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The Effects of Atoh8 on Postnatal Murine Neurogenesis. Atoh8对小鼠出生后神经发生的影响
IF 2.9 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2025-01-01 Epub Date: 2024-08-27 DOI: 10.1159/000540440
Dilek Culhalik, Morris Gellisch, Gabriela Morosan-Puopolo, Darius Saberi
<p><strong>Introduction: </strong>Basic helix-loop-helix (bHLH) transcription factors are expressed in various organs and are involved in diverse developmental processes. The mouse atonal homolog 8 (Atoh8), a bHLH transcription factor, plays a crucial role in various developmental processes, especially as a regulator of neurogenesis in the retina. Besides, Atoh8 expression has been observed in the central nervous system. The function of Atoh8 during the postnatal neurogenesis is still unclear.</p><p><strong>Methods: </strong>This study focuses on elucidating the impact of Atoh8 on postnatal neurogenesis in the brain, particularly in selected regions: the subventricular zone (SVZ), rostral migratory stream (RMS), and olfactory bulb (OB), across different life stages, using male homozygous Atoh8-knockout (M6KO) mice. Our morphometric analysis is based on immunohistochemically labeled markers for neuroblasts (doublecortin) and proliferation (phospho-histone H3, PHH3) as well as pan neuronal markers.</p><p><strong>Results: </strong>In Atoh8-/- mice, alteration in the postnatal neurogenesis can be observed. Immunohistochemical analysis revealed a significant reduction in doublecortin-positive neuroblasts within the SVZ of neonatal M6KO mice compared to wild-type mice. Interestingly, no differences in cell number and distribution were observed in the subsequent migration of neuroblasts through the RMS to the OB. Proliferating PHH3-positive neuronal progenitor cells were significantly diminished in the proliferation rate in both the SVZ and RMS of neonatal and young M6KO mice. Furthermore, in the glomerular layer of the OB, significantly fewer neurons were detected in the neonatal stage.</p><p><strong>Conclusion: </strong>In conclusion, Atoh8 emerges as a positive regulator of postnatal neurogenesis in the brain. Its role encompasses the promotion of neuroblast formation, modulation of proliferation rates, differentiation, and maintenance of mature neurons. Understanding the intricacies of Atoh8 function provides valuable insights into the complex regulatory mechanisms governing neurogenesis.</p><p><strong>Introduction: </strong>Basic helix-loop-helix (bHLH) transcription factors are expressed in various organs and are involved in diverse developmental processes. The mouse atonal homolog 8 (Atoh8), a bHLH transcription factor, plays a crucial role in various developmental processes, especially as a regulator of neurogenesis in the retina. Besides, Atoh8 expression has been observed in the central nervous system. The function of Atoh8 during the postnatal neurogenesis is still unclear.</p><p><strong>Methods: </strong>This study focuses on elucidating the impact of Atoh8 on postnatal neurogenesis in the brain, particularly in selected regions: the subventricular zone (SVZ), rostral migratory stream (RMS), and olfactory bulb (OB), across different life stages, using male homozygous Atoh8-knockout (M6KO) mice. Our morphometric analysis is based on immunohis
导言 基本螺旋-环-螺旋(bHLH)转录因子在各种器官中都有表达,并参与多种发育过程。小鼠阿通同源物 8(Atoh8)是一种 bHLH 转录因子,在各种发育过程中发挥着重要作用,尤其是视网膜神经发生的调节因子。此外,在中枢神经系统中也观察到 Atoh8 的表达。目前还不清楚 Atoh8 在出生后神经发生过程中的功能。方法 本研究利用雄性同基因Atoh8基因敲除(M6KO)小鼠,重点阐明Atoh8对出生后大脑神经发生的影响,尤其是在选定的区域:室下区(SVZ)、喙迁徙流(RMS)和嗅球(OB),以及在不同生命阶段的影响。我们的形态计量分析基于神经母细胞(Doublecortin)和增殖(Phospho-Histone H3,PHH3)的免疫组化标记以及泛神经元标记。结果 在 Atoh8-/- 小鼠中可以观察到出生后神经发生的改变。免疫组化分析显示,与野生型(WT)小鼠相比,新生 M6KO 小鼠 SVZ 中双皮质素阳性的神经母细胞明显减少。有趣的是,在神经母细胞随后通过喙迁移流(RMS)向嗅球(OB)迁移的过程中,并没有观察到细胞数量和分布的差异。在新生小鼠和幼年 M6KO 小鼠的 SVZ 和 RMS 中,PHH3 阳性神经元祖细胞的增殖率明显降低。此外,在 OB 肾小球层检测到的神经元数量在新生儿期明显减少。结论 总之,Atoh8 是出生后大脑神经发生的积极调节因子。它的作用包括促进神经母细胞的形成、调节增殖率、分化和维持成熟的神经元。了解 Atoh8 功能的复杂性为了解神经发生的复杂调控机制提供了宝贵的见解。
{"title":"The Effects of Atoh8 on Postnatal Murine Neurogenesis.","authors":"Dilek Culhalik, Morris Gellisch, Gabriela Morosan-Puopolo, Darius Saberi","doi":"10.1159/000540440","DOIUrl":"10.1159/000540440","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Basic helix-loop-helix (bHLH) transcription factors are expressed in various organs and are involved in diverse developmental processes. The mouse atonal homolog 8 (Atoh8), a bHLH transcription factor, plays a crucial role in various developmental processes, especially as a regulator of neurogenesis in the retina. Besides, Atoh8 expression has been observed in the central nervous system. The function of Atoh8 during the postnatal neurogenesis is still unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study focuses on elucidating the impact of Atoh8 on postnatal neurogenesis in the brain, particularly in selected regions: the subventricular zone (SVZ), rostral migratory stream (RMS), and olfactory bulb (OB), across different life stages, using male homozygous Atoh8-knockout (M6KO) mice. Our morphometric analysis is based on immunohistochemically labeled markers for neuroblasts (doublecortin) and proliferation (phospho-histone H3, PHH3) as well as pan neuronal markers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In Atoh8-/- mice, alteration in the postnatal neurogenesis can be observed. Immunohistochemical analysis revealed a significant reduction in doublecortin-positive neuroblasts within the SVZ of neonatal M6KO mice compared to wild-type mice. Interestingly, no differences in cell number and distribution were observed in the subsequent migration of neuroblasts through the RMS to the OB. Proliferating PHH3-positive neuronal progenitor cells were significantly diminished in the proliferation rate in both the SVZ and RMS of neonatal and young M6KO mice. Furthermore, in the glomerular layer of the OB, significantly fewer neurons were detected in the neonatal stage.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In conclusion, Atoh8 emerges as a positive regulator of postnatal neurogenesis in the brain. Its role encompasses the promotion of neuroblast formation, modulation of proliferation rates, differentiation, and maintenance of mature neurons. Understanding the intricacies of Atoh8 function provides valuable insights into the complex regulatory mechanisms governing neurogenesis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Basic helix-loop-helix (bHLH) transcription factors are expressed in various organs and are involved in diverse developmental processes. The mouse atonal homolog 8 (Atoh8), a bHLH transcription factor, plays a crucial role in various developmental processes, especially as a regulator of neurogenesis in the retina. Besides, Atoh8 expression has been observed in the central nervous system. The function of Atoh8 during the postnatal neurogenesis is still unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study focuses on elucidating the impact of Atoh8 on postnatal neurogenesis in the brain, particularly in selected regions: the subventricular zone (SVZ), rostral migratory stream (RMS), and olfactory bulb (OB), across different life stages, using male homozygous Atoh8-knockout (M6KO) mice. Our morphometric analysis is based on immunohis","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"96-103"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Maternal Early Overfeeding Negatively Impacts Cardiac Progenitor Cell Differentiation and Cardiomyocyte Maturation in the Neonatal Offspring. 母体早期过度喂养会对新生儿后代的心脏祖细胞分化和心肌细胞成熟产生负面影响。
IF 1.9 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2025-01-01 Epub Date: 2024-11-06 DOI: 10.1159/000542436
Daniela Caldas Andrade, Thiago Freire, Beatriz Moitinho Ferreira Silva, Andressa Cardoso Guimarães, Elaine de Oliveira, Erica Patricia Garcia-Souza, Simone Nunes de Carvalho, Alessandra Alves Thole, Erika Cortez

Introduction: Maternal obesity has been positively correlated with an increased cardiometabolic risk in the offspring throughout life, implying intergenerational transmission. However, little is known about the early-life cardiac cell modifications that imply the onset of heart diseases later in life. This study analyzed cardiac progenitor cells and cardiomyocyte differentiation on day of birth in the offspring born to obese dams.

Methods: The litter size reduction model was used to induce obesity in female Swiss mice. Both maternal groups, the Small Litter Dams (SLD-F1), which were overfed during lactation, and the Normal Litter Dams (NLD-F1), control group, were mated to healthy male mice. Their first-generation offspring (SLD-F2 and NLD-F2, n = 6 by group) were euthanized on birth.

Results: Mothers from SLD had increased body mass, Lee Index, fat deposits, hyperglycemia, and glucose intolerance, confirming the obese phenotype. The offspring born from SLD-F1 had also increased body mass, Lee Index, and fasting hyperglycemia. The heart of SLD-F2 showed decreased cardiac mass/body mass ratio, increased cardiac collagen deposits, a greater number of undifferentiated cardiac c-kit+ and Sca-1+ progenitor cells, and increased NKX2.5+ cardiomyoblasts compared to control. In addition, SLD-F2 demonstrated immature cardiomyocytes.

Conclusions: Obese dams negatively impact their offspring, leading to altered biometric and metabolic parameters, along with an immature heart already at birth, with extracellular matrix adverse remodeling, delayed cardiac progenitor cell differentiation, and restrained cardiomyocyte maturation, which can be related to the development of cardiometabolic disease in the adulthood.

简介母亲肥胖与后代一生中心脏代谢风险的增加呈正相关,这意味着代际遗传。然而,人们对生命早期心脏细胞的改变意味着日后心脏疾病的发生知之甚少。本研究分析了肥胖母鼠所生后代出生当天的心脏祖细胞和心肌细胞分化情况:方法:采用减少产仔数模型诱导雌性瑞士小鼠肥胖。方法:采用产仔数减少模型诱导肥胖雌性瑞士小鼠。两组母鼠,即哺乳期过度喂养的小窝母鼠(SLD-F1)和正常窝母鼠(NLD-F1),均与健康雄性小鼠交配。它们的第一代后代(SLD-F2和NLD-F2,每组6只)在出生时被安乐死:结果:SLD母亲的体重、Lee指数、脂肪沉积、高血糖和糖耐量均增加,证实了肥胖表型。SLD-F1的后代体重、Lee指数和空腹高血糖也有所增加。与对照组相比,SLD-F2的心脏显示心脏质量/体重比值下降,心脏胶原沉积增加,未分化的心脏c-kit+和Sca-1+祖细胞数量增加,NKX2.5+心肌母细胞增加。此外,SLD-F2 显示出心肌细胞未成熟:结论:肥胖母体会对其后代产生负面影响,导致生物计量和代谢参数的改变,以及出生时心脏不成熟、细胞外基质重塑不良、心脏祖细胞分化延迟和心肌细胞成熟受限,这可能与成年后心脏代谢疾病的发展有关。
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引用次数: 0
Care and Treatment for an Antiphospholipid Syndrome-Related Lower Limb Skin Ulcer Unhealed for 7 Years: A Case Report. 抗磷脂综合征相关下肢皮肤溃疡 7 年未愈合的护理和治疗:病例报告。
IF 2.9 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2024-12-01 Epub Date: 2022-03-31 DOI: 10.1177/15347346221090079
Min Wei, Yan Xu, Dongyun Xia, Jian Li, Shan Dong

Antiphospholipid syndrome (APS) is a group of rare autoimmune diseases caused by antiphospholipid antibodies that is mainly associated with arterial or venous thrombosis and/or complications during pregnancy. Skin lesions occur in approximately 30% of APS patients as initial manifestations. However, previous studies have primarily focused on the treatment of APS rather than the management of skin lesions. Here, the authors report a case of an APS-related lower limb skin ulcer that had remained unhealed for more than 7 years. The difficulties in this case were the diagnosis of APS, the risk of bleeding during debridement, wound infection, biofilm formation, reduced venous return from the lower limbs, and compliance with compression therapy and follow-up. A three-step wound care regimen based on a multidisciplinary team approach resulted in effective control of APS and healing of the ulcer to the lower leg in 95 days. Over two follow-ups, there was no recurrence of the ulcer.

抗磷脂综合征(APS)是一组由抗磷脂抗体引起的罕见自身免疫性疾病,主要与动脉或静脉血栓和/或妊娠并发症有关。约有 30% 的 APS 患者最初表现为皮肤损害。然而,以往的研究主要集中在 APS 的治疗上,而不是皮损的处理上。在此,作者报告了一例与 APS 相关的下肢皮肤溃疡病例,该溃疡超过 7 年仍未愈合。该病例的难点在于 APS 的诊断、清创过程中的出血风险、伤口感染、生物膜的形成、下肢静脉回流的减少以及对加压疗法和随访的依从性。多学科团队采用三步伤口护理方案,在 95 天内有效控制了 APS,小腿溃疡愈合。在两次随访中,溃疡没有复发。
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引用次数: 0
Spheroid-Hydrogel Integrated Biomimetic System (SHIBS): A New Frontier in Advanced 3D Cell Culture Technology. 球状-水凝胶一体化仿生系统(SHIBS):先进三维细胞培养技术的新前沿。
IF 2.7 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2024-09-12 DOI: 10.1159/000541416
Seungyeop Yoo,Hyun Jong Lee
BACKGROUNDDespite significant advances in three-dimensional (3D) cell culture technologies, creating accurate in vitro models that faithfully recapitulate complex in vivo environments remains a major challenge in biomedical research. Traditional culture methods often fail to simultaneously facilitate critical cell-cell and cell-extracellular matrix (ECM) interactions while providing control over mechanical and biochemical properties.SUMMARYThis review introduces the spheroid-hydrogel integrated biomimetic system (SHIBS), a groundbreaking approach that synergistically combines spheroid culture with tailored hydrogel technologies. SHIBS uniquely bridges the gap between traditional culture methods and physiological conditions by offering unprecedented control over both cellular interactions and environmental properties. We explore how SHIBS is revolutionizing fields ranging from drug discovery and disease modeling to regenerative medicine and basic biological research. The review discusses current challenges in SHIBS technology, including reproducibility, scalability, and high-resolution imaging, and outlines ongoing research addressing these issues. Furthermore, we envision the future evolution of SHIBS into more sophisticated organoid-hydrogel integrated biomimetic systems (OHIBS) and its integration with cutting-edge technologies such as microfluidics, 3D bioprinting, and artificial intelligence.KEY MESSAGESSHIBS represents a paradigm shift in 3D cell culture technology, offering a unique solution to recreate complex in vivo environments. Its potential to accelerate the development of personalized therapies across various biomedical fields is significant. While challenges persist, the ongoing advancements in SHIBS technology promise to overcome current limitations, paving the way for more accurate and reliable in vitro models. The future integration of SHIBS with emerging technologies may revolutionize biomimetic modeling, potentially reducing the need for animal testing and expediting drug discovery processes. This comprehensive review provides researchers and clinicians with a holistic understanding of SHIBS technology, its current capabilities, and its future prospects in advancing biomedical research and therapeutic innovations.
背景尽管三维(3D)细胞培养技术取得了重大进展,但创建能忠实再现复杂体内环境的精确体外模型仍是生物医学研究中的一大挑战。传统的培养方法往往无法同时促进关键的细胞-细胞和细胞-细胞外基质(ECM)相互作用,同时提供对机械和生化特性的控制。摘要 本综述介绍了球形-水凝胶集成仿生系统(SHIBS),这是一种突破性的方法,它将球形培养与定制的水凝胶技术协同结合在一起。通过对细胞相互作用和环境特性进行前所未有的控制,SHIBS 在传统培养方法和生理条件之间架起了一座独特的桥梁。我们将探讨 SHIBS 如何彻底改变从药物发现和疾病建模到再生医学和基础生物学研究等领域。综述讨论了 SHIBS 技术目前面临的挑战,包括可重复性、可扩展性和高分辨率成像,并概述了正在进行的解决这些问题的研究。此外,我们还展望了 SHIBS 未来向更复杂的类器官-水凝胶集成仿生系统(OHIBS)的发展,以及它与微流控、三维生物打印和人工智能等尖端技术的整合。它在加速各生物医学领域个性化疗法的开发方面潜力巨大。虽然挑战依然存在,但 SHIBS 技术的不断进步有望克服当前的局限性,为建立更准确、更可靠的体外模型铺平道路。未来,SHIBS 与新兴技术的整合可能会彻底改变生物仿生建模,从而有可能减少动物试验的需求并加快药物发现过程。这篇全面的综述让研究人员和临床医生全面了解了 SHIBS 技术、其当前的功能及其在推动生物医学研究和治疗创新方面的未来前景。
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引用次数: 0
Three-Dimensional Imaging Analysis of the Developmental Process of Posterior Meniscofemoral Ligaments in Rat Embryos. 大鼠胚胎半月板后韧带发育过程的三维成像分析。
IF 2.9 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2024-01-01 Epub Date: 2024-01-05 DOI: 10.1159/000536108
Momoko Nagai-Tanima, Kanon Ishida, Aoi Ishikawa, Shigehito Yamada, Tetsuya Takakuwa, Tomoki Aoyama

Introduction: The posterior meniscofemoral ligament (pMFL) of knee joint is a ligament that runs posterior to the posterior cruciate ligament and it is known that the height of the pMFL attachment site causes meniscus avulsion. Therefore, understanding the three-dimensional (3D) structure of the pMFL attachment site is essential to better understand the pathogenesis of meniscus disorders. However, the developmental process of pMFL has not been well investigated. The purpose of this study was to analyze pMFL development in rat knee joints using 3D reconstructed images produced from episcopic fluorescence image capture (EFIC) images and examine its relationship with other knee joint components.

Methods: Knee joints of Wistar rat embryos between embryonic day (E) 16 and E21 were observed with HE-stained tissues. Serial EFIC images of the hind limbs of E17-E21 were, respectively, captured from which 3D images were reconstructed and the features of pMFL structure: length and angle were measured. Besides, the chronological volume changes and the volume ratio of the knee joint components compared to E17 were calculated to identify the differences in growth by components.

Results: pMFL was observed from E17 and was attached to the medial femoral condyle and lateral meniscus at all developmental stages, as in mature rats. The lack of marked variation in the attachment site and angle of the pMFL with the developmental stage indicates that the pMFL and surrounding knee joint components developed while maintaining their positional relationship from the onset of development.

Conclusion: Current results may support to congenital etiology of meniscus disorder.

简介膝关节的后半月板韧带(pMFL)是一条位于后交叉韧带(PCL)后方的韧带,众所周知,pMFL附着部位的高度会导致半月板撕脱。因此,了解 pMFL 附着部位的三维(3D)结构对于更好地理解半月板疾病的发病机制至关重要。然而,pMFL 的发育过程尚未得到很好的研究。本研究的目的是利用外显子荧光图像采集(EFIC)图像生成的三维重建图像分析大鼠膝关节中 pMFL 的发育过程,并研究其与膝关节其他组成部分的关系:方法:使用 HE 染色组织观察胚胎第(E)16 天至第 21 天 Wistar 大鼠胚胎的膝关节。方法:用 HE 染色组织观察 Wistar 大鼠胚胎 E16 至 E21 天的膝关节,分别采集 E17 至 E21 天后肢的序列 EFIC 图像,重建三维图像并测量 pMFL 结构的特征:长度和角度。结果:pMFL从E17开始就被观察到,并且在所有发育阶段都附着在股骨内侧髁和外侧半月板上,与成熟大鼠相同。pMFL的附着部位和角度随发育阶段的变化不明显,这表明pMFL和周围膝关节成分在发育过程中一直保持着位置关系:结论:目前的研究结果可能支持半月板紊乱的先天性病因。
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引用次数: 0
Twenty Years of Epithelial-Mesenchymal Transition: A State of the Field from TEMTIA X. 急救医疗二十年:TEMTIA X 的领域现状。
IF 2.9 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2024-01-01 Epub Date: 2024-01-09 DOI: 10.1159/000536096
Pierre Savagner, Thomas Brabletz, Chonghui Cheng, Christine Gilles, Tian Hong, Myriam Polette, Guojun Sheng, Marc P Stemmler, Erik W Thompson

This report summarizes the 10th biennial meeting of The Epithelial Mesenchymal Transition International Association (TEMTIA), that took place in Paris on November 7-10, 2022. It provides a short but comprehensive introduction to the presentations and discussions that took place during the 3-day meeting. Similarly to previous TEMTIA meetings, TEMTIA X reviewed the most recent aspects of the epithelial-mesenchymal transition (EMT), a cellular process involved during distinct stages of development but also during wound healing and fibrosis to some degree. EMT has also been associated at various levels during tumor cell progression and metastasis. The meeting emphasized the intermediate stages of EMT (partial EMT or EM hybrid cells) involved in the malignant process and their potential physiological or pathological importance, taking advantage of advancements in molecular methods at the single-cell level. It also introduced novel descriptions of EMT occurrences during early embryogenesis. Sessions explored relationships between EMT and cell metabolism and how EMT can affect immune responses, particularly during tumor progression, providing new targets for cancer therapy. Finally, it introduced a new perception of EMT biological meaning based on an evolutionary perspective. The meeting integrated the TEMTIA general assembly, allowing general discussion about the future of the association and the site of the next meeting, now decided to take place in Seattle, USA, in November 2024. This report provides a comprehensive introduction to the presentations and discussions that took place during the 10th biennial meeting of TEMTIA, that occurred in Paris on November 7-10, 2022. It includes all the sessions and follows the chronological order during the 3-day meeting. A general purpose of the meeting was to explore the boundaries of the EMT process, including new concepts and developments, as illustrated by our leitmotiv for the meeting, inspired by the proximity of the Cluny Museum in Paris.

由上皮-间质转化国际协会(TEMTIA)主办的第十届 TEMTIA X 研讨会于 2022 年 11 月 7 日至 10 日在巴黎举行。与前几次会议类似,本次会议回顾了上皮-间质转化的最新进展,这是一种细胞过程,不仅涉及发育的不同阶段,还在一定程度上涉及伤口愈合和纤维化。同样,在肿瘤细胞的发展和转移过程中,上皮-间质转化过程也有不同程度的描述。会议强调了这一过程所涉及的中间阶段及其潜在的生理或病理重要性,利用了单细胞水平分子方法的扩展。会议还对早期胚胎发生过程中的 EMT 现象进行了新的描述。此外,会议还探讨了 EMT 如何反映细胞新陈代谢,以及这一过程如何与免疫反应相结合,特别是在肿瘤进展过程中,为癌症治疗提供了新的靶点。最后,会议从进化的角度介绍了对 EMT 生物学意义的新认识。会议还包括 TEMTIA 大会,就协会的未来进行了一般性讨论,首先是下届会议的地点,目前已决定于 2024 年底在美国西雅图举行。
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引用次数: 0
Erratum. 勘误。
IF 2.9 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2024-01-01 Epub Date: 2024-06-20 DOI: 10.1159/000539752
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引用次数: 0
Osteoclastogenesis Requires Primary Cilia Disassembly and Can Be Inhibited by Promoting Primary Cilia Formation Pharmacologically. 破骨细胞的生成需要初级纤毛的解体,可以通过药物促进初级纤毛的形成来抑制破骨细胞的生成。
IF 2.7 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2024-01-01 Epub Date: 2023-05-22 DOI: 10.1159/000531098
Michael M Sutton, Michael P Duffy, Stefaan W Verbruggen, Christopher R Jacobs

The primary cilium is a solitary, sensory organelle with many roles in bone development, maintenance, and function. In the osteogenic cell lineage, including skeletal stem cells, osteoblasts, and osteocytes, the primary cilium plays a vital role in the regulation of bone formation, and this has made it a promising pharmaceutical target to maintain bone health. While the role of the primary cilium in the osteogenic cell lineage has been increasingly characterized, little is known about the potential impact of targeting the cilium in relation to osteoclasts, a hematopoietic cell responsible for bone resorption. The objective of this study was to determine whether osteoclasts have a primary cilium and to investigate whether or not the primary cilium of macrophages, osteoclast precursors, serves a functional role in osteoclast formation. Using immunocytochemistry, we showed the macrophages have a primary cilium, while osteoclasts lack this organelle. Furthermore, we increased macrophage primary cilia incidence and length using fenoldopam mesylate and found that cells undergoing such treatment showed a significant decrease in the expression of osteoclast markers tartrate-resistant acid phosphatase, cathepsin K, and c-Fos, as well as decreased osteoclast formation. This work is the first to show that macrophage primary cilia resorption may be a necessary step for osteoclast differentiation. Since primary cilia and preosteoclasts are responsive to fluid flow, we applied fluid flow at magnitudes present in the bone marrow to differentiating cells and found that osteoclastic gene expression by macrophages was not affected by fluid flow mechanical stimulation, suggesting that the role of the primary cilium in osteoclastogenesis is not a mechanosensory one. The primary cilium has been suggested to play a role in bone formation, and our findings indicate that it may also present a means to regulate bone resorption, presenting a dual benefit of developing ciliary-targeted pharmaceuticals for bone disease.

初级纤毛是一种独居的感觉细胞器,在骨骼发育、维护和功能方面发挥着多种作用。在成骨细胞系(包括骨骼干细胞、成骨细胞和骨细胞)中,初级纤毛在调节骨形成方面发挥着重要作用,这使其成为保持骨骼健康的一个有前景的药物靶点。尽管初级纤毛在成骨细胞系中的作用已被越来越多地描述出来,但人们对以纤毛为靶点对破骨细胞(一种负责骨吸收的造血细胞)的潜在影响却知之甚少。本研究的目的是确定破骨细胞是否具有初级纤毛,并研究破骨细胞前体--巨噬细胞的初级纤毛是否在破骨细胞形成过程中发挥功能性作用。通过免疫细胞化学,我们发现巨噬细胞具有初级纤毛,而破骨细胞缺乏这种细胞器。此外,我们使用甲磺酸非诺多泮增加了巨噬细胞初级纤毛的发生率和长度,并发现经过这种处理的细胞显示破骨细胞标志物抗酒石酸磷酸酶、酪蛋白酶 K 和 c-Fos 的表达显著减少,破骨细胞的形成也减少了。这项研究首次表明,巨噬细胞初级纤毛的吸收可能是破骨细胞分化的必要步骤。由于初级纤毛和前破骨细胞对液流有反应,我们对分化细胞施加了骨髓中存在的液流,结果发现巨噬细胞的破骨细胞基因表达不受液流机械刺激的影响,这表明初级纤毛在破骨细胞生成中的作用不是机械感觉作用。有人认为初级纤毛在骨形成中发挥作用,而我们的研究结果表明,初级纤毛也可能是调节骨吸收的一种手段,这为开发纤毛靶向药物治疗骨病带来了双重益处。
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引用次数: 0
Potential Contribution of Cell Adhesion Molecule 1 to the Binding of SARS-CoV-2 Spike Protein to Mouse Nasal Mucosa. 细胞粘附分子1对严重急性呼吸系统综合征冠状病毒2型刺突蛋白与小鼠鼻粘膜结合的潜在贡献。
IF 2.9 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2024-01-01 Epub Date: 2023-10-30 DOI: 10.1159/000534892
Fuka Takeuchi, Aki Sugano, Azusa Yoneshige, Man Hagiyama, Takao Inoue, Akihiro Wada, Yutaka Takaoka, Akihiko Ito

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first infects the host nasal mucosa, where the viral spike protein binds to angiotensin-converting enzyme 2 (ACE2) on the mucosal cells. This study aimed at searching host cell surface molecules that could contribute to the infection in two views; abundance on host cells and affinity to the spike protein. Since the nasal mucosa is lined by respiratory and olfactory epithelia, and both express an immunoglobulin superfamily member cell adhesion molecule 1 (CADM1), whether CADM1 would participate in the spike protein binding was examined. Immunohistochemistry on the mouse nasal cavity detected CADM1 strongly in the olfactory epithelium at cell-cell contacts and on the apical surface but just faintly in the respiratory epithelium. In contrast, ACE2 was detected in the respiratory, not olfactory, epithelium. When mice were administered intranasally with SARS-CoV-2 S1 spike protein and an anti-CADM1 ectodomain antibody separately, both were detected exclusively on the olfactory, not respiratory, epithelium. Then, the antibody and S1 spike protein were administered intranasally to mice in this order with an interval of 1 h. After 3 h, S1 spike protein was detected as a protein aggregate floating in the nasal cavity. Next, S1 spike protein labeled with fluorescein was added to the monolayer cultures of epithelial cells exogenously expressing ACE2 or CADM1. Quantitative detection of fluorescein bound to the cells revealed that S1 spike protein bound to CADM1 with affinity half as high as to ACE2. Consistently, docking simulation analyses revealed that S1 spike protein could bind to CADM1 three-quarters as strongly as to ACE2 and that the interface of ACE2 was similar in both binding modes. Collectively, intranasal S1 spike protein appeared to prefer to accumulate on the olfactory epithelium, and CADM1 was suggested to contribute to this preference of S1 spike protein based on the molecular abundance and affinity.

严重急性呼吸系统综合征冠状病毒2型首先感染宿主鼻粘膜,病毒刺突蛋白与粘膜细胞上的血管紧张素转化酶2(ACE2)结合。这项研究旨在从两个方面寻找可能导致感染的宿主细胞表面分子;宿主细胞上的丰度和对刺突蛋白的亲和力。由于鼻粘膜由呼吸上皮和嗅觉上皮排列,并且两者都表达免疫球蛋白超家族成员细胞粘附分子1(CADM1),因此检测了CADM1是否参与刺突蛋白结合。小鼠鼻腔免疫组织化学在细胞-细胞接触的嗅觉上皮和顶端表面强烈检测到CADM1,但在呼吸上皮中仅微弱检测到。相反,ACE2是在呼吸上皮而非嗅觉上皮中检测到的。当小鼠分别用严重急性呼吸系统综合征冠状病毒2型S1刺突蛋白和抗CADM1胞外结构域抗体鼻内给药时,两者都只在嗅觉上皮上检测到,而不是在呼吸上皮上。然后,抗体和S1刺突蛋白按此顺序以1小时的间隔经鼻给药于小鼠。3小时后,S1刺突蛋白被检测为漂浮在鼻腔中的蛋白质聚集体。接下来,将用荧光素标记的S1刺突蛋白添加到外源表达ACE2或CADM1的上皮细胞的单层培养物中。结合细胞的荧光素的定量检测显示,S1刺突蛋白结合CADM1的亲和力是结合ACE2的一半。一致地,对接模拟分析显示,S1刺突蛋白与CADM1的结合强度是与ACE2的四分之三,并且ACE2的界面在两种结合模式中都相似。总的来说,鼻内S1刺突蛋白似乎更喜欢在嗅觉上皮上积累,基于分子丰度和亲和力,CADM1被认为有助于S1刺突蛋白质的这种偏好。
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引用次数: 0
Allogenic Platelet-Rich Plasma for Treating Cartilage Injury: A Systematic Review of the Evidence on the Basic Sciences for Potential Future Applications. 富含血小板的同种异体血浆治疗软骨损伤:对基础科学证据的系统综述,以备未来应用。
IF 2.9 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2024-01-01 Epub Date: 2023-11-09 DOI: 10.1159/000535018
Nur Hidayah Hassan, Raja Elina Ahmad, Tunku Kamarul, Qi Hao Daniel Looi, Pan Pan Chong

It is apparent that whilst many reports are available regarding platelet-rich-plasma (PRP), the larger majority of these have been mainly focussed on autologous sources, and for good reason. Issues relating to allogenic source have been consciously avoided owing to concerns of cross infectivity and immune rejection. However, this topic today is now revisited and is of interest since progress over the year has demonstrated its safety, efficacy, and its abundance of supply. The present systematic review was thus conducted to elucidate advances made in this area, with the aim to provide a wider and deeper understanding of studies relevant to the application of allogenic PRP in cartilage repair. Literature search was conducted systematically using Medline, ProQuest, Web of Science, Cochrane Central Register of Controlled Trials, and snowballing searching strategy to identify relevant studies using topic-specific keywords in various combinations including "allogenic, platelet, rich, plasma" OR "allogeneic, platelet, rich, plasma" OR "allogenic platelet-rich plasma" OR "allogeneic platelet-rich plasma" OR "allogenic platelet rich plasma" OR "allogeneic platelet rich plasma" AND cartilage OR chondrocytes OR synoviocytes OR stem cells. Studies that used allogenic PRP in an attempt to facilitate cartilage repair were included. The risk of bias was assessed by the SYRCLE's checklist. Of 206 studies identified, 12 were found eligible. Only those studies that are clearly related and specific to allogenic PRP were included. Of these, nine investigated the efficacy of allogenic PRP in animal models, while three articles employed an in vitro model. Allogenic PRP promotes cell proliferation, cartilage matrix production, and anti-inflammatory effects in vitro. The in vivo studies reported histological evidence of significant acceleration of cartilage repair in treated animals. Despite several conflicting findings, all studies agreed that allogenic PRP is safe and potentially efficacious for cartilage repair, with the advantages of allogenic sources apparent.

很明显,尽管有许多关于富血小板血浆(PRP)的报道,但其中大部分主要集中在自体来源上,这是有充分理由的。由于担心交叉感染和免疫排斥,有意识地避免了与同种异体来源有关的问题。然而,由于一年来的进展证明了它的安全性、有效性和丰富的供应,今天这个话题再次被讨论,并引起了人们的兴趣。因此,本系统综述旨在阐明该领域的进展,目的是对同种异体PRP在软骨修复中的应用相关研究提供更广泛、更深入的了解。文献检索使用Medline、ProQuest、Web of Science、Cochrane对照试验中央注册中心、,以及滚雪球搜索策略,使用各种组合的特定主题关键词来识别相关研究,包括“同种异体、血小板、富集、血浆”或“同种异体,血小板、富集,血浆”或“同种异体富含血小板的血浆和软骨或软骨细胞或滑膜细胞或干细胞。使用同种异体PRP来促进软骨修复的研究也包括在内。SYRCLE的检查表评估了偏倚的风险。在206项研究中,12项符合条件。只有那些与同种异体PRP明确相关和特异的研究才包括在内研究了同种异体PRP在动物模型中的疗效,而三篇文章采用了体外模型。异基因PRP在体外促进细胞增殖、软骨基质的产生和抗炎作用。体内研究报告了治疗动物软骨修复显著加速的组织学证据。尽管有几个相互矛盾的发现,但所有研究都一致认为,同种异体PRP对软骨修复是安全且潜在有效的,同种异体来源的优势显而易见。
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