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RETRACTION: Epigallocatechin Gallate in Combination With Eugenol or Amarogentin Shows Synergistic Chemotherapeutic Potential in Cervical Cancer Cell Line 撤回:表没食子儿茶素没食子酸酯与丁香酚或苦豆素联合在宫颈癌细胞系中显示出协同化疗的潜力
IF 4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2026-02-08 DOI: 10.1002/jcp.70143

RETRACTION: D. Pal, S. Sur, R. Roy, S. Mandal, and C. Kumar Panda, “Epigallocatechin Gallate in Combination With Eugenol or Amarogentin Shows Synergistic Chemotherapeutic Potential in Cervical Cancer Cell Line,” Journal of Cellular Physiology 234, no. 1 (2019): 825–836, https://doi.org/10.1002/jcp.26900.

The above article, published online on 4 August 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Robert Heath; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties. Figures 3A and 7B were found to contain duplicated image elements that were presented in different scientific contexts. Due to the time elapsed since publication, the authors were unable to retrieve the raw data underlying the article, and the clarification they provided was insufficient to address the concerns. Accordingly, the article has been retracted, as the editors have lost confidence in the accuracy and the integrity of the whole body of data presented. The authors have been informed of the retraction decision and disagree with it.

撤回:D. Pal, S. Sur, R. Roy, S. Mandal, C. Kumar Panda,“儿茶素没食子酸儿茶素与丁香酚或Amarogentin联合使用对宫颈癌细胞的增效化疗潜力”,细胞生理学杂志,第234期。1 (2019): 825-836, https://doi.org/10.1002/jcp.26900.The上述文章于2018年8月4日在线发表在Wiley online Library (wileyonlinelibrary.com)上,经主编Robert Heath同意撤回;和Wiley期刊有限责任公司。由于第三方提出的担忧,已同意撤回。发现图3A和7B包含在不同科学背景下呈现的重复图像元素。由于文章发表已经过了一段时间,作者无法检索文章的原始数据,他们提供的澄清也不足以解决这些问题。因此,这篇文章已被撤回,因为编辑对所提供的整个数据的准确性和完整性失去了信心。作者已被告知撤稿决定并不同意。
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引用次数: 0
Calpain-1 and Cholesterol Regulate the Dynamics of the Lipid Membrane Domains Essential for Suitable Capacitation and Acrosomal Reactions. 钙蛋白酶-1和胆固醇调节脂质膜结构域的动力学,这是适当的能化和顶体反应所必需的。
IF 4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2026-02-01 DOI: 10.1002/jcp.70147
Aide A Muñoz-Sánchez, Monica L Salgado-Lucio, Coral Y Jorge-Cruz, Ana L Roa-Espitia, Rafael Baltiérrez-Hoyos, Enrique O Hernández-González

Calpain-1 and -2 are calcium-dependent cysteine proteases associated with sperm processes, such as capacitation, the acrosomal reaction, and motility, making them important for the acquisition of fertilizing capacity among spermatozoa. Moreover, their inhibition significantly reduces in vitro fertilization. Guinea pig spermatozoa express only calpain-1, which has been implicated in spectrin cytoskeletal remodeling and NOX2 and NOX4 activation during capacitation. However, little is known about the mechanisms by which calpains participate in capacitation and the acrosomal reaction. The interaction of spectrin with phospholipids maintains the asymmetry of the plasma membrane. Since spectrin is a significant target of calpain, calpain may be involved in the dynamics of phospholipids and other membrane lipids during the capacitation process. Therefore, this work aims to elucidate the role of calpain in capacitation and acrosomal reactions, as well as its relationship with the dynamics of different membrane lipids related to capacitation and the acrosomal reaction. The results show that calpain-1 inhibition by calpeptin significantly reduced the number of spermatozoa that underwent capacitation and acrosomal reactions. Inhibition of calpain-1 also blocked protein phosphorylation at Tyr, as well as calcium influx and actin polymerization, which required for successful capacitation. Calpain inhibition also prevented phosphatidylserine translocation and the dynamics of caveolin-1, both processes associated with capacitation and the acrosome reaction. Sperm capacitation in the presence of cholesterol prevented the dynamics of phosphatidylserine, GM1 and caveolin-1. However, calpain-1 inhibition did not prevent cholesterol or GM1 ganglioside dynamics. The results of this investigation provide strong evidence for the mechanisms by which calpain-1 regulates capacitation and the acrosome reaction in guinea pig spermatozoa, suggesting that calpain-1 is a key player in optimal capacitation and the acrosome reaction.

Calpain-1和-2是钙依赖性半胱氨酸蛋白酶,与精子过程相关,如获能、顶体反应和运动,使它们对精子受精能力的获得很重要。此外,它们的抑制作用显著降低了体外受精。豚鼠精子仅表达calpain-1,该蛋白在获能过程中参与细胞骨架重塑和NOX2和NOX4的激活。然而,calpain参与获能和顶体反应的机制尚不清楚。谱蛋白与磷脂的相互作用维持了质膜的不对称性。由于spectrin是calpain的重要靶点,因此在获能过程中,calpain可能参与磷脂和其他膜脂的动力学。因此,本工作旨在阐明钙蛋白酶在获能和顶体反应中的作用,以及它与获能和顶体反应相关的不同膜脂动力学的关系。结果表明,calpeptin对calpain-1的抑制作用显著减少了发生获能和顶体反应的精子数量。calpain-1的抑制也阻断了Tyr蛋白磷酸化,以及钙内流和肌动蛋白聚合,这是成功获能所必需的。Calpain抑制也阻止了磷脂酰丝氨酸易位和小窝蛋白-1的动力学,这两个过程都与能化和顶体反应有关。在胆固醇存在的情况下,精子获能阻止了磷脂酰丝氨酸、GM1和小泡蛋白-1的动态变化。然而,calpain-1抑制并不能阻止胆固醇或GM1神经节苷脂的动态变化。本研究结果为calpain-1调控豚鼠精子获能和顶体反应的机制提供了有力的证据,表明calpain-1在最佳获能和顶体反应中起着关键作用。
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引用次数: 0
Dose-Dependent Biphasic Effect of Palmitic Acid on Oligodendrocyte Function: Impacts on Viability, Differentiation, and Myelination. 棕榈酸对少突胶质细胞功能的剂量依赖性双相效应:对活力、分化和髓鞘形成的影响。
IF 4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2026-02-01 DOI: 10.1002/jcp.70145
Anna Palmiero, Luca Pipicelli, Giuliana La Rosa, Concetta Sozio, Carolina Punziano, Maddalena Raia, Raffaella Faraonio, Giovanna Vitolo, Mariarosaria Cammarota, Francesca Boscia, Ciro Menale, Mariarosaria Santillo, Simona Damiano

Palmitic acid (PA), the most abundant saturated fatty acid (SFA) in humans, plays a key role in energy metabolism, membrane synthesis, and signaling. Oligodendrocyte precursor cells (OPCs), which generate mature oligodendrocytes (OLs) forming the myelin sheath, are responsive to metabolic and redox signals. Despite increasing interest in lipid metabolism and mitochondrial dynamics as regulators of OPC fate, the effects of PA remain unclear. This study investigates the biphasic, dose-dependent effects of PA on OPCs using the oligodendrocyte precursor MO3.13 cell line and employs rat organotypic slice cultures to evaluate the effects of non-toxic PA doses under pathological conditions and on axonal (re)-myelination. In MO3.13 cells, high-dose PA (100 µM) induces mitochondrial fragmentation and caspase-7 activation, accompanied by reduced mitofusin-2 (MFN2) and phosphorylated dynamin-related protein 1 at Ser616 (p-DRP1), indicating altered fusion-fission balance and impaired reactive oxygen species (ROS) generation. In contrast, low-dose PA (25 µM) triggers a protective response involving nuclear factor erythroid 2-related factor 2 (Nrf2) activation and upregulation of antioxidant and lipid-regulatory genes (glutamate-cysteine ligase modifier subunit [GCLM], NAD(P)H dehydrogenase [quinone] 1 [NQO1], peroxisome proliferator-activated receptor gamma [PPARγ], and cluster of differentiation 36 [CD36]) resulting in reduced intracellular ROS and enhanced lipid mobilization. PA 25 µM promotes OPC differentiation by inhibiting migration and cell cycle progression and increasing myelin basic protein (MBP) and proteolipid protein (PLP) expression. Notably, early exposure (1 day) favors mitochondrial fusion, whereas prolonged exposure (4 days) shows a physiological shift to fission. PA 25 µM prevents neurodegeneration in hippocampal organotypic slice cultures exposed to a neuroinflammatory insult. In cerebellar organotypic slice cultures, PA 25 µM enhances axonal myelination and accelerates remyelination following lysolecithin-induced demyelination. These findings highlight the physiological relevance of low-dose PA in modulating OLs.

棕榈酸(PA)是人体最丰富的饱和脂肪酸(SFA),在能量代谢、膜合成和信号传导中起着关键作用。少突胶质前体细胞(OPCs)产生成熟的少突胶质细胞(OLs)形成髓鞘,对代谢和氧化还原信号有反应。尽管人们越来越关注脂质代谢和线粒体动力学作为OPC命运的调节因子,但PA的作用仍不清楚。本研究利用少突胶质细胞前体MO3.13细胞系研究了PA对OPCs的双期、剂量依赖性作用,并采用大鼠器官型切片培养来评估病理条件下无毒PA剂量和对轴突(再)髓鞘形成的影响。在MO3.13细胞中,高剂量PA(100µM)诱导线粒体断裂和caspase-7活化,并伴有mitofusin-2 (MFN2)减少和动力蛋白相关蛋白1 Ser616 (p-DRP1)磷酸化,表明融合-裂变平衡改变和活性氧(ROS)生成受损。相比之下,低剂量PA(25µM)触发的保护反应涉及核因子-红细胞2相关因子2 (Nrf2)激活和抗氧化和脂质调节基因(谷氨酸-半胱氨酸连接酶修饰子亚基[GCLM]、NAD(P)H脱氢酶[醌]1 [NQO1]、过氧化物酶体增殖物激活受体γ [PPARγ]和分化簇36 [CD36])的上调,导致细胞内ROS减少和脂质动员增强。PA 25µM通过抑制迁移和细胞周期进程,增加髓鞘碱性蛋白(MBP)和蛋白脂蛋白(PLP)表达,促进OPC分化。值得注意的是,早期暴露(1天)有利于线粒体融合,而长时间暴露(4天)则显示出向裂变的生理转变。PA 25µM可防止神经炎症损伤下海马器官型切片培养的神经变性。在小脑器官型切片培养中,PA 25µM增强轴突髓鞘形成,并加速溶卵磷脂诱导脱髓鞘后的再髓鞘形成。这些发现强调了低剂量PA在调节ol中的生理相关性。
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引用次数: 0
RETRACTION: CircFUT10 Reduces Proliferation and Facilitates Differentiation of Myoblasts by Sponging miR-133a. 回撤:cirfut10通过海绵化miR-133a抑制成肌细胞增殖并促进分化。
IF 4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2026-02-01 DOI: 10.1002/jcp.70144

Retraction: H. Li, J. Yang, X. Wei, C. Song, D. Dong, Y. Huang, X. Lan, M. Plath, C. Lei, Y. Ma, X. Qi, Y. Bai, and H. Chen, "CircFUT10 Reduces Proliferation and Facilitates Differentiation of Myoblasts by Sponging miR-133a," Journal of Cellular Physiology 233, no. 6 (2018): 4643-4651, https://doi.org/10.1002/jcp.26230. The above article, published online on 18 October 2017 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Robert Heath; and Wiley Periodicals LLC. The retraction has been agreed upon following concerns raised by a third party regarding data presented in the article. An investigation identified duplication between the two MyoD bands shown in Figure 3B and two MyhC bands in Figure 3H. All MyhC bands in Figure 3H were also found to be identical to western blot bands published in another article by the same authors, where they were presented as representing a different protein. Furthermore, overlaps were identified between images in Figure 6 A and images published in another article by the same authors, which were also used to represent different material. Finally, the miR-133a flow cytometry data shown in Figure 6B was also found to be identical to a dot plot found in another article published by the same authors, again representing different material. The authors cooperated with the investigation and provided some supporting data; however, this was not sufficient to restore the editors' confidence in the results. The editors consider the results and conclusions unreliable. The authors did not respond when asked to agree to the final wording of the retraction.

引用本文:李慧,杨军,魏晓霞,宋超,董东,黄艳,兰霞,M. Plath,雷长青,马艳,齐晓霞,白艳,陈慧,“cirfut10通过海绵吸附miR-133a抑制成肌细胞增殖和促进分化”,细胞生理学杂志,第33期,第1期。6 (2018): 4643-4651, https://doi.org/10.1002/jcp.26230。上述文章于2017年10月18日在线发表在Wiley在线图书馆(wileyonlinelibrary.com)上,经期刊主编Robert Heath同意撤回;和Wiley期刊有限责任公司。在第三方对文章中提供的数据提出担忧后,已同意撤回。一项调查发现了图3B所示的两条MyoD带和图3H所示的两条MyhC带之间的重复。图3H中的所有MyhC条带也被发现与同一作者在另一篇文章中发表的western blot条带相同,在该文章中,它们被表示为代表不同的蛋白质。此外,图6 A中的图像与同一作者在另一篇文章中发表的图像之间存在重叠,这些图像也用于表示不同的材料。最后,图6B所示的miR-133a流式细胞术数据也被发现与同一作者发表的另一篇文章中的点阵图相同,同样代表不同的材料。作者配合调查并提供一些支持数据;然而,这还不足以恢复编辑们对结果的信心。编辑认为结果和结论不可靠。当被要求同意撤稿的最终措辞时,作者没有回应。
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引用次数: 0
Correction to "Blocking Sphingosine 1-phosphate Metabolism With Fingolimod Prevents the Progression of Vascular Smooth Muscle Cells Calcification in Chronic Kidney Disease". 修正“芬戈莫德阻断鞘氨醇1-磷酸代谢可防止慢性肾病血管平滑肌细胞钙化进展”。
IF 4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2026-02-01 DOI: 10.1002/jcp.70149
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引用次数: 0
Correction to "PCTR1 Improves Pulmonary Edema Fluid Clearance Through Activating the Sodium Channel and Lymphatic Drainage in Lipopolysaccharide-Induced ARDS". 修正“PCTR1通过激活钠通道和淋巴引流在脂多糖诱导的ARDS中改善肺水肿液体清除”。
IF 4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2026-02-01 DOI: 10.1002/jcp.70146
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引用次数: 0
Calcium Signaling Pathways in Head and Neck Squamous Cell Carcinoma Therapy: A Review 钙信号通路在头颈部鳞状细胞癌治疗中的研究进展。
IF 4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2026-01-22 DOI: 10.1002/jcp.70142
Qi Yu, Xiaoze Jiang

Calcium ion (Ca2+) is a crucial secondary messenger in cells and participates in multiple physiological activities, during which various calcium regulatory proteins regulate the Ca2+ homeostasis. It has been verified that calcium signaling differs significantly between tumor and normal cells. Additionally, the heterogeneity in calcium signaling is found across head and neck squamous cell carcinoma (HNSCC) with different pathological subtypes and infection status of human papillomavirus. The abnormality of calcium signaling is related to the initiation, progression, therapeutic response, and clinical prognosis of HNSCC. Moreover, the calcium signaling plays a vital role in regulating the tumor microenvironment, which is closely related to the tumor cell and shares constant interaction with it, by metabolic reprogramming and immunosuppressive effects. Understanding the changes in calcium signaling may provide a potential target for the treatment of HNSCC.

钙离子(Ca2+)是细胞中重要的次生信使,参与多种生理活动,各种钙调节蛋白调节Ca2+的稳态。肿瘤细胞与正常细胞的钙信号传导有显著差异。此外,钙信号在不同病理亚型和人乳头瘤病毒感染状态的头颈部鳞状细胞癌(HNSCC)中存在异质性。钙信号的异常与HNSCC的发生、发展、治疗反应及临床预后有关。此外,钙信号通过代谢重编程和免疫抑制作用,在调节与肿瘤细胞密切相关并持续相互作用的肿瘤微环境中起着至关重要的作用。了解钙信号的变化可能为治疗HNSCC提供一个潜在的靶点。
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引用次数: 0
MeHg-Induced Cytotoxicity Associated With Oxidative Stress and Early Calcium Mobility in Rat Cerebral Cortical Astrocytes mehg诱导的细胞毒性与氧化应激和大鼠大脑皮质星形胶质细胞早期钙迁移相关。
IF 4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2026-01-22 DOI: 10.1002/jcp.70141
Yei-Tsung Chen, Sung-Ho Chen, Yu-Jen Chen, Chih-Jung Yao, Bo-Ying Bao, Ferry Saputra, Ngan Tra Tran, Chien-Chih Chiu, Shoei-Yn Lin-Shiau

Methylmercury (MeHg) is a potent neurotoxin that can cross the blood–brain barrier and disrupt neurological function in animals. Emerging evidence suggests that MeHg neurotoxicity may originate from compromised astrocytes, as they are strategically positioned to metabolize and process substances that enter the central nervous system. Thus, a better characterization of the timely cellular responses of astrocytes upon MeHg exposure is key to delineating the toxicology of MeHg. Here, MeHg exposure caused a transient increase in reactive oxygen species (ROS) and intracellular calcium concentration ([Ca²⁺]i), which peaked within 3 h and 30 min, respectively, in astrocytes. Further analyses indicated that the increase in [Ca²⁺]i after MeHg exposure might involve both extracellular Ca²⁺ influx and Ca²⁺ release from intracellular stores, as evidenced by alteration of Ca²⁺ dynamics in cells by targeting specific Ca²⁺ channels with blockers. Further cytotoxicity analyses revealed that antagonizing Ca²⁺-dependent signaling pathways and ROS levels markedly protected astrocytes against MeHg-induced cell death. Treatment with lipopolysaccharide improved cell survival under MeHg exposure, suggesting a reciprocal interaction of proinflammatory signaling and MeHg on [Ca²⁺]i kinetics and nitric oxide production. Collectively, our findings indicated that transient alterations in free radical and Ca²⁺ levels in astrocytes may be associated with MeHg-induced cytotoxicity. Targeting oxidative stress and Ca²⁺ signaling in astrocytes may provide potential strategies for mitigating MeHg-induced neurotoxicity.

甲基汞(MeHg)是一种强效的神经毒素,可以穿过血脑屏障,破坏动物的神经功能。新出现的证据表明,甲基汞神经毒性可能源于受损的星形胶质细胞,因为它们处于代谢和处理进入中枢神经系统的物质的战略位置。因此,更好地表征星形胶质细胞在甲基汞暴露后的及时细胞反应是描述甲基汞毒理学的关键。在这里,MeHg暴露引起星形胶质细胞中活性氧(ROS)和细胞内钙浓度([Ca 2 +]i)的短暂增加,分别在3 h和30 min内达到峰值。进一步的分析表明,MeHg暴露后[Ca 2 +]i的增加可能涉及细胞外Ca 2 +的内流和细胞内Ca 2 +的释放,这可以通过阻滞剂靶向特定的Ca 2 +通道改变细胞中Ca 2 +的动力学来证明。进一步的细胞毒性分析显示,拮抗Ca 2 +依赖的信号通路和ROS水平可显著保护星形胶质细胞免受mehg诱导的细胞死亡。脂多糖处理提高了MeHg暴露下的细胞存活率,表明促炎信号和MeHg对[Ca 2]i动力学和一氧化氮生成有相互作用。总的来说,我们的发现表明星形胶质细胞中自由基和Ca 2 +水平的短暂改变可能与mehg诱导的细胞毒性有关。靶向星形胶质细胞中的氧化应激和Ca 2 +信号传导可能为减轻mehg诱导的神经毒性提供潜在的策略。
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引用次数: 0
Pathological Degeneration of Disc and Bone Is Associated With Chronic Low Back Pain in a Rat Model With Intradiscal Monosodium Iodoacetate 椎间盘内碘乙酸单钠大鼠模型中椎间盘和骨的病理性退变与慢性腰痛相关
IF 4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2026-01-22 DOI: 10.1002/jcp.70140
Yun-Ho Cho, Cham Choi, Minji Kwon, Jinju Kwon, Hogwang Ok, Dawon Ryu, Kyung-Sook Yang, Junesun Kim, Eui Ho Park

This study aimed to determine whether degeneration of intervertebral discs and subchondral bone correlates with the development of persistent low back pain (LBP) in a rat model with intradiscal monosodium iodoacetate (MIA), focusing on structural alterations, neuronal sensitization, and pain-related behavior. Male Sprague Dawley rats received MIA injections (2 mg in 2 μl) into L4/5 and L5/6 lumbar discs to induce degeneration. LBP-related behaviors were assessed over 42 days via dynamic weight-bearing and hindpaw withdrawal thresholds. Neuronal sensitization was evaluated via electrophysiological recordings of mechanosensitive afferent nerves (MSAN) and calcium imaging of labeled dorsal root ganglia (DRG) neurons innervating discs. Structural alterations in subchondral bone and disc were analyzed using in vivo/ex vivo µCT imaging, along with immunohistochemistry for TRPV1 and CGRP expression. Intradiscal MIA induced long-term LBP behaviors, characterized by forelimb weight-bearing shifts and reduced hindpaw withdrawal thresholds. MSAN exhibited hyperexcitability and lowered firing thresholds to intradiscal pressure, while DRG neurons showed enhanced TRPV1- and TRPA1-mediated calcium influx. µCT imaging revealed decreased disc volume and deteriorated trabecular bone quality. Histology confirmed disc and subchondral bone degeneration, with upregulated TRPV1 and CGRP expression in subchondral bone, indicating nociceptive fiber ingrowth. Linear discriminant analysis identified weight-bearing asymmetry (HindFore AUC), trabecular thickness, connectivity, and trabecular pattern factor as strong predictors of LBP development. Pathological degeneration of disc and bone is associated with chronic LBP through structural remodeling and peripheral neuronal sensitization. These findings suggest that therapeutic strategies targeting both tissues can alleviate chronic pain in degenerative spine conditions.

本研究旨在确定椎间盘内碘乙酸钠(MIA)大鼠模型中椎间盘和软骨下骨退变是否与持续性腰痛(LBP)的发展相关,重点研究结构改变、神经元致敏和疼痛相关行为。雄性Sprague Dawley大鼠在L4/5和L5/6腰椎间盘注射MIA (2 mg / 2 μl)诱导退变。在42天内,通过动态负重和后爪退出阈值评估lbp相关行为。通过机械敏感传入神经(MSAN)的电生理记录和支配椎间盘的标记背根神经节(DRG)神经元的钙显像来评估神经元的致敏性。采用体内/离体微CT成像和免疫组化检测TRPV1和CGRP表达,分析软骨下骨和椎间盘的结构变化。椎间盘内MIA诱导长期LBP行为,其特征是前肢负重变化和后爪退缩阈值降低。MSAN表现出高兴奋性,并降低了对椎间盘内压力的放电阈值,而DRG神经元表现出增强的TRPV1-和trpa1介导的钙内流。微CT成像显示椎间盘体积减小,骨小梁质量恶化。组织学证实椎间盘和软骨下骨变性,软骨下骨TRPV1和CGRP表达上调,提示伤害纤维向内生长。线性判别分析发现,负重不对称性(HindFore AUC)、小梁厚度、连连性和小梁模式因子是腰痛发展的有力预测因素。椎间盘和骨的病理性退变通过结构重塑和周围神经致敏与慢性腰痛相关。这些发现表明,针对这两种组织的治疗策略可以减轻退行性脊柱疾病的慢性疼痛。
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引用次数: 0
Endoglin Regulates Pluripotency and Differentiation in Human Embryonic Stem Cells Through Wnt and TGF-β Signaling Crosstalk 内啡肽通过Wnt和TGF-β信号串扰调控人胚胎干细胞的多能性和分化。
IF 4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2026-01-22 DOI: 10.1002/jcp.70135
Min-Tae Kim, Minje Kang, Suji Jeong, Hyebin Koh, Xing Zhen, Seung-Joon Lee, Do-Yeon Kim, Seok-Ho Hong, Jong-Hee Lee

Although endoglin (ENG) is traditionally recognized as a coreceptor in TGF-β signaling, its role in human pluripotent stem cells (hPSCs) remains unexplored. Here, we report that ENG knockout (ENG-/-) hPSCs maintain core pluripotency markers yet undergo spontaneous differentiation and exhibit markedly reduced potential to form mesoderm, ectoderm, and endoderm lineages. Contrary to expectations, pharmacological inhibition of TGF-β signaling failed to replicate or rescue this phenotype, implicating pathways beyond TGF-β in governing the ENG-/- phenotype. Instead, we observed aberrant WNT activation in ENG-/- cells, which correlated with the emergence of peripherally localized differentiated cells and compromised multilineage commitment. Notably, blocking WNT secretion with IWP2 suppressed spontaneous peripheral differentiated cell formation and partially restored ectodermal and endodermal differentiation. These findings establish a novel regulatory role for ENG in balancing WNT signaling, to preserve hPSCs' developmental potential, thereby illuminating an unrecognized mechanism of stem cell fate control and revealing ENG as a critical mediator of hPSCs' self-renewal and lineage fidelity.

虽然内啡肽(engin)传统上被认为是TGF-β信号的辅助受体,但其在人类多能干细胞(hPSCs)中的作用仍未被探索。在这里,我们报道了ENG基因敲除(ENG-/-)的人乳头状细胞维持核心多能性标记,但进行自发分化,并表现出明显降低形成中胚层、外胚层和内胚层谱系的潜力。与预期相反,TGF-β信号的药理抑制未能复制或挽救这种表型,暗示TGF-β以外的途径控制ENG-/-表型。相反,我们在ENG-/-细胞中观察到异常的WNT激活,这与外周定位分化细胞的出现和多谱系承诺受损有关。值得注意的是,用IWP2阻断WNT分泌可抑制自发外周分化细胞的形成,并部分恢复外胚层和内胚层的分化。这些发现确立了ENG在平衡WNT信号方面的新调控作用,以保持人乳头状细胞的发育潜力,从而阐明了一个未被认识的干细胞命运控制机制,并揭示了ENG是人乳头状细胞自我更新和谱系保真度的关键介质。
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引用次数: 0
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