EXPERIMENTAL STUDY OF COCHLEAR HAIR CELL LOSS IN THE GUINEA PIG

The damage to spiral organs related to age and sex in guinea pigs was studied by the surface preparation technique. Hair cell loss of spiral organs of the following four age groups: 8month, 1, 2, and 2.5-year old pigs, was assessed. Each group was divided Into two subgroups according to different sexes. The decrease of hair cell population was linearly related to age, but not related to sex. The damage rate was greater in outer hair cells than in inner hair calls. In all of animals of different ages and both sexes, outer hair cell loss was prominent at the apex of cochlea. Less damage to outer hair cell was found at the base of cochlea. Damage to inner hair cell was also increased with age, but to a lesser extent.

PTEN inhibitor bisperoxovanadium protects against noise-induced hearing loss

Studies have shown that phosphatase and tensin homolog deleted on chromosome ten(PTEN)participates in the regulation of cochlear hair cell survival.Bisperoxovanadium protects against neurodegeneration by inhibiting PTEN expression.However,whether bisperoxovanadium can protect against noise-induced hearing loss and the underlying mechanism remains unclear.In this study,we established a mouse model of noise-induced hearing loss by exposure to 105 dB sound for 2 hours.We found that PTEN expression was increased in the organ of Corti,including outer hair cells,inner hair cells,and lateral wall tissues.Intraperitoneal administration of bisperoxovanadium decreased the auditory threshold and the loss of cochlear hair cells and inner hair cell ribbons.In addition,noise exposure decreased p-PI3K and p-Akt levels.Bisperoxovanadium preconditioning or PTEN knockdown upregulated the activity of PI3K-Akt.Bisperoxovanadium also prevented H_(2)O_(2)-induced hair cell death by reducing mitochondrial reactive oxygen species generation in cochlear explants.These findings suggest that bisperoxovanadium reduces noise-induced hearing injury and reduces cochlear hair cell loss.

Correlation of PDCD5 and Apoptosis in Hair Cells and Spiral Ganglion Neurons of Different Age of C57BL/6J Mice

This study examined the expression pattern of programmed cell death 5 (PDCD5) in co-chlear hair cells and spiral ganglion neurons (SGNs) and its association with age-related hearing loss in mice.Sixty C57BL/6J (C57) mice at different ages were divided into four groups (3,6,9 or 12 months).PDCD5 expression was detected by using immunohistochemistry,real-time PCR and Western blot.Morphological change of the cochleae was also evaluated by using immunoassay.The results showed that the expression of PDCD5 had a gradual increase with ageing in both protein and RNA levels in C57 mice,as well as gradually increased apoptosis of cochlear hair cells and SGNs.In addition,we also found that caspase-3 activity was enhanced and its expression was enhanced with ageing.It is implied that overexpression of PDCD5 causes the increase in caspase-3 activity and the subsequent increase of apoptosis in cochlear hair cells and SGNs,and thereby plays a role in the pathogenesis of presbycusis.Thus,PDCD5 may be a new target site for the treatment and prevention of age-related hearing loss.

Inner ear hair cell regeneration A look from the past to the future

Most recent studies on regeneration of inner ear hair cells focus on use of stem cells, gene therapy and neurotrophic factors. Cochlear gene therapy has been successfully used in the treatment of neu- rosensory hearing loss. This suggests that cochlear hair cell regeneration is possible. The objective of this paper is to review research and clinical application of inner near hair cell regeneration.

防脱育发草本精粹对毛发生长及其抗氧化、抗炎的性质研究

目的 探究防脱育发草本精粹防脱育发能力。方法 通过细胞计数试剂盒8测定防脱育发草本精粹对真皮乳头细胞(DPC)增殖与抗氧化能力作用,利用实时荧光定量PCR检测防脱育发草本精粹对DPC抗氧化、抗炎症关键基因的表达影响,通过动物实验验证其对于毛发生长的作用。结果 防脱育发草本精粹(250μg/ml)能显著促进DPC增殖与抗氧化能力,显著抑制白细胞介素-6(IL-6)和促进抗氧化相关基因:谷氨酸-半胱氨酸连接酶修饰剂亚基基因(GCLM)、血红素加氧酶1基因(HMOX1)、铁蛋白重链1基因(FTH1)、铁蛋白轻链基因(FTL)、NAD(P)H:醌氧化还原酶1(NQO1)的表达,差异有统计学意义(P <0.05)。动物实验验证显示,防脱育发草本精粹缩短了小鼠毛囊的休止期。结论 该防脱育发草本精粹显著促进DPC的增殖、抗氧化及抗炎症能力,缩短毛囊的休止期和促进毛发生长。

The potential of miR-183 family expression in inner ear for regeneration,treatment,diagnosis and prognosis of hearing loss

miRNA-183 family, in normal biology, is expressed in a harmonious and stable manner in the neurosensory organs and cells. Studies have also shown that miRNA-183 family, in different pathways, affects the neurosensory development, maintenance, survival and function. In addition, it has potential neuroprotective effects in response to neurosensory destructive stimulations. miRNA-96 mutation causes hereditary deafness in humans and mice, and therefore affects the inner ear activity and its maintenance. Certain roles have been identified for mi R-96 in the maintenance and function of the inner ear. The comparison of the target genes of family-183 in transcriptomes of newborn and adult hair cells shows that hundreds of target genes in this family may affect development and maintenance of the ears. Identifying the genes that are regulated by miRNA-183 family provides researchers with important information about the complex development and environmental regulation of the inner ear, and can offer new approaches to the maintenance and regeneration of hair cells and auditory nerve.

THE GENETIC-INDUCED HEARING lOSS CAN BLOCK THE EFFECT OF NOISE TRAUMA IN WAlTZING GUINEA PIG

The waltzing guinea pig may be a good model to investigate if genetic factor can change the sensitivity in noise-induced hearing loss. A total of 34 waltzig guinea pigs were studied and we found that there is no any significant increased sensitivity to noise trauma if the age-induced hearing loss was considered in waltz-ing guinea pig.

不同种属实验动物耳蜗毛细胞年龄相关性缺失的不同模式

目的展示自然衰老和耳聋相关基因遗传缺陷之间耳蜗毛细胞缺失的不同模式。方法用不同龄的长尾猴、南美栗鼠、豚鼠、Sprague-Dawley大鼠、CBA/CaJ小鼠、C57BL/6J小鼠、A/J小鼠、DBA/2J小鼠和侏儒灰色突变纯合子(dwg/dwg)小鼠作为受试对象。所有测试动物的耳蜗基底膜都被制作成平坦的耳蜗基底膜铺片。沿着耳蜗基底膜的全长,基底膜上所有的内外毛细胞都被完整计数,毛细胞的计数结果被输入到耳蜗图软件并自动生成每组实验条件的平均耳蜗图。结果在天然衰老的动物中,耳蜗毛细胞的缺失总是发生在老年阶段。与此不同的是,在耳聋相关基因缺陷的动物中,耳蜗毛细胞的缺失却是发生在青年阶段甚至幼年阶段。发生在天然老化动物的耳蜗毛细胞缺失总是呈均匀分布或从耳蜗的顶回向底回扩展。但是,发生在具有耳聋相关基因遗传缺陷动物的耳蜗毛细胞缺失却通常表现为从耳蜗的底回向顶回扩展。结论本实验观察结果表明,发生在天然衰老的不具备耳聋相关基因缺陷动物身上的年龄相关性耳蜗毛细胞缺失反映的是真正由衰老引起的耳蜗退化性病变,而发生在伴有耳聋相关基因遗传缺陷的年幼动物身上的年龄相关性耳蜗毛细胞缺失可能与耳聋相关基因的遗传缺陷有关。

Polyphenol-Rich Olive Mill Wastewater Extract and Its Potential Use in Hair Care Products

In this work, the influence of phenol-enriched olive mill wastewater (OMWW) extract on hair growth was investigated in vitro on human follicle dermal papilla cells. OMWW has already shown great potential for use in skincare products, and its high polyphenol content is predestined to have a positive effect on hair growth. The studies included caffeine, a positive modulator of hair growth, and dihydrotestosterone, which causes hair loss in vivo, as controls. The impact of the investigated compounds on hair growth was evaluated by studies on cell viability and proliferation, the release of growth factors (insulin-like growth factor-1 and vascular endothelial growth factor), and the reduction of reactive oxygen species formation. OMWW showed a positive influence on the proliferation of the human follicle dermal papilla cells. Moreover, the extract leads to a significantly increased secretion of insulin-like growth factor-1, and a considerable reduction in reactive oxygen species formation was observed. Overall, our results show that the investigated phenol-enriched OMWW extract is a promising ingredient for hair care to improve hair growth, prevent hair loss due to oxidative stress and maintain a healthy scalp.

柴胡皂苷A对噪声诱发听力损失小鼠受损毛细胞及氧化应激的影响

【目的】探讨柴胡皂苷A对噪声诱发听力损失小鼠的干预作用及机制。【方法】将45只C57BL/6小鼠随机分为正常组、噪声暴露组、柴胡皂苷A组,每组15只。柴胡皂苷A组接受噪声暴露的同时给予柴胡皂苷A 10.0 g·kg^(-1)·d^(-1)灌胃;噪声暴露组接受噪声暴露,给予等体积生理盐水灌胃;正常组不接受噪声暴露,给予等体积生理盐水灌胃。每日1次灌胃,连续4周。给药结束后,检测小鼠听力脑干反应(ABR),采用Hoechst荧光染色法和扫描电镜分别对应观察耳蜗毛细胞数量、形态,采用8-羟基脱氧鸟苷(8-OHdG)免疫荧光染色法观察耳蜗组织氧化应激损伤情况,Western Blot法检测耳蜗组织4-羟基壬烯醛(4-HNE)及3-硝基酪氨酸(3-NT)表达。【结果】(1)与正常组比较,噪声暴露组小鼠ABR域值明显增加(P<0.001);与噪声暴露组比较,柴胡皂苷A组小鼠ABR域值明显降低(P<0.01)。(2)正常组小鼠耳蜗毛细胞核完整、纤毛排列有序;噪声暴露组耳蜗毛细胞核部分丢失,纤毛出现倾斜、部分破裂;柴胡皂苷A组耳蜗毛细胞核完整性、纤毛形态较噪声暴露组得到明显改善。(3)与正常组比较,噪声暴露组小鼠耳蜗毛细胞中8-OHdG及耳蜗组织4-HNE、3-NT表达水平明显升高(P<0.001);与噪声暴露组比较,柴胡皂苷A组小鼠耳蜗毛细胞中8-OHdG及耳蜗组织4-HNE、3-NT表达水平明显降低(P<0.01)。【结论】柴胡皂苷A可有效干预小鼠噪声性听力损失,其机制与抑制氧化应激、保护耳蜗毛细胞有关。

沙利度胺联合CHOP化疗方案对B细胞非霍奇金淋巴瘤患者免疫功能的影响

目的探讨沙利度胺联合CHOP化疗方案对B细胞非霍奇金淋巴瘤患者免疫功能的影响。方法选取2018年6月至2021年6月期间在聊城市第二人民医院行一线化疗的B细胞非霍奇金淋巴瘤患者共86例。按照随机数字表法分为对照组和研究组,对照组43例中男21例,女22例,年龄范围16~55岁,中位年龄32.7岁;联合组43例中男22例,女21例,年龄范围16~58岁,中位年龄33.6岁。对照组接受CHOP化疗方案[长春新碱(1.4 mg/m2 d1)+表柔比星(50 mg/m2 d1)+环磷酰胺(750 mg/m2 d1)+泼尼松(100 mg qd d1~5)];联合组在CHOP化疗方案的基础上另给予沙利度胺(100 mg/d)治疗,21 d为1个治疗周期。对比两组患者近期疗效、免疫功能水平[CD3+、免疫球蛋白G(IgG)]、不良反应发生率。统计学方法采用t检验、χ^(2)检验。结果对照组患者完全缓解13例、部分缓解8例、未缓解22例;联合组完全缓解22例、部分缓解8例、未缓解13例;联合组治疗有效率为69.77%(30/43),高于对照组的48.44%(21/43)(χ^(2)=4.900,P=0.027)。两组患者治疗前CD3+、IgG水平比较差异均无统计学意义(t=0.240、0.146,P=0.811、0.884);治疗后,两组CD3+、IgG水平均高于同组治疗前(均P<0.05),且联合组的CD3+、IgG水平均高于对照组(t=2.131、11.939,P=0.036、<0.001)。联合组治疗期间不良反应总发生率为18.60%(8/43),对照组为16.28%(7/43),差异无统计学意义(χ^(2)=0.081,P=0.776)。结论B细胞非霍奇金淋巴瘤患者采用沙利度胺联合CHOP化疗方案治疗可提高临床疗效,改善免疫功能,且安全性良好,值得推广。

前庭神经鞘膜瘤外泌体对小鼠耳蜗基底膜的影响研究

目的研究前庭神经鞘膜瘤(vestibular schwannoma,VS)外泌体对小鼠耳蜗基底膜的影响,探讨其在VS患者听力下降中的潜在作用。方法收集2020年9月至2021年6月于上海交通大学医学院附属第九人民医院耳鼻咽喉头颈外科手术治疗的6例Ⅱ、Ⅲ期中小型VS患者的肿瘤组织及临床资料,根据AAO-HNS听力分级分为听力好组(Good Hearing,GH)和听力差组(Poor Hearing,PH);采用超速离心法提取VS原代细胞上清中的外泌体,通过Western-blot、透射电镜、纳米流式鉴定外泌体;免疫荧光染色技术探究VS外泌体对小鼠耳蜗基底膜毛细胞形态及数量的影响。结果在一定浓度下,PH组外泌体造成小鼠基底膜毛细胞数量减少,细胞形态异常,细胞排列紊乱;而GH组外泌体对毛细胞的形态及数量几乎无影响;当外泌体浓度下降,PH组外泌体仅造成毛细胞出现极少数量的丢失。结论VS外泌体具有不同程度的耳毒性,对小鼠耳蜗毛细胞的损伤具有浓度依赖性。

自噬在感音神经性耳聋中的研究进展

自噬能够清除细胞内损伤的细胞器及错误折叠的蛋白质,是细胞应对损伤、维持稳态的一种方式。自噬在各种疾病的发生发展中都发挥重要作用,在药物性耳聋、老年性耳聋以及噪声性耳聋中能够减少毛细胞死亡,从而保护听力。本综述总结了自噬在感音神经性耳聋中的研究进展,以期为自噬在毛细胞损伤中的作用及机制研究提供参考。

老年性耳聋病因及分子机制的研究进展

老年性耳聋是老年人群中最常见的感觉缺陷之一,又称为年龄相关性听力损失,是老年人最普遍的感觉缺陷。随着社会逐渐老龄化,老年性耳聋的发病率越来越高。老年性耳聋严重影响了老年人的身心健康,导致老年人的生活质量下降、认知能力改变、社交孤立以及抑郁、沟通障碍等。研究其病因及发病机制对老年性耳聋的诊断、治疗和预防具有重要意义。本综述总结了老年性耳聋分子机制、致病因素、病理分型、治疗手段等。

MCU在感音神经性耳聋中的研究进展

感音神经性耳聋(sensorineural hearing loss, SNHL)是世界性的公共健康问题,其制约人际交流,给社会造成严重负担。线粒体功能障碍和氧化胁迫是目前公认的SNHL的发病机制之一。线粒体钙离子单向转运体(mitochondrial calcium uniporter, MCU)作为线粒体的重要钙通道,参与维持细胞的信号传导与钙离子稳态。然而,其在SNHL的研究机制尚不明确,本文旨在讨论MCU及其维持的钙稳态在SNHL等疾病中的研究进展,为SNHL的防治指明可能的方向。

基于内耳干细胞的毛细胞再生调控研究进展

听力损失的发病率和致残率很高,给社会和经济带来沉重负担。毛细胞的不可逆性损失是感音神经性耳聋的主要原因。明确损伤修复的机制并开发新的防治策略迫在眉睫。利用多种信号和转录因子触发内耳干细胞的激活并再生功能性毛细胞是有希望的治疗手段。本文对诱导退变毛细胞有效功能再生的信号通路和调控策略进行了回顾和总结,并讨论了未来潜在的治疗方法,如小分子药物和基因治疗用于临床再生功能性毛细胞的可行性。

干细胞在毛发再生中的应用进展

现代生活节奏快、压力大等原因,使得越来越多的人受到病理性脱发的困扰。目前脱发的治疗方法仍存在多种挑战,例如药物疗效、副作用、患者依从性、毛囊移植的不利结局等因素。近年来,再生医学和毛发组织工程领域的显著进步,为脱发的干细胞疗法带来了新希望。基于干细胞的治疗方法,可以在实验室环境中产生毛发样结构或操纵其天然生态位中的细胞以重建毛囊。现阶段基于干细胞的脱发治疗可分为三类:干细胞移植、干细胞条件培养基的使用及干细胞外泌体的使用。本文主要总结使用基于干细胞的方法进行脱发治疗的最新进展。

乙酰基四肽-11防脱发作用的研究

将乙酰基四肽-11应用于小鼠进行脱发研究。通过对C57BL/6雌性小鼠背部进行脱毛处理,实验组连续涂抹3个质量浓度梯度(10,20和30μg/mL)的乙酰基四肽-11水溶液18天,对照组涂抹生理盐水,观察小鼠背部毛发生长情况,HE染色进行组织学分析,并初步进行了志愿者试用评估。结果表明,一定质量浓度的乙酰基四肽-11可以预防小鼠脱发,避免毛囊微型化,同时可以维持小鼠表皮紧致。志愿者试用评估表明测试样品对所有志愿者都有防脱发效果,85%志愿者反馈头发密度变大。

线粒体自噬在感音神经性耳聋中的研究进展

大部分感音神经性聋是由于内耳毛细胞不可逆的损伤导致的,外界或自身因素导致的自由基的积累、炎症、凋亡/坏死等是毛细胞损伤的主要途径。线粒体作为细胞内的能量代谢中心,同时也参与调节活性氧代谢和介导炎症及凋亡的发生。线粒体自噬作为重要的线粒体质量控制系统,是体内维持线粒体稳态和清除损伤线粒体的主要形式。已有研究表明,在听力损失动物模型中观察到异常的线粒体自噬,并通过干预可以减少部分毛细胞的损伤程度。本文旨在系统性的介绍近期关于线粒体自噬在感音神经性聋领域中取得的研究进展。

Atoh1基因与POU4F3、Gfi1协同作用促毛细胞再生的研究进展

听力损失是导致语言障碍和影响人口素质的一种世界性顽疾,主要由内耳毛细胞不可逆损伤所致。治疗此类顽疾的核心是毛细胞再生。直接重编程作为一种细胞再生技术,无需经过多能性细胞阶段便可将一种终末分化细胞直接转变为其他类型的功能细胞或祖细胞,因此也称为谱系重编程[1-2],包括直接和间接两种方式。直接的方式是通过导入谱系特异性转录因子诱导一种类型终末分化细胞转化为另一种细胞类型,如慢病毒载体携带转录因子编码基因感染支持细胞或成纤维细胞,经细胞形态、相关基因和蛋白表达等参数验证获得与正常内耳毛细胞相似的细胞,从而实现毛细胞再生的目的[3-5]。