Biochemistry and Biophysics Reports最新文献_第7页

Potential role of circ_WHSC1 and miR-145-5p in breast cancer promotion circ_WHSC1和miR-145-5p在乳腺癌促进中的潜在作用

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-03-01 Epub Date: 2026-01-30 DOI: 10.1016/j.bbrep.2026.102472

Maryam Abtin , Asghar Hosseinzadeh , Nahid Nafisi , Ramesh Omranipour , Leyla Sahebi , Mohsen Ahmadi , Soudeh Ghafouri-Fard , Abbas Shakoori

Purpose

This study aims to investigate the potential interplay between circ_WHSC1 and miR-145-5p in breast cancer pathogenesis using in silico tools, assess their clinical relevance, and evaluate the diagnostic utility of circ_WHSC1 in clinical samples as a biomarker for breast cancer.

Materials and methods

This multi-component study employed a combination of bioinformatic analyses and laboratory validation. First, in silico tools were used to investigate miR-145-5p and circ_WHSC1 using public databases. Subsequently, their expression, correlation, and clinical relevance were experimentally assessed in a cohort of breast cancer patients.

Results

Circ_WHSC1 level was significantly higher in breast tumor compared with patient-matched adjacent normal tissues (4.17-fold change, p-value <0.01). Additionally, significant reduction of miR-145-5p (9.11-fold downregulation, p-value <0.01) level was detected in breast tumors compared with neighboring non-tumor tissues. A weak negative correlation was detected between levels of circ_WHSC1 and miR-145-5p (r = −0.314, p-value <0.05). Circ_WHSC1 may serve as a weak biomarker for breast cancer (AUC = 0.683; p-value <0.01) with 71 % specificity and 70 % sensitivity. Up-regulation of circ_WHSC1 in breast tumor was linked with lymph node invasion (p-value = 0.005), HER2 negativity (p-value = 0.031) and positive family history (p-value = 0.012).

Conclusion

Cumulatively, circ_WHSC1/miR-145-5p can be suggested as a potential molecular axis contributing to the pathogenesis of breast cancer. However, further functional assays are needed to validate this hypothesis.

目的本研究旨在利用计算机工具研究circ_WHSC1和miR-145-5p在乳腺癌发病机制中的潜在相互作用，评估其临床相关性，并评估circ_WHSC1在临床样本中作为乳腺癌生物标志物的诊断效用。材料和方法本研究采用生物信息学分析和实验室验证相结合的方法。首先，使用计算机工具使用公共数据库研究miR-145-5p和circ_WHSC1。随后，在一组乳腺癌患者中实验评估了它们的表达、相关性和临床相关性。结果乳腺肿瘤组织中scirc_whsc1水平明显高于患者匹配的邻近正常组织（变化4.17倍，p值<；0.01）。此外，与邻近非肿瘤组织相比，乳腺肿瘤组织中miR-145-5p水平显著降低（下调9.11倍，p值<；0.01）。circ_WHSC1水平与miR-145-5p水平呈弱负相关（r = −0.314，p值<；0.05）。Circ_WHSC1可能作为乳腺癌的弱生物标志物（AUC = 0.683；p值<；0.01），特异性为71 %，敏感性为70 %。circ_WHSC1在乳腺肿瘤中的表达上调与淋巴结浸润（p值 = 0.005）、HER2阴性（p值 = 0.031）、家族史阳性（p值 = 0.012）相关。综上所述，circ_WHSC1/miR-145-5p可能是参与乳腺癌发病机制的潜在分子轴。然而，需要进一步的功能分析来验证这一假设。

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引用次数: 0

Comprehensive multi-omics analysis reveals RUNX1's prognostic value, immune associations, and MUC13-Mediated mechanistic role in hepatocellular carcinoma pathogenesis 综合多组学分析揭示了RUNX1在肝细胞癌发病中的预后价值、免疫关联和muc13介导的机制作用。

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-03-01 Epub Date: 2026-02-02 DOI: 10.1016/j.bbrep.2026.102446

Tahani Ahmad ALMatrafi

Hepatocellular carcinoma (HCC) is a biologically and clinically heterogeneous malignancy, posing major challenges for early diagnosis, prognostic prediction, and therapeutic intervention. The Runt-related transcription factor (RUNX) family, comprising RUNX1, RUNX2, and RUNX3, plays essential roles in cellular processes and contribute to the pathogenesis of numerous malignancies. This study aims to elucidate their role in tumor progression and its clinical implications. We performed an integrative pan-cancer multi-omics analysis across 33 cancer types to characterize RUNX family expression patterns, prognostic associations, and immune correlations using publicly available datasets. Expression and functional roles were experimentally validated in HCC through in vitro and in vivo assays. Relationships between RUNX1 expression and clinical stage, immune subtypes, checkpoint gene expression, immunotherapy sensitivity, and immune-related co-expression networks were assessed. The prognostic significance of RUNX1 was determined using Kaplan–Meier survival analysis, Cox regression, and ROC curve evaluation. Transcriptional regulation was investigated via bioinformatic tools, database interrogation, and chromatin immunoprecipitation (ChIP) assays. Functional studies were conducted to determine the effects of RUNX1 knockdown on HCC cell proliferation, migration, and invasion. RUNX1 was upregulated in multiple tumor types, including breast, lung, liver, and brain cancers, and its elevated expression correlated with poorer overall (OS) and disease-specific survival (DSS). In HCC, RUNX1 expression was significantly associated with advanced clinical stage, distinct immune subtypes, and altered checkpoint expression profiles, indicating a role in shaping the tumor immune microenvironment. Mechanistically, MUC13 was identified as a direct transcriptional target of RUNX1, as confirmed by promoter-binding prediction, ChIP validation, and dual-luciferase assays. RUNX1 knockdown suppressed HCC cell proliferation, migration, and invasion by attenuating Wnt/β-catenin/EMT signaling activity. These findings highlight RUNX1 as a potential prognostic biomarker and therapeutic target, offering mechanistic insight into HCC pathogenesis and avenues for improved precision oncology.

肝细胞癌（HCC）是一种生物学和临床异质性的恶性肿瘤，对早期诊断、预后预测和治疗干预提出了重大挑战。runt相关转录因子（RUNX）家族包括RUNX1、RUNX2和RUNX3，在细胞过程中发挥重要作用，并参与许多恶性肿瘤的发病机制。本研究旨在阐明它们在肿瘤进展中的作用及其临床意义。我们使用公开的数据集对33种癌症类型进行了综合泛癌症多组学分析，以表征RUNX家族表达模式、预后关联和免疫相关性。通过体外和体内实验验证了其在HCC中的表达和功能作用。评估RUNX1表达与临床分期、免疫亚型、检查点基因表达、免疫治疗敏感性和免疫相关共表达网络的关系。采用Kaplan-Meier生存分析、Cox回归和ROC曲线评价RUNX1的预后意义。通过生物信息学工具、数据库查询和染色质免疫沉淀（ChIP）测定来研究转录调控。我们进行了功能研究，以确定RUNX1基因敲低对HCC细胞增殖、迁移和侵袭的影响。RUNX1在多种肿瘤类型中上调，包括乳腺癌、肺癌、肝癌和脑癌，其表达升高与较差的总体（OS）和疾病特异性生存（DSS）相关。在HCC中，RUNX1的表达与晚期临床阶段、不同的免疫亚型和检查点表达谱的改变显著相关，表明在塑造肿瘤免疫微环境中起作用。通过启动子结合预测、ChIP验证和双荧光素酶测定，MUC13被确定为RUNX1的直接转录靶点。RUNX1敲低通过减弱Wnt/β-catenin/EMT信号活性抑制HCC细胞增殖、迁移和侵袭。这些发现突出了RUNX1作为潜在的预后生物标志物和治疗靶点，为HCC发病机制和提高精准肿瘤学的途径提供了机制见解。

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引用次数: 0

Exploring the impact of hAMSCs secretome on Panc1 cells via TNF-α/NF-κB (p50/p65)/Caspase 3 signaling pathways: An in vitro study 探讨hAMSCs分泌组通过TNF-α/NF-κB (p50/p65)/Caspase 3信号通路对Panc1细胞的影响：体外研究

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-03-01 Epub Date: 2025-12-12 DOI: 10.1016/j.bbrep.2025.102411

Aynaz Khalafi, Fatemeh Safari

The second most prevalent cause of mortality worldwide is cancer. Pancreatic cancer, known as the “king of cancers” due to its unfavorable prognosis and absence of symptoms, is among the fatal types of cancer. Despite the availability of various cancer therapy options, current strategies are often ineffective. Therefore, there is a constant need to explore novel platforms with low side effects and high efficacy. The application of stem cells or their derivatives in treating diseases including cancer, has become well-established. This study, focuses on investigating the effects of the secretome of human mesenchymal stem cells (hAMSCs) on Panc1 pancreatic cancer cells through the tumor necrosis factor-alpha (TNF-α)/nuclear factor-κB (NF-κB)/Caspase 3 signaling pathways. A co-culture system using 6-well plates transwell was utilized for this purpose. After 72 h, cell death in hAMSCs-treated Panc1 cells was analyzed through the TNF-α/NF-κB (p50/p65)/Caspase 3 signaling pathways using Western blot and enzyme-linked immunosorbent assay (ELISA). DAPI staining was used to visualize cell death in hAMSCs-treated Panc1 cells. The results showed an up-regulation of TNF-α, IL-1β, IL-8, p-IKK, p-IKKα, p-IKKβ, p-IκB, p53, PUMA, Caspase 3, and NF-κB (p50/p65) as well as a down-regulation of IKβ. These findings suggest that the secretome of hAMSCs promotes both inflammation and apoptosis in Panc1 pancreatic cancer cells simultaneously.

全球第二大死因是癌症。胰腺癌因预后不良、无症状而被称为“癌症之王”，是致命的癌症之一。尽管有各种各样的癌症治疗选择，目前的策略往往是无效的。因此，不断需要探索副作用低、疗效高的新型平台。干细胞或其衍生物在治疗包括癌症在内的疾病方面的应用已经得到证实。本研究主要探讨人间充质干细胞（hAMSCs）分泌组通过肿瘤坏死因子-α (TNF-α)/核因子-κB (NF-κB)/Caspase 3信号通路对胰腺胰腺胰腺细胞Panc1的影响。为此，采用transwell 6孔板共培养系统。72 h后，采用Western blot和酶联免疫吸附试验（ELISA），通过TNF-α/NF-κB (p50/p65)/Caspase 3信号通路分析hamscs处理的Panc1细胞的细胞死亡情况。DAPI染色显示hamscs处理的Panc1细胞的细胞死亡情况。结果显示TNF-α、IL-1β、IL-8、p-IKK、p-IKKα、p-IKKβ、p- i -κB、p53、PUMA、Caspase 3、NF-κB （p50/p65）表达上调，IKβ表达下调。这些发现表明hAMSCs分泌组同时促进Panc1胰腺癌细胞的炎症和凋亡。

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引用次数: 0

RNA binding protein HuD regulates the biosynthesis of glucagon-like peptide 1 in intestinal L-cells RNA结合蛋白HuD调节肠l细胞胰高血糖素样肽1的生物合成

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-03-01 Epub Date: 2025-12-15 DOI: 10.1016/j.bbrep.2025.102415

Sukyoung Han , Myeongwoo Jung , Seungyeon Ryu , Seongho Cha , Hyosun Tak , Seung Min Jeong , Eun Kyung Lee

We investigated HuD (ELAVL4), a neuronal RNA-binding protein with emerging endocrine functions, as a regulator of GLP-1 biogenesis in intestinal L-cells. Using absolute qPCR and immunofluorescence, we found that HuD was significantly expressed in the GLUTag cells derived from mice intestinal L-cell line and was co-localized with GLP-1-positive cells in the small intestine of mice. RNA interference-mediated HuD knockdown reduced both GLP-1 immunoreactivity and levels. Mechanistically, RNA immunoprecipitation and biotinylated 3′UTR pull-down demonstrated that HuD binds to the mRNAs of the Gcg and Pcsk1 (PC1/3) genes. The levels of the proglucagon (∼17 kDa) and PC1/3 proteins decreased without significant changes in their mRNAs, suggesting post-transcriptional control. Metabolic stress converged on this module: palmitate decreased proglucagon/PC1/3 in GLUTag cells, and a high-fat diet reduced GLP-1 and PC1/3 signals in the mouse intestine. Interestingly, zinc sulfate partially restored proglucagon and PC1/3 levels following palmitate treatment. These findings reveal a HuD–Gcg/Pcsk1 axis is crucial for GLP-1 biogenesis and which is susceptible to lipotoxic stress.

我们研究了HuD (ELAVL4)，一种具有新兴内分泌功能的神经元rna结合蛋白，作为肠l细胞GLP-1生物发生的调节剂。利用绝对qPCR和免疫荧光技术，我们发现HuD在小鼠肠l细胞系GLUTag细胞中显著表达，并与小鼠小肠glp -1阳性细胞共定位。RNA干扰介导的HuD敲低可降低GLP-1的免疫反应性和水平。在机制上，RNA免疫沉淀和生物素化的3'UTR下拉表明HuD与Gcg和Pcsk1 （PC1/3）基因的mrna结合。胰高血糖素原（~ 17 kDa）和PC1/3蛋白的水平下降，但其mrna没有显著变化，提示转录后控制。代谢应激集中在这个模块上：棕榈酸降低了GLUTag细胞中的胰高血糖素原/PC1/3，高脂肪饮食降低了小鼠肠道中的GLP-1和PC1/3信号。有趣的是，硫酸锌在棕榈酸治疗后部分恢复了胰高血糖素原和PC1/3水平。这些发现表明，HuD-Gcg /Pcsk1轴对GLP-1的生物生成至关重要，并且易受脂毒性应激的影响。

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引用次数: 0

Identification and analysis of small RNAs in exosome-like nanoparticles derived from onion (Allium cepa L.) 洋葱（Allium cepa L.）类外泌体纳米颗粒小rna的鉴定与分析

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-03-01 Epub Date: 2026-01-31 DOI: 10.1016/j.bbrep.2026.102460

Zhaofeng Liang , Yuning Gu , Jiajia Song , Wenhui Yang , Xuezhong Xu

Small RNAs (sRNAs) in plant-derived exosome-like nanoparticles (PELNs) have attracted considerable attention as biologically active substances that play a crucial role in cross-kingdom regulatory processes. However, there is insufficient research dedicated to identifying sRNAs within PELNs. We aimed to analyze the expression profile of sRNAs in onion-derived exosomes-like nanoparticles (OELNs) and explore their potential role in cross-kingdom regulation. In this study, OELNs were extracted, possessing an optimal particle size of approximately 139 nm and a Zeta potential of roughly −20 mV. Subsequently, high-throughput small RNA sequencing was conducted to analyze sRNAs in onion tissues and OELNs. The expression profile of sRNAs in OELNs was elucidated, and it was predicted that highly expressed microRNAs (miRNAs) in OELNs may exert potential regulatory effects on the human genome. By comparing with the reference genome of onion (Allium cepa L.), 11 known miRNAs and 248 novel miRNAs were identified in both onion tissues and OELNs. Target gene prediction analysis of the human genome has revealed that 20 miRNAs highly expressed in OELNs potentially participate in the regulation of human tumor and cardiovascular-related signaling pathways. Furthermore, differential analysis was conducted on small/short interfering RNA (siRNA), small nucleolar RNA (snoRNA), and transfer ribonucleic acid (tRNA) in OELNs. This study laid a theoretical foundation for further exploring the cross-kingdom role of non-coding RNAs in OELNs, and provided new ideas for the development of plant-derived functional components.

植物衍生的外泌体样纳米颗粒（peln）中的小rna （sRNAs）作为生物活性物质在跨界调节过程中起着至关重要的作用，引起了广泛的关注。然而，目前还没有足够的研究专门用于鉴定peln内的sRNAs。我们的目的是分析sRNAs在洋葱衍生的外泌体样纳米颗粒（oeln）中的表达谱，并探讨它们在跨界调控中的潜在作用。在本研究中，oeln的最佳粒径约为139 nm， Zeta电位约为- 20 mV。随后，进行高通量小RNA测序，分析洋葱组织和oeln中的sRNAs。通过对OELNs中sRNAs表达谱的分析，预测OELNs中高表达的microRNAs （miRNAs）可能对人类基因组具有潜在的调控作用。通过与洋葱（Allium cepa L.）参考基因组的比较，在洋葱组织和oeln中分别鉴定出11个已知mirna和248个新mirna。人类基因组靶基因预测分析显示，在oeln中高表达的20种mirna可能参与人类肿瘤和心血管相关信号通路的调控。此外，对oeln中的小/短干扰RNA （siRNA）、小核仁RNA （snoRNA）和转移核糖核酸（tRNA）进行了差异分析。本研究为进一步探索非编码rna在oeln中的跨界作用奠定了理论基础，并为植物源性功能成分的开发提供了新思路。

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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 : 2026-03-01 Epub 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

Integration of inter-simple sequence repeats with machine learning approach for diversity analysis and authentication of Iranian cotton cultivars 基于简单重复序列的伊朗棉品种多样性分析与鉴定

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-03-01 Epub Date: 2026-01-06 DOI: 10.1016/j.bbrep.2025.102435

Rasmieh Hamid , Zahra Ghorbanzadeh , Bahman Panahi

Cotton (Gossypium hirsutum L.) has experienced extensive breeding in recent decades, leading to a narrowed genetic base that presents challenges for accurate germplasm differentiation and cultivar authentication. This study primarily addresses the lack of reliable, scalable, and interpretable tools for distinguishing closely related Iranian cotton cultivars. To overcome this limitation, the research integrates inter-simple sequence repeat (ISSR) markers with machine learning (ML) algorithms to evaluate genetic diversity and establish diagnostic criteria for cultivar identification. Eighteen commercial cultivars were genotyped using 14 ISSR primers and binary scored data (presence/absence of bands) were used to calculate genetic diversity parameters, including the observed number of alleles (Na), effective number of alleles (Ne), Shannon's information index (I), and expected heterozygosity (He) were calculated. Primers 13, 10, and 26 were identified as the most informative loci, yielding the highest values across diversity parameters. Unweighted Pair Group Method with Arithmetic Mean (UPGMA) clustering and principal coordinates analysis (PCoA) revealed five cultivar groups, with several accessions (e.g., Jahesh, Fakhr, Sahel) showing marked genetic distinctiveness. To enhance cultivar authentication, ISSR data were analyzed using ML classifiers. A decision tree model generated transparent band-based rules, while Random Forest feature selection highlighted key diagnostic loci (Primer24_525, Primer2_766). The combined framework achieved high classification accuracy and reproducibility, enabling reliable discrimination among closely related cultivars. These findings demonstrate the novelty and practical utility of integrating multilocus ISSR markers with ML for cultivar authentication, seed certification, and genetic resource management, while also highlighting previously underexplored genetic diversity that can inform cotton breeding programs in Iran.

近几十年来，棉花（Gossypium hirsutum L.）经历了广泛的育种，导致遗传基础缩小，这给准确的种质分化和品种鉴定带来了挑战。本研究主要解决缺乏可靠、可扩展和可解释的工具来区分密切相关的伊朗棉花品种。为了克服这一限制，本研究将ISSR标记与机器学习算法相结合，以评估遗传多样性并建立品种鉴定的诊断标准。利用14条ISSR引物对18个商品品种进行基因分型，利用二元评分数据（条带存在/缺失）计算遗传多样性参数，包括观察等位基因数（Na）、有效等位基因数（Ne）、香农信息指数(I)和期望杂合度（He）。引物13、10和26被确定为信息量最大的位点，在多样性参数中产生最高的值。利用UPGMA聚类和主坐标分析（PCoA）的非加权对类群分析发现了5个品种类群，其中Jahesh、Fakhr、Sahel等品种表现出显著的遗传差异。为了加强品种鉴定，利用ML分类器对ISSR数据进行分析。决策树模型生成透明的基于频带的规则，而随机森林特征选择突出了关键诊断位点（Primer24_525, Primer2_766）。该组合框架具有较高的分类精度和可重复性，能够对近缘品种进行可靠的鉴别。这些发现证明了将多位点ISSR标记与ML结合用于品种鉴定、种子认证和遗传资源管理的新颖性和实用性，同时也强调了以前未被充分开发的遗传多样性，可以为伊朗的棉花育种计划提供信息。

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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 : 2026-03-01 Epub 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

Unraveling the molecular landscape of clear cell renal cell carcinoma through integrative transcriptomic analysis and validation using clinical samples 通过整合转录组学分析和临床样本验证，揭示透明细胞肾细胞癌的分子景观

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-03-01 Epub Date: 2025-11-28 DOI: 10.1016/j.bbrep.2025.102384

Amir Taherkhani , Simindokht Sarvmeili , Hamed Manoochehri , Mahmoud Gholyaf

Background and aims

Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal malignancies, distinguished by its aggressive nature and poor prognosis in advanced stages. Identifying prognostic biomarkers and unraveling underlying molecular events contributing to ccRCC pathogenesis is crucial for developing precise prognostic models and tailored therapeutic interventions. The objective of this research was to identify differentially expressed genes (DEGs), construct protein-protein interaction networks, pinpoint hub genes and enriched pathways, assess the prognostic relevance of these hub genes, and predict upstream regulators, thereby providing insights into the onset and progression of ccRCC.

Methods

The GSE66270 dataset was reanalyzed to uncover DEGs between 14 ccRCC tumors and 14 normal tissues. Hub genes, clusters, and enriched functional categories were identified from the protein-protein interaction network. Survival analysis was performed to assess the prognostic relevance of the identified hub genes. An upstream transcription factor network was generated using the iRegulon plugin. Expression of hub genes in six cancer and six normal renal tissues was confirmed via real-time PCR.

Results

A prognostic signature comprising five genes—FCGR1A, FOXM1, TOP2A, BIRC5, and CCNA2—effectively stratified ccRCC prognosis. FOXM1 was identified as the primary upstream regulator. A significant upregulation of FOXM1 was observed in renal cancer samples compared with normal renal tissues (p-value <0.001).

Conclusion

These findings shed light on implicated pathways and processes, prognostic biomarkers, and the crucial role of the immune system in ccRCC pathogenesis.

背景和目的：透明细胞肾细胞癌（ccRCC）是肾脏恶性肿瘤中最常见的亚型，其特点是其侵袭性和晚期预后差。确定预后生物标志物和揭示导致ccRCC发病机制的潜在分子事件对于开发精确的预后模型和量身定制的治疗干预措施至关重要。本研究的目的是鉴定差异表达基因（DEGs），构建蛋白-蛋白相互作用网络，确定中心基因和富集途径，评估这些中心基因的预后相关性，并预测上游调控因子，从而深入了解ccRCC的发病和进展。方法重新分析GSE66270数据集，发现14例ccRCC肿瘤与14例正常组织之间的基因差异。从蛋白质相互作用网络中鉴定出枢纽基因、簇和富集的功能类别。进行生存分析以评估所鉴定的中枢基因与预后的相关性。使用iRegulon插件生成上游转录因子网络。通过实时荧光定量PCR证实了6个癌组织和6个正常肾组织中hub基因的表达。结果由5个基因（fcgr1a、FOXM1、TOP2A、BIRC5和ccna2）组成的预后特征可以有效地对ccRCC的预后进行分层。FOXM1被确定为主要的上游调控因子。与正常肾组织相比，在肾癌样本中FOXM1显著上调（p值<；0.001）。结论这些发现揭示了ccRCC的相关途径和过程、预后生物标志物以及免疫系统在ccRCC发病机制中的关键作用。

{"title":"Unraveling the molecular landscape of clear cell renal cell carcinoma through integrative transcriptomic analysis and validation using clinical samples","authors":"Amir Taherkhani , Simindokht Sarvmeili , Hamed Manoochehri , Mahmoud Gholyaf","doi":"10.1016/j.bbrep.2025.102384","DOIUrl":"10.1016/j.bbrep.2025.102384","url":null,"abstract":"<div><h3>Background and aims</h3><div>Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal malignancies, distinguished by its aggressive nature and poor prognosis in advanced stages. Identifying prognostic biomarkers and unraveling underlying molecular events contributing to ccRCC pathogenesis is crucial for developing precise prognostic models and tailored therapeutic interventions. The objective of this research was to identify differentially expressed genes (DEGs), construct protein-protein interaction networks, pinpoint hub genes and enriched pathways, assess the prognostic relevance of these hub genes, and predict upstream regulators, thereby providing insights into the onset and progression of ccRCC.</div></div><div><h3>Methods</h3><div>The GSE66270 dataset was reanalyzed to uncover DEGs between 14 ccRCC tumors and 14 normal tissues. Hub genes, clusters, and enriched functional categories were identified from the protein-protein interaction network. Survival analysis was performed to assess the prognostic relevance of the identified hub genes. An upstream transcription factor network was generated using the iRegulon plugin. Expression of hub genes in six cancer and six normal renal tissues was confirmed via real-time PCR.</div></div><div><h3>Results</h3><div>A prognostic signature comprising five genes—<em>FCGR1A</em>, <em>FOXM1</em>, <em>TOP2A</em>, <em>BIRC5</em>, and <em>CCNA2</em>—effectively stratified ccRCC prognosis. <em>FOXM1</em> was identified as the primary upstream regulator. A significant upregulation of <em>FOXM1</em> was observed in renal cancer samples compared with normal renal tissues (p-value <0.001).</div></div><div><h3>Conclusion</h3><div>These findings shed light on implicated pathways and processes, prognostic biomarkers, and the crucial role of the immune system in ccRCC pathogenesis.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102384"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622886","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

Comparative analysis of activation of macrophages/microglia in diabetic retinopathy and Familial Exudative Vitreoretinopathy 糖尿病视网膜病变与家族性渗出性玻璃体视网膜病变中巨噬细胞/小胶质细胞活化的比较分析

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2026-03-01 Epub Date: 2025-12-09 DOI: 10.1016/j.bbrep.2025.102396

Jiakai Li , Ping Fei , Xiang Zhang , Yuqing Rao , Jing Li , Peiquan Zhao

Familial Exudative Vitreoretinopathy (FEVR) and Diabetic Retinopathy (DR) are two prominent retinal diseases. The role of macrophages/microglia in the vascular dynamics of FEVR and DR is unknown and thus addressed in this study. FZD4 knockout mouse, a model for FEVR in human characterized by genetic mutations affecting angiogenesis, exhibited reduced b-wave amplitudes and decreased vascular density, replicating human FEVR symptoms. Conversely, STZ-treated C57/BL6 mouse developed heightened fasting glucose levels, reduced insulin content, and increased retinal vasculature, aligning with DR features. Further analysis revealed significant differences in macrophage/microglia populations between the two diseases. In DR, a marked increase in both number and M2-like polarization of retinal macrophages/microglia was observed, contrasting with FEVR. Moreover, DR induced substantial proinflammatory differentiation of macrophages/microglia, evidenced by elevated cytokines such as IL-1β, TNF-α, and IFNɣ. Both conditions significantly upregulated Ang-1 and IL-10, with a more pronounced IL-10 increase in DR, suggesting a more active role in tissue and vessel remodeling. Notably, DR induced higher levels of anti-inflammatory factors like bFGF, TIMP-1, TGFβ1, and VEGF-A compared to FEVR, suggesting a balance of inflammation initiation, progression and resolution. These findings highlight the distinct roles of macrophages/microglia in FEVR and DR, providing insights into their contributions to disease pathogenesis and potential therapeutic strategies through reprogramming macrophages/microglia.

家族性渗出性玻璃体视网膜病变（FEVR）和糖尿病性视网膜病变（DR）是两种突出的视网膜疾病。巨噬细胞/小胶质细胞在FEVR和DR的血管动力学中的作用尚不清楚，因此在本研究中进行了研究。FZD4基因敲除小鼠是一种以影响血管生成的基因突变为特征的人类FEVR模型，其表现出b波振幅降低和血管密度降低，复制了人类FEVR症状。相反，stz处理的C57/BL6小鼠空腹血糖水平升高，胰岛素含量降低，视网膜血管增加，与DR特征一致。进一步分析显示，两种疾病之间巨噬细胞/小胶质细胞群存在显著差异。在DR中，与FEVR相比，视网膜巨噬细胞/小胶质细胞的数量和m2样极化均明显增加。此外，DR诱导巨噬细胞/小胶质细胞大量促炎分化，IL-1β、TNF-α和IFN α等细胞因子升高证明了这一点。两种情况下均显著上调Ang-1和IL-10，其中IL-10在DR中升高更为明显，表明其在组织和血管重塑中发挥更积极的作用。值得注意的是，与FEVR相比，DR诱导了更高水平的抗炎因子，如bFGF、TIMP-1、tgf - β1和VEGF-A，这表明炎症的发生、进展和消退是平衡的。这些发现突出了巨噬细胞/小胶质细胞在FEVR和DR中的独特作用，为巨噬细胞/小胶质细胞重编程对疾病发病机制和潜在治疗策略的贡献提供了见解。

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引用次数: 0