Cell Biology International最新文献

Role of low-density cholesterol and Interleukin-17 interaction in breast cancer pathogenesis and treatment 低密度胆固醇与白细胞介素-17 的相互作用在乳腺癌发病和治疗中的作用

IF 3.9 3区生物学 Q3 CELL BIOLOGY

Cell Biology International

Pub Date : 2024-09-24 DOI: 10.1002/cbin.12250

Qingqing Liu, Rongyuan Yang, Dawei Wang, Qing Liu

Breast cancer (BC) has become the most prevalent cancer worldwide, and further research is being conducted to deepen our understanding of its pathogenesis and treatment. Lipid metabolism disorder is a significant alteration in cancer cells, and the investigation into the role of Interleukin-17 (IL-17) in malignant tumors has emerged as a research focus in recent years. Thus, exploring changes in lipid metabolism and inflammatory factors in BC cells is crucial in identifying potential therapeutic targets. This article summarizes the progress made in the research on the main low-density cholesterol (LDL) transporter and IL-17 in lipid metabolism, and their potential involvement in the development of BC. The article aims to establish a theoretical foundation for the development of BC-related therapies.

乳腺癌（BC）已成为全球发病率最高的癌症，为了加深对其发病机制和治疗方法的了解，我们正在开展进一步的研究。脂质代谢紊乱是癌细胞的一个重要改变，而白细胞介素-17（IL-17）在恶性肿瘤中的作用也成为近年来的研究重点。因此，探索 BC 细胞中脂质代谢和炎症因子的变化对于确定潜在的治疗靶点至关重要。本文总结了脂质代谢中主要的低密度胆固醇（LDL）转运体和IL-17的研究进展，以及它们在BC发病中的潜在参与。文章旨在为开发 BC 相关疗法奠定理论基础。

引用次数: 0

EML4-ALK G1202R and EML4-ALK L1196M mutations induce crizotinib resistance in non-small cell lung cancer cells through activating epithelial–mesenchymal transition mediated by MDM2/MEK/ERK signal axis EML4-ALK G1202R和EML4-ALK L1196M突变通过激活MDM2/MEK/ERK信号轴介导的上皮-间质转化，诱导非小细胞肺癌细胞对克唑替尼产生耐药性

IF 3.9 3区生物学 Q3 CELL BIOLOGY

Cell Biology International

Pub Date : 2024-09-24 DOI: 10.1002/cbin.12249

Yuying Yang, Huan Yang, Yunhui Gao, Qian Yang, Xinya Zhu, Qianying Miao, Xiaobo Xu, Zengqiang Li, Daiying Zuo

Crizotinib, as the first-generation of anaplastic lymphoma kinase (ALK) inhibitor, effectively improves the survival time of ALK-positive non-small cell lung cancer (NSCLC) patients. However, its efficacy is severely limited by drug resistance caused by secondary mutations. G1202R and L1196M are classical mutation sites located in ALK kinase domain. They may hinder the binding of ALK inhibitors to the target kinase domain, resulting in drug resistance in patients. However, the exact mechanism of drug resistance mediated by these mutations remains unclear. In this study, we aimed to evaluate how G1202R and L1196M mutations mediate crizotinib resistance. To explore the resistance mechanism, we constructed EML4-ALK G1202R and L1196M mutant cell lines with A549 cells. The results showed that the mutant cells exhibited significant epithelial–mesenchymal transition (EMT) and metastasis compared to control (A549-vector) or wild type (A549-EML4-ALK) cells. Subsequently, it was found that the occurrence of EMT was correlated to the high expression of murine double minute 2 (MDM2) protein and the activation of mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway in mutant cells. Down-regulation of MDM2 inhibited the activation of MEK/ERK pathway, thus reversed the EMT process and markedly increased the inhibitory effect of crizotinib on the growth of mutant cells. Collectively, resistance of ALK-positive NSCLC cells to crizotinib is induced by G1202R and L1196M mutations through activation of the MDM2/MEK/ERK signalling axis, promoting EMT process and metastasis. These findings suggest that the combination of MDM2 inhibitors and crizotinib could be a potential therapeutic strategy.

克唑替尼作为第一代无性淋巴瘤激酶（ALK）抑制剂，能有效改善ALK阳性非小细胞肺癌（NSCLC）患者的生存时间。然而，由于二次突变导致的耐药性，其疗效受到严重限制。G1202R和L1196M是位于ALK激酶结构域的典型突变位点。它们可能会阻碍ALK抑制剂与靶激酶结构域的结合，从而导致患者产生耐药性。然而，这些突变介导耐药的确切机制仍不清楚。在本研究中，我们旨在评估G1202R和L1196M突变如何介导克唑替尼耐药。为了探索耐药机制，我们用A549细胞构建了EML4-ALK G1202R和L1196M突变细胞系。结果显示，与对照（A549-vector）或野生型（A549-EML4-ALK）细胞相比，突变细胞表现出明显的上皮-间质转化（EMT）和转移。随后研究发现，EMT的发生与突变型细胞中鼠双分化2（MDM2）蛋白的高表达和丝裂原活化蛋白激酶（MEK）/细胞外信号调节激酶（ERK）通路的激活有关。下调MDM2抑制了MEK/ERK通路的激活，从而逆转了EMT过程，并显著增强了克唑替尼对突变细胞生长的抑制作用。总之，ALK阳性NSCLC细胞对克唑替尼的耐药性是由G1202R和L1196M突变通过激活MDM2/MEK/ERK信号轴诱导的，促进了EMT过程和转移。这些研究结果表明，MDM2抑制剂与克唑替尼的结合可能是一种潜在的治疗策略。

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引用次数: 0

Erucic acid increases the potency of cisplatin-induced colorectal cancer cell death and oxidative stress by upregulating the TRPM2 channel. 芥酸通过上调 TRPM2 通道增加顺铂诱导的结直肠癌细胞死亡和氧化应激的效力。

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Biology International

Pub Date : 2024-09-23 DOI: 10.1002/cbin.12248

Ayşenur Nazıroğlu, Ahmet Çarhan, Mustafa Nazıroğlu

Erucic acid (ErA) is a source of omega-9 monounsaturated fatty acids. ErA exhibited antitumor effects by causing apoptosis and oxidative stress in tumor cells, with the exception of the HT-29 human colorectal cancer cell line. The apoptotic and Ca²⁺ signaling pathways in tumor cells are triggered when mitochondrial Ca²⁺ and Zn²⁺ accumulation produce reactive free oxygen species (ROS), which in turn activate TRPM2. ErA-induced ROS and TRPM2 stimulation may augment the anticancer action of cisplatin (CSP). We aimed to study the effects of ErA and CSP incubations on ROS, apoptosis, and cell death in the HT-29 cells by activating TRPM2. The cells were divided into five groups: control, ErA (200 µM for 48 h), CSP (25 µM for 24 h), and ErA + CSP + TRPM2 antagonists (200 µM carvacrol and 25 µM N-(p-amylcinnamoyl)anthranilic acid for 24 h). The TRPM2 antagonists reduced ErA plus CSP-induced increases in H₂O₂-induced intracellular free Ca²⁺ concentration ([Ca²⁺]_c) and adenosine diphosphate-ribose-caused TRPM2 currents. ErA and CSP were found to cause apoptosis and cell death by raising the intracellular free Zn²⁺ concentration (Zn²⁺]_c), caspase-3, -8, and -9, mitochondrial membrane dysfunction, and ROS, while lowering reduced glutathione, cell viability, and cell number. The oxidative, apoptotic, and tumor cell death effects of CSP in the cells were enhanced by the increase of ErA-mediated [Ca²⁺]_c and Zn²⁺]_c entering mitochondria through the activation of TRPM2. In conclusion, we observed that the combination of ErA and CSP was synergistic via TRPM2 activation for the treatment of HT-29 tumor cells.

芥酸（ErA）是欧米茄-9 单不饱和脂肪酸的一种来源。ErA 可导致肿瘤细胞凋亡和氧化应激，具有抗肿瘤作用，但 HT-29 人类结直肠癌细胞系除外。线粒体 Ca2+ 和 Zn2+ 积累会产生活性自由氧（ROS），进而激活 TRPM2，从而触发肿瘤细胞的凋亡和 Ca2+ 信号通路。我们将细胞分为五组：对照组、ErA 组（200 µM，48 小时）、CSP 组（25 µM，24 小时）和 ErA + CSP + TRPM2 拮抗剂组（200 µM 香芹酚和 25 µM N-（对戊基肉桂酰）蒽二酸，24 小时）。TRPM2 拮抗剂降低了 ErA 和 CSP 诱导的 H2O2-诱导的细胞内游离 Ca2+ 浓度（[Ca2+]c）和二磷酸腺苷核糖诱导的 TRPM2 电流的增加。研究发现，ErA 和 CSP 通过提高细胞内游离 Zn2+ 浓度（Zn2+]c）、caspase-3、-8 和 -9、线粒体膜功能障碍和 ROS，同时降低还原型谷胱甘肽、细胞活力和细胞数量，导致细胞凋亡和细胞死亡。通过激活TRPM2，ErA介导的进入线粒体的[Ca2+]c和Zn2+]c增加，从而增强了CSP对细胞的氧化、凋亡和肿瘤细胞死亡效应。总之，我们观察到，通过激活TRPM2，ErA和CSP联合治疗HT-29肿瘤细胞具有协同作用。

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引用次数: 0

Pax6 expressing neuroectodermal and ocular stem cells: Its role from a developmental biology perspective. 表达 Pax6 的神经外胚层和眼干细胞：从发育生物学角度看其作用

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Biology International

Pub Date : 2024-09-23 DOI: 10.1002/cbin.12246

Shubhangi More, Sumit Mallick, Sudheer Shenoy P, Bipasha Bose

Pax-6 emerges as a critical transcription factor that guides the fate of stem cells towards neural lineages. Its expression influences the differentiation of neural progenitors into diverse neuronal subtypes, glial cells, and other neural cell types. Pax-6 operates with other regulatory factors to ensure the precise patterning and organization of the developing nervous system. The intricate interplay between Pax-6 and other signaling pathways, transcription factors, and epigenetic modifiers underpins the complicated balance between stem cell maintenance, proliferation, and differentiation in neuroectodermal and ocular contexts. Dysfunction of Pax-6 can lead to a spectrum of developmental anomalies, underscoring its importance in these processes. This review highlights the essential role of Pax-6 expression in neuroectodermal and ocular stem cells, shedding light on its significance in orchestrating the intricate journey from stem cell fate determination to the emergence of diverse neural and ocular cell types. The comprehensive understanding of Pax-6 function gained from a developmental biology perspective offers valuable insights into normal development and potential therapeutic avenues for neuroectodermal and ocular disorders.

Pax-6 是一个关键的转录因子，能引导干细胞的命运向神经系发展。它的表达会影响神经祖细胞分化成不同的神经元亚型、神经胶质细胞和其他神经细胞类型。Pax-6 与其他调控因子共同作用，确保神经系统发育的精确模式化和组织化。Pax-6与其他信号通路、转录因子和表观遗传修饰因子之间错综复杂的相互作用，是神经外胚层和眼部环境中干细胞维持、增殖和分化之间复杂平衡的基础。Pax-6的功能障碍可导致一系列发育异常，凸显了其在这些过程中的重要性。这篇综述强调了Pax-6在神经外胚层和眼干细胞中表达的重要作用，阐明了它在协调从干细胞命运决定到多种神经和眼细胞类型出现的复杂过程中的重要意义。从发育生物学角度对Pax-6功能的全面了解，为神经外胚层和眼部疾病的正常发育和潜在治疗途径提供了宝贵的见解。

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引用次数: 0

Predictive action of oncomiR in suppressing TP53 signaling pathway in hypoxia‐conditioned colon cancer cell line HCT‐116 oncomiR抑制低氧条件下结肠癌细胞系HCT-116中TP53信号通路的预测作用

IF 3.9 3区生物学 Q3 CELL BIOLOGY

Cell Biology International

Pub Date : 2024-09-17 DOI: 10.1002/cbin.12243

R. Susanti, Muchamad Dafip, Dewi Mustikaningtyas, Agung Putra

Hypoxia‐induced heterogeneity in colorectal cancer (CRC) significantly impacts patient survival by promoting chemoresistance. These conditions alter the regulation of miRNAs, key regulators of crucial processes like proliferation, apoptosis, and invasion, leading to tumor progression. Despite their promising potential as diagnostic and therapeutic targets, the underlying mechanisms by which miRNAs influence hypoxia‐mediated tumorigenesis remain largely unexplored. This study aims to elucidate the action of miRNAs in HCT‐116 colorectal cancer stem cells (CSCs) under hypoxia, providing valuable insights into their role in tumor adaptation and progression. MiRNA expression was determined using Nanostring nCounter, and bioinformatic analysis was performed to explain the molecular pathway. A total of 50 miRNAs were obtained with an average count of ≥ 20 reads for comparative expression analysis. The results showed that hypoxia‐affected 36 oncomiRs were increased in HCT‐116, and 14 suppressor‐miRs were increased in MSCs. The increase in miRNA expression occurred consistently from normoxia to hypoxia and significantly differed between mesenchymal stem cells (MSCs) and HCT‐116. Furthermore, miR‐16‐5p and miR‐29a‐3p were dominant in regulating the p53 signaling pathway, which is thought to be related to the escape mechanism against hypoxia and maintaining cell proliferation. More research with a genome‐transcriptome axis approach is needed to fully understand miRNAs’ role in adapting CRC cells and MSCs to hypoxia. Further research could focus on developing specific biomarkers for diagnosis. In addition, anti‐miR can be developed as a therapy to prevent cancer proliferation or inhibit the adaptation of cancer cells to hypoxia.

低氧诱导的结直肠癌（CRC）异质性会促进化疗耐药性，从而严重影响患者的生存。这些条件改变了 miRNA 的调控，而 miRNA 是增殖、凋亡和侵袭等关键过程的关键调控因子，会导致肿瘤进展。尽管 miRNAs 具有作为诊断和治疗靶点的巨大潜力，但其影响缺氧介导的肿瘤发生的潜在机制在很大程度上仍未得到探索。本研究旨在阐明缺氧条件下 miRNA 在 HCT-116 大肠癌干细胞（CSCs）中的作用，为了解它们在肿瘤适应和进展中的作用提供有价值的见解。研究人员利用Nanostring nCounter测定了miRNA的表达，并进行了生物信息学分析以解释其分子通路。共获得 50 个平均计数≥ 20 个读数的 miRNA 进行了表达比较分析。结果表明，在 HCT-116 中，受缺氧影响的 36 个 oncomiRs 表达增加，在间充质干细胞中，14 个抑制型 miRs 表达增加。miRNA表达的增加从正常缺氧到低氧持续发生，间充质干细胞（MSCs）和HCT-116之间存在显著差异。此外，miR-16-5p和miR-29a-3p在调节p53信号通路方面占主导地位，而p53信号通路被认为与缺氧逃逸机制和维持细胞增殖有关。要全面了解 miRNA 在使 CRC 细胞和间充质干细胞适应低氧环境中的作用，还需要更多的基因组-转录组轴方法研究。进一步的研究可侧重于开发用于诊断的特定生物标志物。此外，还可以开发抗 miR 疗法，以防止癌症增殖或抑制癌细胞对缺氧的适应。

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引用次数: 0

The m6A modification of ACSL4 mRNA sensitized esophageal squamous cell carcinoma to irradiation via accelerating ferroptosis ACSL4 mRNA 的 m6A 修饰通过加速铁变态反应使食管鳞状细胞癌对辐照敏感

IF 3.9 3区生物学 Q3 CELL BIOLOGY

Cell Biology International

Pub Date : 2024-09-17 DOI: 10.1002/cbin.12245

Yingying Jin, Shupei Pan, Mincong Wang, Shan Huang, Yue Ke, Dan Li, Hen Luo, Zhanfeng Kou, Dongwen Shi, Weihua Kou, Hongxiao Fu, Jiyuan Pan

Radioresistance is a major obstacle for the therapy of esophageal squamous cell carcinoma (ESCC) and lead to a poor prognosis. Ferroptosis is supposed to be responsible for radioresistance. However, the ferroptosis‐induced radioresistance in ESCC and its related regulatory mechanisms are not yet fully understood. In this study, human ESCC cell line and the corresponding radioresistance cells were irradiated with 6 megavolts (MV) X‐ray. It was showed that irradiation led to less ferroptosis in radioresistant ESCC cells as compared to the parental cells, as depicted by transmission electron microscopy, intracellular Fe2+ iron contents, lipid peroxidation, and expression of COX2. The increase of ASCL4 expression levels in radioresistant cells after radiotherapy was smaller than that in the parental cells. ACSL4 overexpression significantly enhanced ferroptosis. The fold increase in ACSL4 m6A modification in the radioresistant cells was significantly smaller than that in the parental cells as detected by methylated RNA immunoprecipitation with qRT‐PCR. METTL14 overexpression accelerated ferroptosis induced by irradiation via upregulating m6A modification of ACSL4 mRNA. In conclusions, ferroptosis ablation was responsible for the radioresistant of ESCC. The METTL14‐mediated m6A modification of ACSL4 mRNA sensitized ESCC to irradiation via accelerating ferroptosis. This study sheds new light on our understanding of radioresistant in ESCC, and provides potential strategies for ESCC radiotherapy.

放射抗性是食管鳞状细胞癌（ESCC）治疗的主要障碍，并导致不良预后。铁蛋白沉积应该是导致放射抗性的原因。然而，ESCC中铁蛋白诱导的放射抗性及其相关调控机制尚未完全明了。本研究用 6 兆伏特（MV）X 射线照射人 ESCC 细胞系和相应的放射抗性细胞。通过透射电子显微镜、细胞内Fe2+铁含量、脂质过氧化和COX2的表达可以看出，与亲代细胞相比，辐照导致抗放射ESCC细胞铁变态反应较少。放射治疗后，耐药细胞中ASCL4表达水平的升高幅度小于亲代细胞。ACSL4的过表达显著增强了铁凋亡。通过甲基化RNA免疫沉淀和qRT-PCR检测，耐放射细胞中ACSL4 m6A修饰的增加倍数明显小于亲代细胞。METTL14的过表达通过上调ACSL4 mRNA的m6A修饰加速了辐照诱导的铁变态反应。结论是，铁突变消融是ESCC具有放射耐受性的原因。METTL14 介导的 ACSL4 mRNA m6A 修饰通过加速铁突变使 ESCC 对辐照敏感。这项研究为我们了解 ESCC 的放射抗性提供了新的视角，并为 ESCC 放射治疗提供了潜在的策略。

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引用次数: 0

Ectonucleotidase activity driven by acid ectophosphatase in luminal A MCF‐7 breast cancer cells 腔 A MCF-7 乳腺癌细胞中由酸性异磷酸酶驱动的异核苷酸酶活性

IF 3.9 3区生物学 Q3 CELL BIOLOGY

Cell Biology International

Pub Date : 2024-09-17 DOI: 10.1002/cbin.12237

Marco Antonio Lacerda‐Abreu, Bruna dos Santos Mendonça, Gabriela Nestal de Moraes, José Roberto Meyer‐Fernandes

Ectophosphatases catalyse the hydrolysis of phosphorylated molecules, such as phospho‐amino acids, in the extracellular environment. Nevertheless, the hydrolysis of nucleotides in the extracellular environment is typically catalysed by ectonucleotidases. Studies have shown that acid ectophosphatase, or transmembrane‐prostatic acid phosphatase (TM‐PAP), a membrane‐bound splice variant of prostatic acid phosphatase, has ecto‐5′‐nucleotidase activity. Furthermore, it was demonstrated that ectophosphatase cannot hydrolyse ATP, ADP, or AMP in triple‐negative breast cancer cells. In contrast to previous findings in MDA‐MB‐231 cells, the ectophosphatase studied in the present work displayed a remarkable capacity to hydrolyse AMP in luminal A breast cancer cells (MCF‐7). We showed that AMP dose‐dependently inhibited p‐nitrophenylphosphate (p‐NPP) hydrolysis. The p‐NPP and AMP hydrolysis showed similar biochemical behaviours, such as increased hydrolysis under acidic conditions and comparable inhibition by NiCl2, ammonium molybdate, and sodium orthovanadate. In addition, this ectophosphatase with ectonucleotidase activity was essential for the release of adenosine and inorganic phosphate from phosphorylated molecules available in the extracellular microenvironment. This is the first study to show that prostatic acid phosphatase on the membrane surface of breast cancer cells (MCF‐7) is correlated with cell adhesion and migration.

外磷酸酶催化细胞外环境中磷酸化分子（如磷酸氨基酸）的水解。然而，细胞外环境中核苷酸的水解通常是由外切核苷酸酶催化的。研究表明，酸性外切磷酸酶或跨膜前列腺酸性磷酸酶（TM-PAP）（前列腺酸性磷酸酶的膜结合剪接变体）具有外切-5′-核苷酸酶活性。此外，研究还证明，在三阴性乳腺癌细胞中，外切磷酸酶不能水解 ATP、ADP 或 AMP。与之前在 MDA-MB-231 细胞中的发现不同，本研究中研究的外切磷酸酶在腔 A 型乳腺癌细胞（MCF-7）中显示出了水解 AMP 的显著能力。我们发现，AMP 对对硝基苯磷酸（p-NPP）的水解具有剂量依赖性抑制作用。对硝基苯磷酸（p-NPP）和 AMP 的水解表现出相似的生化行为，如在酸性条件下水解增加，氯化镍、钼酸铵和正钒酸钠的抑制作用相当。此外，这种具有外切核苷酸酶活性的外切磷酸酶对于从细胞外微环境中的磷酸化分子中释放腺苷和无机磷酸盐至关重要。这是首次研究表明，乳腺癌细胞（MCF-7）膜表面的前列腺酸性磷酸酶与细胞粘附和迁移有关。

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引用次数: 0

Establishment and characterization of fibroblast lines from the northern tiger cat (Leopardus tigrinus, Schreber, 1775) during extended passage and cryopreservation 北方虎猫（Leopardus tigrinus, Schreber, 1775）成纤维细胞系的建立及其在延长通过和冷冻保存过程中的特征描述

IF 3.9 3区生物学 Q3 CELL BIOLOGY

Cell Biology International

Pub Date : 2024-09-17 DOI: 10.1002/cbin.12244

João Vitor da Silva Viana, Lhara Ricarliany Medeiros de Oliveira, Luanna Lorenna Vieira Rodrigues, Yara Letícia Frutuoso e Silva, Ana Lívia Rocha Rodrigues, Alexandre Rodrigues Silva, Patrícia Vasconcelos Alves, Herlon Victor Rodrigues Silva, Alexsandra Fernandes Pereira

The establishment of fibroblast lines enables several applications from the formation of biobanks for the conservation of biodiversity to the use of these cells in physiological and toxicological assays. Considered a species vulnerable to extinction, the characterization of fibroblastic lines of northern tiger cat would contribute to its conservation. Therefore, we established and characterized fibroblasts derived from northern tiger cat during extended passage (third, seventh, and eleventh passages) and cryopreservation with regard to the morphology, viability, apoptotic classification, metabolism, proliferative activity, and oxidative stress by reactive oxygen species (ROS) levels and mitochondrial membrane potential (ΔΨm). Initially, we identified four dermal fibroblast lines by morphology, immunophenotyping, and karyotyping assays. In vitro culture after the third, seventh, and eleventh passages did not affect the viability, apoptotic classification, and ROS levels. Nevertheless, cells at seventh and eleventh passages featured a reduction in metabolism and an alteration in ΔΨm when compared to third passage cells. Additionally, cells at eleventh passage showed changes in the proliferative activity and morphology when compared to other passages. Regarding cryopreservation, no effect was observed on cryopreserved cells for morphology, viability, apoptotic classification, metabolism, and proliferative activity. Nevertheless, cryopreserved cells had alteration for ROS levels and ΔΨm. In summary, fibroblasts from northern tiger cat were affected by extended passage (seventh and eleventh passages) and cryopreservation. Adjustments to the in vitro culture and cryopreservation are necessary to reduce cellular oxidative stress caused by in vitro conditions.

成纤维细胞系的建立可以应用于多种领域，从建立生物库以保护生物多样性，到将这些细胞用于生理和毒理学检测。北方虎猫被认为是一种容易灭绝的物种，对其成纤维细胞系进行鉴定将有助于对其进行保护。因此，我们建立了北方虎猫成纤维细胞，并通过活性氧（ROS）水平和线粒体膜电位（ΔΨm）对成纤维细胞的形态、存活率、凋亡分类、新陈代谢、增殖活性和氧化应激进行了鉴定。最初，我们通过形态学、免疫分型和核型分析确定了四种真皮成纤维细胞系。第三、第七和第十一次传代后的体外培养不会影响细胞的存活率、凋亡分类和 ROS 水平。然而，与第三代细胞相比，第七代和第十一代细胞的新陈代谢降低，ΔΨm也发生了变化。此外，与其他各层次细胞相比，第 11 层细胞的增殖活性和形态也发生了变化。在冷冻保存方面，没有观察到冷冻保存的细胞在形态、存活率、凋亡分类、新陈代谢和增殖活性方面有任何影响。不过，低温保存的细胞在 ROS 水平和 ΔΨm 方面有所改变。总之，北方虎猫的成纤维细胞受到延长传代（第七和第十一次传代）和冷冻保存的影响。有必要对体外培养和冷冻保存进行调整，以减少体外条件造成的细胞氧化应激。

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引用次数: 0

Breast cancer cell derived exosomes reduces glycolysis of activated CD8 + T cells in a AKT-mTOR dependent manner 乳腺癌细胞衍生的外泌体以 AKT-mTOR 依赖性方式减少活化的 CD8 + T 细胞的糖酵解作用

IF 3.9 3区生物学 Q3 CELL BIOLOGY

Cell Biology International

Pub Date : 2024-09-16 DOI: 10.1002/cbin.12241

Abhishek Choudhury, Soumya Chatterjee, Shauryabrota Dalui, Pronabesh Ghosh, Altamas Hossain Daptary, Golam Kibria Mollah, Arindam Bhattacharyya

Cytotoxic CD8⁺ T cells plays a pivotal role in the adaptive immune system to protect the organism against infections and cancer. During activation and response, T cells undergo a metabolic reprogramming that involves various metabolic pathways, with a predominant reliance on glycolysis to meet their increased energy demands and enhanced effector response. Recently, extracellular vesicles (EVs) known as exosomes have been recognized as crucial signaling mediators in regulating the tumor microenvironment (TME). Recent reports indicates that exosomes may transfer biologically functional molecules to the recipient cells, thereby facilitate cancer progression, angiogenesis, metastasis, drug resistance, and immunosuppression by reprogramming the metabolism of cancer cells. This study sought to enlighten possible involvement of cancer-derived exosomes in CD8 + T cell glucose metabolism and discover a regulated signalome as a mechanism of action. We observed reduction in glucose metabolism due to downregulation of AKT/mTOR signalome in activated CD8 + T cells after cancer derived exosome exposure. In-vivo murine breast tumor studies showed better tumor control and antitumor CD8 + T cell glycolysis and effector response after abrogation of exosome release from breast cancer cells. Summarizing, the present study establishes an immune evasion mechanism of breast cancer cell secreted exosomes that will act as a foundation for future precision cancer therapeutics.

细胞毒性 CD8+ T 细胞在适应性免疫系统中发挥着保护机体免受感染和癌症侵害的关键作用。在激活和反应过程中，T 细胞会进行新陈代谢重编程，其中涉及各种新陈代谢途径，主要依赖糖酵解来满足其增加的能量需求和增强效应反应。最近，被称为外泌体的细胞外囊泡（EV）被认为是调节肿瘤微环境（TME）的重要信号介质。最近的报道表明，外泌体可将生物功能分子转移到受体细胞，从而通过重编程癌细胞的新陈代谢促进癌症进展、血管生成、转移、耐药性和免疫抑制。本研究试图揭示癌症衍生外泌体可能参与 CD8 + T 细胞葡萄糖代谢的情况，并发现作为作用机制的调控信号组。我们观察到，暴露于癌症衍生外泌体后，活化的CD8 + T细胞中AKT/mTOR信号组下调，导致葡萄糖代谢降低。体内小鼠乳腺肿瘤研究表明，乳腺癌细胞释放的外泌体被削弱后，肿瘤控制和抗肿瘤 CD8 + T 细胞糖酵解及效应反应均有所改善。综上所述，本研究建立了乳腺癌细胞分泌外泌体的免疫逃避机制，这将为未来的癌症精准治疗奠定基础。

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引用次数: 0

Lactate‐mitochondrial crosstalk: A new direction in the treatment of sepsis‐induced acute kidney injury 乳酸-线粒体串联：治疗败血症所致急性肾损伤的新方向

IF 3.9 3区生物学 Q3 CELL BIOLOGY

Cell Biology International

Pub Date : 2024-09-10 DOI: 10.1002/cbin.12240

Zhixiong Wu, Wei Qing Liu, Liang Tang, Qiong Yuan, Yaling Li, Hongyu Hu, Xin Luo, Fan Ouyang

Independent risk factors for sepsis‐associated acute kidney injury (S‐AKI) patients include elevated lactate levels, but the specific mechanism remains unclear. Recently, An et al. discovered that excessive acetylation and inactivation of PDHA1 lead to overproduction of lactate, resulting in mitochondrial fragmentation, ATP depletion, excessive mtROS production, and mitochondrial apoptosis, thereby exacerbating AKI in sepsis. Therefore, understanding the pathophysiological processes of mitochondrial function and lactate generation in SAKI is essential and can aid in the development of novel therapeutic strategies. This review elucidates the pathological mechanisms of mitochondrial autophagy and dynamics in AKI. We also discuss the sources of lactate in SAKI and some consequences of lactonization, which may provide new strategies for improving renal injury and delaying the progression of these diseases.

脓毒症相关急性肾损伤（S-AKI）患者的独立危险因素包括乳酸水平升高，但具体机制仍不清楚。最近，An 等人发现，PDHA1 的过度乙酰化和失活导致乳酸生成过多，导致线粒体破碎、ATP 耗竭、mtROS 生成过多和线粒体凋亡，从而加剧了脓毒症中的 AKI。因此，了解 SAKI 中线粒体功能和乳酸生成的病理生理过程至关重要，有助于开发新的治疗策略。本综述阐明了 AKI 中线粒体自噬和动态的病理机制。我们还讨论了 SAKI 中乳酸的来源以及乳酸化的一些后果，这可能会为改善肾损伤和延缓这些疾病的进展提供新的策略。

引用次数: 0