r e s s i o n[J].JG a s t r o i n t e s tO n c o l,2022,13(2):754-767.[21] H uZ,Z h a n g H,L i u W,e ta l.M e c h a n i s m o f H B V-p o s i t i v el i v e r c a n c e r c e l l e x o s o m a lm i R-142-3p b y i n d u c i n g f e r r o p t o s i so fM1m a c r o p h a g e s t o p r o m o t e l i v e rc a n c e r p r o g r e s s i o n[J].T r a n s l C a n c e rR e s,2022,11(5):1173-1187.[22] Z h a n g B,B a o W,Z h a n g S,e t a l.L n c R N A H E P F A La c c e l e r a t e s f e r r o p t o s i s i n h e p a t o c e l l u l a r c a r c i n o m ab yr e g u l a t i n g S L C7A11u b i q u i t i n a t i o n[J].C e l lD e a t hD i s,2022,13(8):734.[23] K a n g X,H u o Y,J i aS,e ta l.S i l e n c e d L I N C01134e n h a n c e so x a l i p l a t i n s e n s i t i v i t y b y f a c i l i t a t i n g f e r r o p t o s i s t h r o u g hG P X4i nh e p a t o c a r c i n o m a[J].F r o n tO n c o l,2022,12:939605.[24] Z h a n g Y,L u oM,C u i X,e t a l.L o n g n o n c o d i n g R N A N E A T1p r o m o t e s f e r r o p t o s i sb y m o d u l a t i n g t h e m i R-362-3p/M I O Xa x i s a s a c e R N A[J].C e l lD e a t hD i f f e r,2022,29(9):1850-1863.[25] G u a nL,W a n g F,W a n g M,e ta l.D o w n r e g u l a t i o no fHU L CI n d u c e s F e r r o p t o s i s i n H e p a t o c e l l u l a r C a r c i n o m a v i aT a r g e t i n g o f t h em i R-3200-5p/A T F4A x i s[J].O x i dM e dC e l lL o n g e v,2022,2022:9613095.[26] Q iW,L i Z,X i aL,e t a l.L n c R N AG A B P B1-A S1a n dG A B P B1r e g u l a t e o x i d a t i v e s t r e s sd u r i n g e r a s t i n-i n d u c e d f e r r o p t o s i s i nH e p G2h e p a t o c e l l u l a rc a r c i n o m ac e l l s[J].S c iR e p,2019,9(1):16185.[27] L y uN,Z e n g Y,K o n g Y,e t a l.F e r r o p t o s i s i s i n v o l v e d i nt h ep r o g r e s s i o n o f h e p a t o c e l l u l a r c a r c i n o m a t h r o u g h t h ec i r c0097009/m i R-1261/S L C7A11a x i s[J].A n nT r a n s lM e d,2021,9(8):675.[28] X u Q,Z h o u L,Y a n g G,e t a l.C i r c I L4R f a c i l i t a t e s t h et u m o r i g e n e s i s a n d i n h i b i t s f e r r o p t o s i s i n h e p a t o c e l l u l a rc a r c i n o m ab y r e g u l a t i n g t h em i R-541-3p/G P X4a x i s[J].C e l lB i o l I n t,2020,44(11):2344-2356.[29] L i uZ,W a n g Q,W a n g X,e t a l.C i r c u l a rR N Ac I A R S r e g u l a t e sf e r r o p t o s i si n H C C c e l l s t h r o ughi n t e r a c t i n g w i t h R N Ab i n d i n gp r o t e i nA L K B H5[J].C e l lD e a t hD i sc o v,2020,6:72.(本文编辑:刘斯静)㊃591㊃李林林等非编码R N A调控铁死亡在肝细胞癌中作用的研究进展。
姜黄素诱导胃癌细胞凋亡中MicroRNA表达谱的分析
姜黄素诱导胃癌细胞凋亡中MicroRNA表达谱的分析发表时间：2016-06-24T10:24:39.783Z 来源：《医药前沿》2016年6月第17期作者：李强王斌生（通讯作者）柴琛[导读] 胃癌是我国最为常见的恶性肿瘤之一，我国胃癌的发病率高居所有癌症发病率之首，严重威胁着人们的健康和经济水平。
李强王斌生（通讯作者）柴琛（兰州大学第一医院甘肃兰州 730000）【摘要】目的：研究姜黄素诱导胃癌细胞凋亡中MicroRNA表达谱的变化和在致凋亡中的作用，为临床使用姜黄素治疗胃癌提供理论依据。
方法：将BGC823和SGC7901两种胃癌细胞系分别培养于含10%胎牛血清、1000U/ml青链霉素的RIMP1640培养基，分别采用DMSO，10uM，50uM姜黄素进行感染处理48小时后采用流式细胞术对各组细胞凋亡情况进行检测，同时采用miRNA芯片技术检测miRNA 的表达，筛选表达差异miRNA，进行层次聚类分析。
结果随着姜黄素作用浓度的升高，BGC823和SGC7901两株胃癌细胞株的凋亡率逐渐上升，两种细胞株50uM姜黄素处理组凋亡率较10uM组升高约3倍左右，与对照组相比，姜黄素处理组凋亡率明显升高，P均小于0.01。
MicroRNA芯片分析显示在初步筛选出的129条MicroRNA中，与10uM姜黄素处理组相比，50uM姜黄素处理组表达差异在2倍以上的MicroRNA共计6条，上调表达MicroRNA2条，分别为miR-150和miR-34a；下调表达MicroRNA共计4条，分别为miR-92b、miR-650、miR-9和miR-125b。
结论：姜黄素诱导可使胃癌细胞系BGC823和SGC7901的MicroRNA表达谱发生变化，提示某些MicroRNA可能参与了姜黄素所致胃癌细胞凋亡。
【关键词】姜黄素；胃癌；MicroRNA；表达谱【中图分类号】R735.2 【文献标识码】A 【文章编号】2095-1752（2016）17-0160-03 胃癌是我国最为常见的恶性肿瘤之一，我国胃癌的发病率高居所有癌症发病率之首，严重威胁着人们的健康和经济水平。
中山大学历史学系2013年招收攻读硕士学位研究生拟录取名单
180
45
160
55
90
50
90
55
90
55
90
55
90
60
115
60
90
50
90
55
90
50
90
60
90
60
90
50
180
45
80
2
2 / 62
【育明教育】中国考研考博专业课辅导第一品牌
官方网站：
开设课程：【网络函授班】 【精品小班】 【高端一对一】 【状元集训营】 【定向保录】
刘 星 文物与博
36
辰
物馆
蔡 杜 文物与博
37
财
物馆
中西文化经济交流史 中美关系史 不分方向 不分方向 不分方向 不分方向 不分方向 不分方向 不分方向 不分方向 不分方向
非奖助 非奖助 非奖助 非奖助 非奖助 非奖助 非奖助 非奖助 非奖助 非奖助 非奖助
二、相关说明
1、该名单根据各报考专业（中国史、世界史、文物与博物馆）考生初试、复试结果总分确定，
8
8 / 62
【育明教育】中国考研考博专业课辅导第一品牌
官方网站：
开设课程：【网络函授班】 【精品小班】 【高端一对一】 【状元集训营】 【定向保录】
京：人民卫生出版社，2012.
331 社会工作原理 1.《社会工作概论》，王思斌，高等教育出版社，1999（2004）。 2.《社会学》，戴维.波普诺,中国人民大学出版社,2000。3.《西方社会学理论教程》侯均生主 编，南开大学出版社，2001。
历史地理
奖助
周芳 9
羽
中国史
明清史
AR-A014418_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:AR–A014418 is a selective and effective GSK3β inhibitor with an IC 50 value of 104 nM, and has no significant inhibition on 26 other kinases.IC50 & Target: IC50: 104 nM (GSK3β)In Vitro: AR–A014418 inhibits tau phosphorylation at a GSK3–specific site (Ser–396) in 3T3 fibroblasts expressing human four–repeat tau protein with IC 50 of 2.7 μM, and protects cultured N2A cells from death induced by blocking PI3K/PKB pathway. In hippocampal slices, AR–A014418 inhibits neurodegeneration mediated by beta–amyloid peptide [1]. While in NGP and SH–5Y–SY cells,AR–A014418 reduces neuroendocrine markers and suppresses neuroblastoma cell growth [2].In Vivo: In ALS mouse model with the G93A mutant human SOD1, AR–A014418 (0–4 mg/kg, i.p.) delays the onset of symptoms,improves motor activity, slows down disease progression, and postpons the endpoint of the disease [3]. In addition, AR–A014418produces inhibition effect on acetic acid– and formalin–induced nociception in mice by modulating NMDA and metabotropic receptor signaling as well as TNF–α and IL–1β transmission in the spinal cord [4].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[1]The competition experiments are carried out in duplicate with 10 concentrations of the inhibitor inclear–bottomed microtiter plates. The biotinylated peptide substrate, biotin–AAEELDSRAGS(PO3H2)PQL, is added at a final concentration of 2 μM in an assay buffer containing 6 milliunits of recombinant human GSK3 (equal mix of both α and β), 12mM MOPS, pH 7.0, 0.3 mM EDTA, 0.01% β–mercaptoethanol, 0.004% Brij 35, 0.5% glycerol, and 0.5 μg of bovine serumalbumin/25 μL and preincubated for 10–15 min. The reaction is initiated by the addition of 0.04 μCi of [γ–33P]ATP and unlabeled ATP in 50 mM Mg(Ac)2 to a final concentration of 1 μM ATP and assay volume of 25 μL. Blank controls without peptide substrate are used.After incubation for 20 min at room temperature, each reaction is terminated by the addition of 25 μL of stop solution containing 5mM EDTA, 50 μM ATP, 0.1% Triton X–100, and 0.25 mg of streptavidin–coated SPA beads corresponding to appr 35 pmol of binding capacity. After 6 h the radioactivity is determined in a liquid scintillation counter. Inhibition curves are analyzed by non–linear regression using GraphPad Prism.Cell Assay: AR–A014418 is dissolved in DMSO.[1]Cell viability is assessed by calcein/propidium iodide uptake. Calcein AM is taken up and cleaved by esterases present within living cells, yielding yellowish–green fluorescence, whereas PI is only taken up by dead cells,which become orange–red fluorescent. In brief, N2A cells are cultured for 2 days in vitro and then treated with 50 μM LY–294002 in the presence of AR–A014418 or vehicle (DMSO) for 24 h. Subsequently, N2A cells are incubated for 30 min with 2 μM PI and 1 μM calcein–AM. The cultures are then rinsed three times with Hanks' buffered saline solution containing 2 mM CaCl 2, and the cells are visualized by fluorescence microscopy using a Zeiss Axiovert 135 microscope. Three fields (selected at random) are analyzed per well (appr 300 cells/field) in at least three different experiments. Cell death is expressed as percentage of PI–positive cells from the total number of cells. In every experiment, specific cell death is obtained after subtracting the number of dead cells present inProduct Name:AR–A014418Cat. No.:HY-10512CAS No.:487021-52-3Molecular Formula:C 12H 12N 4O 4S Molecular Weight:308.31Target:GSK–3; GSK–3Pathway:Stem Cell/Wnt; PI3K/Akt/mTOR Solubility:10 mM in DMSOvehicle–treated cultures.Animal Administration: AR–A014418 is formulated in normal saline.[3]First, to examine the effects of GSK–3 inhibition on the clinical symptoms, life span, and motor behavior function of ALS, 56 Tg mice are divided into four groups. In each group, 0.5 mL of normal saline is mixed with either 0 μg (control group), 1 μg (group A), 2 μg (group B) or 4 μg (group C) of AR–A014418 per gram of mouse, and injected intraperitoneally into 14 animals per group 5 days a week beginning 60 days after birth. The mice are sacrificed at the endpoint described below.References:[1]. Bhat R, Xue Y, Berg S, Structural insights and biological effects of glycogen synthase kinase 3–specific inhibitor AR–A014418. J Biol Chem. 2003 Nov 14; 278(46):45937–45.[2]. Carter YM, et al. Specific glycogen synthase kinase–3 inhibition reduces neuroendocrine markers and suppresses neuroblastoma cell growth. Cancer Biol Ther. 2014 May;15(5):510–5.[3]. Koh SH, et al. Inhibition of glycogen synthase kinase–3 suppresses the onset of symptoms and disease progression of G93A–SOD1 mouse model of ALS. Exp Neurol. 2007 Jun;205(2):336–46.[4]. Martins DF, et al. The antinociceptive effects of AR–A014418, a selective inhibitor of glycogen synthase kinase–3 beta, in mice. J Pain. 2011 Mar;12(3):315–22.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
河南农业大学考研专业课《现代分子生物学》考试试卷(3960)
河南农业大学考研专业课《现代分子生物学》课程试卷（含答案）__________学年第___学期考试类型：（闭卷）考试考试时间：90 分钟年级专业_____________学号_____________ 姓名_____________1、分析题（5分，每题5分）1. 根据A基因序列设计原核表达引物。
A基因序列如下：ATGTCCGAAGTAATCGAAGAACATCTTCTCAGCGATAATTCTGATGATTCCAGCTCGGAAT TGACTTCTAC………GGACGAACCACGAAGAGACGATATTAApET28a多克隆位点如下引物设计必须满足：要求在引物两端分别加上BamHI（GGATCC）和EcoRI（GAATTC）。
要求表达的重组蛋白C端带His标签。
答案：设计引物时应需注意：（1）酶切位点前后应去除1～6个保护碱基，以提高限制性核酸内切酶的切割效率。
（2）His标签位于酶切位点的下游，且靠近终止密码子，且mRNA的翻译方向是由N端向C端，所以目的目的片段插入前会的顺序不颠倒。
（3）引物长度一般在18～27bp，且与目的片段有合适的互补长度以保证引物可以顺利结合。
上游引物可为（5′端至3′端）：CGCGGATCCGCGATGTCCGAAGTA。
下游引物可为（5′端至3′端）：GGCCTTAAGGCCAATTATAGCAGA。
解析：2、判断题（55分，每题5分）1. 同一种真核mRNA前体，由于在不用细胞或组织中的差异剪辑，可以表达出多种氨基酸序列、长度及糖基化程度不同的多肽。
（）答案：错误解析：糖基化程度差异与差异剪辑不相关。
2. 原核生物的冈崎片段短，真核生物的冈崎片段长。
（）答案：错误解析：一般情况下，原核生物的冈崎片段比真核生物的长。
3. 蛋白质的磷酸化和去磷酸化是可逆反应，该可逆反应是由同一种酶催化完成的。
（）答案：错误解析：蛋白质磷酸化是由蛋白激酶催化的，而去磷酸化是由蛋白质磷酸酯酶催化。