Experimental cell research最新文献_第3页

The dynamic interplay between melanoma cells and CAFs: Implications drug resistance and immune evasion and possible therapeutics 黑色素瘤细胞与CAFs之间的动态相互作用：耐药性和免疫逃避的意义以及可能的治疗方法

IF 3.3 3区生物学

Experimental cell research Pub Date : 2025-04-29 DOI: 10.1016/j.yexcr.2025.114581

Chou-Yi Hsu , Raed Obaid Saleh , Jaafaru Sani Mohammed , Nasrin Mansuri , M.M. Rekha , Mayank Kundlas , Alex Anand , Samir Sahoo , Ahmed Hussein Zwamel , Hanen Mahmod Hulail

{"title":"The dynamic interplay between melanoma cells and CAFs: Implications drug resistance and immune evasion and possible therapeutics","authors":"Chou-Yi Hsu , Raed Obaid Saleh , Jaafaru Sani Mohammed , Nasrin Mansuri , M.M. Rekha , Mayank Kundlas , Alex Anand , Samir Sahoo , Ahmed Hussein Zwamel , Hanen Mahmod Hulail","doi":"10.1016/j.yexcr.2025.114581","DOIUrl":"10.1016/j.yexcr.2025.114581","url":null,"abstract":"<div><div>Melanoma, a malignancy of varying prognoses across primary sites (cutaneous, ocular, and mucosal), typically displays peculiar treatment challenges in metastatic and refractory settings. Cancer-associated fibroblasts (CAFs) have long been recognized as pivotal components within melanoma's tumor microenvironment (TME), originating from various sources and manifesting considerable heterogeneity. These cells actively produce extracellular matrix (ECM), induce angiogenesis, provide metabolic support, contribute to drug resistance, and feed tumor progression and metastasis. Among the many growth factors and cytokines they secrete, including TGF-β and IL-6, they aid in anti-tumor immunity by recruiting immunosuppressive cells and inhibiting cytotoxic T-cell activity, contributing to immune evasion. These dynamic cells sculpt the tumor's niche, allowing cancer cells to survive and proliferate, and their existence is widely correlated with poor prognosis. Taking a cue from the previously established groundwork of how the surroundings heavily influence tumor development, this review attempts to profile the intricate interaction of melanoma cells with the CAFs, the ECM, and signaling molecules. We explore different subtypes of CAFs, their origins, and how they have evolved in their pro-tumorigenic roles in melanoma. Additionally, we review recent advancements in the therapeutic arsenal targeting CAFs to achieve a more effective treatment response. By detailing the specific roles played by different CAFs subtypes in the modulation of immuno-responses and treatment outcomes, this review will further provide insights into the targeted therapy to disrupt CAFs-mediated tumor support in melanoma.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"449 1","pages":"Article 114581"},"PeriodicalIF":3.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Portrayal of the complex molecular landscape of multidrug resistance in gastric cancer: Unveiling the potential targets 描述胃癌多药耐药的复杂分子格局：揭示潜在靶点

IF 3.3 3区生物学

Experimental cell research Pub Date : 2025-04-29 DOI: 10.1016/j.yexcr.2025.114580

Siddhant Biswas , Riya Kanodia , Suman Seervi , Rajinder Kaur , Sakshi Shukla , Samer Singh , Juni Banerjee , Shuvomoy Banerjee

{"title":"Portrayal of the complex molecular landscape of multidrug resistance in gastric cancer: Unveiling the potential targets","authors":"Siddhant Biswas , Riya Kanodia , Suman Seervi , Rajinder Kaur , Sakshi Shukla , Samer Singh , Juni Banerjee , Shuvomoy Banerjee","doi":"10.1016/j.yexcr.2025.114580","DOIUrl":"10.1016/j.yexcr.2025.114580","url":null,"abstract":"<div><div>Gastric cancer (GC) is an aggressive malignancy among all Gastrointestinal cancer (GIC) types. Worldwide, among all cancer types, gastric cancer incidence and related mortality remain in fifth position. Multidrug resistance (MDR) in GC presents a major challenge to chemotherapy, and it significantly affects patient survival. A better understanding of the dynamic interaction of cellular factors contributing to MDR phenotype, e.g., the presence and expression of variants of MDR-related genes, including various drug-detoxifying and drug-efflux transporters, and expression of regulatory ncRNAs affecting the expression of MDR-related genes, is required to comprehend the molecular mechanisms for MDR development in GCs. This review article provides a holistic discussion of the cellular factors involved in the MDR development in GC cells, i.e., their roles and cross-talk between specific molecules that give rise to drug-sensitive and drug-resistant phenotypes. Moreover, the pharmacological perspective of drug resistance and the underlying biological processes that allow the escape of GC cells from the cytotoxic effects of drugs have also been discussed. Additionally, this review article provides an in-depth discussion on most potential candidates that can serve as MDR biomarkers in GIC cancer and the growing research interest in non-coding RNAs (ncRNAs) in GC. Notably, the miRNAs, circRNAs, and lncRNAs are not only emerging as crucial prognostic biomarkers of MDR in gastric cancers but also as potential targets for personalized medicine to combat the MDR challenge in GC patients.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"449 1","pages":"Article 114580"},"PeriodicalIF":3.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NF-κB signaling and its anti-apoptotic effects in liver & skeletal muscle of dehydrated Xenopus laevis 脱水非洲爪蟾肝脏及骨骼肌NF-κB信号传导及其抗凋亡作用

IF 3.3 3区生物学

Experimental cell research Pub Date : 2025-04-28 DOI: 10.1016/j.yexcr.2025.114579

Yulia Biggar , Akshay A. Kamath , Sarah A. Breedon , Kenneth B. Storey

{"title":"NF-κB signaling and its anti-apoptotic effects in liver & skeletal muscle of dehydrated Xenopus laevis","authors":"Yulia Biggar , Akshay A. Kamath , Sarah A. Breedon , Kenneth B. Storey","doi":"10.1016/j.yexcr.2025.114579","DOIUrl":"10.1016/j.yexcr.2025.114579","url":null,"abstract":"<div><div>The African clawed frog, <em>Xenopus laevis</em>, is able to survive prolonged arid conditions during seasonal droughts. During these conditions, <em>X. laevis</em> enters aestivation whereby its metabolic rate is suppressed, urea and ammonia levels increase, and its physiological functions slow. Various molecular mechanisms are employed by <em>X. laevis</em> to mitigate the deleterious effects of severe dehydration and hypometabolism, including pro-survival cellular processes that protect cells and tissues from damage and atrophy. While previous research has focused on antioxidant proteins’ role in preventing oxidative stress, information on the role of anti-apoptotic signaling in <em>X. laevis</em> is lacking. As such, we investigated the role of nuclear factor-kappa B (NF-κB) signaling and its downstream target genes in liver and skeletal muscle tissue of <em>X. laevis</em>. The transcription factor, NF-κB, and its downstream target genes work to inhibit apoptotic machinery and promote cell survival. Herein, we found that NF-κB signaling activation in liver tissue leads to the selective upregulation of downstream anti-apoptotic proteins. In contrast, this upregulation occurs independently of NF-κB signaling in skeletal muscle tissue. Overall, our results serve to expand our knowledge of the anti-apoptotic mechanisms underlying the natural dehydration-tolerance of <em>X. laevis</em>, including its likely use in mitigating tissue atrophy during aestivation.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"449 1","pages":"Article 114579"},"PeriodicalIF":3.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Basal and AT2 cells promote IPF-lung cancer co-occurrence via EMT: Single-cell analysis 基底细胞和AT2细胞通过EMT促进ipf -肺癌共发生：单细胞分析

IF 3.3 3区生物学

Experimental cell research Pub Date : 2025-04-26 DOI: 10.1016/j.yexcr.2025.114578

Cheng Ren , Yawan Zi , Xiaobin Zhang , Xiuqing Liao , Hong Chen

{"title":"Basal and AT2 cells promote IPF-lung cancer co-occurrence via EMT: Single-cell analysis","authors":"Cheng Ren , Yawan Zi , Xiaobin Zhang , Xiuqing Liao , Hong Chen","doi":"10.1016/j.yexcr.2025.114578","DOIUrl":"10.1016/j.yexcr.2025.114578","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung disease. With IPF, the probability of complication with lung cancer (LCA) increases considerably, and the prognosis is worse than that of simple IPF. To understand the pathological mechanisms and molecular pathways shared by these two diseases, we used the single-cell analysis from the Gene Expression Omnibus (GEO) database, and find that basal cells (BCs) and alveolar type 2 cells (AT2 cells) are important components of lung epithelial cells. Changes in molecular pathways in BCs and AT2 cells may be involved in the common pathogenesis of IPF and LCA. <em>KRT17</em> and <em>S100A14</em> in BCs may promote the IPF co-occurrence with LCA by mediating the EMT. <em>WFDC2</em> and <em>KRT19</em> may be the elements in AT2 cells that activate the EMT process to promote IPF co-occurrence with LCA. In both IPF and LCA, FN1-WNT axis may be involved in the interaction between BCs and AT2 cells. Importantly, the results of immunofluorescence colocalization experiments on tissue samples from patients with IPF and LCA were consistent with these conclusions. Basal-macrophage interactions may have also induced the IPF co-occurrence with LCA via the <em>CYBA</em>-ERK1/2 axis. The regulation of M2 macrophage polarization by <em>JUN/SOD2</em>-glycolysis axis may therefore be involved in the co-morbidity mechanism of IPF and LCA. Therefore, our results suggest that molecular changes in BCs, AT2 cells and macrophages may play important roles in the pathogenesis of IPF co-occurrence with LCA, and the cellular interactions between these cells may be critical for the progression of both diseases.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"448 2","pages":"Article 114578"},"PeriodicalIF":3.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TACO1 facilitates the proliferation and migration of gastric cancer cells via Notch1/Hes1 signaling and is associated with immune cell infiltration TACO1通过Notch1/Hes1信号通路促进胃癌细胞的增殖和迁移，并与免疫细胞浸润有关

IF 3.3 3区生物学

Experimental cell research Pub Date : 2025-04-25 DOI: 10.1016/j.yexcr.2025.114574

Na Li , Zijie Wei , Xiang Li , Jiayu Jian , Lulu Zhou , Siqi Wang , Miao Chen , Yu Cheng

{"title":"TACO1 facilitates the proliferation and migration of gastric cancer cells via Notch1/Hes1 signaling and is associated with immune cell infiltration","authors":"Na Li , Zijie Wei , Xiang Li , Jiayu Jian , Lulu Zhou , Siqi Wang , Miao Chen , Yu Cheng","doi":"10.1016/j.yexcr.2025.114574","DOIUrl":"10.1016/j.yexcr.2025.114574","url":null,"abstract":"<div><div>Translational activator of cytochrome <em>c</em> oxidase 1 (TACO1) is a mitochondrial RNA-binding protein playing a fundamental role in mitochondrial translation. However, no studies to date have evaluated changes in the expression, biological functions, and potential molecular mechanisms of action of TACO1 in gastric cancer. Therefore, we investigated the clinical significance, biological function, and immune system modulation associated with TACO1 in gastric cancer. We found that TACO1 expression was upregulated in gastric cancer and associated with poor prognosis. Mechanistically, TACO1 facilitated gastric cancer cell proliferation and migration through modulation of the Notch1/Hes1 signaling pathways. Moreover, the change in TACO1 expression affected multiple immunological components to regulate the generation of an immunosuppressive tumor microenvironment (TME). In conclusion, we first report on the role of TACO1 in gastric cancer, with findings suggesting that TACO1 could represent a promising prognostic and immunological biomarker for gastric cancer.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"448 2","pages":"Article 114574"},"PeriodicalIF":3.3,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cedrol derivative attenuates muscle atrophy through regulation of myostatin transcription via Ca2+-CaMK-FoxO3a signaling pathways 雪松醇衍生物通过Ca2+-CaMK-FoxO3a信号通路调节肌肉生长抑制素转录，从而减轻肌肉萎缩

IF 3.3 3区生物学

Experimental cell research Pub Date : 2025-04-24 DOI: 10.1016/j.yexcr.2025.114577

Min Ju Kang , Sung Kwan Hwang , Chang Ha Park , Ji Wook Moon , Do Won Kim , Se Eun Bae , Jeong Hyeon Kim , Jeong Min Nam , Su Jin Kim , Jihye Bang , Hyun Joung Lim , Kyung-Ok Uhm , Hyeon Soo Kim

{"title":"Cedrol derivative attenuates muscle atrophy through regulation of myostatin transcription via Ca2+-CaMK-FoxO3a signaling pathways","authors":"Min Ju Kang , Sung Kwan Hwang , Chang Ha Park , Ji Wook Moon , Do Won Kim , Se Eun Bae , Jeong Hyeon Kim , Jeong Min Nam , Su Jin Kim , Jihye Bang , Hyun Joung Lim , Kyung-Ok Uhm , Hyeon Soo Kim","doi":"10.1016/j.yexcr.2025.114577","DOIUrl":"10.1016/j.yexcr.2025.114577","url":null,"abstract":"<div><div>Sarcopenia is a progressive and generalized muscle wasting syndrome characterized by loss of muscle strength and mass. Although many drug candidates have been developed to treat sarcopenia, their results were unsuccessful due to adverse or off-target effects. In this study, we identified a cedrol derivative which is a bioactive sesquiterpene having substantial suppressive effects on muscle atrophy. We demonstrated that the cedrol analog regulated myostatin expression via transcriptional regulation and that the cedrol derivative regulated this expression more effectively than the original form. Cedrol derivative stimulated Ca<sup>2+</sup> via the mouse olfactory receptor 23 (MOR23) and induced interactions between phospho-CaMKII and FoxO3a in a calcium-dependent manner. In animal models, the transcript-level expressions of myostatin and MuRF1 were lower in the extensor digitorum longus (EDL) and soleus muscles of mice fed with cedrol-derivative diet. These findings reveal that cedrol derivative suppresses sarcopenia by inhibiting myostatin and MuRF1 expressions in both in vitro and in vivo models, thus suggesting that cedrol derivatives can be potential therapeutic agents for sarcopenia.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"448 2","pages":"Article 114577"},"PeriodicalIF":3.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

METTL3-m6A methylase regulates the osteo-/odontogenic potential of stem cells from apical papilla via NFIC in apical periodontitis METTL3-m6A甲基化酶通过NFIC调节根尖牙周炎中根尖乳头干细胞的成骨/成牙潜能

IF 3.3 3区生物学

Experimental cell research Pub Date : 2025-04-23 DOI: 10.1016/j.yexcr.2025.114576

Yongna Zhu , Xiang Ge , Zhi Chen , Tingting Chen , Yue Wu , Hebao Wen , Zeyu He , Caiyun Ma

{"title":"METTL3-m6A methylase regulates the osteo-/odontogenic potential of stem cells from apical papilla via NFIC in apical periodontitis","authors":"Yongna Zhu , Xiang Ge , Zhi Chen , Tingting Chen , Yue Wu , Hebao Wen , Zeyu He , Caiyun Ma","doi":"10.1016/j.yexcr.2025.114576","DOIUrl":"10.1016/j.yexcr.2025.114576","url":null,"abstract":"<div><div>Stem cells from the apical papilla (SCAPs) show strong odontogenic ability and can form root dentin. However, the underlying mechanisms that control the odontogenic differentiation of SCAPs in an inflammatory environment need further exploration. In the present study, we explored the regulatory role of METTL3 in the differentiation of SCAPs originating from tooth with apical periodontitis. Stem cells from the apical papilla derived from healthy teeth (SCAPs) and teeth with apical periodontitis (AP-SCAPs) were successfully isolated and cultured. The expressions of tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) were higher in AP-SCAPs. A decrease in METTL3 expression accompanied the decreased osteo-/odontogenic differentiation ability of AP-SCAPs. Exploring the role of METTL3 on the osteo-/odontogenic differentiation of AP-SCAPs revealed that overexpression of METTL3 upregulated the odontogenic ability of AP-SCAPs. However, silencing METTL3 exerted the opposite effect. Overexpression of METTL3 suppressed the expression of TNF-α and IL-6 in AP-SCAPs, whereas knockdown of METTL3 in these cells enhanced TNF-α and IL-6 expression. METTL3 regulates the osteo-/odontogenic differentiation of SCAPs and modulates their inflammatory response. Furthermore, overexpression of METTL3 upregulated the methylation level, mRNA, and protein expression of nuclear factor-IC (NFIC) during mineralization induction. NFIC silencing attenuated osteo-/odontogenic differentiation of METTL3-overexpressed AP-SCAPs. In conclusion, METTL3-mediated-m6A upregulated the odontogenic differentiation of AP-SCAPs via NFIC. This paper elucidates a novel mechanism regulating the odontogenic differentiation of AP-SCAPs, and METTL3 may be a new target for regenerative endodontic treatment.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"448 2","pages":"Article 114576"},"PeriodicalIF":3.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Runx1 activates the transformation of adipocytes into cancer-associated adipocytes by downregulating Plin1 Runx1通过下调Plin1激活脂肪细胞向癌症相关脂肪细胞的转化

IF 3.3 3区生物学

Experimental cell research Pub Date : 2025-04-23 DOI: 10.1016/j.yexcr.2025.114573

Boning Guo , Kai Wang , Jing Wu , Huimin Yu , Chong Geng , Yi Jin , Yongfeng Song

{"title":"Runx1 activates the transformation of adipocytes into cancer-associated adipocytes by downregulating Plin1","authors":"Boning Guo , Kai Wang , Jing Wu , Huimin Yu , Chong Geng , Yi Jin , Yongfeng Song","doi":"10.1016/j.yexcr.2025.114573","DOIUrl":"10.1016/j.yexcr.2025.114573","url":null,"abstract":"<div><div>Adipocytes play a pivotal role in the breast tumor microenvironment, with the capacity to differentiate into cancer-associated adipocytes (CAAs) under the influence of breast cancer cells. This transformation significantly contributes to the formation and progression of breast cancer; however, the mechanisms underlying this interaction remain poorly understood. This study aims to illuminate these interactions by establishing an <em>in vitro</em> co-culture system of mature adipocytes and breast cancer cells. RNA sequencing analysis identified elevated runt-related transcription factor 1 (<em>Runx1</em>) expression in CAAs. Furthermore, <em>Runx1</em> expression was also increased in the peritumoral adipose tissue of both breast cancer mouse models and clinical patient samples. Overexpression of <em>Runx1</em> in 3T3-L1 preadipocytes resulted in reduced adipocyte volume, decreased lipid droplet size, diminished expression of mature adipocyte markers, and an increase in pro-inflammatory factor levels. These findings suggest that <em>Runx1</em> overexpression facilitates the transformation of adipocytes into CAAs, thereby enhancing breast cancer cell migration and invasion. Conversely, <em>Runx1</em> knockdown in CAAs diminished their supportive role in cancer progression. Mechanically, <em>Runx1</em> enhances breast cancer development by regulating perilipin 1 (<em>Plin1</em>) levels, the overexpression of <em>Plin1</em> in adipocytes inhibited the effect of <em>R</em><em>unx</em><em>1</em> to promote the transition of adipocytes into CAAs. Our findings propose that targeting <em>Runx1</em> in CAAs may represent a novel therapeutic strategy for breast cancer intervention.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"448 2","pages":"Article 114573"},"PeriodicalIF":3.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ionizing radiation induces mild and dose-independent damage to mitochondria in newt cells 电离辐射对蝾螈细胞的线粒体造成轻度和剂量无关的损伤

IF 3.3 3区生物学

Experimental cell research Pub Date : 2025-04-23 DOI: 10.1016/j.yexcr.2025.114575

Md Mahmudul Hasan , Tsuyoshi Kawabata , Chen Yan , Reiko Sekiya , Shinji Goto , Yoshishige Urata , Tao-Sheng Li

{"title":"Ionizing radiation induces mild and dose-independent damage to mitochondria in newt cells","authors":"Md Mahmudul Hasan , Tsuyoshi Kawabata , Chen Yan , Reiko Sekiya , Shinji Goto , Yoshishige Urata , Tao-Sheng Li","doi":"10.1016/j.yexcr.2025.114575","DOIUrl":"10.1016/j.yexcr.2025.114575","url":null,"abstract":"<div><div>In addition to remarkable regenerative abilities, newts demonstrate a heightened tolerance to radiation compared to mammals. Mitochondria play profound role in cell survival when cells undergo environmental stresses. Thus, our study sought to elucidate the impact of ionizing radiation (IR) on the mitochondria of a newt model <em>Pleurodeles waltl</em>. Primary cells derived from limb tissue of <em>P. waltl</em> were exposed to 0, 5, 10, or 15 Gy X-ray and analyzed at 24h post-irradiation (PIR). Analysis using MitoTracker Red labeling revealed a maximal (p < 0.001) in mitochondrial fission in cells exposed to 5 Gy IR, while mitochondrial fission in cells exposed to 10 and 15 Gy IR was comparable (p < 0.01). Mitochondrial superoxide levels increased in a reverse dose-dependent manner; notably, cells treated with 5 Gy IR produced significantly (p < 0.05) higher mitochondrial superoxide. Mitochondrial membrane potential (<em>ΔΨm</em>) decreased significantly (p < 0.01) with similar extent across all IR-treated groups. Though <em>ΔΨm</em> declined, the ATP content was not changed due to IR. Result from the MTT assay indicated no impairment in mitochondrial activity. Cell counting data suggest negligible impact of IR on viability of cells; however, the phase contrast imaging revealed senescent like morphology of cells. Taken together, cells of <em>P. waltl</em> show mild changes in morphology and function of the mitochondria in response to IR, but seem highly tolerant.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"448 2","pages":"Article 114575"},"PeriodicalIF":3.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

UPRmt alleviates bone cancer pain through the restoration of mitochondrial function upmt通过恢复线粒体功能减轻骨癌疼痛

IF 3.3 3区生物学

Experimental cell research Pub Date : 2025-04-22 DOI: 10.1016/j.yexcr.2025.114568

Dan Li , Mingming Xie , Haohao Zeng , Jiacheng Yu , Rui Xu , Zhen Wang , Yulin Huang , Yan Yang , Yu'e Sun

{"title":"UPRmt alleviates bone cancer pain through the restoration of mitochondrial function","authors":"Dan Li , Mingming Xie , Haohao Zeng , Jiacheng Yu , Rui Xu , Zhen Wang , Yulin Huang , Yan Yang , Yu'e Sun","doi":"10.1016/j.yexcr.2025.114568","DOIUrl":"10.1016/j.yexcr.2025.114568","url":null,"abstract":"<div><div>The mitochondrial unfolded protein response (UPR<sup>mt</sup>) is an intracellular retrograde signaling process that facilitates the restoration of mitochondrial homeostasis. Mitochondria are essential for neuronal signaling, and their dysfunction has been implicated as a significant mechanism in the development of chronic pain. Nevertheless, little is known about the exact function of UPR<sup>mt</sup> in bone cancer pain (BCP). This research intended to explore the connection between UPR<sup>mt</sup> and the progression of BCP. In BCP group, the ultrastructure of spinal cord mitochondria was disrupted, accompanied by a decline in ATP levels and a decrease in Mitochondrial membrane potential (MMP). Concurrently, mRNA and protein levels of UPR<sup>mt</sup> marker proteins (Atf5, Hsp60, LonP1, and ClpP) were upregulated, with the expression of Atf5, a key transcription factor of UPR<sup>mt</sup>, notably enhanced in spinal dorsal horn neurons. Nicotinamide riboside (NR)-mediated pharmacological augmentation of the UPR<sup>mt</sup> significantly alleviated BCP-induced nociceptive hypersensitivity, as demonstrated by elevated mechanical withdrawal thresholds and diminished spontaneous flinching behavior. Concomitant mitochondrial functional recovery was evidenced by restoration of MMP and normalization of ATP level. Notably, genetic knockdown of activating transcription factor 5 (Atf5) abolished both NR-induced UPR<sup>mt</sup> activation and the consequent protection against rotenone-mediated mitochondrial dysfunction. These findings establish UPR<sup>mt</sup> potentiation as an effective strategy for ameliorating mitochondrial dysfunction and attenuating BCP-associated nociception, proposing this pathway as a novel therapeutic target for clinical pain management.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"448 2","pages":"Article 114568"},"PeriodicalIF":3.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0