Biochemistry and Biophysics Reports最新文献_第3页

Recognition of immunogenomic signature and prognostic value of the subtype of epithelial-mesenchymal transition in breast cancer 乳腺癌上皮-间质转化亚型的免疫基因组特征识别及其预后价值

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-01-19 DOI: 10.1016/j.bbrep.2026.102456

Wei Liang , Zi-ying Wang , Quan-feng Shao , Yuan-yuan Li , Bei Zhu , Xi-hu Qin , Wei-xian Chen

Background

Accumulating evidence has revealed that epithelial-mesenchymal transition (EMT) plays a crucial role in tumor progression and the immune microenvironment, which further results in a high rate of recurrence and metastasis. The EMT immune signaling pathway provides a great perspective for designing personalized therapies.

Methods

In this study, 1223 RNA-seq samples were obtained from the TCGA-BRCA dataset. A total of 381 EMT-related differentially expressed genes were analyzed and combined with clinical parameters, and the matrix was randomly divided into training and testing cohorts at a ratio of 7:3. The training cohort was used to develop an EMT signature, including GKN2, FZD2, NDRG2, SCUBE2, ALX4, CCL19, SDC1, EZR, CPEB1, and HRG genes, and the accuracy of this signature was validated by testing and GSE158309 cohorts.

Results

A risk score model and clinical parameters were used to establish a nomogram for predicting prognosis. The C-index (0.719), calibration curves, and model comparison with four previous studies demonstrated the reliability of the EMT signature, the biological phenotypes of which were tested for functional enrichment, immune infiltration, and tumor mutation. Additionally, patients' responses to immunotherapy and chemotherapy were assessed. Our results showed that the low-risk group had higher immune infiltration, tumor mutational burden, microsatellite instability levels, immune checkpoint inhibitor expression, tumor immune dysfunction and exclusion scores, and immunophenoscore, which could predict patient sensitivity to immunotherapy. Moreover, low-risk patients exhibit better sensitivity to chemotherapy.

Conclusion

This novel EMT signature offers excellent potential for predicting the prognosis, tumor immune heterogeneity, and therapeutic responses in breast cancer.

越来越多的证据表明，上皮间质转化（epithelial-mesenchymal transition， EMT）在肿瘤的进展和免疫微环境中起着至关重要的作用，这进一步导致了肿瘤的高复发和转移率。EMT免疫信号通路为设计个性化治疗提供了一个很好的视角。方法本研究从TCGA-BRCA数据集中获得1223个RNA-seq样本。共分析381个emt相关差异表达基因并结合临床参数，将基质按7:3的比例随机分为训练组和测试组。训练队列用于建立EMT签名，包括GKN2、FZD2、NDRG2、SCUBE2、ALX4、CCL19、SDC1、EZR、CPEB1和HRG基因，并通过测试和GSE158309队列验证该签名的准确性。结果采用风险评分模型和临床参数建立预测预后的nomogram。c -指数（0.719）、校准曲线以及与先前4项研究的模型比较证明了EMT特征的可靠性，并对其进行了功能富集、免疫浸润和肿瘤突变的生物学表型检测。此外，还评估了患者对免疫治疗和化疗的反应。我们的研究结果显示，低危组免疫浸润、肿瘤突变负担、微卫星不稳定性水平、免疫检查点抑制剂表达、肿瘤免疫功能障碍和排斥评分以及免疫表型评分较高，可以预测患者对免疫治疗的敏感性。此外，低风险患者对化疗的敏感性更好。结论这种新的EMT特征在预测乳腺癌的预后、肿瘤免疫异质性和治疗反应方面具有很好的潜力。

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引用次数: 0

Breast cancer susceptibility gene 2 upregulation alleviated cardiac hypertrophy in angiotensin II-treated mice 乳腺癌易感基因2上调可减轻血管紧张素ii处理小鼠心肌肥厚

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-01-19 DOI: 10.1016/j.bbrep.2026.102445

Kun Liu , Xiao-Xuan Gong , Yong Li , Ming-Zhu Li , Chen Si , Lei Zhou

Loss of breast cancer susceptibility gene 2 (BRCA2) function was found to exacerbate doxorubicin-mediated cardiomyocyte apoptosis and promote heart failure progression. We hypothesized that upregulation of BRCA2 may alleviate hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy was established in mice via chronic angiotensin II (Ang II) administration (1.44 mg/kg/day) using osmotic minipumps. Cardiac BRCA2 expression was significantly downregulated in Ang II-treated mice. Cardiac hypertrophy triggered by Ang II in mice was significantly attenuated upon BRCA2 overexpression. Similarly, in cultured primary cardiomyocytes, Ang II-induced hypertrophic responses were suppressed by BRCA2 upregulation. The cardiac fibrosis was significantly attenuated after upregulation of BRCA2 in Ang II-induced hypertrophic cardiomyopathy. The myocardial inflammatory response to Ang II, characterized by elevated interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) levels, was markedly reduced with BRCA2 overexpression. The apoptotic biomarkers including Bax and cleaved caspase 3 (CC3) increased in the heart of hypertrophic cardiomyopathy, and attenuated after upregulation of BRCA2. These results indicated that upregulation of BRCA2 could improve hypertrophic cardiomyopathy. BRCA2 alleviated cardiac hypertrophy via attenuation of inflammation and apoptosis.

发现乳腺癌易感基因2 （BRCA2）功能的丧失会加剧阿霉素介导的心肌细胞凋亡并促进心力衰竭的进展。我们假设BRCA2的上调可能减轻肥厚性心肌病。通过渗透微型泵给药慢性血管紧张素II (Ang II)（1.44 mg/kg/day）建立小鼠肥厚性心肌病。在angii处理的小鼠中，心脏BRCA2表达显著下调。在BRCA2过表达后，Ang II引发的小鼠心肌肥厚显著减弱。同样，在培养的原代心肌细胞中，angii诱导的肥厚反应被BRCA2上调抑制。在angii诱导的肥厚性心肌病中，BRCA2上调后，心脏纤维化显著减弱。心肌对Ang II的炎症反应，以白细胞介素(IL)-1β、IL-6和肿瘤坏死因子α (TNF-α)水平升高为特征，随着BRCA2过表达而显著降低。包括Bax和cleaved caspase 3 （CC3）在内的凋亡生物标志物在肥厚性心肌病心脏中升高，在BRCA2上调后减弱。这些结果表明，上调BRCA2可以改善肥厚性心肌病。BRCA2通过抑制炎症和细胞凋亡减轻心肌肥厚。

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引用次数: 0

Influence of fluid shear stress on human limbal epithelial cells 流体剪切应力对人角膜缘上皮细胞的影响

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-01-17 DOI: 10.1016/j.bbrep.2026.102453

Sophia Masterton , Mark Ahearne

Background/aims

Limbal epithelial cells (LECs) have a crucial role in the maintenance of the corneal surface by migrating from the limbus to the cornea and replacing corneal epithelial cells. These cells are subjected to shear stress via blinking and tear film movement but the influence this stress has on the cells is poorly understood. The aim of this study was to examine how fluidic shear stress can affect the behaviour of LECs from different donors.

Methods

A commercial fluid flow system (ibidi) was used to apply fluid shear at two different flow rates, with no flow being used as a control. Cells from three different donors were examined for phenotype, stratification, TRPV4 activation, cell adhesion and barrier function.

Results

Both low and high shear stresses resulted in changes to the cell phenotype and these changes were highly donor dependent. Expression of TRPV4, a mechanosensitive ion-channel, was up-regulated for all donors exposed to shear stress. Stratification of cells only occurred with cells exposed to shear stress.

Conclusion

This study show the importance of shear stress on modulating the behaviour of LECs and how donor to donor variations and the heterogeneity of cell populations need to be considered when conducting cell based studies.

背景/目的角膜缘上皮细胞（lec）通过从角膜缘向角膜迁移并替代角膜上皮细胞，在维持角膜表面中起着至关重要的作用。这些细胞通过眨眼和撕裂膜运动受到剪切应力，但这种应力对细胞的影响尚不清楚。本研究的目的是研究流体剪切应力如何影响来自不同供体的LECs的行为。方法采用商业流体流动系统（ibidi）在两种不同流速下施加流体剪切，不使用流量作为对照。对来自三种不同供体的细胞进行表型、分层、TRPV4活化、细胞粘附和屏障功能检测。结果低剪应力和高剪应力均可引起细胞表型的变化，且这些变化高度依赖于供体。TRPV4（一种机械敏感离子通道）的表达在所有暴露于剪切应力的供体中均上调。细胞分层只发生在细胞受到剪切应力时。本研究显示了剪切应力对调节LECs行为的重要性，以及在进行基于细胞的研究时，如何考虑供体之间的差异和细胞群体的异质性。

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引用次数: 0

Effects of branched-chain amino acids on iron deficiency-induced muscle atrophy 支链氨基酸对缺铁所致肌肉萎缩的影响

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-01-17 DOI: 10.1016/j.bbrep.2026.102451

Miki Kawanaka , Mingyuan Wang , Toru Iwahashi , Mai Konishi , Katsuyuki Konishi , Seira Sato , Hiroyuki Tanaka , Ken Nakata

Iron deficiency (ID) is a potential contributor to skeletal muscle atrophy through disruption of the balance between protein synthesis and degradation. This muscle loss is associated with sarcopenia and locomotive syndrome, conditions that impair mobility and reduce healthy life expectancy. While branched-chain amino acids (BCAA) are known to attenuate dexamethasone-induced muscle atrophy, its effectiveness against ID-induced atrophy has not been fully elucidated. This study aims to investigate the effects of BCAA on ID-induced muscle atrophy in C2C12 myotubes treated with the iron chelator deferoxamine (DFO). Results showed that DFO significantly reduced myotube diameter and upregulated atrogenes such as Atrogin-1 and MuRF-1, accompanied by increased p-AMPK and p-eEF2, and decreased p-Akt levels. BCAA supplementation partially suppressed Atrogin-1 expression but had no effect on MuRF-1 or myotube diameter. Additionally, p-p70S6K was significantly upregulated in the BCAA + DFO group, while p-eEF2 levels remained elevated, similar to the DFO group. These findings suggest that ID may activate alternative catabolic signaling, such as the NF-kB pathway, thereby counteracting the anabolic effects of BCAA via the Akt signaling pathway. Thus, BCAA has limited efficacy in preventing muscle atrophy under iron-deficient conditions. In conclusion, BCAA may partially promote muscle protein synthesis-related signaling pathways, but is insufficient to prevent muscle atrophy induced by ID.

缺铁（ID）是一个潜在的贡献者骨骼肌萎缩通过破坏蛋白质合成和降解之间的平衡。这种肌肉损失与肌肉减少症和运动综合症有关，这些疾病会损害活动能力，降低健康预期寿命。虽然已知支链氨基酸（BCAA）可以减轻地塞米松诱导的肌肉萎缩，但其对id诱导的萎缩的有效性尚未完全阐明。本研究旨在探讨支链氨基酸对铁螯合剂去铁胺（DFO）处理的C2C12肌管id诱导的肌肉萎缩的影响。结果显示，DFO显著降低了肌管直径，上调了atrogen -1和MuRF-1等atrogenes，同时增加了p-AMPK和p-eEF2，降低了p-Akt水平。补充BCAA部分抑制了atrojin -1的表达，但对MuRF-1和肌管直径没有影响。此外，p-p70S6K在BCAA + DFO组中显著上调，而p-eEF2水平保持升高，与DFO组相似。这些发现表明，ID可能激活其他分解代谢信号，如NF-kB信号通路，从而通过Akt信号通路抵消BCAA的合成代谢作用。因此，BCAA在预防缺铁条件下肌肉萎缩的功效有限。综上所述，BCAA可能部分促进肌肉蛋白合成相关信号通路，但不足以预防ID诱导的肌肉萎缩。

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引用次数: 0

NLRP3 inflammasome regulates Th17/Treg cell balance in experimental autoimmune myocarditis NLRP3炎性体调节实验性自身免疫性心肌炎中Th17/Treg细胞平衡

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-01-16 DOI: 10.1016/j.bbrep.2026.102447

Lijun Su , Nan Qu , Lili Chen , Yuying Lin , Huiwen Mo , Yanlan Huang

Objective

This study aimed to investigate whether the NLRP3 inflammasome modulates the Th17/Treg cell balance in experimental autoimmune myocarditis (EAM).

Methods

BALB/c mice were immunized subcutaneously with purified cardiac myosin heavy chain-α to induce EAM, injected NLRP3 inhibitor (MCC950) or PBS into the EAM mice by intraperitoneal injection. Splenic CD4⁺ T cells were isolated for in vitro culture. Myocardial inflammation was evaluated by HE staining. Th17/Treg ratios were analyzed by flow cytometry in cardiac tissue and cultured cells. RORγt and Foxp3 mRNA expression was measured by RT-PCR and IL-17/IL-10 levels by ELISA.

Results

Our study demonstrates that NLRP3 inhibition significantly attenuates myocardial inflammatory cell infiltration and preserves cardiac architecture in EAM mice. The EAM group exhibited significantly increased Th17/Treg ratios and RORγt mRNA expression in myocardial tissue compared to both MCC950-treated and control groups while demonstrating markedly decreased Foxp3 mRNA levels. In vitro experiments using cultured CD4⁺ T cells revealed substantially higher Th17 cell proportions, RORγt expression, and IL-17 secretion in the EAM group versus MCC950-treated cells, accompanied by significantly reduced Treg cell frequencies, Foxp3 mRNA levels, and IL-10 production.

Conclusion

During the pathogenesis of experimental autoimmune myocarditis (EAM), the NLRP3 inflammasome promotes Th17 cell differentiation while suppressing Treg cell development. Inhibition of the NLRP3 inflammasome restores the Th17/Treg balance and mitigates myocardial injury. These findings suggest that the NLRP3 inflammasome is a critical signaling hub in modulating immune responses in EAM. Targeting NLRP3 may represent a novel immunotherapeutic strategy for myocarditis.

目的探讨NLRP3炎性小体是否调节实验性自身免疫性心肌炎（EAM）中Th17/Treg细胞的平衡。方法用纯化心肌肌球蛋白重链α皮下免疫balb /c小鼠诱导EAM，并腹腔注射NLRP3抑制剂（MCC950）或PBS。分离脾CD4+ T细胞进行体外培养。HE染色评价心肌炎症反应。流式细胞术分析心肌组织和培养细胞的Th17/Treg比值。RT-PCR检测RORγt和Foxp3 mRNA表达，ELISA检测IL-17/IL-10水平。结果NLRP3抑制可显著减轻EAM小鼠心肌炎症细胞浸润，保留心脏结构。与mcc950处理组和对照组相比，EAM组心肌组织中Th17/Treg比率和rr γt mRNA表达显著增加，Foxp3 mRNA水平显著降低。体外培养CD4+ T细胞实验显示，与mcc950处理的细胞相比，EAM组Th17 细胞比例、RORγt表达和IL-17分泌显著增加，Treg细胞频率、Foxp3 mRNA水平和IL-10产生显著降低。结论在实验性自身免疫性心肌炎（EAM）发病过程中，NLRP3炎性小体促进Th17 细胞分化，抑制Treg细胞发育。抑制NLRP3炎性小体可恢复Th17/Treg平衡，减轻心肌损伤。这些发现表明NLRP3炎症小体是调节EAM免疫反应的关键信号中枢。靶向NLRP3可能是一种新的心肌炎免疫治疗策略。

{"title":"NLRP3 inflammasome regulates Th17/Treg cell balance in experimental autoimmune myocarditis","authors":"Lijun Su , Nan Qu , Lili Chen , Yuying Lin , Huiwen Mo , Yanlan Huang","doi":"10.1016/j.bbrep.2026.102447","DOIUrl":"10.1016/j.bbrep.2026.102447","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate whether the NLRP3 inflammasome modulates the Th17/Treg cell balance in experimental autoimmune myocarditis (EAM).</div></div><div><h3>Methods</h3><div>BALB/c mice were immunized subcutaneously with purified cardiac myosin heavy chain-α to induce EAM, injected NLRP3 inhibitor (MCC950) or PBS into the EAM mice by intraperitoneal injection. Splenic CD4<sup>+</sup> T cells were isolated for in vitro culture. Myocardial inflammation was evaluated by HE staining. Th17/Treg ratios were analyzed by flow cytometry in cardiac tissue and cultured cells. RORγt and Foxp3 mRNA expression was measured by RT-PCR and IL-17/IL-10 levels by ELISA.</div></div><div><h3>Results</h3><div>Our study demonstrates that NLRP3 inhibition significantly attenuates myocardial inflammatory cell infiltration and preserves cardiac architecture in EAM mice. The EAM group exhibited significantly increased Th17/Treg ratios and RORγt mRNA expression in myocardial tissue compared to both MCC950-treated and control groups while demonstrating markedly decreased Foxp3 mRNA levels. In vitro experiments using cultured CD4<sup>+</sup> T cells revealed substantially higher Th17 cell proportions, RORγt expression, and IL-17 secretion in the EAM group versus MCC950-treated cells, accompanied by significantly reduced Treg cell frequencies, Foxp3 mRNA levels, and IL-10 production.</div></div><div><h3>Conclusion</h3><div>During the pathogenesis of experimental autoimmune myocarditis (EAM), the NLRP3 inflammasome promotes Th17 cell differentiation while suppressing Treg cell development. Inhibition of the NLRP3 inflammasome restores the Th17/Treg balance and mitigates myocardial injury. These findings suggest that the NLRP3 inflammasome is a critical signaling hub in modulating immune responses in EAM. Targeting NLRP3 may represent a novel immunotherapeutic strategy for myocarditis.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102447"},"PeriodicalIF":2.2,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bifendate inhibits cell PARthanatos by activating the MEK/ERK pathway 联苯双酯通过激活MEK/ERK通路抑制细胞PARthanatos

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-01-15 DOI: 10.1016/j.bbrep.2026.102454

Ao-meng Hu , Meng Chen , Can-can Zhu , Zai-man Zhu , Xiao-hui Xu

PARthanatos is a form of programmed cell death increasingly implicated in neurodegenerative diseases and ischemic stroke. Although classical PARP-1 inhibitors can interrupt this pathway, their prolonged use carries a risk of genomic instability. Screening an NMPA-approved compound library identified compound Bifendate (DDB), a clinical used anti-hepatitis drug, as a effective PARthanatos suppressor. In HeLa and SH-SY5Y cells exposed to the PARthanatos inducer MNNG, DDB increased cell viability by approximately 30 % and 70 %, respectively. This inhibitory effect was not attributable to altered protein levels of PARP-1, AIF, or MIF, but to the blockade of AIF translocation from mitochondria to the cytoplasm and nucleus. Mechanistic analyses revealed that DDB treatment can significantly activate MEK, ERK and then phosphorylate Bad. This activation helps to maintain the mitochondrial membrane potential and permeability, and prevent the release of AIF, and thereby blocks the PARthanatos cascade downstream of PARP-1 activation. Unlike PARP-1 inhibitors, DDB does not interfere with PARP-1 enzymatic activity. Instead, DDB exerts its effects by modulating ERK signaling and enhancing ERK activation. Collectively, these findings provide novel insights into the development of neuroprotective drugs that inhibit PARthanatos without compromising PARP-1 function, highlighting DDB as a promising therapeutic candidate for neurological disorders.

PARthanatos是一种程序性细胞死亡形式，与神经退行性疾病和缺血性中风的关系日益密切。尽管经典的PARP-1抑制剂可以阻断这一途径，但长期使用它们会带来基因组不稳定的风险。筛选nmpa批准的化合物文库，发现临床常用抗肝炎药物联苯双酯（DDB）是一种有效的PARthanatos抑制剂。在暴露于PARthanatos诱导剂MNNG的HeLa和SH-SY5Y细胞中，DDB分别提高了约30% %和70% %的细胞活力。这种抑制作用不是由于PARP-1、AIF或MIF蛋白水平的改变，而是由于阻断了AIF从线粒体向细胞质和细胞核的易位。机制分析表明，DDB处理能显著激活MEK、ERK，使Bad磷酸化。这种激活有助于维持线粒体膜电位和通透性，阻止AIF的释放，从而阻断PARP-1激活下游的PARthanatos级联反应。与PARP-1抑制剂不同，DDB不干扰PARP-1酶活性。相反，DDB通过调节ERK信号和增强ERK激活来发挥作用。总的来说，这些发现为开发抑制PARthanatos而不损害PARP-1功能的神经保护药物提供了新的见解，突出了DDB作为神经系统疾病的有前途的治疗候选药物。

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引用次数: 0

Single-cell transcriptome sequencing revealing the microenvironment of breast fibroepithelial tumor 单细胞转录组测序揭示乳腺纤维上皮肿瘤的微环境

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-01-14 DOI: 10.1016/j.bbrep.2026.102448

Tianrun Shu , Jing Wang , Fuying Yang , Dechun Yang , Shengnan Ren , Min Zhao , Yafeng Lv , Ying Song , Hanhui Xie , Xuan Yang , Cong Jiang , Rong Guo , Shicong Tang

Background

Giant juvenile fibroepithelial tumors of the breast are rare lesions that mainly affect adolescent girls. Their pathogenesis is poorly understood, and current management relies almost entirely on surgery, which may interfere with breast development. To clarify the biological basis of these tumors, we performed single-cell RNA sequencing.

Methods

We profiled 15,295 cells from three juvenile cases (ages 12–16) and 11,442 cells from one adult patient (age 42) using the BD Rhapsody™ platform. This dataset provided a detailed cellular atlas of fibroepithelial lesions and enabled direct comparison of tumor microenvironments between juvenile and adult cases.

Results

Distinct molecular signatures in epithelial cells and fibroblasts: Juvenile FT epithelial cells exhibited significant enrichment of proliferation-associated pathways (e.g., PI3K-Akt signaling, p = 3.2 × 10⁻⁵; GnRH signaling, p = 1.8 × 10⁻⁴), whereas adult lesions were dominated by estrogen receptor pathways (p = 2.6 × 10⁻⁶). Juvenile-specific antigen-presenting fibroblasts: Comprising 18.7 % of stromal cells (vs. <1 % in adults), these were immunohistochemically validated to express high levels of HLA-DRA and CD74. Enhanced intercellular communication networks: Juvenile lesions showed active stromal-epithelial crosstalk mediated by ligand-receptor interactions such as PTN-SDC4 (p < 0.001) and MDK-NCL (p = 0.003), suggesting a role in tumor progression.

Conclusions

Our findings reveal molecular features that may underlie the rapid growth of juvenile giant fibroepithelial tumors. The data point to hormone-independent proliferative programs and immune-modulating fibroblast subtypes as key contributors. These insights broaden our understanding of tumor biology and may guide the development of targeted, less invasive treatments for young patients.

背景：巨大的幼年性乳腺纤维上皮肿瘤是一种罕见的病变，主要发生在青春期女孩身上。其发病机制尚不清楚，目前的治疗几乎完全依赖于手术，这可能会干扰乳房发育。为了阐明这些肿瘤的生物学基础，我们进行了单细胞RNA测序。方法我们使用BD Rhapsody™平台分析了来自3例青少年（12-16岁）的15,295个 细胞和来自1例成年患者（42岁）的11,442个 细胞。该数据集提供了纤维上皮病变的详细细胞图谱，并可以直接比较青少年和成人病例之间的肿瘤微环境。ResultsDistinct分子特征的上皮细胞和成纤维细胞:少年英尺上皮细胞表现出显著的富集proliferation-associated途径(如PI3K-Akt信号,p = 3.2  × 10−5;促信号p = 1.8  × 10−4),而成年病变是由雌激素受体通路(p = 2.6 × 10−6)。青少年特异性抗原呈递成纤维细胞：占基质细胞18.7 %（成人为1 %），经免疫组织化学验证，可表达高水平的HLA-DRA和CD74。增强的细胞间通讯网络：幼年病变表现出由配体-受体相互作用介导的活跃的间质-上皮串扰，如PTN-SDC4 （p <； 0.001）和MDK-NCL (p = 0.003)，提示其在肿瘤进展中起作用。结论sour的发现揭示了幼年巨大纤维上皮肿瘤快速生长的分子机制。数据表明，激素非依赖性增殖程序和免疫调节成纤维细胞亚型是关键因素。这些见解拓宽了我们对肿瘤生物学的理解，并可能指导针对年轻患者的靶向性、低侵入性治疗的发展。

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引用次数: 0

Integrated bioinformatics and tissue-based validation reveal the oncogenic role of hsa_circ_0043256 and hsa_circ_0004789 in gastric cancer 综合生物信息学和基于组织的验证揭示了hsa_circ_0043256和hsa_circ_0004789在胃癌中的致癌作用

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-01-09 DOI: 10.1016/j.bbrep.2026.102442

Somayeh Aslani , Ashkan Kalantary-Charvadeh , Pejman Morovat , Roghayeh Abbasalipourkabir , Issa Nourmohammadi , Amirnader Emami Razavi , Nasrin Ziamajidi

Circular RNAs (circRNAs) play a key role in gastric cancer (GC) pathogenesis. This study hsa_circ_0043256 and hsa_circ_0004789, and their interactions with miR-28–5p/Cyclin B1 (CCNB1) and miR-5683/CCNB1, via bioinformatic and experimental methods. We retrieved expression data for circRNAs, miRNAs, and mRNAs in GC from Gene Expression Omnibus and The Cancer Genome Atlas. Using online databases and R tools, we identified downstream miRNAs and target mRNAs to build a competing endogenous RNA (ceRNA) network. After identification of hub genes and performing functional enrichment, we defined two regulatory axes: hsa_circ_0043256/miR-28–5p/CCNB1 and hsa_circ_0004789/miR-5683/CCNB1. We studied 32 paired tumor and adjacent tissues to assess all genes and CCNB1 protein expression, along with correlations, histopathological associations, ROC curves, and survival outcomes. We identified 58 circRNAs, 123 miRNAs, and 2126 mRNAs, and, further, by novelty checking and downstream RNA analysis, identified two axes. The expression of hsa_circ_0043256, hsa_circ_0004789, and CCNB1 mRNA and protein levels was elevated, while miR-28–5p and miR-5683 levels were reduced. Correlations observed among axis components supported the ceRNA hypothesis. The hsa_circ_0004789/miR-5683/CCNB1 axis showed an AUC value for the combined ROC curve near 1, suggesting strong diagnostic potential. Lower CCNB1 and higher miR-5683 levels were correlated with better survival. Both circ_0043256 and circ_0004789 were associated with histological grade, lymphatic invasion, perineural invasion, and lymph node involvement. This study highlights circ_0043256/miR-28–5p/CCNB1 and circ_0004789/miR-5683/CCNB1 as promising axes for GC diagnosis and treatment strategies.

环状rna （circRNAs）在胃癌（GC）发病机制中起关键作用。本研究通过生物信息学和实验方法研究了hsa_circ_0043256和hsa_circ_0004789及其与miR-28-5p /Cyclin B1 （CCNB1）和miR-5683/CCNB1的相互作用。我们从Gene expression Omnibus和The Cancer Genome Atlas中检索了GC中circRNAs、miRNAs和mrna的表达数据。利用在线数据库和R工具，我们确定了下游mirna和目标mrna，以构建竞争的内源性RNA （ceRNA）网络。在鉴定了枢纽基因并进行功能富集后，我们定义了两个调控轴：hsa_circ_0043256/ miR-28-5p /CCNB1和hsa_circ_0004789/miR-5683/CCNB1。我们研究了32对肿瘤和邻近组织，以评估所有基因和CCNB1蛋白表达，以及相关性、组织病理学关联、ROC曲线和生存结果。我们鉴定了58个circrna， 123个mirna和2126个mrna，并且进一步通过新颖性检查和下游RNA分析鉴定了两个轴。hsa_circ_0043256、hsa_circ_0004789和CCNB1 mRNA和蛋白表达水平升高，miR-28-5p和miR-5683水平降低。轴组分之间观察到的相关性支持ceRNA假设。hsa_circ_0004789/miR-5683/CCNB1轴显示联合ROC曲线的AUC值接近1，提示较强的诊断潜力。较低的CCNB1水平和较高的miR-5683水平与较好的生存率相关。circ_0043256和circ_0004789均与组织学分级、淋巴浸润、神经周围浸润和淋巴结受累有关。本研究强调circ_0043256/ miR-28-5p /CCNB1和circ_0004789/miR-5683/CCNB1是GC诊断和治疗策略的有希望的轴。

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引用次数: 0

The role of metformin in extracellular matrix-based three-dimensional cell culture Models: A mini-review on therapeutic potentials 二甲双胍在基于细胞外基质的三维细胞培养模型中的作用：对治疗潜力的简要回顾

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-01-08 DOI: 10.1016/j.bbrep.2025.102424

Mahshid Zamani , Nepton Soltani

Metformin, a widely used antidiabetic agent, exhibits pleiotropic effects extending beyond glycemic control, including the modulation of the extracellular matrix (ECM). Although traditional two-dimensional (2D) cell cultures have provided foundational insights, they inadequately replicate the complex tissue microenvironment in which metformin exerts its therapeutic actions. Emerging evidence underscores the pivotal role of ECM composition, stiffness, and cellular context in determining metformin's efficacy—particularly in cancer, fibrosis, and metabolic diseases. However, a comprehensive synthesis of its actions within physiologically relevant three-dimensional (3D) models remains lacking.

This mini-review addresses this gap by systematically analyzing the interplay between metformin and the ECM in advanced 3D cell culture systems. We focus on metformin's ability to reprogram stromal cells, modulate mechanotransduction pathways (e.g., AMPK/mTOR), and influence cell-ECM dynamics within specific disease contexts. Furthermore, we discuss the integration of metformin-loaded biomaterials with 3D platforms, highlighting their dual function as drug delivery vehicles and active components of disease models.

By synthesizing recent findings, this review emphasizes the bidirectional relationship between metformin and the ECM, positioning 3D culture models as indispensable tools for elucidating context-dependent drug responses. We also identify key challenges, including the lack of standardized ECM-based systems and the underrepresentation of immune and vascular components, and propose future directions for translating these models into personalized therapeutic strategies. This work underscores the necessity of moving beyond conventional 2D paradigms to fully harness metformin's therapeutic potential through the adoption of 3D ECM-based systems.

二甲双胍是一种广泛使用的降糖药，除血糖控制外，还具有多种作用，包括调节细胞外基质（ECM）。尽管传统的二维（2D）细胞培养提供了基本的见解，但它们不能充分复制复杂的组织微环境，二甲双胍在其中发挥其治疗作用。新出现的证据强调了ECM组成、硬度和细胞环境在决定二甲双胍疗效中的关键作用，特别是在癌症、纤维化和代谢性疾病中。然而，在生理学相关的三维（3D）模型中，其作用的综合仍然缺乏。这篇迷你综述通过系统地分析二甲双胍和先进的3D细胞培养系统中的ECM之间的相互作用来解决这一差距。我们专注于二甲双胍重编程基质细胞、调节机械转导途径（例如AMPK/mTOR）以及在特定疾病背景下影响细胞- ecm动力学的能力。此外，我们还讨论了二甲双胍负载生物材料与3D平台的整合，强调了它们作为药物递送载体和疾病模型活性成分的双重功能。通过综合最近的研究结果，本综述强调了二甲双胍和ECM之间的双向关系，将3D培养模型定位为阐明情境依赖性药物反应不可或缺的工具。我们还确定了关键的挑战，包括缺乏标准化的基于ecm的系统和免疫和血管成分的代表性不足，并提出了将这些模型转化为个性化治疗策略的未来方向。这项工作强调了超越传统2D范例的必要性，通过采用基于3D ecm的系统来充分利用二甲双胍的治疗潜力。

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引用次数: 0

Heat-induced antigen retrieval by using Tris-EDTA solution destroys nuclear structure in certain tissues 利用Tris-EDTA溶液热诱导抗原回收可破坏某些组织的核结构

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-01-08 DOI: 10.1016/j.bbrep.2026.102443

Haizhen Wang , Xingyi Luo , Xian Qiang , Xiuliang Dai

Tris-EDTA buffer (pH 9.0) is widely used for heat-induced antigen retrieval (HIAR) in immunohistochemistry due to its high efficiency. However, it remains unclear whether Tris-EDTA is equally suitable for all tissues and for the detection of both nuclear and non-nuclear antigens. In this study, we systematically evaluated the effects of Tris-EDTA HIAR on mouse and human tissues. Nuclear morphology was assessed by DAPI and hematoxylin staining, while immunohistochemistry and immunofluorescence were used to detect nuclear and non-nuclear antigens. We found that Tris-EDTA HIAR caused selective nuclear disruption (nuclear content leakage) in thyroid, lung, and kidney tissues, manifested as weak or abnormal staining. Consequently, nuclear antigens in these tissues showed poor detection, including weak signals, mislocalization, or complete loss. In contrast, nuclear antigen detection was preserved when citrate buffer (pH 6.0) was used. For non-nuclear antigens, however, Tris-EDTA HIAR generally produced stronger staining than citrate buffer. Although nuclear content leakage may lead to slightly higher background, Tris-EDTA HIAR did not appear to damage the antigens themselves. In addition, both the pH and the antigen retrieval method influence the nuclear morphology in Tris-EDTA–treated sensitive tissues. In conclusion, Tris-EDTA HIAR should be used with caution for nuclear antigen detection in thyroid, lung, and kidney tissues but remains effective for non-nuclear antigens. These findings provide practical guidance for optimizing antigen retrieval strategies in both clinical diagnostics and research.

Tris-EDTA缓冲液（pH 9.0）因其高效，在免疫组织化学中广泛应用于热诱导抗原回收（HIAR）。然而，Tris-EDTA是否同样适用于所有组织，是否同样适用于核抗原和非核抗原的检测，目前尚不清楚。在本研究中，我们系统地评估了Tris-EDTA HIAR对小鼠和人体组织的影响。DAPI和苏木精染色检测细胞核形态，免疫组织化学和免疫荧光检测核抗原和非核抗原。我们发现Tris-EDTA HIAR在甲状腺、肺和肾组织中引起选择性核破坏（核内容物泄漏），表现为染色弱或异常。因此，核抗原在这些组织中表现出较差的检测，包括信号弱、定位错误或完全丢失。使用柠檬酸缓冲液（pH 6.0）保存核抗原检测。然而，对于非核抗原，Tris-EDTA HIAR通常比柠檬酸缓冲液产生更强的染色。尽管核内容物泄漏可能导致背景值略高，但Tris-EDTA HIAR似乎并未损害抗原本身。此外，pH值和抗原回收方法都会影响tris - edta处理的敏感组织的核形态。总之，Tris-EDTA HIAR在检测甲状腺、肺和肾组织的核抗原时应谨慎使用，但在检测非核抗原时仍有效。这些发现为优化临床诊断和研究中的抗原回收策略提供了实用指导。

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引用次数: 0