Acta histochemica最新文献

The impact of formic acid treatment on brain tissues for prion inactivation 甲酸对脑组织对朊病毒失活的影响

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2026-01-30 DOI: 10.1016/j.acthis.2026.152324

Dalia Shaaban , Alyssa Seerley , Lilia Crew , Clairissa Kaylor , Sayre McElroy , Emma Guter , June Pounder , Andrea Grindeland Panter

There are significant risks in clinical, diagnostic, and research settings to those who investigate prion diseases, due to the difficult nature of inactivating prion proteins with standard decontamination methods. Formic acid treatment has been shown to be effective for decontaminating infectious prions and commonly used in biosafety practice to prevent occupational exposure. However, the impact of formic acid protocols on the morphology of tissue samples has not been adequately documented. The goal of this study is to examine morphologic effects of formic acid treatment on central nervous system tissue, using mouse model brain hemisphere tissues that exhibit varying degrees of neurodegeneration as a model. This study included normal, non-diseased wild-type tissues and a 5xFAD model, which recapitulates aspects of Alzheimer’s Disease (AD). A model exhibiting Chronic Wasting Disease (CWD), a prion disease of deer and elk, was also used to analyze the effects of formic acid on tissues with spongiform changes. Tissues from both formic acid and untreated control treatment groups were embedded in paraffin, sectioned, stained, and imaged microscopically. Anatomical regions were analyzed and evaluated quantitatively to determine the width, area, and structural integrity of the tissue between treatment groups. Our findings demonstrated that while formic acid has been previously reported to effectively inactivate prions, it compromised the morphology of mouse brain tissues. Furthermore, the effects of formic acid were not distributed equally between regions of the brain. Age did not play a role in the morphologic changes seen in the formic acid treatment group. Interestingly, the presence of neurodegeneration in the tissues did not appear to exacerbate the effects of morphological changes post-formic acid treatment. These results emphasize the need to explore alternative prion inactivation methods that ensure the safety and reliability of handling prion-infected tissues without compromising the integrity of tissues.

由于标准去污方法难以使朊病毒蛋白失活，因此在临床、诊断和研究环境中，对调查朊病毒疾病的人员存在重大风险。甲酸处理已被证明是有效的去污传染性朊病毒和常用的生物安全实践，以防止职业接触。然而，甲酸对组织样品形态学的影响还没有充分的文献记录。本研究的目的是研究甲酸治疗对中枢神经系统组织的形态学影响，使用表现出不同程度神经退行性变的小鼠模型大脑半球组织作为模型。这项研究包括正常的、未患病的野生型组织和5xFAD模型，该模型概括了阿尔茨海默病（AD）的各个方面。研究人员还利用鹿和麋鹿的一种朊病毒疾病——慢性消耗性疾病（CWD）模型，分析了甲酸对海绵状组织变化的影响。甲酸组和未处理对照组的组织均包埋石蜡，切片，染色，显微镜成像。对解剖区域进行定量分析和评估，以确定治疗组间组织的宽度、面积和结构完整性。我们的研究结果表明，虽然甲酸以前曾报道过能有效灭活朊病毒，但它损害了小鼠脑组织的形态。此外，甲酸的作用在大脑的不同区域之间并不是均匀分布的。甲酸治疗组的形态学变化与年龄无关。有趣的是，组织中神经退行性变的存在似乎并没有加剧甲酸治疗后形态学变化的影响。这些结果强调需要探索替代的朊病毒灭活方法，以确保处理朊病毒感染组织的安全性和可靠性，同时不损害组织的完整性。

{"title":"The impact of formic acid treatment on brain tissues for prion inactivation","authors":"Dalia Shaaban , Alyssa Seerley , Lilia Crew , Clairissa Kaylor , Sayre McElroy , Emma Guter , June Pounder , Andrea Grindeland Panter","doi":"10.1016/j.acthis.2026.152324","DOIUrl":"10.1016/j.acthis.2026.152324","url":null,"abstract":"<div><div>There are significant risks in clinical, diagnostic, and research settings to those who investigate prion diseases, due to the difficult nature of inactivating prion proteins with standard decontamination methods. Formic acid treatment has been shown to be effective for decontaminating infectious prions and commonly used in biosafety practice to prevent occupational exposure. However, the impact of formic acid protocols on the morphology of tissue samples has not been adequately documented. The goal of this study is to examine morphologic effects of formic acid treatment on central nervous system tissue, using mouse model brain hemisphere tissues that exhibit varying degrees of neurodegeneration as a model. This study included normal, non-diseased wild-type tissues and a 5xFAD model, which recapitulates aspects of Alzheimer’s Disease (AD). A model exhibiting Chronic Wasting Disease (CWD), a prion disease of deer and elk, was also used to analyze the effects of formic acid on tissues with spongiform changes. Tissues from both formic acid and untreated control treatment groups were embedded in paraffin, sectioned, stained, and imaged microscopically. Anatomical regions were analyzed and evaluated quantitatively to determine the width, area, and structural integrity of the tissue between treatment groups. Our findings demonstrated that while formic acid has been previously reported to effectively inactivate prions, it compromised the morphology of mouse brain tissues. Furthermore, the effects of formic acid were not distributed equally between regions of the brain. Age did not play a role in the morphologic changes seen in the formic acid treatment group. Interestingly, the presence of neurodegeneration in the tissues did not appear to exacerbate the effects of morphological changes post-formic acid treatment. These results emphasize the need to explore alternative prion inactivation methods that ensure the safety and reliability of handling prion-infected tissues without compromising the integrity of tissues.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"128 2","pages":"Article 152324"},"PeriodicalIF":2.4,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Commentary on: “Cellular landscape of reactive and neoplastic human lymph nodes in 3D” by Diederich et al.” 对Diederich等人的“反应性和肿瘤性人类淋巴结的三维细胞景观”的评论。

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2026-01-29 DOI: 10.1016/j.acthis.2026.152326

Rajesh Prasad Jayaswal

引用次数: 0

Anticancer drug-treated fibroblasts modulate colon cancer cell behavior through lysophosphatidic acid (LPA) receptor-mediated signaling 抗癌药物处理的成纤维细胞通过溶血磷脂酸（LPA）受体介导的信号传导调节结肠癌细胞的行为

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2026-01-28 DOI: 10.1016/j.acthis.2026.152325

Mao Yamamoto, Narumi Yashiro, Yuka Kusumoto, Shion Nagano, Moemi Tamura, Nanami Shimomura, Toshifumi Tsujiuchi

Lysophosphatidic acid (LPA) receptor-mediated signaling contributes to the pathogenesis of cancer. The tumor microenvironment (TME), composed of cancer cells and surrounding stromal cells, plays a key role in promoting malignant traits, including resistance to anticancer drugs. In this study, we investigated the roles of LPA receptor-1 (LPA₁) and LPA₂ in colon cancer DLD-1 cell functions modulated by 3T3 fibroblasts chronically exposed to chemotherapy. 3T3 cells were treated long-term with fluorouracil (5-FU), irinotecan (CPT-11), or cisplatin (CDDP) to generate 3T3–5FU, 3T3-CPT11, and 3T3-CDDP cells, respectively. Co-culture with anticancer drug-treated 3T3 cells altered LPA receptor expression in DLD-1 cells, characterized by reduced LPAR1 and elevated LPAR2 levels, compared with co-culture with untreated fibroblasts (n = 3 independent experiments). Under these conditions, LPA stimulation enhanced DLD-1 cell proliferation and motility. Pharmacological modulation of LPA signaling further supported receptor-specific effects: the LPA₁ antagonist AM966 and the LPA₂ agonist GRI-977143 promoted DLD-1 cell growth, while AM966 suppressed and GRI-977143 enhanced cell motility in co-culture with drug-treated fibroblasts. These findings suggest that chemotherapy-conditioned fibroblasts reshape LPA receptor-dependent signaling in colon cancer cells, suggesting potential therapeutic relevance of distinct roles for LPA₁ and LPA₂ within the drug-modified TME.

溶血磷脂酸（LPA）受体介导的信号传导参与了癌症的发病机制。肿瘤微环境（tumor microenvironment， TME）由癌细胞和周围基质细胞组成，在促进恶性肿瘤特征，包括对抗癌药物的耐药性中起着关键作用。在这项研究中，我们研究了LPA受体1 （LPA1）和LPA2在慢性化疗3T3成纤维细胞调节结肠癌DLD-1细胞功能中的作用。用氟尿嘧啶（5-FU）、伊立替康（CPT-11）或顺铂（CDDP）长期处理3T3细胞，分别生成3T3- 5fu、3T3- cpt11和3T3-CDDP细胞。与未处理的成纤维细胞共培养相比，与抗癌药物处理的3T3细胞共培养改变了DLD-1细胞中LPA受体的表达，其特征是LPAR1水平降低，LPAR2水平升高（n = 3个独立实验）。在这些条件下，LPA刺激可增强DLD-1细胞的增殖和运动能力。LPA信号的药理调节进一步支持受体特异性作用：LPA1拮抗剂AM966和LPA2激动剂GRI-977143促进DLD-1细胞生长，而AM966抑制和GRI-977143增强了药物处理成纤维细胞的细胞运动性。这些发现表明，化疗条件下的成纤维细胞重塑结肠癌细胞中LPA受体依赖的信号，表明LPA1和LPA2在药物修饰的TME中具有不同的潜在治疗相关性。

{"title":"Anticancer drug-treated fibroblasts modulate colon cancer cell behavior through lysophosphatidic acid (LPA) receptor-mediated signaling","authors":"Mao Yamamoto, Narumi Yashiro, Yuka Kusumoto, Shion Nagano, Moemi Tamura, Nanami Shimomura, Toshifumi Tsujiuchi","doi":"10.1016/j.acthis.2026.152325","DOIUrl":"10.1016/j.acthis.2026.152325","url":null,"abstract":"<div><div>Lysophosphatidic acid (LPA) receptor-mediated signaling contributes to the pathogenesis of cancer. The tumor microenvironment (TME), composed of cancer cells and surrounding stromal cells, plays a key role in promoting malignant traits, including resistance to anticancer drugs. In this study, we investigated the roles of LPA receptor-1 (LPA<sub>1</sub>) and LPA<sub>2</sub> in colon cancer DLD-1 cell functions modulated by 3T3 fibroblasts chronically exposed to chemotherapy. 3T3 cells were treated long-term with fluorouracil (5-FU), irinotecan (CPT-11), or cisplatin (CDDP) to generate 3T3–5FU, 3T3-CPT11, and 3T3-CDDP cells, respectively. Co-culture with anticancer drug-treated 3T3 cells altered LPA receptor expression in DLD-1 cells, characterized by reduced <em>LPAR1</em> and elevated <em>LPAR2</em> levels, compared with co-culture with untreated fibroblasts (n = 3 independent experiments). Under these conditions, LPA stimulation enhanced DLD-1 cell proliferation and motility. Pharmacological modulation of LPA signaling further supported receptor-specific effects: the LPA<sub>1</sub> antagonist AM966 and the LPA<sub>2</sub> agonist GRI-977143 promoted DLD-1 cell growth, while AM966 suppressed and GRI-977143 enhanced cell motility in co-culture with drug-treated fibroblasts. These findings suggest that chemotherapy-conditioned fibroblasts reshape LPA receptor-dependent signaling in colon cancer cells<strong>,</strong> suggesting potential therapeutic relevance of distinct roles for LPA<sub>1</sub> and LPA<sub>2</sub> within the drug-modified TME.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"128 2","pages":"Article 152325"},"PeriodicalIF":2.4,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stiffness-tunable alginate-hyaluronic acid-collagen hydrogel mimics chondrocyte microenvironment for osteoarthritis pathophysiological modeling 刚度可调海藻酸-透明质酸-胶原水凝胶模拟骨关节炎病理生理模型的软骨细胞微环境

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2026-01-19 DOI: 10.1016/j.acthis.2026.152323

Genlai Du , Diyu Wang , Qingqian Chen , Jiaqi Zhang , Jiaru Sun , Qizhi Shuai , Li Li , Xun Huang , Quanyou Zhang , Shaowei Wang , Qin Zhang , Chongwei Chen , Ruyi Shi

Osteoarthritis (OA) is a degenerative joint disease characterized by an increasing prevalence and complex pathogenesis. Despite significant research efforts, understanding its mechanisms and developing effective treatments remain challenging. The development of in vitro models that accurately mimic the native articular microenvironment while preserving chondrocyte phenotype is crucial for advancing OA research. In this study, we constructed an Alginate-Hyaluronic Acid-Type I Collagen (Alg-HA-Col) composite hydrogel through physical mixing and chemical cross-linking. This composite matrix exhibited exceptional stability over 28 days under simulated physiological conditions. Neonatal murine chondrocytes encapsulated within Alg-HA-Col hydrogels for 28 days maintained their phenotype better than those cultured in monolayer, as evidenced by higher expression levels of SOX9, type II collagen, and aggrecan. Furthermore, by adjusting the component ratios, the stiffness of Alg-HA-Col hydrogels could mimic the stiffness of the pericellular matrix (PCM) in both physiological and pathological states, referred to as Firm and Soft. Chondrocytes cultured in Alg-HA-Col hydrogels with varying stiffness showed decreased expression of marker proteins, increased cellular mortality, and elevated inflammatory factor expression as stiffness decreased. Therefore, Alg-HA-Col hydrogels with tunable stiffness effectively simulated the physiological and pathological states of cartilage, providing an ideal three-dimensional (3D) matrix for chondrocyte culture. Additionally, this model's long-term culture stability offers potential applications in osteoarthritis drug therapy and cartilage tissue engineering.

骨关节炎（OA）是一种发病率越来越高、发病机制复杂的退行性关节疾病。尽管进行了大量的研究，但了解其机制和开发有效的治疗方法仍然具有挑战性。在保留软骨细胞表型的同时，开发能够准确模拟天然关节微环境的体外模型对于推进OA研究至关重要。在本研究中，我们通过物理混合和化学交联构建了海藻酸盐-透明质酸- I型胶原蛋白（algi - ha - col）复合水凝胶。在模拟生理条件下，该复合基质在28天内表现出优异的稳定性。在Alg-HA-Col水凝胶中包裹28天的新生小鼠软骨细胞比单层培养的小鼠保持了更好的表型，SOX9、II型胶原和聚集蛋白的表达水平更高。此外，通过调整组分比例，Alg-HA-Col水凝胶的硬度可以模拟细胞周围基质（PCM）在生理和病理状态下的硬度，称为硬和软。在不同硬度的Alg-HA-Col水凝胶中培养的软骨细胞显示，随着硬度的降低，标记蛋白的表达降低，细胞死亡率增加，炎症因子的表达升高。因此，具有可调刚度的al - ha - col水凝胶可以有效地模拟软骨的生理和病理状态，为软骨细胞培养提供了理想的三维（3D）基质。此外，该模型的长期培养稳定性为骨关节炎药物治疗和软骨组织工程提供了潜在的应用。

{"title":"Stiffness-tunable alginate-hyaluronic acid-collagen hydrogel mimics chondrocyte microenvironment for osteoarthritis pathophysiological modeling","authors":"Genlai Du , Diyu Wang , Qingqian Chen , Jiaqi Zhang , Jiaru Sun , Qizhi Shuai , Li Li , Xun Huang , Quanyou Zhang , Shaowei Wang , Qin Zhang , Chongwei Chen , Ruyi Shi","doi":"10.1016/j.acthis.2026.152323","DOIUrl":"10.1016/j.acthis.2026.152323","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a degenerative joint disease characterized by an increasing prevalence and complex pathogenesis. Despite significant research efforts, understanding its mechanisms and developing effective treatments remain challenging. The development of <em>in vitro</em> models that accurately mimic the native articular microenvironment while preserving chondrocyte phenotype is crucial for advancing OA research. In this study, we constructed an Alginate-Hyaluronic Acid-Type I Collagen (Alg-HA-Col) composite hydrogel through physical mixing and chemical cross-linking. This composite matrix exhibited exceptional stability over 28 days under simulated physiological conditions. Neonatal murine chondrocytes encapsulated within Alg-HA-Col hydrogels for 28 days maintained their phenotype better than those cultured in monolayer, as evidenced by higher expression levels of SOX9, type II collagen, and aggrecan. Furthermore, by adjusting the component ratios, the stiffness of Alg-HA-Col hydrogels could mimic the stiffness of the pericellular matrix (PCM) in both physiological and pathological states, referred to as Firm and Soft. Chondrocytes cultured in Alg-HA-Col hydrogels with varying stiffness showed decreased expression of marker proteins, increased cellular mortality, and elevated inflammatory factor expression as stiffness decreased. Therefore, Alg-HA-Col hydrogels with tunable stiffness effectively simulated the physiological and pathological states of cartilage, providing an ideal three-dimensional (3D) matrix for chondrocyte culture. Additionally, this model's long-term culture stability offers potential applications in osteoarthritis drug therapy and cartilage tissue engineering.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"128 2","pages":"Article 152323"},"PeriodicalIF":2.4,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145993577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Optimizing the resolution-fidelity trade-off in SRRF nanoscopy for live-cell clathrin imaging SRRF纳米显微镜在活细胞网格蛋白成像中的分辨率-保真度权衡优化

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2026-01-02 DOI: 10.1016/j.acthis.2025.152315

Sanhua Fang , Li Liu, Dan Yang, Shuangshuang Liu, Wei Yin, Qiong Huang, Jingyao Chen

Total internal reflection fluorescence microscopy (TIRFM) enables live-cell imaging of clathrin-coated pits (CCPs) but is diffraction-limited (∼250 nm), hindering visualization of their dense nanostructures (∼150 nm). Super-Resolution Radial Fluctuations (SRRF) provides computational super-resolution; however, unoptimized parameters can disrupt the critical balance between resolution and structural fidelity. Here, we establish a comprehensive parameter optimization framework for SRRF-based nanoscopy of live CCPs. Using multi-modal metrics in CLTA-GFP HeLa cells, we identify a ring radius of 1.0 as optimal, balancing resolution (full width at half maximum = 180 ± 29 nm, p < 0.05 vs. TIRFM) with fidelity (resolution-scaled Pearson = 0.935 ± 0.018). The temporal radiality pairwise product mean (TRPPM) mode achieved superior resolution (154 ± 30 nm) while maintaining fidelity metrics comparable to Temporal radiality average (TRA) mode. In contrast, temporal radiality auto-correlations (TRAC) introduced artifactual structures and reduced fidelity. Parameters such as “remove positivity constraint” and gradient weighting induced severe artifacts and should be avoided. This optimized framework resolves the resolution–fidelity trade-off, enabling robust nanoscale imaging of clathrin-mediated endocytosis in live cells.

全内反射荧光显微镜（TIRFM）能够对网格蛋白包被凹坑（ccp）进行活细胞成像，但其衍射范围有限（~ 250 nm），阻碍了其致密纳米结构的可视化（~ 150 nm）。超分辨率径向波动（SRRF）提供计算超分辨率；然而，未优化的参数会破坏分辨率和结构保真度之间的关键平衡。在这里，我们建立了一个基于srrf的活ccp纳米显微镜的综合参数优化框架。使用CLTA-GFP HeLa细胞的多模态指标，我们确定了1.0的环半径为最佳，平衡分辨率（最大一半的全宽度= 180 ± 29 nm, p <； 0.05 vs. TIRFM）和保真度（分辨率缩放的Pearson = 0.935 ± 0.018）。时间径向两两乘积平均（TRPPM）模式获得了更高的分辨率（154 ± 30 nm），同时保持了与时间径向平均（TRA）模式相当的保真度指标。相比之下，时间径向性自相关（TRAC）引入了人工结构，降低了保真度。诸如“去除正性约束”和梯度加权等参数会引起严重的伪影，应避免。这个优化的框架解决了分辨率和保真度之间的权衡，实现了活细胞中网格蛋白介导的内吞作用的强大纳米级成像。

{"title":"Optimizing the resolution-fidelity trade-off in SRRF nanoscopy for live-cell clathrin imaging","authors":"Sanhua Fang , Li Liu, Dan Yang, Shuangshuang Liu, Wei Yin, Qiong Huang, Jingyao Chen","doi":"10.1016/j.acthis.2025.152315","DOIUrl":"10.1016/j.acthis.2025.152315","url":null,"abstract":"<div><div>Total internal reflection fluorescence microscopy (TIRFM) enables live-cell imaging of clathrin-coated pits (CCPs) but is diffraction-limited (∼250 nm), hindering visualization of their dense nanostructures (∼150 nm). Super-Resolution Radial Fluctuations (SRRF) provides computational super-resolution; however, unoptimized parameters can disrupt the critical balance between resolution and structural fidelity. Here, we establish a comprehensive parameter optimization framework for SRRF-based nanoscopy of live CCPs. Using multi-modal metrics in CLTA-GFP HeLa cells, we identify a ring radius of 1.0 as optimal, balancing resolution (full width at half maximum = 180 ± 29 nm, p < 0.05 vs. TIRFM) with fidelity (resolution-scaled Pearson = 0.935 ± 0.018). The temporal radiality pairwise product mean (TRPPM) mode achieved superior resolution (154 ± 30 nm) while maintaining fidelity metrics comparable to Temporal radiality average (TRA) mode. In contrast, temporal radiality auto-correlations (TRAC) introduced artifactual structures and reduced fidelity. Parameters such as “remove positivity constraint” and gradient weighting induced severe artifacts and should be avoided. This optimized framework resolves the resolution–fidelity trade-off, enabling robust nanoscale imaging of clathrin-mediated endocytosis in live cells.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"128 1","pages":"Article 152315"},"PeriodicalIF":2.4,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From membranes to medicine: Emerging insights into Ezrin’s Role in human disease — A comprehensive overview 从膜到医学：对Ezrin在人类疾病中的作用的新见解-全面概述

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2025-12-31 DOI: 10.1016/j.acthis.2025.152314

Himanshu Kumar , Kanika Vashisht , Shavinder Kumari , Rimpi Arora , Pratima Ashawat , Mahendra Singh Ashawat , Shiv Kumar Kushawaha

Ezrin, a dynamic member of the Ezrin-Radixin-Moesin (ERM) family, plays a crucial role in orchestrating fundamental cellular functions, including membrane-cytoskeleton interactions, signal transduction, cell adhesion, migration, and immune regulation. Due to its broad functional repertoire, Ezrin has been increasingly recognized for its involvement in the pathogenesis of numerous human diseases, ranging from cancers and neurodegenerative disorders to renal and i conditions. In the central nervous system, Ezrin contributes to neurological homeostasis by preserving blood–brain barrier (BBB) integrity, modulating neuroinflammatory responses, and supporting synaptic plasticity and neuronal viability. Over the past few decades, scientific interest in Ezrin has grown significantly, as reflected by a marked increase in publications detailing its physiological and pathological roles. This review provides a comprehensive and uniquely alphabetized overview of Ezrin associations with a wide array of diseases, making it the first of its kind to catalog Ezrin biological relevance from A to Z. We examine its structural and biochemical characteristics, underscoring its potential as a diagnostic and prognostic biomarker, as well as an emerging therapeutic target. By addressing critical knowledge gaps, this review highlights Ezrin central role at the intersection of cancer biology, immunology, and neurotherapeutics.

Ezrin是Ezrin- radixin - moesin （ERM）家族的动态成员，在协调基本细胞功能，包括膜-细胞骨架相互作用，信号转导，细胞粘附，迁移和免疫调节中起着至关重要的作用。由于其广泛的功能库，Ezrin已被越来越多地认识到其参与许多人类疾病的发病机制，从癌症和神经退行性疾病到肾脏和i疾病。在中枢神经系统中，Ezrin通过保持血脑屏障（BBB）的完整性、调节神经炎症反应、支持突触可塑性和神经元活力来促进神经稳态。在过去的几十年里，对Ezrin的科学兴趣显著增长，这反映在详细介绍其生理和病理作用的出版物显著增加。这篇综述提供了Ezrin与一系列疾病的全面和独特的字母顺序概述，使其成为第一个从a到z的Ezrin生物学相关性目录。我们研究了它的结构和生化特征，强调了它作为诊断和预后生物标志物的潜力，以及一个新兴的治疗靶点。通过解决关键的知识空白，本综述强调了Ezrin在癌症生物学、免疫学和神经治疗学交叉领域的核心作用。

{"title":"From membranes to medicine: Emerging insights into Ezrin’s Role in human disease — A comprehensive overview","authors":"Himanshu Kumar , Kanika Vashisht , Shavinder Kumari , Rimpi Arora , Pratima Ashawat , Mahendra Singh Ashawat , Shiv Kumar Kushawaha","doi":"10.1016/j.acthis.2025.152314","DOIUrl":"10.1016/j.acthis.2025.152314","url":null,"abstract":"<div><div>Ezrin, a dynamic member of the Ezrin-Radixin-Moesin (ERM) family, plays a crucial role in orchestrating fundamental cellular functions, including membrane-cytoskeleton interactions, signal transduction, cell adhesion, migration, and immune regulation. Due to its broad functional repertoire, Ezrin has been increasingly recognized for its involvement in the pathogenesis of numerous human diseases, ranging from cancers and neurodegenerative disorders to renal and i conditions. In the central nervous system, Ezrin contributes to neurological homeostasis by preserving blood–brain barrier (BBB) integrity, modulating neuroinflammatory responses, and supporting synaptic plasticity and neuronal viability. Over the past few decades, scientific interest in Ezrin has grown significantly, as reflected by a marked increase in publications detailing its physiological and pathological roles. This review provides a comprehensive and uniquely alphabetized overview of Ezrin associations with a wide array of diseases, making it the first of its kind to catalog Ezrin biological relevance from A to Z. We examine its structural and biochemical characteristics, underscoring its potential as a diagnostic and prognostic biomarker, as well as an emerging therapeutic target. By addressing critical knowledge gaps, this review highlights Ezrin central role at the intersection of cancer biology, immunology, and neurotherapeutics.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"128 1","pages":"Article 152314"},"PeriodicalIF":2.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cisplatin treatment induces a shift toward a quiescent Ki-67⁻/CD44⁺/CD133⁺ cancer stem cell subpopulation in a tumorsphere model derived from a murine non-small cell lung cancer cell line 在来源于小鼠非小细胞肺癌细胞系的肿瘤球模型中，顺铂治疗诱导向静止的Ki-67⁻/CD44 + /CD133 +癌症干细胞亚群转移

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2025-12-31 DOI: 10.1016/j.acthis.2025.152313

Bryan Ôrtero Perez Gonçalves , Milla Reis Almeida , Vivian Vasconcelos Costa , Helen Lima Del Puerto , Alexander Birbrair , Luciana Maria Silva Lopes

Non-small cell lung cancer (NSCLC) exhibits substantial cellular and molecular heterogeneity, partly due to the presence of cancer stem cells (CSCs). CSCs can arise from a coordinated process known as epithelial–mesenchymal transition (EMT). EMT promotes a more aggressive phenotype, contributing significantly to tumor heterogeneity and drug resistance. Here, using state-of-the-art techniques—including confocal microscopy, flow cytometry, and transcript analysis—we investigated the cisplatin response of the LL/2 (LLC1) cell line cultured in both monolayer and tumorsphere (3D) models. Strikingly, LL/2 (LLC1) tumorspheres represent a model of cisplatin resistance, showing a remarkable increase in EMT and pluripotency mRNA regulators such as Zeb1, Zeb2, Snail, Twist, Tgfb1, Vimentin, FoxA2, Nanog, and Pou5f1 (Oct-4). Moreover, pseudotime trajectory analysis demonstrated that cisplatin treatment modulates a CSC-like phenotype differently in cells grown as monolayer versus tumorsphere. Our findings provide important insights into the role of cisplatin in NSCLC and highlight potential targets within the lung cancer microenvironment.

非小细胞肺癌（NSCLC）表现出大量的细胞和分子异质性，部分原因是癌症干细胞（CSCs）的存在。CSCs可以通过被称为上皮-间充质转化（EMT）的协调过程产生。EMT促进更具侵袭性的表型，显著促进肿瘤异质性和耐药性。在这里，我们使用最先进的技术——包括共聚焦显微镜、流式细胞术和转录分析——研究了在单层和肿瘤球（3D）模型中培养的LL/2 （LLC1）细胞系的顺铂反应。引人注目的是，LL/2 （LLC1）肿瘤球代表了顺铂耐药模型，显示出EMT和多能mRNA调控因子如Zeb1、Zeb2、Snail、Twist、Tgfb1、Vimentin、FoxA2、Nanog和Pou5f1的显著增加（Oct-4）。此外，伪时间轨迹分析表明，顺铂治疗在单层细胞和肿瘤细胞中对csc样表型的调节不同。我们的研究结果为顺铂在非小细胞肺癌中的作用提供了重要的见解，并突出了肺癌微环境中的潜在靶点。

{"title":"Cisplatin treatment induces a shift toward a quiescent Ki-67⁻/CD44⁺/CD133⁺ cancer stem cell subpopulation in a tumorsphere model derived from a murine non-small cell lung cancer cell line","authors":"Bryan Ôrtero Perez Gonçalves , Milla Reis Almeida , Vivian Vasconcelos Costa , Helen Lima Del Puerto , Alexander Birbrair , Luciana Maria Silva Lopes","doi":"10.1016/j.acthis.2025.152313","DOIUrl":"10.1016/j.acthis.2025.152313","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC) exhibits substantial cellular and molecular heterogeneity, partly due to the presence of cancer stem cells (CSCs). CSCs can arise from a coordinated process known as epithelial–mesenchymal transition (EMT). EMT promotes a more aggressive phenotype, contributing significantly to tumor heterogeneity and drug resistance. Here, using state-of-the-art techniques—including confocal microscopy, flow cytometry, and transcript analysis—we investigated the cisplatin response of the LL/2 (LLC1) cell line cultured in both monolayer and tumorsphere (3D) models. Strikingly, LL/2 (LLC1) tumorspheres represent a model of cisplatin resistance, showing a remarkable increase in EMT and pluripotency mRNA regulators such as <em>Zeb1</em>, <em>Zeb2</em>, <em>Snail</em>, <em>Twist</em>, <em>Tgfb1</em>, <em>Vimentin</em>, <em>FoxA2</em>, <em>Nanog</em>, and <em>Pou5f1</em> (Oct-4). Moreover, pseudotime trajectory analysis demonstrated that cisplatin treatment modulates a CSC-like phenotype differently in cells grown as monolayer versus tumorsphere. Our findings provide important insights into the role of cisplatin in NSCLC and highlight potential targets within the lung cancer microenvironment.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"128 1","pages":"Article 152313"},"PeriodicalIF":2.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhancing bone regeneration: The role of short fiber reinforced hydrogel with CO2-controlled release on the osteogenic differentiation of bone marrow mesenchymal stem cells 促进骨再生：二氧化碳控释短纤维增强水凝胶对骨髓间充质干细胞成骨分化的作用

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2025-12-27 DOI: 10.1016/j.acthis.2025.152311

Shiyou Dai , Chen Liang , Xiao Fan , Wenting Li , Lei Zhao

The utilization of hydrogels in bone defect repair applications faces numerous challenges, while carbon dioxide (CO₂) demonstrates potential beneficial effects in bone healing processes. Based on this, the current study proposes a novel approach, namely, the deployment of a hydrogel scaffold laden with CO₂-controlled release material to promote bone defect repair, successfully proving its beneficial impact. By combining Poly-L-lactic Acid (PLLA), Gelatin Methacryloyl (GelMA), Nano-Hydroxyapatite (nHA), and Ammonium Bicarbonate (NH₄HCO₃) into a composite material, CO₂ may be produced in a 37°C PBS environment, primarily due to the decomposition of NH₄HCO₃. Additionally, the material can be thermosensitive, and the application of near-infrared (NIR) light may further enhance the CO₂ release by increasing the temperature locally, facilitating the decomposition of NH₄HCO₃. Bone marrow stromal cells (BMSCs) were cultured on the composite hydrogel to evaluate cell proliferation and osteogenic differentiation in vitro, while a rat cranial bone defect model was employed to assess in vivo bone regeneration. The research results indicate that this composite material significantly promotes BMSC cell proliferation and osteogenic differentiation and successfully accelerates bone healing in a rat cranial bone defect model. The substantiated insights and empirical evidence proffered herein lay a robust foundation for subsequent explorations in this vanguard domain of research.

水凝胶在骨缺损修复中的应用面临许多挑战，而二氧化碳（CO2）在骨愈合过程中显示出潜在的有益作用。基于此，本研究提出了一种新颖的方法，即部署负载co2控释材料的水凝胶支架来促进骨缺损修复，并成功证明了其有益作用。通过将聚l -乳酸（PLLA）、明胶甲基丙烯酰（GelMA）、纳米羟基磷灰石（nHA）和碳酸氢铵（NH₄HCO₃）结合成一种复合材料，CO₂可以在37°C的PBS环境中产生，主要是由于NH₄HCO₃的分解。此外，这种材料是热敏的，使用近红外（NIR）光可以通过局部升高温度来进一步促进CO₂的释放，促进NH₄HCO₃的分解。采用复合水凝胶体外培养骨髓基质细胞（BMSCs），评估细胞增殖和成骨分化，并采用大鼠颅骨骨缺损模型评估体内骨再生。研究结果表明，该复合材料可显著促进大鼠颅骨骨缺损模型BMSC细胞增殖和成骨分化，并成功加速骨愈合。本文提供的经证实的见解和经验证据为这一前沿研究领域的后续探索奠定了坚实的基础。

{"title":"Enhancing bone regeneration: The role of short fiber reinforced hydrogel with CO2-controlled release on the osteogenic differentiation of bone marrow mesenchymal stem cells","authors":"Shiyou Dai , Chen Liang , Xiao Fan , Wenting Li , Lei Zhao","doi":"10.1016/j.acthis.2025.152311","DOIUrl":"10.1016/j.acthis.2025.152311","url":null,"abstract":"<div><div>The utilization of hydrogels in bone defect repair applications faces numerous challenges, while carbon dioxide (CO<sub>2</sub>) demonstrates potential beneficial effects in bone healing processes. Based on this, the current study proposes a novel approach, namely, the deployment of a hydrogel scaffold laden with CO<sub>2</sub>-controlled release material to promote bone defect repair, successfully proving its beneficial impact. By combining Poly-<span>L</span>-lactic Acid (PLLA), Gelatin Methacryloyl (GelMA), Nano-Hydroxyapatite (nHA), and Ammonium Bicarbonate (NH₄HCO₃) into a composite material, CO₂ may be produced in a 37°C PBS environment, primarily due to the decomposition of NH₄HCO₃. Additionally, the material can be thermosensitive, and the application of near-infrared (NIR) light may further enhance the CO₂ release by increasing the temperature locally, facilitating the decomposition of NH₄HCO₃. Bone marrow stromal cells (BMSCs) were cultured on the composite hydrogel to evaluate cell proliferation and osteogenic differentiation in vitro, while a rat cranial bone defect model was employed to assess in vivo bone regeneration. The research results indicate that this composite material significantly promotes BMSC cell proliferation and osteogenic differentiation and successfully accelerates bone healing in a rat cranial bone defect model. The substantiated insights and empirical evidence proffered herein lay a robust foundation for subsequent explorations in this vanguard domain of research.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"128 1","pages":"Article 152311"},"PeriodicalIF":2.4,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145836365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An immunohistochemical study of Saussurea lappa nanoparticle on transformed cells in mice induced with benzo[a]pyrene for oral squamous cell carcinoma 雪莲纳米颗粒对苯并[a]芘诱导小鼠口腔鳞癌转化细胞的免疫组化研究。

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2025-12-23 DOI: 10.1016/j.acthis.2025.152312

Theresia Indah Budhy , Ira Arundina , Anis Irmawati , Cheng Hwee Ming , Meircurius Dwi Condro Surboyo , Azzahra Salsabila Adira Moelyanto , Pandu Dewanata , Naqiya Saqifa

Background

Saussurea lappa, a plant used in traditional medicine, has shown promise in cancer treatment This study aimed to evaluate the therapeutic efficacy of Saussurea lappa nanoparticles using immunohistochemical analysis in a benzo[a]pyrene-induced mouse model of oral squamous cell carcinoma (OSCC). The investigation focused on the expression of markers related to apoptosis (Bax, Caspase-3, BCL-2), inflammation (TNF-α), proliferation (Ki-67), and tumor suppression (p53).

Methods

A true experimental design was employed using male Mus musculus mice. OSCC was induced via exposure to benzo[a]pyrene. Following induction, mice were treated perorally with Saussurea lappa nanoparticles at doses of 50, 100, and 200 mg/kg body weight, while the control group received CMC-Na. Buccal mucosa samples were collected for immunohistochemical analysis, assessing dose-dependent effects of Saussurea lappa nanoparticles on the expression of Bax, Caspase-3, BCL-2, TNF-α, Ki-67 and p53.

Result

Saussurea lappa nanoparticles demonstrated dose-dependent therapeutic effects in the OSCC mouse model. They significantly upregulated Bax, Caspase-3, TNF-α, and p53, while downregulating BCL-2 and Ki-67expression. The highest dose (200 mg/kg) showed the most pronounced effects, indicating enhanced apoptosis, reduced proliferation, and modulation of the inflammatory environment.

Conclusion

These findings suggest that Saussurea lappa nanoparticles, particularly at a dose of 200 mg/kg BW, effectively promote apoptosis, inhibit cell proliferation, and suppress anti-apoptotic pathways. This highlights their potential as a promising therapeutic candidate for the treatment of oral mucosal malignancies.

背景：雪莲是一种传统的药用植物，在癌症治疗中显示出前景。本研究旨在通过免疫组织化学分析评估雪莲纳米颗粒在苯并芘诱导的口腔鳞状细胞癌（OSCC）小鼠模型中的治疗效果。研究重点关注与凋亡（Bax, Caspase-3, BCL-2），炎症（TNF-α），增殖（Ki-67）和肿瘤抑制（p53）相关的标志物的表达。方法：采用真实实验设计，选用雄性小家鼠。暴露于苯并[a]芘诱导OSCC。诱导后，小鼠按50、100和200 mg/kg体重口服雪莲纳米颗粒，对照组给予CMC-Na。采集口腔黏膜标本进行免疫组化分析，评估雪丹纳米颗粒对Bax、Caspase-3、BCL-2、TNF-α、Ki-67和p53表达的剂量依赖性影响。结果：雪莲纳米颗粒在OSCC小鼠模型中表现出剂量依赖性的治疗作用。它们显著上调Bax、Caspase-3、TNF-α和p53的表达，下调BCL-2和ki -67的表达。最高剂量（200 mg/kg）显示出最明显的效果，表明细胞凋亡增强，增殖减少，炎症环境调节。结论：雪莲纳米颗粒，特别是200 mg/kg BW剂量下，能有效促进细胞凋亡，抑制细胞增殖，抑制抗凋亡通路。这突出了它们作为治疗口腔黏膜恶性肿瘤的有希望的治疗候选药物的潜力。

{"title":"An immunohistochemical study of Saussurea lappa nanoparticle on transformed cells in mice induced with benzo[a]pyrene for oral squamous cell carcinoma","authors":"Theresia Indah Budhy , Ira Arundina , Anis Irmawati , Cheng Hwee Ming , Meircurius Dwi Condro Surboyo , Azzahra Salsabila Adira Moelyanto , Pandu Dewanata , Naqiya Saqifa","doi":"10.1016/j.acthis.2025.152312","DOIUrl":"10.1016/j.acthis.2025.152312","url":null,"abstract":"<div><h3>Background</h3><div><em>Saussurea lappa</em>, a plant used in traditional medicine, has shown promise in cancer treatment This study aimed to evaluate the therapeutic efficacy of <em>Saussurea lappa</em> nanoparticles using immunohistochemical analysis in a benzo[<em>a</em>]pyrene-induced mouse model of oral squamous cell carcinoma (OSCC). The investigation focused on the expression of markers related to apoptosis (Bax, Caspase-3, BCL-2), inflammation (TNF-α), proliferation (Ki-67), and tumor suppression (p53).</div></div><div><h3>Methods</h3><div>A true experimental design was employed using male <em>Mus musculus</em> mice. OSCC was induced via exposure to benzo[<em>a</em>]pyrene. Following induction, mice were treated perorally with <em>Saussurea lappa</em> nanoparticles at doses of 50, 100, and 200 mg/kg body weight, while the control group received CMC-Na. Buccal mucosa samples were collected for immunohistochemical analysis, assessing dose-dependent effects of <em>Saussurea lappa</em> nanoparticles on the expression of Bax, Caspase-3, BCL-2, TNF-α, Ki-67 and p53.</div></div><div><h3>Result</h3><div><em>Saussurea lappa</em> nanoparticles demonstrated dose-dependent therapeutic effects in the OSCC mouse model. They significantly upregulated Bax, Caspase-3, TNF-α, and p53, while downregulating BCL-2 and Ki-67expression. The highest dose (200 mg/kg) showed the most pronounced effects, indicating enhanced apoptosis, reduced proliferation, and modulation of the inflammatory environment.</div></div><div><h3>Conclusion</h3><div>These findings suggest that <em>Saussurea lappa</em> nanoparticles, particularly at a dose of 200 mg/kg BW, effectively promote apoptosis, inhibit cell proliferation, and suppress anti-apoptotic pathways. This highlights their potential as a promising therapeutic candidate for the treatment of oral mucosal malignancies.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"128 1","pages":"Article 152312"},"PeriodicalIF":2.4,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145825600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cellular landscape of reactive and neoplastic human lymph nodes in 3D 反应性和肿瘤性人类淋巴结的三维细胞景观。

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2025-12-16 DOI: 10.1016/j.acthis.2025.152308

Victoria Julia Diederich , Sonja Scharf , Hendrik Schäfer , Sylvia Hartmann , Martin-Leo Hansmann , Patrick Wurzel

Lymph nodes function according to cellular and structural regulations. When these rules deviate from the benign equilibrium, dysregulations occur leading to the onset of diseases. In the development of malignant lymph node diseases, processes can be observed that consistently follow the same pattern. This study aims to define the structural and cellular parameters of the reactive lymph node and to demonstrate how lymph nodes change during tumorigenesis.

We analysed benign cases diagnosed as Lymphadenitis (8 patients). Malignant cases with the diagnosis of Nodular Sclerosis classical Hodgkin Lymphoma (5 patients), Mixed Cellularity classical Hodgkin Lymphoma (5 patients), Follicular Lymphoma (7 patients), and diffuse large B-cell Lymphoma (2 patients) were selected. Confocal microscopy was used to visualise immune cells and their compartments in 3D. Based on the fibroblastic reticular cell network we defined five compartments in reactive lymph nodes: Subcapsular sinus, marginal sinus, follicle, T-zone, and medulla. We analysed the cellular composition based on dendritic cells, macrophages, T cells and B cells and extended this analysis to include the presence of extracellular vesicles. During tumorigenesis, the compartmentalisation of the lymph node is progressively destroyed. Despite this ongoing destruction and loss of strict compartmental delineations, at least two distinct structural regions are still visible, defined as follicle-like and T-zone-like compartments. A comparison between reactive and neoplastic cases reveals a progressive cellular and structural homogenisation. Higher masses of CD8⁺ T cells were found under neoplastic conditions and higher masses of CD30⁺ were found in Hodgkin Lymphoma. The volume of CD20⁺ cells in follicles was consistently lower in malignant tissues compared to benign, but higher in T-zones in malignant cases. An increase in vesicles was detected in most neoplasms.

These findings offer new insights into cellular and structural remodelling, deepening our understanding of tumorigenesis and paving the way for more precise therapeutic interventions.

淋巴结的功能取决于细胞和结构的调节。当这些规则偏离良性平衡时，就会发生失调，导致疾病的发生。在恶性淋巴结疾病的发展过程中，可以观察到始终遵循相同模式的过程。本研究旨在定义反应性淋巴结的结构和细胞参数，并展示淋巴结在肿瘤发生过程中的变化。我们分析诊断为淋巴结炎的良性病例（8例）。选择诊断为结节硬化经典霍奇金淋巴瘤（5例）、混合细胞性经典霍奇金淋巴瘤（5例）、滤泡性淋巴瘤（7例）、弥漫性大b细胞淋巴瘤（2例）的恶性病例。用共聚焦显微镜观察免疫细胞及其胞室的三维图像。基于纤维母细胞网状细胞网络，我们在反应性淋巴结中定义了五个区室：包膜下窦、边缘窦、滤泡、t区和髓质。我们分析了基于树突状细胞、巨噬细胞、T细胞和B细胞的细胞组成，并将分析扩展到包括细胞外囊泡的存在。在肿瘤发生过程中，淋巴结的区隔逐渐被破坏。尽管这种持续的破坏和严格的区室划分的丧失，至少两个不同的结构区域仍然可见，定义为卵泡样和t区样区室。反应性和肿瘤性病例的比较显示细胞和结构均质化的进展。肿瘤中CD8+ T细胞较多，霍奇金淋巴瘤中CD30+细胞较多。与良性组织相比，恶性组织中卵泡中CD20+细胞的体积始终较低，但在恶性病例的t区中CD20+细胞的体积较高。大多数肿瘤均可见囊泡增多。这些发现为细胞和结构重塑提供了新的见解，加深了我们对肿瘤发生的理解，并为更精确的治疗干预铺平了道路。

{"title":"Cellular landscape of reactive and neoplastic human lymph nodes in 3D","authors":"Victoria Julia Diederich , Sonja Scharf , Hendrik Schäfer , Sylvia Hartmann , Martin-Leo Hansmann , Patrick Wurzel","doi":"10.1016/j.acthis.2025.152308","DOIUrl":"10.1016/j.acthis.2025.152308","url":null,"abstract":"<div><div>Lymph nodes function according to cellular and structural regulations. When these rules deviate from the benign equilibrium, dysregulations occur leading to the onset of diseases. In the development of malignant lymph node diseases, processes can be observed that consistently follow the same pattern. This study aims to define the structural and cellular parameters of the reactive lymph node and to demonstrate how lymph nodes change during tumorigenesis.</div><div>We analysed benign cases diagnosed as Lymphadenitis (8 patients). Malignant cases with the diagnosis of Nodular Sclerosis classical Hodgkin Lymphoma (5 patients), Mixed Cellularity classical Hodgkin Lymphoma (5 patients), Follicular Lymphoma (7 patients), and diffuse large B-cell Lymphoma (2 patients) were selected. Confocal microscopy was used to visualise immune cells and their compartments in 3D. Based on the fibroblastic reticular cell network we defined five compartments in reactive lymph nodes: Subcapsular sinus, marginal sinus, follicle, T-zone, and medulla. We analysed the cellular composition based on dendritic cells, macrophages, T cells and B cells and extended this analysis to include the presence of extracellular vesicles. During tumorigenesis, the compartmentalisation of the lymph node is progressively destroyed. Despite this ongoing destruction and loss of strict compartmental delineations, at least two distinct structural regions are still visible, defined as follicle-like and T-zone-like compartments. A comparison between reactive and neoplastic cases reveals a progressive cellular and structural homogenisation. Higher masses of CD8<sup>+</sup> T cells were found under neoplastic conditions and higher masses of CD30<sup>+</sup> were found in Hodgkin Lymphoma. The volume of CD20<sup>+</sup> cells in follicles was consistently lower in malignant tissues compared to benign, but higher in T-zones in malignant cases. An increase in vesicles was detected in most neoplasms.</div><div>These findings offer new insights into cellular and structural remodelling, deepening our understanding of tumorigenesis and paving the way for more precise therapeutic interventions.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"128 1","pages":"Article 152308"},"PeriodicalIF":2.4,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0