Cell Biology and Toxicology最新文献

{"title":"Myeloid cells are involved in tumor immunity, metastasis and metabolism in tumor microenvironment.","authors":"Chenbo Zhang, Ying Song, Huanming Yang, Kui Wu","doi":"10.1007/s10565-025-10012-y","DOIUrl":"10.1007/s10565-025-10012-y","url":null,"abstract":"<p><p>Bone marrow-derived cells in the tumor microenvironment, including macrophages, neutrophils, dendritic cells, myeloid-derived suppressor cells, eosinophils and basophils, participate in the generation, development, invasion and metastasis of tumors by producing different cytokines and interacting with other cell types, and play a pro-tumor or anti-tumor role in regulating tumor immunity. Due to the complexity of cell types in the tumor microenvironment and the unknown process of tumor development and metastasis, cancer treatment to achieve better survival status remains challenging. In this article, we summarize the effects of myeloid cells in tumor microenvironment on tumor immunity, cancer migration, and crosstalk with metabolism (including glucose metabolism, lipid metabolism, and amino acid metabolism), which will help to further study the tumor microenvironment and seek targeted therapeutic strategies for patients.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"62"},"PeriodicalIF":5.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CUL1-neddylation contributes to K29-linked ubiquitination on p27 for autophagic degradation in sorafenib-resistant liver cancer.","authors":"Haitao Xu, Shaoyue Zheng, Qiuqi Zhang, Ying Xu, Hanbo Zhang, Tianming Hu, Xiaoling Zhang, Jiaoting E, Xuedong Li, Ruitao Wang, Hongyan Liu, Rui Xie","doi":"10.1007/s10565-025-10008-8","DOIUrl":"10.1007/s10565-025-10008-8","url":null,"abstract":"<p><p>Sorafenib has demonstrated great efficacy in liver cancer, however, its application as first-line treatment has been hampered due to the emerging drug resistance. This study is aimed to investigate the mechanism underlying acquired sorafenib resistance in liver cancer. Based on GSE109211 and TCGA datasets, bioinformatics analysis was conducted to find the potential genes implicated in the sorafenib resistance in liver cancer. mCherry-/eGFP-LC3B dual-fluorescent system was used to assess autophagic state. Wild and mutant types of HA-labeled ubiquitin (K27, K29, K33, K48, K63, K29R and K48R) were used to identify the type of polyubiquitin chains added to p27 by CUL1. Herein, we identified that F-box protein (SCF) ubiquitin ligase complexes (CUL1 and SKP2) and NEDD8 were highly expressed in sorafenib-resistant tissues using both the public data and clinical samples. NEDD8-mediated CUL1 neddylation enhanced SCF ubiquitin ligase complex to target p27 and subsequently linked K29-linked polyubiquitin chains to p27. Furthermore, NBR1 facilitated the degradation of ubiquitinated p27 protein by enhancing autophagy flux. Knocking down of CUL1 could prevent ubiquitination- and autophagy-mediated p27 protein degradation. The resistance to sorafenib was suppressed with CUL1 knockdown both in vitro and in vivo. In conclusion, our findings indicated that blocking neddylation or autophagy can restore drug sensitivity, thus providing a potential strategy for overcoming sorafenib resistance in the future.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"61"},"PeriodicalIF":5.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Olfactory mucosal mesenchymal stem cell-derived exosome Lnc A2M-AS1 ameliorates oxidative stress by regulating TP53INP1-mediated mitochondrial autophagy through interacting with IGF2BP1 in Parkinson's diseases.","authors":"Jiangshan Zhang, Chuang Wang, Guoshuai Yang, Yanhui Zhou, Dan Hou, Ying Xia","doi":"10.1007/s10565-025-10009-7","DOIUrl":"10.1007/s10565-025-10009-7","url":null,"abstract":"<p><strong>Background: </strong>Exosome Lnc A2M-AS1 from olfactory mucosa mesenchymal stem cells (OM-MSCs) can ameliorate oxidative stress by improving mitophagy in cardiomuscular cells; however, it remains unclear whether this effect exists in the brain tissues of patients with Parkinson's disease (PD).</p><p><strong>Methods: </strong>OM-MSC-Exosomes were isolated and verified based on morphology and specific biomarkers. The effects of OM-MSC-Exo on mitochondrial autophagy, oxidative stress, and lncRNA A2M-AS1 were detected in MPP⁺-treated HT22 cells. The effects of OM-MSC-Exos on mitochondrial autophagy and oxidative stress were detected in an MPTP-induced Parkinson's disease (PD) model in C57BL/6 mice. The interaction between IGF2BP1, A2M-AS1, and TP53INP1 was assessed via RNA pull-down/RNA Immunoprecipitation and RNA stability assays. The effects of lnc A2M-AS1 on IGF2BP1/TP53INP1-mediated mitochondrial autophagy and oxidative stress were verified in MPP⁺-treated HT22 cells and MPTP-induced PD mouse models.</p><p><strong>Results: </strong>Exosomes isolated from olfactory mucosa mesenchymal stem cells were found to be rich in Lnc A2M-AS1. Lnc A2M-AS1 was proved to be able to ameliorate oxidative stress induced by MPP⁺ in HT22 cells. lncRNA A2M-AS1 regulates oxidative stress by enhancing mitophagy in HT22 cells. In addition, lncRNA A2M-AS1 induced mitophagy through TP53INP1 and mediated TP53INP1 expression by binding to IGF2BP1. Furthermore, OM-MSC-Exo and Lnc A2M-AS1 treatment improved symptoms and ameliorated oxidative stress in MPTP-induced PD mouse models.</p><p><strong>Conclusion: </strong>Collectively, lncRNA A2M-AS1 from OM-MSC-derived exosomes regulates TP53INP1 expression by targeting IGF2BP1 to induce mitophagy and ameliorate oxidative stress. OM-MSC-derived exosomes could potentially serve as promising candidates for new treatment methods for PD.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"60"},"PeriodicalIF":5.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosome-mediated effects of BRCA1 on cardiovascular artery disease.","authors":"Hairui Yu, Dong Wei, Weiqian Liao, Xiaoming Shang, Dandan Li, Chunzhao Liu, Qimei Deng, Haiquan Huangfu","doi":"10.1007/s10565-025-09996-4","DOIUrl":"10.1007/s10565-025-09996-4","url":null,"abstract":"<p><p>The progression of coronary artery disease atherosclerosis (CAD) is closely associated with cardiomyocyte apoptosis and inflammatory responses. This study focused on investigating the impact of BRCA1 in exosomes (Exo) derived from M1 macrophages on CAD. Through the analysis of single-cell RNA-seq datasets, significant communication between macrophages and cardiomyocytes in CAD patients was observed. BRCA1, identified as a significant apoptosis-related gene, was pinpointed through the assessment of differential gene expression and weighted gene co-expression network analysis (WGCNA). Experimental procedures involved BRCA1 lentivirus transfection of M1 macrophages, isolation of Exo for application to cardiomyocytes and smooth muscle cells, cell viability assessments, and characterization of Exo. The results showed that BRCA1-Exo from M1 macrophages induced cardiomyocyte apoptosis and affected smooth muscle cell behavior. In vivo studies further supported the exacerbating effects of BRCA1-Exo on CAD progression. Overall, the involvement of Exo carrying BRCA1 from M1 macrophages is evident in the induction of cardiomyocyte apoptosis and the regulation of smooth muscle cell behaviors, thereby contributing to CAD atherosclerosis progression. These findings unveil novel molecular targets that could have potential implications for CAD treatment strategies.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"59"},"PeriodicalIF":5.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted nanoparticle delivery system for tumor-associated macrophage reprogramming to enhance TNBC therapy.","authors":"Xiaoshen Dong, Xiaoou Wang, Xinyu Zheng, Haiyang Jiang, Lu Liu, Ningye Ma, Shuo Wang","doi":"10.1007/s10565-025-10001-1","DOIUrl":"10.1007/s10565-025-10001-1","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) poses as a daunting and intricate manifestation of breast cancer, highlighted by few treatment options and a poor outlook. The crucial element in fostering tumor growth and immune resistance is the polarization of tumor-associated macrophages (TAMs) into the M2 state within the tumor microenvironment (TME). To address this, we developed M2 targeting peptide-chitosan-curcumin nanoparticles (M2pep-Cs-Cur NPs), a targeted delivery system utilizing chitosan (Cs) as a carrier, curcumin (Cur) as a therapeutic agent, and targeting peptides for specificity. These NPs effectively inhibited TNBC cell proliferation (~ 70%) and invasion (~ 70%), while increasing the responsiveness of tumors to anti-PD-L1 treatment (~ 50% survival enhancement) in vitro and in vivo. Bioinformatics analysis suggested that Cur modulates TAM polarization by influencing key genes such as COX-2, offering insights into its underlying mechanisms. This study highlights the potential of M2pep-Cs-Cur NPs to reverse M2 polarization in TAMs, providing a promising targeted therapeutic strategy to overcome immunotherapy resistance and improve TNBC outcomes.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"58"},"PeriodicalIF":5.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic changes in oxidative stress, immunity, and cancer pathways caused by cannabis vapor on alveolar epithelial cells.","authors":"Emily T Wilson, Percival Graham, David H Eidelman, Carolyn J Baglole","doi":"10.1007/s10565-025-09997-3","DOIUrl":"10.1007/s10565-025-09997-3","url":null,"abstract":"<p><p>As legalization of cannabis increases worldwide, vaping cannabis is gaining popularity due to the belief that it is less harmful than smoking cannabis. However, the safety of cannabis vaping remains untested. To address this, we developed a physiologically relevant method for in vitro assessment of cannabis vapor on alveolar epithelial cell cultures. We compared the transcriptional response in three in vitro models of cannabis vapor exposure using A549 epithelial cells in submerged culture, pseudo-air liquid interface (ALI) culture, and ALI culture coupled with the expoCube™ advanced exposure system. Baseline gene expression in ALI-maintained A549 cells showed higher expression of type 2 alveolar epithelial (AEC2) genes related to surfactant production, ion movement, and barrier integrity. Acute exposure to cannabis vapor significantly affected gene expression in AEC2 cells belonging to pathways related to cancer, oxidative stress, and the immune response without being associated with a DNA damage response. This study identifies potential risks of cannabis vaping and underscores the need for further exploration into its respiratory health implications.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"57"},"PeriodicalIF":5.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Andrographolide ameliorates sepsis-induced acute liver injury by attenuating endoplasmic reticulum stress through the FKBP1A-mediated NOTCH1/AK2 pathway.","authors":"Jiaqi He, Zepeng Huang, Rui Zou","doi":"10.1007/s10565-025-10007-9","DOIUrl":"10.1007/s10565-025-10007-9","url":null,"abstract":"<p><p>Andrographolide (AP) has been shown to possess anti-inflammatory activities. In this study, the impact of AP in sepsis-induced acute liver injury (ALI) and the molecules involved were dissected. FKBP1A was predicted to be the sole target protein of AP that was also differentially expressed in the GSE166868 dataset. AP induced the protein expression of FKBP1A and suppressed that of NOTCH1 in a dose-dependent manner. AP ameliorated ALI in mice induced by D-galactosamine and LPS and inhibited LPS-induced liver parenchymal cell injury in vitro. By contrast, the protective effect of AP was significantly lost after the knockdown of FKBP1A. As a positive control, the therapeutic effect of dexamethasone on ALI may be related to NOTCH1, which was not related to FKBP1A. NOTCH1 promoted AK2 transcription in liver parenchymal cells, and FKBP1A inhibited endoplasmic reticulum (ER) stress by impairing NOTCH1/AK2 signaling. Restoration of NOTCH1 significantly reversed the hepatoprotective effect of AP in ALI mice and LPS-induced liver parenchymal cell injury by activating the ER stress pathway. Therefore, AP-promoted FKBP1A expression inhibits ALI progression by blocking the NOTCH1/AK2-mediated ER pathway.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"56"},"PeriodicalIF":5.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The microRNA-mediated apoptotic signaling axis in male reproduction: a possible and targetable culprit in male infertility.","authors":"Pengxia Yu, Xue Zhao, Dan Zhou, Songtao Wang, Zihuan Hu, Kai Lian, Nanhui Zhang, Peng Duan","doi":"10.1007/s10565-025-10006-w","DOIUrl":"10.1007/s10565-025-10006-w","url":null,"abstract":"<p><p>Recently, infertility has emerged as a significant and prevalent public health concern warranting considerable attention. Apoptosis, recognized as programmed cell death, constitutes a crucial process essential for the maintenance of normal spermatogenesis. Multiple investigations have illustrated that the dysregulated apoptosis of reproductive cells, encompassing spermatogonial stem cells, Sertoli cells, and Leydig cells, serves as a causative factor in male infertility. MicroRNAs represent a class of small RNA molecules that exert negative regulatory control over gene expression using direct interaction with messenger RNA transcripts. Previous studies have established that aberrant expression of miRNAs induces apoptosis in reproductive tissues, correlating with reproductive dysfunctions and infertility. In this review, we offer a comprehensive overview of miRNAs and their respective target genes implicated in the apoptotic process. As well, miRNAs are involved in multiple apoptotic signaling pathways, namely the PI3K/AKT, NOTCH, Wnt/β-catenin, and mTOR signaling cascades, exerting both negative and positive effects. We additionally elucidate the significant functions played by lncRNAs and circular RNAs as competing endogenous RNAs in the process of apoptosis within reproductive cells. We further illustrate that external factors, including silica nanoparticles, Cyclosporine A, and smoking, induce dysregulation of miRNAs, resulting in apoptosis within reproductive cells and subsequent male reproductive toxicity. Further, we discuss the implication of heat stress, hypoxia, and diabetes in reproductive cell apoptosis induced by miRNA dysregulation in male infertility. Finally, we demonstrate that the modulation of miRNAs via traditional and novel medicine could protect reproductive cells from apoptosis and be implemented as a therapeutic approach in male infertility.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"54"},"PeriodicalIF":5.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil-derived heparin-binding protein increases endothelial permeability in acute lung injury by promoting TRIM21 and the ubiquitination of P65.","authors":"Jian Zhang, Yong Cao, Wenqi Shu, Senxiao Dong, Yini Sun, Xiaochun Ma","doi":"10.1007/s10565-025-10005-x","DOIUrl":"10.1007/s10565-025-10005-x","url":null,"abstract":"<p><p>Acute lung injury (ALI), which poses a significant public health threat, is commonly caused by sepsis. ALI is associated with permeability and glycolysis changes in pulmonary microvascular endothelial cells. Our study demonstrates that heparin-binding protein (HBP), released from neutrophils during sepsis, exacerbates endothelial permeability and glycolysis, thereby triggering ALI. Through coimmunoprecipitation and mass spectrometry, TRIM21 was identified as a HBP interaction partner. Notably, HBP enhances the protein stability of TRIM21 by inhibiting K48 ubiquitination. TRIM21 binds to and promotes K63-linked ubiquitination of P65, facilitating its nuclear translocation. TRIM21 regulates HPMEC permeability and glycolysis in a manner dependent on P65 nuclear translocation. HBP stabilizes TRIM21 and enhances TRIM21 interactions with P65. Rescue experiments conducted in vivo and in vitro demonstrate that modulation of endothelial permeability and glycolysis by HBP is predominantly mediated through the TRIM21-P65 axis. Our results suggest that targeting the HBP/TRIM21/P65 axis is a novel therapeutic strategy to ameliorate ALI.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"55"},"PeriodicalIF":5.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycolysis regulates palatal mesenchyme proliferation through Pten-Glut1 axis via Pten classical and non-classical pathways.","authors":"Yijia Wang, Xia Peng, Xiaotong Wang, Jing Chen, Xiaoyu Zheng, Xige Zhao, Cui Guo, Juan Du","doi":"10.1007/s10565-025-10000-2","DOIUrl":"10.1007/s10565-025-10000-2","url":null,"abstract":"<p><p>Abnormal embryonic development leads to the formation of cleft palate (CP) which is difficult to be detected by genetic screening and needs sequent treatment from infants to adults. There are no interceptive treatment about CP until now. Germline deletion of phosphatase and tensin homolog (Pten) was related to embryonic malformation and regulated tumor cell proliferation through glycolysis. However, the role of Pten in CP and the relationship between CP, Pten, and glycolysis are unknown. In our research, we constructed Pten knockdown models in vitro and in vivo. Our results provided preliminary evidence that blocking Pten by its inhibitor such as VO-OHpic might be an effective interceptive treatment in early period of palate development when pregnant mother expose in harmful environment during the early period of palate development to reducing CP occurring which was related with the crosstalk between Pten, and glycolysis in the process.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":"41 1","pages":"53"},"PeriodicalIF":5.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}