Experimental cell research最新文献_第3页

Analyzing the functions of Translationally controlled tumor protein2 during growth, development and autophagy of Dictyostelium discoideum 分析翻译调控肿瘤蛋白2在盘状盘齿钢的生长发育和自噬中的作用。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-01 DOI: 10.1016/j.yexcr.2024.114400

Chanchal Choudhary, Bhavya Jain, Shweta Saran

Translationally controlled tumor protein (TCTP) is a well conserved and ubiquitously expressed multifunctional protein found in many organisms and is involved in many pathophysiological processes like cell proliferation, differentiation, development and cell death. The role of TCTP in anti-apoptosis and cancer metastasis makes it a promising candidate for cancer therapy. Dictyostelium discoideum, a protist, has two isoforms (TCTP1 and TCTP2, now referred to as TPT1 and TPT2) of which we have earlier elucidated TPT1. Here, we analyzed the role of TPT2 in this organism. tpt2 transcript was present throughout growth and development and is localized in the prestalk/stalk regions of multicellular structures developed. tpt2 gene was disrupted with a BSR cassette using a double homologous recombination method. Disruption of tpt2 gene (tpt2‾) exhibit reduced cell proliferation and nutrient-uptake. Additionally, development in tpt2‾ was delayed by 2 h, formed small-sized aggregates that developed into stalky fruiting bodies with reduced spore viability. In contrast, overexpressed tpt2 (tpt2^OE) showed increased cell proliferation and development, formed large-size aggregates that developed into spory fruiting bodies with increased spore viability. TPT2 regulates prestalk/prespore ratio and cell-type differentiation as abrogation of tpt2 gene resulted in altered localization of cell-type markers and an inclination towards the prestalk/stalk pathway while tpt2^OE showed a prespore/spore biasness when mixed with wild-type cells. Deletion of either tpt1 or tpt2 gene showed increased autophagic flux indicating their involvement in negative regulation of autophagy. This study provides insights into the intricate involvement of TCTP in cellular dynamics and development of D. discoideum.

翻译控制肿瘤蛋白（translation - controlled tumor protein， TCTP）是一种保守且普遍表达的多功能蛋白，存在于多种生物体内，参与细胞增殖、分化、发育和死亡等多种病理生理过程。TCTP在抗细胞凋亡和肿瘤转移中的作用使其成为一种很有前景的肿瘤治疗药物。Dictyostelium disideum是一种原生生物，有两个同工型（TCTP1和TCTP2，现在称为TPT1和TPT2），其中TPT1是我们之前阐明的。在这里，我们分析了TPT2在这种生物体中的作用。Tpt2转录本存在于整个生长发育过程中，定位于发育的多细胞结构的柄前/柄区。采用双同源重组法，用BSR盒对tpt2基因进行了断裂。tpt2基因（tpt2¯）的破坏表现为细胞增殖和营养摄取的减少。此外，tpt2¯的发育延迟了2小时，形成了小的聚集体，发育成茎状子实体，孢子活力降低。而过表达的tpt2 （tpt2OE）细胞增殖发育加快，形成大团聚体，发育成孢子子实体，孢子活力提高。TPT2基因的缺失导致细胞类型标记的定位改变，并倾向于预柄/柄途径，而tpt2OE与野生型细胞混合时表现出预孢子/孢子偏倚，从而调节预柄/孢子比例和细胞类型分化。tpt1或tpt2基因的缺失均显示自噬通量增加，表明它们参与了自噬的负调控。这项研究提供了复杂的见解TCTP参与细胞动力学和d discoideum的发展。

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引用次数: 0

IGSF8 impairs migration and invasion of trophoblast cells and angiogenesis in preeclampsia IGSF8损害子痫前期滋养细胞的迁移、侵袭和血管生成。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-01 DOI: 10.1016/j.yexcr.2025.114405

Xiaodan Chu, Xuan Chen, Man Guo, Xinyue Li, Zhihai Qu, Peiling Li

Insufficient trophoblast cell infiltration is implicated in the progression of preeclampsia (PE). The immunoglobulin superfamily member 8 (IGSF8) has been shown to promote cell migration, invasion, and epithelial mesenchymal transition (EMT). However, the specific impact of IGSF8 on trophoblast cells in PE has not been definitively demonstrated. To address this, placental tissues from PE patients and normal subjects was collected. A PE-like rat model was established by administering L-NAME (60 mg/kg) intragastrically to pregnant rats from the 10th to the 19th day of gestation. Knockdown and overexpression plasmids of IGSF8 were transfected into JEG-3 cells for further experiments. Clinical samples indicated impaired spiral artery remodeling, and high IGSF8 expression in the placental tissues of PE patients. PE rats exhibited increased mean arterial pressure, elevated 24-h urine protein levels, higher abortion rates, and decreased placental and fetal weight compared to rats of sham group. Failure of physiological transformation of spiral arteries was observed in PE rats, along with increased IGSF8 expression. IGSF8 overexpression inhibited JEG-3 cell migration, invasion and EMT, as well as reduced release of VEGF in JEG-3 cells, impairing HUVEC tube formation. mRNA-sequencing analysis of JEG-3 cells transfected with shIGSF8 showed differentially expressed genes related to angiogenesis, and mesenchymal cell differentiation, with IGSF8 knockdown being associated with the activation of pathways involved in blood vessel development and cell migration. Overall, this study suggests that IGSF8 plays a role in the development of PE and provides new insights for potential treatments.

滋养细胞浸润不足与子痫前期（PE）的进展有关。免疫球蛋白超家族成员8 （IGSF8）已被证明可促进细胞迁移、侵袭和上皮间充质转化（EMT）。然而，IGSF8对PE中滋养细胞的特异性影响尚未得到明确证实。为了解决这个问题，我们收集了PE患者和正常人的胎盘组织。采用L-NAME （60 mg/kg）于妊娠第10 ~ 19天灌胃建立pe样大鼠模型。将IGSF8敲低质粒和过表达质粒转染到JEG-3细胞中进行进一步实验。临床样本显示PE患者的螺旋动脉重构受损，胎盘组织IGSF8高表达。与假手术组相比，PE大鼠平均动脉压升高，24小时尿蛋白水平升高，流产率升高，胎盘和胎儿体重下降。PE大鼠螺旋动脉生理转化失败，IGSF8表达升高。IGSF8过表达抑制JEG-3细胞的迁移、侵袭和EMT，减少JEG-3细胞中VEGF的释放，损害HUVEC管的形成。转染了shIGSF8的JEG-3细胞的mrna测序分析显示，与血管生成和间充质细胞分化相关的基因表达存在差异，IGSF8敲低与血管发育和细胞迁移相关通路的激活有关。总的来说，本研究表明IGSF8在PE的发展中发挥了作用，并为潜在的治疗提供了新的见解。

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引用次数: 0

Matrix-mediated activation of murine fibroblast-like synoviocytes 基质介导的小鼠成纤维细胞样滑膜细胞活化。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-01 DOI: 10.1016/j.yexcr.2025.114408

Isabel Zeinert , Luisa Schmidt , Till Baar , Giulio Gatto , Anna De Giuseppe , Adelheid Korb-Pap , Thomas Pap , Esther Mahabir , Frank Zaucke , Bent Brachvogel , Marcus Krüger , Thomas Krieg , Beate Eckes

Fibroblast-like synoviocytes (FLS) are key cells promoting cartilage damage and bone loss in rheumatoid arthritis (RA). They are activated to assume an invasive and migratory phenotype. While mechanisms of FLS activation are unknown, evidence suggests that pre-damaged extracellular matrix (ECM) of the cartilage can trigger FLS activation. Integrin α11β1 might be involved in the activation, as it is increased in RA patients and hTNFtg mice, an RA mouse model.

We treated murine chondrocytes with TNFα to produce a damaged, RA-like matrix. Comparison to healthy chondrocyte matrix revealed decreased ECM proteins, e.g. collagens and proteoglycans, increased matrix-degrading proteins and elevated levels of inflammatory cytokines.

FLS responded to the damaged chondrocyte matrix with a matrix-remodeling and pro-inflammatory phenotype characterized by a gene signature involved in matrix degradation and increased production of CLL11 and CCL19. Damaged chondrocyte matrix stimulated increased Itga11 expression in FLS, correlating with the increased α11β1 amounts in RA patients. FLS deficient in integrin α11β1 released lower amounts of inflammation-associated cytokines.

Our results demonstrate differences in healthy and RA-like chondrocyte ECM and distinctly different responses of wt FLS to damaged versus healthy ECM.

成纤维细胞样滑膜细胞（FLS）是促进类风湿性关节炎（RA）软骨损伤和骨质流失的关键细胞。它们被激活后呈现出侵袭性和迁移性表型。虽然FLS激活的机制尚不清楚，但有证据表明，软骨预损伤的细胞外基质（ECM）可以触发FLS激活。整合素α11β1可能参与了激活，因为它在RA患者和RA小鼠模型hTNFtg小鼠中升高。我们用TNFα处理小鼠软骨细胞以产生受损的ra样基质。与健康软骨细胞基质相比，ECM蛋白（如胶原和蛋白聚糖）减少，基质降解蛋白增加，炎症细胞因子水平升高。FLS对受损的软骨细胞基质有反应，表现为基质重塑和促炎表型，其特征是参与基质降解和CLL11和CCL19产生增加的基因特征。损伤的软骨细胞基质刺激FLS中Itga11表达增加，与RA患者α11β1表达增加相关。整合素α11β1缺失的FLS释放较少的炎症相关细胞因子。我们的研究结果表明，健康和ra样软骨细胞ECM存在差异，并且wt FLS对受损和健康ECM的反应明显不同。

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引用次数: 0

Circular RNA circPFKP suppress gastric cancer progression through targeting miR-346/CAMD3 axis 环状RNA circPFKP通过靶向miR-346/CAMD3轴抑制胃癌进展。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-01 DOI: 10.1016/j.yexcr.2024.114390

Xin Song , Guochao Zhang , Jinwei Niu, Haibin Liu, Chaofeng Li, Wu Ning, Lei Zhou

Studies have demonstrated that circular RNAs (circRNAs) exert an important regulatory function in the pathogenesis of various tumors. However, their role in gastric cancer (GC) is still not completely understood. In our study, the differentially expressed circRNAs in GC tissues and matched adjacent normal tissues were analyzed by utilizing gene chips GSE93541, GSE89143, and GSE78092. The expression of has_circ_0006608 (circPFKP), miR-346, and CAMD3 was analyzed through quantitative real-time polymerase chain reaction (qRT-PCR). The CCK-8 assay and Transwell assay were employed to detect the effect of circPFKP on the proliferation, migration, and invasion of gastric cancer cells. The mice xenograft assay was used to assess the function of circPFKP in vivo. The targeting relationship between circPFKP, miR-346, and CAMD3 was predicted by bioinformatics analysis and confirmed by the dual-luciferase reporter assay and RNA pull-down assay. Our results screened and verified that circPFKP was down-regulated in gastric cancer tissues and cells. Overexpression of circPFKP in GC cells can inhibit cell proliferation, migration, invasion, and tumor growth in vivo. Additionally, circPFKP has been shown to act as a sponge for miR-346 to modulate the expression of CAMD3. Finally, we demonstrated that overexpression of CAMD3 or miR-346 inhibitor significantly reversed the effects of si-circPFKP on the proliferation, migration, and invasion of gastric cancer cells. In conclusion, this study provided that circPFKP inhibits the progression of GC via the miR-346/CAMD3 axis, this may provide a noval biomarker for the diagnosis and treatment of GC.

研究表明，环状rna （circRNAs）在多种肿瘤的发病机制中发挥着重要的调控作用。然而，它们在胃癌（GC）中的作用尚不完全清楚。本研究利用基因芯片GSE93541、GSE89143和GSE78092分析GC组织和匹配的邻近正常组织中差异表达的环状rna。通过定量实时聚合酶链反应（qRT-PCR）分析has_circ_0006608 （circPFKP）、miR-346和CAMD3的表达。采用CCK-8法和Transwell法检测circPFKP对胃癌细胞增殖、迁移和侵袭的影响。采用小鼠异种移植实验评估circPFKP在体内的功能。通过生物信息学分析预测circPFKP、miR-346和CAMD3之间的靶向关系，并通过双荧光素酶报告基因实验和RNA下拉实验证实。我们的研究结果筛选并证实了circPFKP在胃癌组织和细胞中下调。在GC细胞中过表达circPFKP可以抑制细胞的增殖、迁移、侵袭和肿瘤生长。此外，circPFKP已被证明可以作为miR-346的海绵来调节CAMD3的表达。最后，我们证明了CAMD3或miR-346抑制剂的过表达显著逆转了si-circPFKP对胃癌细胞增殖、迁移和侵袭的影响。综上所述，本研究表明circPFKP通过miR-346/CAMD3轴抑制GC的进展，这可能为GC的诊断和治疗提供新的生物标志物。

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引用次数: 0

Cancer-associated fibroblast-derived exosomes in cancer progression: A focus on hepatocellular carcinoma 癌症相关成纤维细胞衍生外泌体在癌症进展中的作用：聚焦于肝细胞癌。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-01 DOI: 10.1016/j.yexcr.2025.114424

Chou-Yi Hsu , Abdulrahman T. Ahmed , Safia Obaidur Rab , Subasini Uthirapathy , Suhas Ballal , Rishiv Kalia , Renu Arya , Deepak Nathiya , Muthena kariem , Abed J. Kadhim

The tumor microenvironment (TME) has drawn much interest recently in the search for innovative cancer therapeutics, especially in light of the growing body of evidence supporting the efficacy of immune checkpoint inhibitors (ICIs). The TME comprises various cell types within the extracellular matrix (ECM), such as immune cells, endothelial cells, and cancer-associated fibroblasts (CAFs). Throughout the malignancy, these cells interact with cancerous cells and with one another. Inside the TME, CAFs are predominant and diverse cell types essential in regulating immune escape, angiogenesis, chemotherapeutic resistance, and cancer cells to invade and metastasize. Extracellular vesicles (EVs) and soluble substances are secreted by CAFs, which also remodel the extracellular matrix to partially coordinate their actions. A subclass of EVs called exosomes comprises proteins, lipids, and nucleic acids. Exosomes contain macromolecules that can transfer from one cell to another, changing the recipient cell's activity. Since exosomes are also circulating, it is possible to investigate their composition as potential biomarkers for cancer patient's diagnosis and prognosis. In this review, we focus on the function of exosomes derived from CAFs in the communications between CAFs and other TME cells and cancerous cells. Initially, we explain the various roles of CAFs in carcinogenesis. Subsequently, we address the processes by which CAFs interact with hepatocellular carcinoma (HCC) cells and other cells within the TME, with a special focus on the function of exosomes. We then go into greater detail regarding the processes by which exosomes derived from CAFs aid in the development of HCC, in addition to the clinical implications of exosomes. Finally, we address facets of exosomes that warrant additional research, such as novel discoveries regarding the enhancement of immune checkpoint inhibitor blockade therapy.

肿瘤微环境（TME）最近在寻找创新的癌症治疗方法中引起了很大的兴趣，特别是考虑到越来越多的证据支持免疫检查点抑制剂（ICIs）的疗效。TME包括细胞外基质（ECM）内的各种细胞类型，如免疫细胞、内皮细胞和癌症相关成纤维细胞（CAFs）。在整个恶性肿瘤中，这些细胞与癌细胞相互作用，彼此之间也相互作用。在TME中，CAFs占主导地位，多种细胞类型在调节免疫逃逸、血管生成、化疗耐药和癌细胞入侵和转移中至关重要。细胞外囊泡（EVs）和可溶性物质由CAFs分泌，它们也重塑细胞外基质以部分协调它们的作用。外泌体是ev的一个亚类，由蛋白质、脂质和核酸组成。外泌体含有大分子，可以从一个细胞转移到另一个细胞，改变受体细胞的活性。由于外泌体也在循环，因此有可能研究它们的组成，作为癌症患者诊断和预后的潜在生物标志物。在这篇综述中，我们将重点关注源自CAFs的外泌体在CAFs与其他TME细胞和癌细胞之间的通讯中的功能。首先，我们解释了CAFs在癌变中的各种作用。随后，我们讨论了CAFs与肝细胞癌（HCC）细胞和TME内其他细胞相互作用的过程，特别关注外泌体的功能。除了外泌体的临床意义外，我们还详细介绍了源自cas的外泌体在HCC发展中的作用过程。最后，我们讨论了需要进一步研究的外泌体的各个方面，例如关于增强免疫检查点抑制剂阻断治疗的新发现。

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引用次数: 0

Exploring the role of exosomal lncRNA in cancer immunopathogenesis: Unraveling the immune response and EMT pathways 探索外泌体lncRNA在癌症免疫发病机制中的作用：揭示免疫反应和EMT途径。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-01 DOI: 10.1016/j.yexcr.2024.114401

Sharif Alhajlah , Saade Abdalkareem Jasim , Farag M.A. Altalbawy , Pooja Bansal , Harpreet Kaur , Jaafaru Sani Mohammed , Mohammed N. Fenjan , Reem Turki Edan , M.K. Sharma , Ahmed Hussein Zwamel

Exosomes are membrane-bound vesicles secreted by diverse cell types, serving as crucial mediators in intercellular communication and significantly influencing cancer development. Exosomes facilitate complex signaling processes in the tumor microenvironment for immunomodulation, metastasis, angiogenesis, and treatment resistance. Notably, long non-coding RNAs (lncRNAs), a class of non-coding RNAs, engage with mRNA, DNA, proteins, and miRNAs to modulate gene expression through multiple mechanisms, including transcriptional, post-transcriptional, translational, and epigenetic pathways. The quantitative dynamics of exosomal lncRNAs show a consistent variation correlating with cancer progression and metastasis, suggesting their potential utility as biomarkers for cancer diagnosis and prognosis. Additionally, exosomal lncRNAs can yield critical insights into therapeutic responses in patients. The identification of exosomal lncRNAs as indicators for various cancer subtypes presents them not only as prognostic tools but also as promising therapeutic targets. Despite their potential, the precise functions of exosomal lncRNAs in the cancer biology landscape remain inadequately understood. This paper delves into the multifaceted roles of exosomal lncRNAs, particularly in the context of breast cancer, highlighting their promise for therapeutic applications. A thorough comprehension of exosomal lncRNAs is imperative for advancing our knowledge of the underlying mechanisms of breast cancer, ultimately paving the way for the development of more effective treatment strategies for patients.

外泌体是由多种细胞类型分泌的膜结合囊泡，是细胞间通讯的重要介质，并显著影响癌症的发展。外泌体促进肿瘤微环境中复杂的信号传导过程，包括免疫调节、转移、血管生成和治疗耐药性。值得注意的是，长链非编码rna （lncRNAs）是一类非编码rna，它与mRNA、DNA、蛋白质和mirna结合，通过多种机制（包括转录、转录后、翻译和表观遗传途径）调节基因表达。外泌体lncrna的定量动态显示出与癌症进展和转移相关的一致变化，表明它们作为癌症诊断和预后的生物标志物的潜在效用。此外，外泌体lncrna可以对患者的治疗反应产生关键的见解。外泌体lncrna作为各种癌症亚型的指标的鉴定不仅使它们成为预后工具，而且是有希望的治疗靶点。尽管它们具有潜力，但外泌体lncrna在癌症生物学领域的确切功能仍然没有得到充分的了解。本文深入研究了外泌体lncrna的多方面作用，特别是在乳腺癌的背景下，强调了它们在治疗应用方面的前景。彻底了解外泌体lncrna对于提高我们对乳腺癌潜在机制的认识至关重要，最终为开发更有效的治疗策略铺平道路。

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引用次数: 0

Temporal dynamics of PM2.5 induced cell death: Emphasizing inflammation as key mediator in the late stages of prolonged myocardial toxicity PM2.5诱导细胞死亡的时间动态：强调炎症是延长心肌毒性后期的关键介质。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-01 DOI: 10.1016/j.yexcr.2025.114423

Bhavana Sivakumar , Gino A. Kurian

Multiple forms of cell death contribute significantly to cardiovascular pathologies, negatively impacting cardiac remodeling and leading to heart failure. While myocardial cell death has been associated with PM_2.5 induced cardiotoxicity, the temporal dynamics of various cell death forms, such as apoptosis, ferroptosis, necroptosis, and pyroptosis, in relation to inflammatory processes, remain underexplored. This study examines the time-dependent onset and progression of these cell death pathways in the myocardium and their correlation with inflammation in a Wistar rat model. Female rats were exposed to 250 μg/m³ of PM_2.5 for 3 h daily over periods of 1, 7, 14, and 21 days. Gene expression analysis revealed that apoptotic markers (caspases 3, 7, and 9) were upregulated after 7 days of exposure, with continued elevation through 21 days. Ferroptotic markers, such as Ferritin and GPX4, declined significantly starting from day 14, while necroptosis (RIPK1) and pyroptosis (GSDMD) were prominent only after 21 days of exposure. In parallel, inflammatory markers, including IL-1β and TNF-α, showed substantial upregulation, particularly in the later stages, suggesting that inflammation plays a key role in amplifying myocardial damage in the prolonged exposure phase. These processes coincided with a progressive decrease in mitochondrial mass, elevated oxidative stress, and compromised bioenergetic function, all contributing to worsened cardiac function and remodeling by day 21.In conclusion, PM_2.5 exposure initiates myocardial damage primarily through apoptosis and ferroptosis in the early stages. However, prolonged exposure exacerbates cell death via necroptosis and pyroptosis, with inflammation emerging as a critical factor driving late-stage myocardial toxicity. This study highlights the temporal dynamics of distinct cell death pathways, offering crucial insights into the mechanisms of PM_2.5 induced cardiotoxicity and identifying potential therapeutic targets to mitigate its impact.

多种形式的细胞死亡对心血管疾病有重要贡献，对心脏重塑产生负面影响并导致心力衰竭。虽然心肌细胞死亡与PM2.5诱导的心脏毒性有关，但与炎症过程相关的各种细胞死亡形式（如凋亡、铁下垂、坏死下垂和焦下垂）的时间动力学仍未得到充分探讨。本研究在Wistar大鼠模型中研究了心肌中这些细胞死亡途径的时间依赖性发生和进展及其与炎症的相关性。雌性大鼠在1,7,14和21天内每天暴露于250 μg/m³的PM2.5中3小时。基因表达分析显示，凋亡标志物（caspases 3、7和9）在暴露7天后上调，并在21天内持续升高。铁溶性标志物，如铁蛋白和GPX4，从第14天开始显著下降，而坏死（RIPK1）和焦亡（GSDMD）仅在暴露21天后才突出。与此同时，炎症标志物，包括IL-1β和TNF-α，显示出显著的上调，特别是在后期，这表明炎症在延长暴露期放大心肌损伤中起关键作用。这些过程与线粒体质量逐渐减少、氧化应激升高和生物能量功能受损相吻合，所有这些都导致第21天心功能恶化和重构。综上所述，PM2.5暴露主要通过早期细胞凋亡和铁下垂引起心肌损伤。然而，长时间的暴露会通过坏死和焦亡加剧细胞死亡，炎症成为驱动晚期心肌毒性的关键因素。这项研究强调了不同细胞死亡途径的时间动态，为PM2.5诱导心脏毒性的机制提供了重要的见解，并确定了减轻其影响的潜在治疗靶点。

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引用次数: 0

The intervention of B. longum metabolites in Fnevs' carcinogenic capacity: A potential double-edged sword 长芽孢杆菌代谢物对Fnevs致癌能力的干预：一把潜在的双刃剑。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-02-01 DOI: 10.1016/j.yexcr.2025.114407

Jingyu Xu , Xinyu Wu , Luyi Yang , Xiaoxi Xu

Colorectal cancer (CRC) ranks among the most prevalent malignant tumors globally. Fusobacterium nucleatum and its metabolites are effective biological targets for colon cancer promotion. Probiotics such as Bifidobacterium can block the occurrence and development of CRC by regulating the host intestinal mucosal immunity, eliminating carcinogens, and interfering with tumor cell proliferation and apoptosis. We selected six Bifidobacterium species to explore the inhibitory effect of their cell-free supernatant (CFS) on Fusobacterium nucleatum, and screened the best functional strain Bifidobacterium longum (B. longum) to explore its intervention effect on Fnevs infection of CRC cells. In the genus Bifidobacterium, B. longum-CFS can effectively inhibit the growth and membrane formation of Fusobacterium nucleatum. The metabolites of B. longum can inhibit the proliferation, migration and invasion of Fnevs-infected CRC cells. However, the transcriptomic analysis of Fnevs-infected CRC cells treated with Bl-CFS revealed that Bl-CFS exerted inhibitory effects on the expression of specific oncogenes (e.g., Myc, IL16, KCNN2, ACSBG1, Pum1, MET, NR5A2), while simultaneously promoting the expression of other oncogenes. This modulation potentially enhances the proliferation, epithelial-mesenchymal transition (EMT), stemness properties and other characteristics associated with CRC cells. Metabolomics also showed that Bl-CFS altered organic acid and lipid metabolism in Fnevs-infected CRC cells, and switched energy supply from aerobic glucose metabolism (TCA cycle) to anaerobic glycolysis, which increased the malignancy potential of CRC cells. The observed outcome may be attributed to the presence of both probiotics and toxic substances in the metabolites derived from Bifidobacterium longum. Therefore, this study concludes that the anti-colorectal cancer (CRC) effect of natural metabolites derived from Bifidobacterium longum is limited. Future investigations should focus on refining these natural substances and optimizing their composition ratios to extract their essence while eliminating impurities, thereby obtaining anticancer biologics with exceptional and consistent efficacy.

结直肠癌（CRC）是全球最常见的恶性肿瘤之一。核梭杆菌及其代谢产物是促进结肠癌的有效生物学靶点。双歧杆菌等益生菌可通过调节宿主肠道黏膜免疫，消除致癌物，干扰肿瘤细胞增殖和凋亡，阻断结直肠癌的发生发展。我们选取6种双歧杆菌，探讨其无细胞上清液（CFS）对核梭杆菌的抑制作用，并筛选功能最佳的长双歧杆菌（B. longum）菌株，探讨其对Fnevs感染结直肠癌细胞的干预作用。在双歧杆菌属中，B. longum-CFS能有效抑制核梭杆菌的生长和成膜。长芽孢杆菌的代谢物可抑制fnev感染的结直肠癌细胞的增殖、迁移和侵袭。然而，用Bl-CFS处理fnev感染的CRC细胞的转录组学分析显示，Bl-CFS对特定癌基因（如Myc、IL16、KCNN2、ACSBG1、Pum1、MET、NR5A2）的表达有抑制作用，同时促进其他癌基因的表达。这种调节可能会增强CRC细胞的增殖、上皮-间质转化（EMT）、干细胞特性和其他与CRC细胞相关的特征。代谢组学还显示，Bl-CFS改变了fnev感染的结直肠癌细胞的有机酸和脂质代谢，并将能量供应从有氧糖代谢（TCA循环）转变为厌氧糖酵解，从而增加了结直肠癌细胞的恶性潜能。观察到的结果可能归因于长双歧杆菌代谢产物中益生菌和有毒物质的存在。因此，本研究得出结论，长双歧杆菌天然代谢物的抗结直肠癌（CRC）作用有限。未来的研究应着眼于对这些天然物质进行提炼，优化其组成比例，提取其精华，同时去除杂质，从而获得具有卓越和稳定疗效的抗癌生物制剂。

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引用次数: 0

Ethyl 2,2-difluoro-2-(2-oxo-2H-chromen-3-yl) acetate inhibits the malignant biological behaviors of colorectal cancer by restricting the phosphorylation and nuclear translocation of STAT3

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-01-24 DOI: 10.1016/j.yexcr.2025.114421

Jie Lin , Weijing Liu , Xiaodan Li , Jiansuo Lin , Xuehong Fang , Yanwen Liang , Wen Zhang , Jianwei Ren , Feng Wang , Liyi Zou , Yi Liu

To investigate the effect of a novel coumarin derivative, ethyl 2,2-difluoro-2 - (2-oxo-2H-chromen-3-yl) acetate (C2F), on the malignant biological behaviors of colorectal cancer (CRC) and elucidate its mechanism. In vitro, the effects of C2F on the proliferation, apoptosis, migration, invasion, and cell cycle of CRC cells were analyzed by MTT assay, EdU staining, colony formation assay, flow cytometry, wound healing and transwell assay. The anti-CRC activity of C2F was evaluated in a nude mice xenograft model in vivo. Western blot was conducted to detect the expression of protein in cells and mice tissue. Then, the potential targets of C2F in CRC were predicted by network pharmacology analysis and molecular docking. The localization of STAT3 was observed through immunofluorescence experiment. C2F inhibits CRC cell proliferation, promotes CRC cell apoptosis, hinders CRC cell migration and invasion, and prevents the cell cycle from entering the G2/M phase. In vivo, C2F inhibited tumor growth in xenograft model. C2F inhibited signal transduction and activator of transcription 3 (STAT3) phosphorylation and blocked interleukin-6 (IL-6)-induced STAT3 nuclear translocation. C2F inhibits the malignant biological behavior of CRC by limiting STAT3 phosphorylation and entry into the nucleus.

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引用次数: 0

FOXA2 regulates endoplasmic reticulum stress, oxidative stress, and apoptosis in spermatogonial cells by the Nrf2 pathway under hypoxic conditions FOXA2通过Nrf2途径调控低氧条件下精原细胞内质网应激、氧化应激和凋亡。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research

Pub Date : 2025-01-15 DOI: 10.1016/j.yexcr.2024.114388

Weiwei Li , Xiurong Yin , Lei Zhang

Hypoxia-caused spermatogenesis impairment may contribute to male infertility. FOXA2 has been found to be abundant in spermatogonial stem cells and critical for spermatogenesis. Here we aimed to explore the roles of FOXA2 in regulating spermatogonial cells against hypoxia stimulation. Our results showed that FOXA2 expression was downregulated in hypoxia-stimulated spermatogonial cells. Overexpression of FOXA2 prevented hypoxia-induced endoplasmic reticulum (ER) stress with decreased expression levels of associated markers including GRP78, CHOP, and ATF-4. FOXA2 overexpression caused a decrease in MDA content and an increase in activities of SOD, CAT, and GSH-Px in spermatogonial cells under hypoxic conditions, implying its inhibitory effect on oxidative stress. Besides, cell apoptosis under hypoxic conditions was also prevented by FOXA2 overexpression, as shown by reduced apoptotic rate and caspase-3 activity. Moreover, we found that hypoxia stimulation inactivated the Nrf2 pathway, which could be prevented by FOXA2 overexpression. Nrf2 knockdown attenuated the effects of FOXA2 overexpression on hypoxia-induced ER stress, oxidative stress, and apoptosis in spermatogonial cells. In conclusion, FOXA2 exerted protective effects on spermatogonial cells against hypoxia-induced ER stress, oxidative stress, and apoptosis via regulating Nrf2/HO-1 signaling. These findings suggested that FOXA2 might be a therapeutic target for treating hypoxia-induced spermatogenesis impairment.

缺氧引起的精子发生障碍可能导致男性不育。FOXA2已被发现在精原干细胞中大量存在，对精子发生至关重要。本研究旨在探讨FOXA2在调节精原细胞抗缺氧刺激中的作用。我们的研究结果表明FOXA2在缺氧刺激的精原细胞中表达下调。FOXA2的过表达通过降低GRP78、CHOP和ATF-4等相关标志物的表达水平来阻止缺氧诱导的内质网（ER）应激。FOXA2过表达导致低氧条件下精原细胞MDA含量降低，SOD、CAT、GSH-Px活性升高，提示其对氧化应激有抑制作用。此外，缺氧条件下FOXA2的过表达也能阻止细胞凋亡，表现为细胞凋亡率和caspase-3活性的降低。此外，我们发现缺氧刺激使Nrf2通路失活，这可以通过FOXA2过表达来阻止。Nrf2敲低可减弱FOXA2过表达对低氧诱导的内质网应激、氧化应激和精原细胞凋亡的影响。综上所述，FOXA2通过调控Nrf2/HO-1信号通路，对低氧诱导的ER应激、氧化应激和凋亡具有保护作用。这些发现提示FOXA2可能是治疗缺氧诱导的精子发生障碍的治疗靶点。

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引用次数: 0