化学去细胞异体神经联合骨髓间充质干细胞修复损伤坐骨神经的生物力学评价

文题释义： 生物力学：是应用力学原理和方法对生物体中的力学问题定量研究的生物物理学分支,其研究范围从生物整体到系统、器官(包括血液、体液、脏器、骨骼等),从鸟飞、鱼游、鞭毛和纤毛运动到植物体液的输运等。生物力学的基础是能量守恒、动量定律、质量守恒定律并加上描写物性的本构方程。生物力学研究的重点是与生理学、医学有关的力学问题。依研究对象的不同可分为生物流体力学、生物固体力学和运动生物力学等。 周围神经研究热点和发展趋势：周围神经损伤的治疗已经取得了突破性的进展,但由于周围神经走行长、结构复杂、功能多样,损伤后其自身和靶器官会发生改变,而且是动态的、有时间效应的改变,因此以整体统一的理念研究周围神经损伤是今后研究重点。如何将基础研究与临床相结合,最终实现成果转化服务于患者,是研究者们的努力方向。国内外学者对自体神经损伤移植替代材料的研究从未间断过。随着组织工程和生物力学的发展,同种异体神经和人工神经已逐渐应用于临床,去细胞神经移植物也已取得了很好的临床效果。背景：以拉伸力学指标评估化学去细胞异体神经联合骨髓间充质干细胞治疗坐骨神经损伤的效果,目前鲜有报道。 目的：评估化学去细胞异体神经联合骨髓间充质干细胞移植治疗坐骨神经损伤的效果。 方法：将45只SD大鼠随机分为自体神经移植组、化学去细胞异体神经移植组、化学去细胞异体神经联合骨髓间充质干细胞移植组,每组15只,制备10 mm坐骨神经损伤模型,分别以自体神经、化学去细胞异体神经、化学去细胞异体神经联合骨髓间充质干细胞修复坐骨神经损伤,术后20周,进行坐骨神经电生理检测和坐骨神经单向拉伸实验。 结果与结论：①化学去细胞异体神经联合骨髓间充质干细胞移植组与自体神经移植组波幅值、运动传导速度值大于化学去细胞异体神经移植组(P < 0.05);②化学去细胞异体神经联合骨髓间充质干细胞移植组与自体神经移植组拉伸弹性限度应变、弹性限度应力、最大应变、最大应力大于化学去细胞异体神经移植组(P < 0.05);③结果表明,化学去细胞异体神经联合骨髓间充质干细胞移植对坐骨神经损伤具有明显的修复效果。ORCID: 0000-0002-1029-8117(吴志峰) 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

脐带间充质干细胞移植可延缓大鼠失神经肌肉的萎缩

背景：周围神经断伤后生长缓慢,失神经支配的肌肉萎缩及运动终板纤维化,导致肢体功能不可逆障碍。脐带间充质干细胞已经广泛应用于多学科研究,但应用于周围神经损伤中延缓大鼠失神经肌肉萎缩鲜有报道。 目的：观察异种异基因脐带间充干细胞移植于大鼠离断坐骨神经断端,延缓失神经肌肉萎缩的效果。 方法：新鲜脐带采集于健康足月产妇,分离鉴定脐带间充质干细胞。制备大鼠坐骨神经SunderlandⅣ度损伤模型,去神经束5 mm,神经外膜修复,5 mm小间隙移植脐带间充质干细胞模型,对照组仅在小间隙内注入同体积生理盐水。测定大鼠坐骨神经功能指数,小腿三头肌湿质量,坐骨神经干潜伏期、动作电位传导速度、波幅,以及骨骼肌纤维横截面积维持率。 结果与结论：造模后4,8及12周,脐带间充质干细胞组大鼠坐骨神经功能指数、右侧小腿三头肌湿质量及骨骼肌纤维横截面积维持率均显著高于对照组(P < 0.05)。造模后12周肌电图显示,脐带间充质干细胞组大鼠坐骨神经干潜伏期显著低于对照组,动作电位传导速度及波幅显著高于生理盐水对照组(P < 0.001)。提示脐带间充质干细胞移植于大鼠离断的坐骨神经断端,可促进神经生长,延缓失神经肌肉萎缩,维持失神经肌肉形态及功能。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

骨髓间充质干细胞移植联合吡拉西坦修复大鼠脊髓损伤

背景：单纯的干细胞移植对脊髓损伤的修复作用并不理想,主要是因为脊髓损伤后损伤区域神经组织的水肿、缺血、缺氧等引起继发性损伤造成的。 目的：在骨髓间充质干细胞移植治疗大鼠脊髓损伤的同时应用吡拉西坦,观察两者对大鼠脊髓损伤恢复的影响。 方法：雌性Wistar大鼠参照改良Allen打击法制备大鼠脊髓损伤模型。随机分成3组,即单纯损伤组、骨髓间充质干细胞移植组及骨髓间充质干细胞移植联合吡拉西坦组。于伤后1,2,4,6,8周进行BBB评分和斜板实验等运动功能检测。第4周取材行病理切片苏木精-伊红染色,通过SRY-PCR检测雄性大鼠Y染色体上特有的基因SRY,从而得知移植骨髓间充质干细胞是否存活。8周后取材,行辣根过氧化物酶示踪观察,并通过透射电镜观察轴突的再生情况。 结果与结论：伤后4周,骨髓间充质干细胞移植组、联合治疗组大鼠后肢运动功能均有较明显恢复,联合治疗组较骨髓间充质干细胞移植组恢复快(P < 0.05)。单纯损伤组亦有所恢复,但程度较轻。病理切片单纯损伤组未见神经轴索通过;骨髓间充质干细胞移植组可见少量神经轴索样结构;联合治疗组可见较多神经轴索样结构。骨髓间充质干细胞移植组、联合治疗组有SRY基因表达,单纯损伤组未检测到SRY基因。辣根过氧化物酶阳性神经纤维数联合治疗组﹥骨髓间充质干细胞移植组>单纯损伤组,差异具有显著性意义(P < 0.05)。透射电镜下,骨髓间充质干细胞移植组、联合治疗组正中横断面可见新生的无髓及有髓神经纤维。提示骨髓间充质干细胞移植联合吡拉西坦促进大鼠损伤脊髓结构和功能恢复的效果明显优于单纯细胞移植组,两者联用具有协同效应。     

骨髓间充质干细胞复合异体骨修复松质骨缺损

背景：有研究表明骨髓间充质干细胞及异体骨可促进骨缺损的修复,但骨髓间充质干细胞复合异体骨对于松质骨缺损的修复效果至今少有报道。 目的：观察骨髓间充质干细胞复合异体骨修复兔松质骨缺损效果。 方法：在新西兰大白兔双侧股骨外侧髁造成0.6 cm×1.2 cm 的松质骨缺损,一侧设为模型组,骨缺损处植入复合骨髓间充质干细胞的异体骨,另一侧设为对照组,单纯植入异体骨。 结果与结论：植入后4,8,12周,大体观察、X射线检查和苏木精-伊红染色观察结果显示,模型组在新骨成长方面,缺损区修复方面均优于对照组。植入后12周,模型组骨缺损区可见大量骨小梁形成及成熟的板层骨组织,骨缺损基本修复。对照组骨缺损区仅可见大量编织骨形成,骨缺损尚未得到有效修复。模型组Lane-Sandhu法X射线结合组织学观察评分高于对照组(P < 0.05)。生物力学检测结果显示,植入后12周,模型组股骨髁最大压力载荷、载荷/应变比值均高于对照组(P < 0.05),最大应变位移较对照组低(P < 0.05)。结果证实,骨髓间充质干细胞复合异体骨可有效修复兔股骨髁松质骨缺损,且修复效果明显优于单纯异体骨移植。     

骨髓间充质干细胞移植治疗失神经肌萎缩

背景:外科显微镜手术和一些辅助治疗方法均无法通过修复损伤的神经细胞来有效延缓或治疗失神经肌萎缩。研究发现骨髓间充质干细胞具有定向分化潜能,并且在一定环境因素下能对损伤的组织进行修复,由此推测其可以对失神经萎缩肌肉起到一定的修复作用。目的:探讨移植骨髓间充质干细胞是否能够减轻和延缓失神经肌肉组织萎缩。方法:分离培养SD大鼠骨髓间充质干细胞,取第3代骨髓间充质干细胞经BrdU标记后用于移植治疗。将30只SD大鼠分为3组,每组10只,对每只大鼠左后肢进行手术。假手术组只暴露坐骨神经主干,不钳夹神经,移植治疗组、模型对照组钳夹坐骨神经主干后,向其支配的腓肠肌注射骨髓间充质干细胞悬液和不含胎牛血清的DMEM培养液。骨髓间充质干细胞移植后1,2周,采用BBB评分评价各组大鼠左后肢运动功能;骨髓间充质干细胞移植后14 d,取腓肠肌组织进行苏木精-伊红染色和BrdU免疫组化染色。结果与结论:第3代骨髓间充质干细胞BrdU标记为阳性;标记的骨髓间充质干细胞能在移植治疗组失神经损伤的肌肉组织中存活并起修复作用;相对于模型对照组,移植治疗组失神经肌纤维由相互融合重新恢复规整。结果表明移植骨髓间充质干细胞能够减轻和延缓失神经肌肉组织萎缩。     

促红细胞生成素基因修饰骨髓间充质干细胞移植治疗大鼠脑梗死

背景：促红细胞生成素具有神经元的保护及促进神经再生的作用。目的：观察促红细胞生成素修饰的骨髓间充质干细胞尾静脉移植对大鼠脑梗死的治疗效果。方法：用Western blot鉴定外源人促红细胞生成素基因在骨髓间充质干细胞中的表达。采用线栓法建立大鼠大脑中动脉阻塞模型,模型组尾静脉注射PBS、骨髓间充质干细胞组注射骨髓间充质干细胞悬液,促红细胞生成素-骨髓间充质干细胞组注射转染了促红细胞生成素的骨髓间充质干细胞悬液。移植后3 d及移植后1,2,3,4 周行改良神经功能评分,检测神经功能的损伤情况。移植后4 周将大鼠麻醉后断头取脑,RT-PCR检测脑组织中bcl-2/bax基因表达变化,用原位末端标记法测定细胞凋亡情况、苏木精-伊红染色及荧光显微镜观察PKH26标记的骨髓间充质干细胞的存活和分布情况。结果与结论：Western blot结果显示,转染人促红细胞生成素基因的骨髓间充质干细胞体外能表达促红细胞生成素蛋白。移植后1-4周,骨髓间充质干细胞组和促红细胞生成素-骨髓间充质干细胞组神经缺损评分明显低于模型组(P < 0.05,P < 0.01)。与骨髓间充质干细胞组及模型组相比,大鼠脑梗死区组织促红细胞生成素-骨髓间充质干细胞组bcl-2基因的表达明显增高(P < 0.05),bax基因的表达明显降低(P < 0.05),凋亡细胞明显减少,PKH26阳性细胞数明显增多(P < 0.05)。结果证实,促红细胞生成素修饰的骨髓间充质干细胞尾静脉移植对脑梗死大鼠脑梗死疗效较好。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

神经节苷脂联合骨髓间充质干细胞移植治疗颅脑创伤

背景：骨髓间充质干细胞可以在体内外诱导下分泌神经营养因子,还可向神经元方向转化,从而促进创伤脑组织再生修复,但骨髓间充质干细胞又存在生存周期短的问题而影响其发挥对损伤脑组织的保护作用。目的：观察骨髓间充质干细胞移植联合神经节苷脂治疗大鼠颅脑创伤的效果。方法：60只Wistar大鼠采用液压颅脑损伤仪制备大鼠重型颅脑创伤模型,建模24 h后按照随机表法随机分为3组：模型组经尾静脉注入1 mL DMEM培养液,移植组经尾静脉注入1 mL(1×10¹⁰ L^-1)骨髓间充质干细胞悬液,联合组经尾静脉注入1 mL(1×10¹⁰ L^-1)骨髓间充质干细胞悬液以及经腹腔注射神经节苷脂水溶液(30 mg/kg),1次/d,共3 d。伤后24 h,细胞移植后3 d及1,2,3,4 周依据Longa 5分法进行神经功能行为学评分;移植后3 d应用RT-PCR、Western blot检测创伤脑组织中水通道蛋白4基因和蛋白的表达;移植后1周,行苏木精-伊红染色观察创伤脑组织病理变化。结果与结论：移植后3 d及1,2,3,4 周,联合组神经行为学功能评分低于移植组(P < 0.05),移植组低于模型组(P < 0.05);移植后3 d,模型组创伤脑周围组织水通道蛋白4蛋白及mRNA的表达高于移植组(P < 0.05),移植组高于联合组(P < 0.05);苏木精-伊红染色观察到联合组脑组织恢复明显优于模型组和移植组(P < 0.05)。结果提示骨髓间充质干细胞移植联合神经节苷脂可以明显改善颅脑创伤大鼠的神经行为学功能。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程      

骨髓间充质干细胞与新型神经导管复合材料修复周围神经缺损

背景：随着医学模式的不断发展进步,人们对于外周神经缺损的治疗以及后期康复水平提出更高的要求,这就使得以干细胞培养为基础的神经组织工程技术为神经缺损治疗提供了新策略。 目的：探讨骨髓间充质干细胞与新型神经导管复合材料修复周围神经缺损的可行性。 方法：选取清洁级纯种新西兰大白兔50只,采用随机数字表法分为实验组与对照组,每组25只,于兔前肢桡骨中段约15 mm处造成外周神经损伤,造模后1周,实验组外周神经损伤处移植骨髓间充质干细胞联合新型神经导管复合材料,对照组外周神经损伤处移植骨髓间充质干细胞。移植后4周,取神经损伤处的神经纤维长约5 mm,进行苏木精-伊红染色和扫描电镜观察,对比两组再生神经组织内神经纤维的密度和直径。 结果与结论：实验组神经纤维密度明显高于对照组,神经纤维直径明显低于对照组,组间相比差异有显著性意义(P < 0.05);实验组再生神经组织表面细胞数较多,细胞生长状态良好,体积较大,胞体发出多个突起,并且细胞之间相互连接交织成网状,其轴突较长和较粗,呈典型的神经元样细胞表现,且生长密度和状态优于对照组,可见骨髓间充质干细胞与新型神经导管复合材料可以用于修复周围神经缺损,且效果确切。 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

基因转染骨髓间充质干细胞复合同种异体骨修复绵羊极限骨缺损

背景：多项体内外实验表明外源性植入碱性成纤维细胞生长因子能明显促进骨形成过程,但外源性碱性成纤维细胞生长因子在体内易降解,影响疗效。 目的：利用分子生物学技术将碱性成纤维细胞生长因子转染至骨髓间充质干细胞中,观察同种异体骨复合基因转染骨髓间充质干细胞修复绵羊极限骨缺损的效果。 方法：将同种异体骨复合碱性成纤维细胞生长因子转染骨髓间充质干细胞组织工程骨、骨髓间充质干细胞复合同种异体支架骨材料、同种异体支架骨材料、β-磷酸三钙材料分别植入羊髂骨极限缺损处,植入后4,8,12周行组织学、免疫组织化学染色观察。 结果与结论：同种异体骨复合碱性成纤维细胞生长因子转染骨髓间充质干细胞组织工程骨植入后12周,手术结合区成软骨样结构较多,术区中央可见大量成骨样细胞,整个术区的支架材料降解较其他组多,支架材料孔洞内爬满纤维结缔组织,材料周围常见破骨样细胞;骨涎蛋白与Ⅰ型胶原呈强阳性表达。其他3组手术结合区虽有成软骨样结构及成骨样细胞出现,但中央区为死骨结构,且骨涎蛋白与Ⅰ型胶原呈弱表达。表明碱性成纤维细胞生长因子转染的骨髓间充质干细胞复合同种异体骨可基本修复绵羊极限骨缺损。     

高压氧联合骨髓间充质干细胞移植修复缺氧缺血性脑损伤

背景：单纯骨髓间充质干细胞移植对脑梗死组织的修复作用并不理想,需要结合药物及生物工程材料等手段进行综合治疗。 目的：验证高压氧结合骨髓间充质干细胞移植修复大鼠缺氧缺血性脑损伤的效果。 方法：体外培养大鼠骨髓间充质干细胞。应用线栓法建立大脑中动脉阻塞大鼠模型,按随机区组法分为3组,即对照组、骨髓间充质干细胞移植组及高压氧+骨髓间充质干细胞移植组。静脉移植后24 h,3 d及伤后1,2 周行Longa行为学评分,检测神经功能的损伤情况。移植2周后,应用RT-PCR法测定生长相关蛋白43 mRNA的表达,并以BrdU免疫组化和苏木精-伊红染色行梗死处组织学检查以证实恢复程度。 结果与结论：移植后1周,高压氧+骨髓间充质干细胞移植组大鼠神经功能障碍评分低于骨髓间充质干细胞移植组,骨髓间充质干细胞移植组低于对照组(P  < 0.05)。2周后脑梗死周围组织生长相关蛋白43 mRNA的表达高压氧+骨髓间充质干细胞移植组高于骨髓间充质干细胞移植组,骨髓间充质干细胞移植组高于对照组(P < 0.05)。BrdU免疫组化和苏木精-伊红切片中的神经元数量高压氧+骨髓间充质干细胞移植组多于骨髓间充质干细胞移植组,骨髓间充质干细胞移植组多于对照组(P < 0.05)。提示高压氧联合骨髓间充质干细胞静脉移植治疗大鼠缺氧缺血性脑损伤可明显改善大鼠的神经功能,效果优于单纯骨髓间充质干细胞移植。     

DNA修复与顺铂耐药

顺铂的主要药理机制是损伤细胞DNA，肿瘤细胞DNA修复能力增强则会导致其对顺铂耐药。目前研究发现，DNA修复途径中的核苷酸切除修复、错配修复、碱基切除修复均与顺铂耐药有关，核苷酸切除修复为其中最为重要的途径。     

Repair of oxidative DNA damage: assessing its contribution to cancer prevention

DNA repair is a crucial factor in maintaining a low steady-state level of oxidative DNA damage and protecting us from cancer. Cancer case-control studies, using indirect assays in which chromosome breakage in lymphocytes is taken as a measure of failure to repair DNA, indicate an association between poor repair and cancer risk, but case-control studies can be misleading. Surprisingly little is known of the variations in repair capacity within healthy human populations. It is likely that differences in repair enzyme activity result from genetic polymorphisms in repair genes, which have been shown, in some cases, to be linked to cancer. There is a need for prospective studies, in which genotype is analysed (for a range of repair and related genes) and repair activity measured before cancer has developed. Using a new method to measure repair in an extract of lymphocytes, based on a modification of the comet assay, we are seeking answers to the following questions: what is the normal range of repair activities in healthy humans; do differences in repair capacity correlate with genetic variations; is low repair capacity associated with a high risk of cancer; how important is DNA repair rate in determining the steady-state level of damage; what is the extent of intra-individual variation; is repair modulated by environmental factors or induced by damage; are there differences in repair capacity between men and women; what is the association of DNA repair with ageing?     

创面修复的一些思考

创面修复是个复杂的过程,随着医学技术的不断进步,创面修复也取得了突飞猛进的发展,包括创面修复机制的不断完善及创面修复各种新技术、新材料的应用。本文着重从创面修复的历史、发展、现状及对创面修复的展望进行相关阐述。     

Changes of DNA repair mechanisms during the aging of the rat

Recent studies have shown a significant reduction in DNA repair capacity in aging rats. Therefore we were interested in investigating which repair mechanism is concerned in this reduction. We investigated: excision repair (ER); single-strand break repair (SSBR); double-strand break repair (DSBR); and gamma-endonuclease susceptibility (ES) by means of the following methods: [3H]thymidine ([3H]dThd) incorporation into DNA after damage by N-methyl-N-nitrosourea (MNU); nucleoid sedimentation after damage by methyl methanesulfonate (MMS); neutral elution techniques after damage by 4-nitroquinoline-1-oxide (NQO); and determination of ES sites by velocity sedimentation in an alkaline sucrose gradient after damage by gamma-irradiation. Studies were done with male Sprague-Dawley rats aged 9, 18 and 28 months using nine different organs. We were able to determine a distinct age dependency of excision repair, a slight reduction of single-strand break repair, an elevation of gamma-endonuclease susceptible sites and no significant change in double-strand break repair in the course of aging. Therefore we see a shift in the pattern of DNA repair: in old age strand break repair mechanisms become more important, while repair replication is reduced. From this we can conclude that genetic expression is altered during the aging process, with all the consequences for the disposition toward certain diseases.     

Danish Hernia Database recommendations for the management of inguinal and femoral hernia in adults

The nationwide Danish Hernia Database, recording more than 10,000 inguinal and 400 femoral hernia repairs annually, provides a unique opportunity to present valid recommendations in the management of Danish patients with groin hernia. The cumulated data have been discussed at biannual meetings and guidelines have been approved by the Danish Surgical Society. Diagnosis of groin hernia is based on clinical examination. Ultrasonography, CT or MRI are rarely needed, while herniography is not recommended. In patients with indicative symptoms of hernia, but no detectable hernia, diagnostic laparoscopy may be an option. Once diagnosed, hernia repair is recommended in the presence of symptoms affecting daily life. In male patients with minimal or absent symptoms watchful waiting is recommended. In females, however, repair is recommended also in asymptomatic patients. In male patients with primary unilateral or bilateral groin hernia the preferred method is mesh repair, either at open surgery (Lichtenstein) or laparoscopically, irrespective of age. Conventional tension-producing methods like Bassini, McVay or Shouldice are no longer recommended in a routine elective setting. Whether repair should be done by open or laparoscopic technique, depends on local expertise, economical considerations and patient preference. Compared to the Lichtenstein operation laparoscopic repair is associated with less acute pain and faster recovery. Furthermore, available data suggest less chronic long-term pain after laparoscopic repair. In female patients laparoscopic repair is the recommended method. In patients with recurrent hernia laparoscopic repair is preferred in patients with a previous open repair, while patients with recurrence after laparoscopic repair should undergo open mesh repair. In open repair it is recommended to use a mesh secured with a nonabsorbable monofilament suture. In laparoscopic repair a mesh without a slit and with a minimum size of 15 by 10 cm is used. For mesh fixation absorbable or nonabsorbable tacks or glue can be used. Elective surgery for groin hernia should be performed in an outpatient setting, using cost-effective local anaesthesia in open mesh repair and general anaesthesia for laparoscopic repair. Spinal anaesthesia is not recommended. Routine prophylactic antibiotics are not indicated. In the early convalescence period there are no physical restrictions. These guidelines will also be available at the website for the Danish Hernia Database (www.herniedatabasen.dk). The guidelines will be updated when new substantial evidence becomes available.     

Proteolysis of a nucleotide excision repair protein by the 26 S proteasome

The 26 S proteasome degrades a broad spectrum of proteins and interacts with several nucleotide excision repair (NER) proteins, including the complex of Rad4 and Rad23 that binds preferentially to UV-damaged DNA. The rate of NER is increased in yeast strains with mutations in genes encoding subunits of the 26 S proteasome, indicating that it could negatively regulate a repair process. The specific function of the 26 S proteasome in DNA repair is unclear. It might degrade DNA repair proteins after repair is completed or act as a molecular chaperone to promote the assembly or disassembly of the repair complex. In this study, we show that Rad4 is ubiquitylated and that Rad23 can control this process. We also find that ubiquitylated Rad4 is degraded by the 26 S proteasome. However, the interaction of Rad23 with Rad4 is not only to control degradation of Rad4, but also to assist in assembling the NER incision complex at UV-induced cyclobutane pyrimidine dimers. We speculate that, following the completion of DNA repair, specific repair proteins might be degraded by the proteasome to regulate repair.     

Does DNA repair occur during somatic hypermutation?

Activation-induced deaminase (AID) initiates a flood of DNA damage in the immunoglobulin loci, leading to abasic sites, single-strand breaks and mismatches. It is compelling that some proteins in the canonical base excision and mismatch repair pathways have been hijacked to increase mutagenesis during somatic hypermutation. Thus, the AID-induced mutagenic pathways involve a mix of DNA repair proteins and low fidelity DNA polymerases to create antibody diversity. In this review, we analyze the roles of base excision repair, mismatch repair, and mutagenesis during somatic hypermutation of rearranged variable genes. The emerging view is that faithful base excision repair occurs simultaneously with mutagenesis, whereas faithful mismatch repair is mostly absent.     

人工鼓膜修补材料的应用与发展

背景：目前鼓膜修补材料仍在不断更新和发展,疗效及疗程各不相同。所以如何选择鼓膜修补材料成为鼓膜修复的关键。 目的：评价人工鼓膜修补材料的性能和应用,寻找合理的鼓膜替代物。 方法：采用电子检索的方式,在万方数据库(http://www.wanfangdata.com.cn/)及Medline数据库(http://www.ncbi.nlm.nih. gov/pubmed/)中检索1999-01/2010-12有关修补材料应用于鼓膜穿孔的研究文章,关键词为“鼓膜修补,组织工程,生物材料”,排除重复研究、普通综述或Meta分析类文章,筛选纳入20篇文献进行评价。 结果与结论：鼓膜穿孔的修复有贴补搭桥法和手术修补法两种。用于鼓膜穿孔的贴补材料有许多种,如鸡蛋衣、棉片、塑料薄膜、淀粉海棉、羊胎膜等等,以上材料也只能是作为一种支架的作用促进穿孔愈合,无促细胞生长的作用。手术修补鼓膜疗效比较确切,需要用颞肌筋膜或乳突骨膜等修补,创伤较大是其缺点,另外手术费较贵。随着医学和组织工程技术的发展,各种合成生物材料相继出现。目前国内使用的鼓膜修补材料有生物蛋白海绵、异种胶原生物膜、组织工程鼓膜、脱细胞真皮基质黏膜组织补片等。虽然自体材料、异体材料、合成生物材料是目前临床上大量使用的鼓膜修补材料,但由于其存在各自不可避免的缺点,鼓膜穿孔修复材料仍需进一步开发。     

DNA repair: kinetics and thresholds

DNA damage is a critical factor in the initiation of chemically induced toxicities (including cancer), and the repair of this damage represents the cell's first line of defense against the deleterious effects of these agents. The various mechanisms of DNA repair are reviewed briefly and the actions of the DNA repair protein O6-alkylguanine DNA alkyltransferase (ATase) are used to illustrate how DNA repair can protect cells against alkylating agent-induced toxicities, mutagenesis, clastogenesis, and carcinogenesis. The effectiveness of this repair protein can be measured based on its ability to deplete levels of its promutagenic substrate O6-methylguanine (O6-meG) in the DNA of cells. These studies reveal that the repair of O6-meG from DNA occurs heterogeneously, both intra- and intercellularly. Even in cells that repair O6-meG hyperefficiently, certain regions of chromatin DNA are repaired with difficulty, and in other regions they are not repaired at all; most likely this lack of repair is a result of the location of the lesion in the DNA sequence. When individual cells are compared within a tissue, some cells are clearly repair deficient, because the O6-meG can persist in DNA for many weeks, whereas in other cells, it is removed within a matter of hours. The role of these repair-deficient cells as targets for alkylating agent induced carcinogenesis is considered. The mechanisms of the homeostatic control of DNA repair function in mammalian cells are not yet well understood. Because there are now indications of the mechanisms by which the level of DNA damage may be sensed (and so influence the activity of the ATase repair protein), this is an important area for future study.