Cell and Bioscience最新文献_第3页

CircRNA Itm2b induces oxidative stress via the interaction with Sirt1-Nox4 to aggravate sleep disturbances after traumatic brain injury. CircRNA Itm2b通过与Sirt1-Nox4相互作用诱导氧化应激，从而加重脑外伤后的睡眠障碍。

IF 6.1 2区生物学

Cell and Bioscience Pub Date : 2025-02-17 DOI: 10.1186/s13578-025-01353-6

Jiayuanyuan Fu, Mengran Du, Biying Wu, Chenrui Wu, Xin Li, Weilin Tan, Xuekang Huang, Ziyu Zhu, Jie Zhang, Zheng Bu Liao

{"title":"CircRNA Itm2b induces oxidative stress via the interaction with Sirt1-Nox4 to aggravate sleep disturbances after traumatic brain injury.","authors":"Jiayuanyuan Fu, Mengran Du, Biying Wu, Chenrui Wu, Xin Li, Weilin Tan, Xuekang Huang, Ziyu Zhu, Jie Zhang, Zheng Bu Liao","doi":"10.1186/s13578-025-01353-6","DOIUrl":"10.1186/s13578-025-01353-6","url":null,"abstract":"Sleep disorders (SD) are common sequelae following traumatic brain injury (TBI) and may be linked to mitochondrial oxidative stress dysregulation after TBI. Increasing evidence showed that circRNAs play crucial roles in nervous system diseases. However, the involvement of circRNAs in sleep disturbances after TBI is not characterized. In this study, differentially expressed circRNAs were identified by RNA sequencing. Sleep quality in TBI patients was assessed through sleep scales and electroencephalograms. Further experiments were conducted to investigate the role of circItm2b. We found that circItm2b was elevated and involved sleep disorder in TBI patients. Over-expression of circItm2b might aggravate sleep disturbances in mice after TBI. Mechanically, circItm2b regulates Nox4 expression through binding Sirt1, which influences mitochondrial oxidative stress-caused circadian protein losses. Moreover, the knockdown of circItm2b attenuated mitochondrial oxidative stress-induced circadian proteins losses via circItm2b/Sirt1/Nox4 axis after TBI, which might suggest that circItm2b may serve as a prognostic marker for improving sleep disorders and represent a promising therapeutic target for TBI-related sleep disturbances.","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"21"},"PeriodicalIF":6.1,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multi-pathway targeted therapy of MASH-HCC using miR-22. 利用miR-22多途径靶向治疗MASH-HCC。

IF 6.1 2区生物学

Cell and Bioscience Pub Date : 2025-02-14 DOI: 10.1186/s13578-025-01352-7

Ying Hu, Tahereh Setayesh, Dongguang Wei, Trenton Testerman, Yutong Ji, Yu-Jui Yvonne Wan

{"title":"Multi-pathway targeted therapy of MASH-HCC using miR-22.","authors":"Ying Hu, Tahereh Setayesh, Dongguang Wei, Trenton Testerman, Yutong Ji, Yu-Jui Yvonne Wan","doi":"10.1186/s13578-025-01352-7","DOIUrl":"10.1186/s13578-025-01352-7","url":null,"abstract":"Background: The treatment options for hepatocellular carcinoma (HCC) are limited, and there is no effective drug that can improve long-term survival rates. Complicated cocktails consisting of multiple medications with toxicities are frequently used to treat cancer. The current study addresses these challenges.Methods: The study uses metabolic dysfunction-associated steatohepatitis (MASH)-HCC and HCC mouse models established by transfecting the livers using myr-AKT1, NRasV12, and Sleeping Beauty transposase. AAV8-miR-22 was delivered to MASH-HCC and HCC to study its preventive and therapeutic effects. Spatial transcriptomic profiling revealed the signaling pathways affected by miR-22 according to histological locations.Results: miR-22 treatment effectively treated MASH-HCC and HCC. Treating mice with miR-22 before tumor initiation prevented oncogenesis. The promising anti-cancer effects were revealed by reduced tumor load, fibrosis, and splenomegaly, extending the survival time. miR-22 treatment generated anti-tumor immunity. The favorable treatment outcomes were accompanied by a reduction in dendritic cells, T and B cells, and plasma cells, which were expanded inside the tumors of MASH-HCC. In all animal trials, miR-22 improved metabolism and reduced glycolysis inside the tumors. Moreover, miR-22 profoundly inhibited extracellular matrix (ECM) and targeted MET, PDGF, tyrosine kinase signaling, and IGF pathways inside the tumors. Furthermore, the roles of miR-22 in blocking collagen formation and cross-assembly of collagen fibrils could be due to miR-22's effects in inhibiting Rho GTPase pathways, revealed at the tumor margin.Conclusion: miR-22 generates anti-HCC effects by targeting many critical pathways in liver carcinogenesis in cancer and tumorigenic niches, potentially revolutionizing HCC treatment.","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"20"},"PeriodicalIF":6.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genome-wide association study of the fatty liver index in the Taiwanese population reveals shared and population-specific genetic risk factors across ethnicities. 台湾人群脂肪肝指数的全基因组关联研究揭示了不同种族之间共有的和特定人群的遗传风险因素。

IF 6.1 2区生物学

Cell and Bioscience Pub Date : 2025-02-08 DOI: 10.1186/s13578-025-01346-5

Pei Pei Lau, Chun-Yu Wei, Min-Rou Lin, Wan-Hsuan Chou, Yu-Jui Yvonne Wan, Wei-Chiao Chang

{"title":"Genome-wide association study of the fatty liver index in the Taiwanese population reveals shared and population-specific genetic risk factors across ethnicities.","authors":"Pei Pei Lau, Chun-Yu Wei, Min-Rou Lin, Wan-Hsuan Chou, Yu-Jui Yvonne Wan, Wei-Chiao Chang","doi":"10.1186/s13578-025-01346-5","DOIUrl":"10.1186/s13578-025-01346-5","url":null,"abstract":"Background and objectives: Although the incidence of fatty liver disease (FLD) is increasing worldwide, the genetic basis of this disease is not fully understood. This study uses the fatty liver index (FLI) to identify and compare genetic variants associated with FLD in Taiwanese and European populations.Results: In this study, a total of 145,356 Taiwan Biobank participants were included in the discovery analysis. Subjects with elevated FLI were found to have a significantly greater risk of developing FLD, as confirmed by imaging data (OR: 4.43; 95% CI: 3.88-5.06). Through genome-wide association studies (GWAS), we identified 6 variants previously associated with nonalcoholic fatty liver disease (NAFLD) and validated 50 shared risk variants located in ZPR1 and FTO between the Taiwanese and European populations. Conditional analysis of 423 significant variants from FLI-defined FLD further revealed 16 independent variants within 14 genes. Pathway analysis of GWAS significant genes revealed that lipid metabolism and the peroxisome proliferator-activated receptor (PPAR) signaling pathway are causes of hepatic fat accumulation.Conclusion: This study identified six independent NAFLD-associated variants in GCKR, LPL, TRIB1AL, and FTO and emphasized ZPR1 and FTO as shared risk genes for FLI-defined FLD in both Taiwanese and European populations. These findings support the utility of the FLI for FLD prediction, provide new genetic insights, and reveal the common genetic pathways of FLD across two ethnic groups. This research offers a valuable framework for advancing personalized medicine and therapeutic strategies for FLD.","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"19"},"PeriodicalIF":6.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TOPBP1 as a potential predictive biomarker for enhanced combinatorial efficacy of olaparib and AZD6738 in PDAC. TOPBP1 是奥拉帕利和 AZD6738 在 PDAC 中增强联合疗效的潜在预测性生物标记物。

IF 6.1 2区生物学

Cell and Bioscience Pub Date : 2025-02-07 DOI: 10.1186/s13578-025-01350-9

Xiao-Mei Tang, Min-Min Shi, Jia-Cheng Wang, Yi-Jin Gu, Yu-Ting Dai, Qin-Xin Yang, Jia Liu, Ling-Jie Ren, Xin-Yun Liu, Chun Yang, Fang-Fang Ma, Ji-Bing Liu, Hong Yu, Da Fu, Yun-Feng Wang

{"title":"TOPBP1 as a potential predictive biomarker for enhanced combinatorial efficacy of olaparib and AZD6738 in PDAC.","authors":"Xiao-Mei Tang, Min-Min Shi, Jia-Cheng Wang, Yi-Jin Gu, Yu-Ting Dai, Qin-Xin Yang, Jia Liu, Ling-Jie Ren, Xin-Yun Liu, Chun Yang, Fang-Fang Ma, Ji-Bing Liu, Hong Yu, Da Fu, Yun-Feng Wang","doi":"10.1186/s13578-025-01350-9","DOIUrl":"10.1186/s13578-025-01350-9","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and often lethal malignancy, requiring the development of enhanced therapeutic approaches. The DNA damage response (DDR) pathway is frequently altered during PDAC development, leading to an increased occurrence of DNA damage. DNA topoisomerase II-binding protein 1 (TOPBP1) plays a supportive role in regulating the DDR pathway, and its overexpression has been linked to the tumorigenesis of various cancers. This study investigated the biological role of TOPBP1 in PDAC pathogenesis and evaluated its clinical relevance in guiding treatment regimens. We examined the relationship between TOPBP1 expression, DDR pathway modulation, and therapeutic response in PDAC cell lines, primary cells, and subcutaneous mouse models. We found that elevated TOPBP1 expression was positively correlated with increased histologic grade and reduced patient survival in PDAC. TOPBP1 knockdown increased the sensitivity of PDAC cells to olaparib treatment and improved therapeutic efficacy in both PDAC cell lines and subcutaneous mouse models. Combination treatment with olaparib and AZD6738 effectively induced P53-dependent apoptosis via inhibiting the ATR pathway and enhancing signaling through the ATM pathway, which significantly reduced the viability of pancreatic cell lines. Notably, this combination therapy was more effective in PDAC cell lines exhibiting high TOPBP1 expression, indicating that TOPBP1 may serve as a useful predictive biomarker. In conclusion, TOPBP1 is a potential marker for optimizing the olaparib and AZD6738 combination therapy in PDAC. This study highlights the clinical significance of TOPBP1 in the treatment of PDAC and emphasizes the potential implications for a broader population of patients.","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"17"},"PeriodicalIF":6.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparison of characteristics and immune responses between paired human nasal and bronchial epithelial organoids. 配对人鼻和支气管上皮类器官特征和免疫应答的比较。

IF 6.1 2区生物学

Cell and Bioscience Pub Date : 2025-02-07 DOI: 10.1186/s13578-024-01342-1

Lu Zhu, Wenhao Yang, Jiaxin Luo, Danli Lu, Yanan Hu, Rui Zhang, Yan Li, Li Qiu, Zelian Chen, Lina Chen, Hanmin Liu

{"title":"Comparison of characteristics and immune responses between paired human nasal and bronchial epithelial organoids.","authors":"Lu Zhu, Wenhao Yang, Jiaxin Luo, Danli Lu, Yanan Hu, Rui Zhang, Yan Li, Li Qiu, Zelian Chen, Lina Chen, Hanmin Liu","doi":"10.1186/s13578-024-01342-1","DOIUrl":"10.1186/s13578-024-01342-1","url":null,"abstract":"Background: The nasal epithelium, as part of a continuous and integrated airway epithelium, provides a more accessible sample source than the bronchial epithelium. However, the similarities and differences in gene expression patterns and immune responses between these two sites have not been extensively studied.Results: Four lines of matched nasal and bronchial airway epithelial cells obtained from the four patients were embedded in Matrigel and cultured in thechemically defined medium to generate patient-derived nasal organoids (NO) and bronchial organoids (BO). Histologic examination of nasal organoid tissue revealed high similarity and a reduced ciliary beat frequency compared to bronchial organoid tissue. Whole exome sequencing revealed that over 99% of single nucleotides were shared between the NO and matched BO and there was a 95% overlap in their RNA transcriptomes. RNA sequencing analysis of differentially expressed genes indicated a significant reduction in the immune response in NO. RSV infection revealed more productive replication in NO, with a downregulated immune pathway identified by RNA sequencing analysis and upregulated levels of pro-inflammatory cytokines in culture supernatants in NO compared to BO.Conclusions: NO and BO serve as robust in vitro models, faithfully recapitulating the biological characteristics of upper respiratory epithelial cells. The different regions of respiratory epithelial cells exhibit distinct immune responses, underscoring their complementary roles in exploring airway immune mechanisms and disease pathophysiology.","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"18"},"PeriodicalIF":6.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comprehensive landscape and oncogenic role of extrachromosomal circular DNA in malignant biliary strictures. 染色体外环状DNA在恶性胆道狭窄中的综合表现及其致癌作用。

IF 6.1 2区生物学

Cell and Bioscience Pub Date : 2025-02-07 DOI: 10.1186/s13578-025-01361-6

Zhuo Cheng, Xuanmei Luo, Wenzheng Liu, Xiaofang Lu, Hong Chang, Yingchun Wang, Wei Zheng, Xiue Yan, Yonghui Huang

{"title":"Comprehensive landscape and oncogenic role of extrachromosomal circular DNA in malignant biliary strictures.","authors":"Zhuo Cheng, Xuanmei Luo, Wenzheng Liu, Xiaofang Lu, Hong Chang, Yingchun Wang, Wei Zheng, Xiue Yan, Yonghui Huang","doi":"10.1186/s13578-025-01361-6","DOIUrl":"10.1186/s13578-025-01361-6","url":null,"abstract":"Background: Extrachromosomal circular DNA (eccDNA) is crucial for carcinogenesis and bile has direct contact with malignant biliary strictures, yet eccDNA features in bile and its function in malignant biliary strictures remain underexplored.Results: We observed the widespread presence of eccDNA in bile and systematically profiled the landscape of bile cell-free eccDNA (bcf-eccDNA). For functional exploration, a simple and efficient workflow was designed to synthesize large eccDNA particularly containing multiple regions. Compared with the noncancer group, bcf-eccDNAs in the cancer group had different origins and larger sizes with six characteristic peaks. These peaks were also identified in the validation cohort (100%). There were more bcf-eccDNA carrying LINC00598 or CELF2 in malignant biliary strictures, showing potential diagnostic performance in training and validation cohorts (all AUCs > 0.9). Bcf-eccDNAs carried cancer-related mutations, which could guide treatment. EccDNA carrying miR-106a/363 cluster or miR-374b/421 cluster were proven to regulate cancer gene expression, accelerate tumor proliferation, and inhibit tumor apoptosis.Conclusions: This study profiles a comprehensive bcf-eccDNA landscape in patients with biliary strictures and offers valuable insights into eccDNA's role in bile liquid biopsy and carcinogenesis.","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"16"},"PeriodicalIF":6.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11804034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plectin, a novel regulator in migration, invasion and adhesion of ovarian cancer. 一种新的卵巢癌迁移、侵袭和粘附调节因子。

IF 6.1 2区生物学

Cell and Bioscience Pub Date : 2025-02-06 DOI: 10.1186/s13578-025-01349-2

Lanning Bai, Xueqian Qian, Hui Zhang, Yi Yuan, Xiaodong Cui, Min Cheng, Yangyang Han

引用次数: 0

Epsin3 promotes non-small cell lung cancer progression via modulating EGFR stability. Epsin3通过调节EGFR稳定性促进非小细胞肺癌的进展。

IF 6.1 2区生物学

Cell and Bioscience Pub Date : 2025-02-05 DOI: 10.1186/s13578-025-01358-1

Huiling Su, Jie Shen, Chenzi Gao, Yue Zhao, Wanyu Deng, Bo Qin, Xin Zhang, Juan Lai, Qian Wang, Jie Dou, Min Guo

{"title":"Epsin3 promotes non-small cell lung cancer progression via modulating EGFR stability.","authors":"Huiling Su, Jie Shen, Chenzi Gao, Yue Zhao, Wanyu Deng, Bo Qin, Xin Zhang, Juan Lai, Qian Wang, Jie Dou, Min Guo","doi":"10.1186/s13578-025-01358-1","DOIUrl":"10.1186/s13578-025-01358-1","url":null,"abstract":"Background: The abnormal expression and overactivation of the epidermal growth factor receptor (EGFR), a typical cancer marker for non-small cell lung cancer (NSCLC), are closely related to the tumorigenesis and progression of NSCLC. However, the endocytosis mechanism of EGFR in lung cancer is not yet known. Epsin3 (EPN3), a member of the endocytic adaptor protein family, is essential for the endocytosis of multiple receptors. In this study, we aimed to investigate the role of EPN3 in modulating EGFR function, its effects on NSCLC progression, and its potential involvement in tyrosine kinase inhibitor (TKI) resistance, which remains a significant hurdle in NSCLC treatment.Results: Our findings revealed that the expression of EPN3 is significantly up-regulated in NSCLC patients. Elevated EPN3 expression was proportional to shorter overall survival in patients with NSCLC. Functional analyses revealed that EPN3 directly interacts with EGFR, enhancing its recycling to the plasma membrane and preventing its degradation via the lysosomal pathway. This stabilization of EGFR led to sustained downstream signalling, promoting NSCLC cell proliferation and migration. Notably, mutations in the EGFR tyrosine kinase domain, which typically confer resistance to TKIs, did not alter the regulatory effect of EPN3.Conclusions: EPN3 enhances EGFR signalling by promoting its recycling and stability, contributing to NSCLC progression and TKI resistance. Targeting EPN3 could offer a novel therapeutic strategy to overcome drug resistance in EGFR-driven NSCLC.","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"14"},"PeriodicalIF":6.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Classifications of triple-negative breast cancer: insights and current therapeutic approaches. 三阴性乳腺癌的分类：见解和当前的治疗方法。

IF 6.1 2区生物学

Cell and Bioscience Pub Date : 2025-02-01 DOI: 10.1186/s13578-025-01359-0

Ziqi Chen, Yumeng Liu, Minchuan Lyu, Chi Ho Chan, Meiheng Sun, Xin Yang, Shuangying Qiao, Zheng Chen, Sifan Yu, Meishen Ren, Aiping Lu, Ge Zhang, Fangfei Li, Yuanyuan Yu

{"title":"Classifications of triple-negative breast cancer: insights and current therapeutic approaches.","authors":"Ziqi Chen, Yumeng Liu, Minchuan Lyu, Chi Ho Chan, Meiheng Sun, Xin Yang, Shuangying Qiao, Zheng Chen, Sifan Yu, Meishen Ren, Aiping Lu, Ge Zhang, Fangfei Li, Yuanyuan Yu","doi":"10.1186/s13578-025-01359-0","DOIUrl":"10.1186/s13578-025-01359-0","url":null,"abstract":"Triple-negative breast cancer (TNBC) is an aggressive and challenging type of cancer, characterized by the absence of specific receptors targeted by current therapies, which limits effective targeted treatment options. TNBC has a high risk of recurrence and distant metastasis, resulting in lower survival rates. Additionally, TNBC exhibits significant heterogeneity at histopathological, proteomic, transcriptomic, and genomic levels, further complicating the development of effective treatments. While some TNBC subtypes may initially respond to chemotherapy, resistance frequently develops, increasing the risk of aggressive recurrence. Therefore, precisely classifying and characterizing the distinct features of TNBC subtypes is crucial for identifying the most suitable molecular-based therapies for individual patients. In this review, we provide a comprehensive overview of these subtypes, highlighting their unique profiles as defined by various classification systems. We also address the limitations of conventional therapeutic approaches and explore innovative biological strategies, all aimed at advancing the development of targeted and effective therapeutic strategies for TNBC.","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"13"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nociceptor-localized KCC2 suppresses brachial plexus avulsion-induced neuropathic pain and related central sensitization. 伤害感受器定位的KCC2抑制臂丛撕脱引起的神经性疼痛和相关的中枢致敏。

IF 6.1 2区生物学

Cell and Bioscience Pub Date : 2025-01-31 DOI: 10.1186/s13578-025-01354-5

Hang Xian, Huan Guo, Yuan-Ying Liu, Sui-Bin Ma, Rui Zhao, Jian-Lei Zhang, Hang Zhang, Rou-Gang Xie, Xu-Cheng Guo, Jie Ren, Sheng-Xi Wu, Ceng Luo, Rui Cong

{"title":"Nociceptor-localized KCC2 suppresses brachial plexus avulsion-induced neuropathic pain and related central sensitization.","authors":"Hang Xian, Huan Guo, Yuan-Ying Liu, Sui-Bin Ma, Rui Zhao, Jian-Lei Zhang, Hang Zhang, Rou-Gang Xie, Xu-Cheng Guo, Jie Ren, Sheng-Xi Wu, Ceng Luo, Rui Cong","doi":"10.1186/s13578-025-01354-5","DOIUrl":"10.1186/s13578-025-01354-5","url":null,"abstract":"Lack in understanding of the mechanism on brachial plexus avulsion (BPA)-induced neuropathic pain (NP) is the key factor restricting its treatment. In the current investigation, we focused on the nociceptor-localized K+-Cl- cotransporter 2 (KCC2) to investigate its role in BPA-induced NP and related pain sensitization. A novel mice model of BPA on the middle trunk (C7) was established, and BPA mice showed a significant reduction in mechanical withdrawal threshold of the affected fore- and hind- paws without affecting the motor function through CatWalk Gait analysis. Decreased expression of KCC2 in dorsal root ganglion (DRG) was detected through Western blot and FISH technology after BPA. Overexpression of KCC2 in DRG could reverse the hyperexcitability of DRG neurons and alleviate the pain of BPA mice synchronously. Meanwhile, the calcium response signal of the affected SDH could be significantly reduced through above method using spinal cord fiber photometry. The synthesis and release of brain-derived neurotrophic factor (BDNF) was also proved reduction through overexpression of KCC2 in DRG, which indicates BDNF can also act as the downstream role in this pain state. As in human-derived tissues, we found decreased expression of KCC2 and increased expression of BDNF and TrκB in avulsed roots of BPA patients compared with normal human DRGs. Our results indicate that nociceptor-localized KCC2 can suppress BPA-induced NP, and peripheral sensitization can be regulated to reverse central sensitization by targeting KCC2 in DRG at the peripheral level through BDNF signaling. The consistent results in both humanity and rodents endow great potential to future transformation of clinical practice.","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"12"},"PeriodicalIF":6.1,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0