Cell Proliferation最新文献_第4页

SIRT1 Alleviates Oxidative Stress-Induced Mitochondrial Dysfunction and Mitochondria-Associated Membrane Dysregulation in Stress Urinary Incontinence.

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-02-21 DOI: 10.1111/cpr.70009

Liying Chen, Jianming Tang, Xiaohu Zuo, Bingshu Li, Cheng Liu, Shasha Hong, Jie Min, Ming Hu, Suting Li, Min Zhou, Mao Chen, Yong He, Ya Xiao, Xiaoyu Huang, Li Hong

{"title":"SIRT1 Alleviates Oxidative Stress-Induced Mitochondrial Dysfunction and Mitochondria-Associated Membrane Dysregulation in Stress Urinary Incontinence.","authors":"Liying Chen, Jianming Tang, Xiaohu Zuo, Bingshu Li, Cheng Liu, Shasha Hong, Jie Min, Ming Hu, Suting Li, Min Zhou, Mao Chen, Yong He, Ya Xiao, Xiaoyu Huang, Li Hong","doi":"10.1111/cpr.70009","DOIUrl":"https://doi.org/10.1111/cpr.70009","url":null,"abstract":"The pathogenesis of stress urinary incontinence (SUI), a condition common in women, remains to be fully elucidated. This study revealed that the incidence of SUI is associated with mitochondrial homeostasis dysregulation following oxidative stress in the fibrous connective tissue of the pelvic floor. SIRT1 is an essential factor for maintaining mitochondrial homeostasis; however, its potential role and mechanism of action in SUI pathogenesis remain unclear. Both in vitro and in vivo, we observed that oxidative stress reduced SIRT1 expression to inhibit the PGC-1α/NRF1/TFAM and PINK1/Parkin signalling pathways, eliciting impairment of mitochondrial biogenesis and mitophagy in L929 cells and SUI mice. Decreased SIRT1 levels induced endoplasmic reticulum (ER) stress and altered the structure of mitochondria-associated membranes (MAMs), disrupting ER-mitochondrial calcium homeostasis and exacerbting ROS accumulation. SIRT1 activation can restore mitochondrial function and the structure of MAMs and alleviate ER stress in fibroblasts, promoting anterior vaginal wall repair and improving urodynamic parameters in the SUI model. Our findings provide novel insights into the role and associated mechanism of SIRT1 in ameliorating oxidative stress-induced mitochondrial dysfunction in fibroblasts of the anterior vaginal wall and propose SIRT1 as a potential therapeutic target for SUI.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70009"},"PeriodicalIF":5.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Human Midbrain Organoids Enriched With Dopaminergic Neurons for Long-Term Functional Evaluation.

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-02-20 DOI: 10.1111/cpr.70005

Xinyue Wang, Gaoying Sun, Mingming Tang, Da Li, Jianhuan Qi, Chuanyue Wang, Yukai Wang, Baoyang Hu

{"title":"Human Midbrain Organoids Enriched With Dopaminergic Neurons for Long-Term Functional Evaluation.","authors":"Xinyue Wang, Gaoying Sun, Mingming Tang, Da Li, Jianhuan Qi, Chuanyue Wang, Yukai Wang, Baoyang Hu","doi":"10.1111/cpr.70005","DOIUrl":"https://doi.org/10.1111/cpr.70005","url":null,"abstract":"Human midbrain organoids with functional dopaminergic (DA) neurons are invaluable for the therapeutic development of Parkinson's disease (PD). However, current methods face significant limitations, including challenges in generating pint-sized organoids enriched with DA neurons and the lack of robust functional assays for efficiently evaluating neural networks over extended periods. Here we present an innovative approach that combines developmental patterning with mechanical cutting to produce small midbrain organoids, with diameters less than 300 μm, suitable for long-term evaluation, along with a comprehensive functional assay system consisting of calcium transient assay, neurite extension assay, and multielectrode array (MEA) assay. Radial cutting of organoids into four to eight portions according to their sizes at the appropriate developmental stage significantly increases the yield of viable organoids while reducing necrotic cell regions. Using the functional assay system, we demonstrate that DA neurons within the organoids extend long projections, respond to dopamine stimulation, and form neural networks characterised by giant depolarising potential-like events. Our approach supports the generation of midbrain organoids and PD models that can be used for long-term functional testing.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70005"},"PeriodicalIF":5.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Organoid Models to Study Human Infectious Diseases.

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-02-20 DOI: 10.1111/cpr.70004

Sijing Zhu, Dan Chen, Xinzhi Yang, Liuliu Yang, Yuling Han

引用次数: 0

Testis-Specific PDHA2 Is Required for Proper Meiotic Recombination and Chromosome Organisation During Spermatogenesis.

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-02-20 DOI: 10.1111/cpr.70003

Guoqiang Wang, Kailun Fang, Yongliang Shang, Xu Zhou, Qiqi Shao, Si Li, Ping Wang, Charlie Degui Chen, Liangran Zhang, Shunxin Wang

{"title":"Testis-Specific PDHA2 Is Required for Proper Meiotic Recombination and Chromosome Organisation During Spermatogenesis.","authors":"Guoqiang Wang, Kailun Fang, Yongliang Shang, Xu Zhou, Qiqi Shao, Si Li, Ping Wang, Charlie Degui Chen, Liangran Zhang, Shunxin Wang","doi":"10.1111/cpr.70003","DOIUrl":"https://doi.org/10.1111/cpr.70003","url":null,"abstract":"Proper segregation of homologous chromosomes during meiosis requires crossovers that are tightly regulated by the chromosome structure. PDHA2 is the testis-specific paralog of PDHA1, a core subunit of pyruvate dehydrogenase. However, its role during spermatogenesis is unclear. We show that PDHA2 knockout results in male infertility in mice, but meiotic DSBs in spermatocytes occur normally and are efficiently repaired. Detailed analysis reveals that mid/late recombination intermediates are moderately reduced, resulting in fewer crossovers and many chromosomes without a crossover. Furthermore, defective chromosome structure is observed, including aberrant histone modifications, defective chromosome ends, precocious release of REC8 from chromosomes and fragmented chromosome axes after pachytene. These defects contribute to the failure of pyruvate conversion to acetyl-CoA, resulting in decreased acetyl-CoA and precursors for metabolites and energy in the absence of PDHA2. These findings reveal the important functions of PDHA2 in ensuring proper crossover formation and in modulating chromosome structure during spermatogenesis.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70003"},"PeriodicalIF":5.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Tetrahedral Framework Nucleic Acid-Based Delivery of DJ-1-saRNA Prevent Retinal Ischaemia-Reperfusion Injury via Inhibiting Ferroptosis.

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-02-20 DOI: 10.1111/cpr.13820

Xianggui Zhang, Zhende Deng, Xiaoxiao Xu, Jingyi Zhu, Zhen Huang, Ya Ye, Jingying Liu, Delun Luo, Jinnan Liu, Ming Yan, Yanping Song

{"title":"Tetrahedral Framework Nucleic Acid-Based Delivery of DJ-1-saRNA Prevent Retinal Ischaemia-Reperfusion Injury via Inhibiting Ferroptosis.","authors":"Xianggui Zhang, Zhende Deng, Xiaoxiao Xu, Jingyi Zhu, Zhen Huang, Ya Ye, Jingying Liu, Delun Luo, Jinnan Liu, Ming Yan, Yanping Song","doi":"10.1111/cpr.13820","DOIUrl":"https://doi.org/10.1111/cpr.13820","url":null,"abstract":"Retinal ischaemia/reperfusion injury (RI/RI) is the primary pathophysiological mechanism underlying retinal ischaemic diseases, potentially resulting in significant and irreversible visual impairment. Currently, there are no effective treatments available for RI/RI, and oxidative stress is a critical factor that contributes to the associated damage. DJ-1, an important endogenous antioxidant, has been proposed as a promising therapeutic agent for RI/RI owing to its potential for overexpression. In this study, tetrahedral frame nucleic acids (tFNAs) were utilised as an effective delivery vehicle for DJ-1 small activating RNA (saRNA), resulting in the synthesis of a novel nanocomposite (tFNAs-DJ-1-saRNA). In vitro experiments demonstrated that tFNAs effectively delivered DJ-1-saRNA to R28 cells, thus exerting a repair effect on oxidative stress injury. In vivo investigations revealed that the intravitreal injection of tFNAs-DJ-1-saRNA facilitated retinal DJ-1 gene expression and mitigated retinal atrophy induced by RI/RI. Mechanistically, tFNAs-DJ-1-saRNA activated the xCT/GPX4 pathway, thereby inhibiting ferroptosis, reducing ganglion cell damage and protecting the retinal tissue. In conclusion, this study demonstrated that the tFNAs-DJ-1-saRNA complex can ameliorate RI/RI by inhibiting ferroptosis, suggesting its potential as a novel agent for the treatment of retinal ischaemic diseases.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13820"},"PeriodicalIF":5.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Featured Cover

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-02-19 DOI: 10.1111/cpr.13821

Tina Meißgeier, Melanie Kappelmann-Fenzl, Sebastian Staebler, Ata Jadid Ahari, Christian Mertes, Julien Gagneur, Lisa Linck-Paulus, Anja Katrin Bosserhoff

引用次数: 0

PD-L1 Promotes Immunological Tolerance and Enhances Visual Protection of hESC-RPE Grafts in Retinal Degeneration.

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-02-14 DOI: 10.1111/cpr.70007

Bowen Li, Xue Zhang, Yajie Fang, Min Chen, Qiyou Li, Yuxiao Zeng, Chunge Ren, Chengang Wang, Yingxue Lv, Jia Lu, Hongling Liu, Yong Liu

{"title":"PD-L1 Promotes Immunological Tolerance and Enhances Visual Protection of hESC-RPE Grafts in Retinal Degeneration.","authors":"Bowen Li, Xue Zhang, Yajie Fang, Min Chen, Qiyou Li, Yuxiao Zeng, Chunge Ren, Chengang Wang, Yingxue Lv, Jia Lu, Hongling Liu, Yong Liu","doi":"10.1111/cpr.70007","DOIUrl":"https://doi.org/10.1111/cpr.70007","url":null,"abstract":"Immune rejection is a major barrier to the successful human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) transplantation for age-related macular degeneration (AMD). Traditional strategies to mitigate immune rejection involve ablating major histocompatibility complex (MHC) molecules on hESC-RPE. An alternative approach is immune checkpoint overexpression, avoiding natural killer (NK) cell-mediated destruction due to MHC-I deficiency. Our study highlights the benefits of PD-L1 overexpression without requiring MHC gene deletion, which preserved the immunosuppressive functions of hESC-RPE on NK cells. In Vivo experiments in retinal degeneration models showed that PD-L1-expressing hESC-RPE grafts exhibited significantly higher survival, reduced apoptosis and enhanced visual protection. Single-cell transcriptomics revealed reduced immune activation and oxidative stress in PD-L1-overexpressing grafts. PD-L1's protective role was further evidenced by improved light transduction in host photoreceptors. These findings support PD-L1 overexpression as a promising strategy to improve the efficiency of hESC-RPE-based therapy for AMD.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70007"},"PeriodicalIF":5.9,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

The Application of Polymeric Nanoparticles as Drug Delivery Carriers to Cells in Neurodegenerative Diseases.

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-02-11 DOI: 10.1111/cpr.13804

Lian Jin, Libo Nie, Yan Deng, Ghulam Jilany Khana, Nongyue He

{"title":"The Application of Polymeric Nanoparticles as Drug Delivery Carriers to Cells in Neurodegenerative Diseases.","authors":"Lian Jin, Libo Nie, Yan Deng, Ghulam Jilany Khana, Nongyue He","doi":"10.1111/cpr.13804","DOIUrl":"https://doi.org/10.1111/cpr.13804","url":null,"abstract":"In spite of great advances in modern medicine, there are a few effective strategies for the treatment of neurodegenerative diseases characterised by neuron loss or degeneration. This results from complex pathogenesis of the diseases and the limited drug uptake of the brain due to the presence of blood-brain barrier. Nanoparticle-based drug delivery systems are expected to improve the drug utilisation. Polymeric nanoparticles represent promising drug delivery carriers to the brain due to their unique advantages such as good biodegradability and biocompatibility, flexibility in surface modification and nontoxicity. In addition, the delivery of genetic drugs may stop the progression of neurodegenerative diseases at the genetic level and even avoid the irreversible damage in the central nervous system. In this review, an overview of studies on polymer-based nanoparticles for drug delivery to the central nervous system in typical neurodegenerative diseases, especially Alzheimer's diseases and Parkinson's diseases, is described. Meanwhile, their applications in gene delivery in these disorders are discussed. And the challenges and future perspectives for the development of polymeric nanoparticles as drug delivery carriers in neurodegenerative diseases are concluded.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13804"},"PeriodicalIF":5.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Klotho Regulates Club Cell Senescence and Differentiation in Chronic Obstructive Pulmonary Disease.

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-02-10 DOI: 10.1111/cpr.70000

Min Li, Bo Chen, Sibo Sun, Kai Wang, Yu Wang, Jianqing Wu

{"title":"Klotho Regulates Club Cell Senescence and Differentiation in Chronic Obstructive Pulmonary Disease.","authors":"Min Li, Bo Chen, Sibo Sun, Kai Wang, Yu Wang, Jianqing Wu","doi":"10.1111/cpr.70000","DOIUrl":"https://doi.org/10.1111/cpr.70000","url":null,"abstract":"Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation and senescence. Previous studies showed that club cells and club cell secretory proteins (CCSP) have anti-inflammatory roles, which reduced in COPD. Klotho (KL) decreased in human COPD lung tissue. KL-deficient mice showed aging phenotypes, such as obvious emphysema and premature senility at the early stage, which are characteristics of COPD. However, little is known about the relationship between KL, club cells, and COPD. We speculated lack of KL would aggravate club cell senescence, which contributes to COPD inflammation. We collected COPD lung tissue using single-cell RNA sequencing (scRNA-seq), revealing club cells heterogeneity and cellular senescence in COPD. In addition, KL and CCSP expressions were downregulated in cigarette smoke (CS)-induced COPD mice, associated with increasing age-related markers. After KL knockout, more ciliated cells appeared where club cells disappeared. Furthermore, KL deficiency aggravated club cell senescence and CSE-induced pulmonary inflammation. To investigate the specific regulation mechanism, hnRNPA2/B1 was recognised and identified it was the key molecule in KL-regulated club cell senescence, and neddylation of club cell was a crucial factor contributing to hnRNPA2/B1 downregulation. In vitro, SA-β-gal staining suggested the aging phenotype was aggravated in hnRNPA2/B1-silenced groups, and hnRNPA2/B1 over-expressed achieved a rescue result. Thus, KL could regulate club cell senescence and differentiation. When CS stimulates the small airway epithelium, KL deficiency aggravates lung inflammation, club cell senescence and dysfunctional of ciliated cell. Targeting neddylation might be a promising strategy to reverse lung aging and club cell senescence. These results provide a mechanism about COPD-linked lung inflammation.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70000"},"PeriodicalIF":5.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Large-Scale Production of Expandable Hepatoblast Organoids and Polarised Hepatocyte Organoids From hESCs Under 3D Static and Dynamic Suspension Conditions.

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-02-08 DOI: 10.1111/cpr.70001

Haibin Wu, Jue Wang, Shoupei Liu, Yiyu Wang, Xianglian Tang, Jinghe Xie, Ning Wang, Huanhuan Shan, Sen Chen, Xueyan Zhang, Weiping Zeng, Chuxin Chen, Yinjie Fu, Liangxue Lai, Yuyou Duan

{"title":"Large-Scale Production of Expandable Hepatoblast Organoids and Polarised Hepatocyte Organoids From hESCs Under 3D Static and Dynamic Suspension Conditions.","authors":"Haibin Wu, Jue Wang, Shoupei Liu, Yiyu Wang, Xianglian Tang, Jinghe Xie, Ning Wang, Huanhuan Shan, Sen Chen, Xueyan Zhang, Weiping Zeng, Chuxin Chen, Yinjie Fu, Liangxue Lai, Yuyou Duan","doi":"10.1111/cpr.70001","DOIUrl":"https://doi.org/10.1111/cpr.70001","url":null,"abstract":"To date, generating viable and functional hepatocytes in large scale remains challenge. By employing 3D suspension condition with the support of low concentration Matrigel, a novel culture system was developed to generate expandable hepatoblast organoids (HB-orgs) and mature polarised hepatocyte organoids (P-hep-orgs) from human embryonic stem cells (hESCs) in both dishes and bioreactors. scRNA-seq and functional assays were used to characterise HB-orgs and P-hep-orgs. hESC-derived HB-orgs could proliferate at least for 15 passages, leading to 1012 in total cells in 4 weeks. P-hep-orgs differentiated from HB-orgs displayed characteristics of mature hepatocytes with polarisation. Moreover, single-cell RNA sequencing exhibited that over 40% of cells in P-hep-orgs were highly fidelity with human primary hepatocytes. Eventually, large-scale production of P-hep-orgs could be generated from massively expanded HB-orgs within 1 week with similar number in bioreactors, which were achieved by the enhancements in energy metabolism contribute to the expansion of HB-orgs and maturation of P-hep-orgs in bioreactors. By providing a cost-efficient and robust platform, our study represents a significant step toward manufacturing large-scale functioning hESC-derived hepatocytes for cell-based therapeutics, disease modelling, pharmacology and toxicology studies.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70001"},"PeriodicalIF":5.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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