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Regeneration of hair cells in the mammalian vestibular system

null

《医学前沿（英文）》 2016年 第10卷 第2期   页码 143-151 doi: 10.1007/s11684-016-0451-1

摘要：

Hair cells regenerate throughout the lifetime of non-mammalian vertebrates, allowing these animals to recover from hearing and balance deficits. Such regeneration does not occur efficiently in humans and other mammals. Thus, balance deficits become permanent and is a common sensory disorder all over the world. Since Forge and Warchol discovered the limited spontaneous regeneration of vestibular hair cells after gentamicin-induced damage in mature mammals, significant efforts have been exerted to trace the origin of the limited vestibular regeneration in mammals after hair cell loss. Moreover, recently many strategies have been developed to promote the hair cell regeneration and subsequent functional recovery of the vestibular system, including manipulating the Wnt, Notch and Atoh1. This article provides an overview of the recent advances in hair cell regeneration in mammalian vestibular epithelia. Furthermore, this review highlights the current limitations of hair cell regeneration and provides the possible solutions to regenerate functional hair cells and to partially restore vestibular function.

关键词： utricle     hair cell     regeneration     Atoh1     Notch     Wnt    

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Behavioral methods for the functional assessment of hair cells in zebrafish

null

《医学前沿（英文）》 2017年 第11卷 第2期   页码 178-190 doi: 10.1007/s11684-017-0507-x

摘要：

Zebrafish is an emerging animal model for studies on auditory system. This model presents high comparability with humans, good accessibility to the hearing organ, and high throughput capacity. To better utilize this animal model, methodologies need to be used to quantify the hearing function of the zebrafish. Zebrafish displays a series of innate and robust behavior related to its auditory function. Here, we reviewed the advantage of using zebrafish in auditory research and then introduced three behavioral tests, as follows: the startle response, the vestibular-ocular reflex, and rheotaxis. These tests are discussed in terms of their physiological characteristics, up-to-date technical development, and apparatus description. Test limitation and areas to improve are also introduced. Finally, we revealed the feasibility of these applications in zebrafish behavioral assessment and their potential in the high-throughput screening on hearing-related genes and drugs.

关键词： zebrafish (Danio rerio)     behavior     auditory     startle response     vestibular-ocular reflex     rheotaxis    

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MicroRNA-148b promotes proliferation of hair follicle cells by targeting

Wanbao YANG,Qinqun LI,Bo SU,Mei YU

《农业科学与工程前沿（英文）》 2016年 第3卷 第1期   页码 72-80 doi: 10.15302/J-FASE-2016089

摘要： MicroRNAs (miRNAs), small non-coding RNAs, are involved in many aspects of biological processes. Previous studies have indicated that miRNAs are important for hair follicle development and growth. In our study, we found by qRT-PCR that miR-148b was significantly upregulated in sheep wool follicle bulbs in anagen phase compared with the telogen phase of the hair follicle cycle. Overexpression of miR-148b promoted proliferation of both HHDPC and HHGMC. By using the TOPFlash system we demonstrated that miR-148b could activate Wnt/β-catenin pathway and , , and were consistently upregulated accordingly. Furthermore, transcript factor nuclear factor of activated T cells type 5 ( ) and were predicted to be the target of miR-148b and this was substantiated using a Dual-Luciferase reporter system. Subsequently was further identified as the target of miR-148b using western blotting. These results were considered to indicate that miR-148b could activate the Wnt/β-catenin signal pathway by targeting to promote the proliferation of human hair follicle cells.

关键词： miR-148b     hair follicle     proliferation     NFAT5     Wnt10b    

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Loss of liver kinase B1 causes planar polarity defects in cochlear hair cells in mice

null

《医学前沿（英文）》 2016年 第10卷 第4期   页码 481-489 doi: 10.1007/s11684-016-0494-3

摘要：

The tumor suppressor gene liver kinase B1 (LKB1), also called STK11, encodes a serine/threonine kinase. LKB1 plays crucial roles in cell differentiation, proliferation, and polarity. In this study, LKB1 conditional knockout mice (LKB1Pax2 CKO mice) were generated using Pax2-Cre mice to investigate the function of LKB1 in inner ear hair cells during early embryonic period. LKB1Pax2 CKO mice died perinatally. Immunofluorescence and scanning electron microscopy revealed that stereociliary bundles in LKB1Pax2 CKO mice were clustered and misoriented, respectively. Moreover, ectopic distribution of kinocilium bundles resulting from abnormal migration of kinocilium was observed in the mutant mice. The orientation of stereociliary bundles and the migration of kinocilia are critical indicators of planar cell polarity (PCP) of hair cells. LKB1 deficiency in LKB1Pax2 CKO mice thus disrupted hair cell planar polarity during embryonic development. Our results suggest that LKB1 is required in PCP formation in cochlear hair cells in mice.

关键词： LKB1     stereociliary bundles     kinocilium     planar cell polarity     hearing     mice    

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Apigenin alleviates neomycin-induced oxidative damage via the Nrf2 signaling pathway in cochlear haircells

《医学前沿（英文）》 2022年 第16卷 第4期   页码 637-650 doi: 10.1007/s11684-021-0864-3

摘要： Oxidative stress plays an important role in the pathogenesis of aminoglycoside-induced hearing loss and represents a promising target for treatment. We tested the potential effect of apigenin, a natural flavonoid with anticancer, anti-inflammatory, and antioxidant activities, on neomycin-induced ototoxicity in cochlear hair cells in vitro. Results showed that apigenin significantly ameliorated the loss of hair cells and the accumulation of reactive oxygen species upon neomycin injury. Further evidence suggested that the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway was activated by apigenin treatment. Disruption of the Nrf2 axis abolished the effects of apigenin on the alleviation of oxidative stress and subsequent apoptosis of hair cells. This study provided evidence of the protective effect of apigenin on cochlear hair cells and its underlying mechanism.

关键词： apigenin     aminoglycosides     ototoxicity     oxidative stress     Nrf2 signaling pathway    

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Alternative splicing of inner-ear-expressed genes

null

《医学前沿（英文）》 2016年 第10卷 第3期   页码 250-257 doi: 10.1007/s11684-016-0454-y

摘要：

Alternative splicing plays a fundamental role in the development and physiological function of the inner ear. Inner-ear-specific gene splicing is necessary to establish the identity and maintain the function of the inner ear. For example, exon 68 of Cadherin 23 (Cdh23) gene is subject to inner-ear-specific alternative splicing, and as a result, Cdh23(+68) is only expressed in inner ear hair cells. Alternative splicing along the tonotopic axis of the cochlea contributes to frequency tuning, particularly in lower vertebrates, such as chickens and turtles. Differential splicing of Kcnma1, which encodes for the α subunit of the Ca2+-activated K+ channel (BK channel), has been suggested to affect the channel gating properties and is important for frequency tuning. Consequently, deficits in alternative splicing have been shown to cause hearing loss, as we can observe in Bronx Waltzer (bv) mice and Sfswap mutant mice. Despite the advances in this field, the regulation of alternative splicing in the inner ear remains elusive. Further investigation is also needed to clarify the mechanism of hearing loss caused by alternative splicing deficits.

关键词： alternative splicing     inner ear     hearing loss     hair cells    

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is essential for the integrity of stereociliary rootlet in cochlear hair cells in mice

Yuqin Men, Xiujuan Li, Hailong Tu, Aizhen Zhang, Xiaolong Fu, Zhishuo Wang, Yecheng Jin, Congzhe Hou, Tingting Zhang, Sen Zhang, Yichen Zhou, Boqin Li, Jianfeng Li, Xiaoyang Sun, Haibo Wang, Jiangang Gao

《医学前沿（英文）》 2019年 第13卷 第6期   页码 690-704 doi: 10.1007/s11684-018-0638-8

摘要： encodes the taperin protein, which is concentrated in the tapered region of hair cell stereocilia in the inner ear. In humans, mutations cause autosomal recessive nonsyndromic deafness (DFNB79) by an unknown mechanism. To determine the role of in hearing, we generated -null mice by clustered regularly interspaced short palindromic repeat/Cas9 genome-editing technology from a CBA/CaJ background. We observed significant hearing loss and progressive degeneration of stereocilia in the outer hair cells of -null mice starting from postnatal day 30. Transmission electron microscopy images of stereociliary bundles in the mutant mice showed some stereociliary rootlets with curved shafts. The central cores of the stereociliary rootlets possessed hollow structures with surrounding loose peripheral dense rings. Radixin, a protein expressed at stereocilia tapering, was abnormally dispersed along the stereocilia shafts in null mice. The expression levels of radixin and -actin significantly decreased. We propose that is critical to the retention of the integrity of the stereociliary rootlet. Loss of in -null mice caused the disruption of the stereociliary rootlet, which resulted in damage to stereociliary bundles and hearing impairments. The generated -null mice are ideal models of human hereditary deafness DFNB79.

关键词： TPRN     stereocilia     stereociliary rootlet     actin filament     CRISPR/Cas9     hearing    

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Role of Wnt and Notch signaling in regulating hair cell regeneration in the cochlea

null

《医学前沿（英文）》 2016年 第10卷 第3期   页码 237-249 doi: 10.1007/s11684-016-0464-9

摘要：

Sensory hair cells in the inner ear are responsible for sound recognition. Damage to hair cells in adult mammals causes permanent hearing impairment because these cells cannot regenerate. By contrast, newborn mammals possess limited regenerative capacity because of the active participation of various signaling pathways, including Wnt and Notch signaling. The Wnt and Notch pathways are highly sophisticated and conserved signaling pathways that control multiple cellular events necessary for the formation of sensory hair cells. Both signaling pathways allow resident supporting cells to regenerate hair cells in the neonatal cochlea. In this regard, Wnt and Notch signaling has gained increased research attention in hair cell regeneration. This review presents the current understanding of the Wnt and Notch signaling pathways in the auditory portion of the inner ear and discusses the possibilities of controlling these pathways with the hair cell fate determiner Atoh1 to regulate hair cell regeneration in the mammalian cochlea.

关键词： inner ear     cochlea     hair cell     regeneration     Wnt     Notch     signaling pathways    

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Relationship between selenium concentration in child hair and the distribution of Kashin-Beck Disease

LI Shunjiang, YANG Linsheng, WANG Wuyi, LI Yonghua, LI Hairong, XIRAO Ruodeng

《医学前沿（英文）》 2007年 第1卷 第2期   页码 223-225 doi: 10.1007/s11684-007-0043-1

摘要： The focus of this study is to determine the relationship between selenium (Se) concentrations in child hair and the distribution of Kashin-Beck disease (KBD) in Tibet. The hair of children in typical KBD-affected areas and non-disease areas was collected, and its Se concentrations were measured by atomic fluorescent spectrometry. The Se concentrations in child hair were (0.13±0.04) and (0.18±0.07) µg/g respectively in KBD areas and non-disease areas respectively, which are significantly different. In areas supplemented with Se in Tibet, the Se concentration of hair in KBD- affected areas was higher than that in non-diseased areas, being (0.28±0.03) and (0.18±0.04) µg/g respectively. There is a close relationship between the Se concentrations in hair and KBD distribution. Se supplement increase the Se concentrations in the human body. Appropriate Se supplementation is important to prevent KBD in Tibet.

关键词： different     relationship     non-disease     selenium     KBD distribution    

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Identification and selection of resistance to

Lizhen ZHU, Jianying LI, Zhongping XU, Hakim MANGHWAR, Sijia LIANG, Suli LI, Muna ALARIQI, Shuangxia JIN, Xianlong ZHANG

《农业科学与工程前沿（英文）》 2018年 第5卷 第2期   页码 236-252 doi: 10.15302/J-FASE-2018223

摘要： Plants have developed sophisticated systems to cope with herbivore challenge, including morphological barriers and secondary metabolites to reduce damage. In this study, 550 genotypes were evaluated for whitefly ( ) resistance in five experiments including two in the field and three in the greenhouse, with 23 resistant and 19 susceptible genotypes selected. Whitefly-resistance index determination showed that a leaf having a high density of hairs had resistance to whitfly egg/nymph production. Longer leaf hairs were also important for resistance. This study revealed that okra shaped leaves reduced adult whitefly oviposition preference, while glabrous leaves and high hair density helped not only in the reduction of the adults but also decreased oviposition preference. Gossypol was also observed to be involved in the reduction of adult whitefly development and/or survival.

关键词： Bemisia tabaci     Gossypium genotypes     gossypol     leaf hair density     leaf hair length    

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Porcine pluripotent stem cells: progress, challenges and prospects

Jianyong HAN, Yi-Liang MIAO, Jinlian HUA, Yan LI, Xue ZHANG, Jilong ZHOU, Na LI, Ying ZHANG, Jinying ZHANG, Zhonghua LIU

《农业科学与工程前沿（英文）》 2019年 第6卷 第1期   页码 8-27 doi: 10.15302/J-FASE-2018233

摘要：

Pluripotent stem cells (PSCs) are characterized by their capacity for high self-renewal and multiple differentiation potential and include embryonic stem cells, embryonic germ cells and induced PSCs. PSCs provide a very suitable model for the studies of human diseases, drugs screening, regenerative medicine and developmental biology research. Pigs are considered as an ideal model for preclinical development of human xenotransplantation, therapeutic approaches and regenerative medicine because of their size and physiological similarity to humans. However, lack of knowledge about the derivation, characterization and pluripotency mechanisms of porcine PSCs hinders progress in these biotechnologies. In this review, we discuss the latest progress on porcine PSCs generation, evaluation criteria for pluripotency, the scientific and technical questions arising from these studies. We also introduce our perspectives on porcine PSC research, in the hope of providing new ideas for generating naive porcine PSCs and animal breeding.

关键词： embryonic germ cells     embryonic stem cells     induced pluripotent stem cells     pigs     pluripotent stem cells    

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Determination of telomerase activity in stem cells and non-stem cells of breast cancer

LI Zhi, HE Yanli, ZHANG Jiahua, ZHANG Jinghui, HUANG Tao

《医学前沿（英文）》 2007年 第1卷 第3期   页码 294-298 doi: 10.1007/s11684-007-0056-9

摘要： Although all normal tissue cells, including stem cells, are genetically homologous, variation in gene expression patterns has already determined the distinct roles for individual cells in the physiological process due to the occurrence of epigenetic modification. This is of special importance for the existence of tissue stem cells because they are exclusively immortal within the body, capable of selfreplicating and differentiating by which tissues renew and repair itself and the total tissue cell population maintains a steady-state. Impairment of tissue stem cells is usually accompanied by a reduction in cell number, slows down the repair process and causes hypofunction. For instance, chemotherapy usually leads to depression of bone marrow and hair loss. Cellular aging is closely associated with the continuous erosion of the telomere while activation of telomerase repairs and maintains telomeres, thus slowing the aging process and prolonging cell life. In normal adults, telomerase activation mainly presents in tissue stem cells and progenitor cells giving them unlimited growth potential. Despite the extensive demonstration of telomerase activation in malignancy (>80%), scientists found that heterogeneity also exists among the tumor cells and only minorities of cells, designated as cancer stem cells, undergo processes analogous to the self-renewal and differentiation of normal stem cells while the rest have limited lifespans. In this study, telomerase activity was measured and compared in breast cancer stem cells and non-stem cells that were phenotypically sorted by examining surface marker expression. The results indicated that cancer stem cells show a higher level of enzyme activity than non-stem cells. In addition, associated with the repair of cancer tissue (or relapse) after chemotherapy, telomerase activity in stem cells was markedly increased.
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Innate and adaptive T cells in influenza disease

null

《医学前沿（英文）》 2018年 第12卷 第1期   页码 34-47 doi: 10.1007/s11684-017-0606-8

摘要：

Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza-specific T-cell responses are yet to be optimized. During natural infection, viral replication is initially controlled by innate immunity before adaptive immune responses (T cells and antibody-producing B cells) achieve viral clearance and host recovery. Adaptive T and B cells maintain immunological memory and provide protection against subsequent infections with related influenza viruses. Recent studies also shed light on the role of innate T-cells (MAIT cells, gd T cells, and NKT cells) in controlling influenza and linking innate and adaptive immune mechanisms, thus making them attractive targets for vaccination strategies. We summarize the current knowledge on influenza-specific innate MAIT and gd T cells as well as adaptive CD8+ and CD4+ T cells, and discuss how these responses can be harnessed by novel vaccine strategies to elicit cross-protective immunity against different influenza strains and subtypes.

关键词： influenza     innate T cells     CD4+ and CD8+ T cells     vaccination    

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Reprogramming of the pig primordial germ cells into pluripotent stem cells: a brief review

Qijing LEI, Qin PAN, Shuai YU, Na LI, Shulin CHEN, Kuldip SIDHU, Jinlian HUA

《农业科学与工程前沿（英文）》 2019年 第6卷 第1期   页码 28-32 doi: 10.15302/J-FASE-2018222

摘要：

Primordial germ cells (PGCs) are regarded as unipotent cells that can produce only either spermatogonia or oocytes. However, PGCs can be converted into the pluripotent state by first dedifferentiation to embryonic germ cells and then by reprogramming to induce them to become pluripotent stem cells (iPSCs). These two stages can be completely implemented with mouse cells. However, authentic porcine iPSCs have not been established. Here, we discuss recent advances in the stem cell field for obtaining iPSCs from PGCs. This knowledge will provide some clues which will contribute to the regulation of reprogramming to pluripotency in farm species.

关键词： pig     pluripotent stem cells     primordial germ cells     reprogramming    

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4-1BBL expressed by eukaryotic cells activates immune cells and suppresses the progression of murine

Hui QIU, Hui ZHANG, Zuohua FENG

《医学前沿（英文）》 2009年 第3卷 第1期   页码 20-25 doi: 10.1007/s11684-009-0006-9

摘要： The interaction by co-stimulatory molecules 4-1BB and 4-1BB ligand (4-1BBL) plays an important role in the activation, proliferation and differentiation of T lymphocytes. The function of 4-1BB/4-1BBL expressed by the immune cells has been the focus for many tumor immunotherapy efforts. In this study, 4-1BBL was expressed in non-immune cells and non-tumor cells, and the role of 4-1BBL in lymphocyte activation and tumor suppression was investigated. The plasmid p4-1BBL containing the full length of mouse 4-1BBL cDNA sequence was constructed, and the plasmid was transfected into baby hamster kidney (BHK) cells and murine muscle cells by means of lipofectin-mediated or naked plasmid DNA injection into the muscle directly. The study demonstrated that the molecule 4-1BBL expressed by BHK cells could enhance the proliferation and cytotoxicity of lymphocytes, and it could increase the expression level of IL-2 and IFN-γ. The treatment with plasmid p4-1BBL revealed that the number of CD8 T cells in the peri-tumoral tissue increased markedly, and the growth rate of the tumor was significantly lower than that of control group. These findings suggest that expression of 4-1BBL by normal cells in the tumor microenvironment can enhance the proliferation and other functions of T lymphocytes. This therapeutic method may provide a promising approach for tumor immunotherapy.

关键词： 4-1BB ligand     tumor immunotherapy     tumor microenvironment    

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标题 作者 时间 类型 操作

Regeneration of hair cells in the mammalian vestibular system

null

期刊论文

Behavioral methods for the functional assessment of hair cells in zebrafish

null

期刊论文

MicroRNA-148b promotes proliferation of hair follicle cells by targeting

Wanbao YANG,Qinqun LI,Bo SU,Mei YU

期刊论文

Loss of liver kinase B1 causes planar polarity defects in cochlear hair cells in mice

null

期刊论文

Apigenin alleviates neomycin-induced oxidative damage via the Nrf2 signaling pathway in cochlear haircells

期刊论文

Alternative splicing of inner-ear-expressed genes

null

期刊论文

is essential for the integrity of stereociliary rootlet in cochlear hair cells in mice

Yuqin Men, Xiujuan Li, Hailong Tu, Aizhen Zhang, Xiaolong Fu, Zhishuo Wang, Yecheng Jin, Congzhe Hou, Tingting Zhang, Sen Zhang, Yichen Zhou, Boqin Li, Jianfeng Li, Xiaoyang Sun, Haibo Wang, Jiangang Gao

期刊论文

Role of Wnt and Notch signaling in regulating hair cell regeneration in the cochlea

null

期刊论文

Relationship between selenium concentration in child hair and the distribution of Kashin-Beck Disease

LI Shunjiang, YANG Linsheng, WANG Wuyi, LI Yonghua, LI Hairong, XIRAO Ruodeng

期刊论文

Identification and selection of resistance to

Lizhen ZHU, Jianying LI, Zhongping XU, Hakim MANGHWAR, Sijia LIANG, Suli LI, Muna ALARIQI, Shuangxia JIN, Xianlong ZHANG

期刊论文

Porcine pluripotent stem cells: progress, challenges and prospects

Jianyong HAN, Yi-Liang MIAO, Jinlian HUA, Yan LI, Xue ZHANG, Jilong ZHOU, Na LI, Ying ZHANG, Jinying ZHANG, Zhonghua LIU

期刊论文

Determination of telomerase activity in stem cells and non-stem cells of breast cancer

LI Zhi, HE Yanli, ZHANG Jiahua, ZHANG Jinghui, HUANG Tao

期刊论文

Innate and adaptive T cells in influenza disease

null

期刊论文

Reprogramming of the pig primordial germ cells into pluripotent stem cells: a brief review

Qijing LEI, Qin PAN, Shuai YU, Na LI, Shulin CHEN, Kuldip SIDHU, Jinlian HUA

期刊论文

4-1BBL expressed by eukaryotic cells activates immune cells and suppresses the progression of murine

Hui QIU, Hui ZHANG, Zuohua FENG

期刊论文