JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献_第8页

A Comparison of Novel Serum Markers of Liver Health in Adolescents With Metabolic Dysfunction-Associated Steatotic Liver Disease 代谢性功能障碍相关脂肪变性肝病青少年肝脏健康新血清标志物的比较

IF 4.2

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-08-28 DOI: 10.1111/jcmm.70817

Neeharika Bade, Diana A. Hellman, David J. Matye, Shaoning Jiang, Jeanie B. Tryggestad, Zhongxin Yu, Kevin R. Short, Sirish K. Palle

{"title":"A Comparison of Novel Serum Markers of Liver Health in Adolescents With Metabolic Dysfunction-Associated Steatotic Liver Disease","authors":"Neeharika Bade, Diana A. Hellman, David J. Matye, Shaoning Jiang, Jeanie B. Tryggestad, Zhongxin Yu, Kevin R. Short, Sirish K. Palle","doi":"10.1111/jcmm.70817","DOIUrl":"https://doi.org/10.1111/jcmm.70817","url":null,"abstract":"Several non-invasive biomarkers for paediatric metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported, but no prior studies directly compared multiple protein or microRNA (miRNA) markers of liver health in adolescents with and without MASLD and determined which serum markers are associated with liver histopathological features. We measured 6 serum protein and 4 miRNA candidates in 3 groups of participants: 23 with obesity and biopsy-proven MASLD, 24 controls with obesity (Ob) and 24 controls with normal weight (NW). The MASLD group had higher median values for cytokeratin 18 (CK-18, 8.5 and 5.6-fold higher than NW and Ob, respectively), CK-18 fragments (2.6- and 2.6-fold), collagen IV (0.9- and 0.6-fold), miR-122 (16.9- and 10.7-fold) and miR-192 (9.7- and 12.0-fold). YKL-40 and N-terminal propeptide of type III procollagen were only higher in the MASLD group compared to the NW group. Serum AST, CK-18, CK-18 fragments, miR-122 and miR-192 were positively correlated with liver fibrosis stage. Area under the receiver operating curve for identifying MASLD for CK-18 (0.962), miR-192 (0.945) and miR-122 (0.944) was higher than ALT (0.935). miR-122 in serum and liver was inversely correlated in MASLD patients but neither was associated with putative mRNA targets AGPAT1 and DGAT1. These results show that CK-18, miR-122 and miR-192 are marginally better predictors of MASLD than ALT and correlated with fibrosis in this cohort, supporting further work to confirm these findings.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 16","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70817","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Simvastatin-Mediated Molecular Mechanisms Underlying the Growth Inhibition of Testicular Leydig Tumour Cells 辛伐他汀介导的睾丸间质肿瘤细胞生长抑制的分子机制

IF 4.2

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-08-28 DOI: 10.1111/jcmm.70786

Arianna De Luca, Lucia Zavaglia, Lucia Francesca Vuono, Francesca Giordano, Davide La Padula, Francesca De Amicis, Vincenzo Pezzi, Adele Chimento

{"title":"Simvastatin-Mediated Molecular Mechanisms Underlying the Growth Inhibition of Testicular Leydig Tumour Cells","authors":"Arianna De Luca, Lucia Zavaglia, Lucia Francesca Vuono, Francesca Giordano, Davide La Padula, Francesca De Amicis, Vincenzo Pezzi, Adele Chimento","doi":"10.1111/jcmm.70786","DOIUrl":"https://doi.org/10.1111/jcmm.70786","url":null,"abstract":"Leydig cell tumours (LCTs) are uncommon stromal neoplasms of the testis, accounting for less than 3% of all gonadal cancers. Most of them are benign, but the malignant ones are very aggressive without specific effective treatment. Several studies reported pharmacologic insight into the use of statins as anti-tumour agents, but their efficacy on LCTs has not been investigated. Previously, we emphasised the central role of insulin-like growth factor 1 (IGF1)/insulin-like growth factor 1 receptor (IGF1R) signalling in Leydig cell tumorigenesis; here, we showed that simvastatin reduces cell proliferation, determines cell cycle arrest at the G1 phase, and induces reactive oxygen species (ROS) accumulation and apoptosis in R2C and LC540 rat Leydig tumour cells. Furthermore, it prevents isoprenoid farnesyl pyrophosphate (FPP) formation and decreases IGF1R expression, leading to the breakdown of the IGF1R signalling pathway. Importantly, we observed that simvastatin synergised with cisplatin in reducing tumour cell proliferation. Collectively, these data suggest that simvastatin is a potential anticancer drug capable of counteracting LCT growth, and it could be proposed as an adjuvant for chemotherapy in LCT treatment.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 16","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70786","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrating Multi-Omics Data Using Machine Learning to Explore New Therapeutic Targets for Acute Kidney Injury 利用机器学习整合多组学数据探索急性肾损伤的新治疗靶点

IF 4.2

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-08-27 DOI: 10.1111/jcmm.70801

Qiming Gong, Yakun Wang, Fahui Liu, Tingting Zhou, Mengqin Tu, Junle Li, Wei Huang, Xu Lin, Wenjuan Sun

{"title":"Integrating Multi-Omics Data Using Machine Learning to Explore New Therapeutic Targets for Acute Kidney Injury","authors":"Qiming Gong, Yakun Wang, Fahui Liu, Tingting Zhou, Mengqin Tu, Junle Li, Wei Huang, Xu Lin, Wenjuan Sun","doi":"10.1111/jcmm.70801","DOIUrl":"https://doi.org/10.1111/jcmm.70801","url":null,"abstract":"Renal ischemia–reperfusion (I/R) injury is an unavoidable complication associated with renal transplantation, and currently, there are no targeted therapeutic interventions. The objective of this study was to explore the molecular mechanisms that contribute to I/R-induced acute kidney injury (I/R-AKI) and to discover potential targets for effective renal safeguarding. Bioinformatics techniques were employed to analyse critical genes regulating I/R-AKI at the single-cell level and to develop diagnostic models. Additionally, key pharmacological agents that inhibit the expression of target genes were identified for subsequent experimental validation. Pathological changes in the kidneys of I/R mice and patients with AKI were observed using immunofluorescence, western blotting, immunohistochemistry and transmission electron microscopy. We developed and validated a robust diagnostic model for I/R-AKI. The results suggest that ADAMTS1 acts as a promoter of renal I/R-AKI. In I/R-AKI, ADAMTS1 was significantly upregulated in renal tubular epithelial cells. Furthermore, apoptosis mediated by the mitochondrial pathway was a critical factor in the progression of renal I/R injury. In mouse models of I/R-AKI, the inhibition of ADAMTS1 with troglitazone significantly reduced both functional and histological damage. The diagnostic model can serve as a valuable instrument for diagnosing I/R-AKI. Furthermore, troglitazone can significantly contribute to managing I/R-AKI by inhibiting the expression of ADAMTS1. This study provides critical insights that may inform future research on therapeutic targets for renal ischaemia–reperfusion injury.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 16","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70801","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthetic Lethality-Based Targets and Their Exploration in Tumour Combination Strategies 基于致死率的合成靶点及其在肿瘤联合策略中的探索

IF 4.2

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-08-27 DOI: 10.1111/jcmm.70756

Lingya Wu, Yixuan Deng, Zhe Lei, Yuhong Wang, Shan Huang

{"title":"Synthetic Lethality-Based Targets and Their Exploration in Tumour Combination Strategies","authors":"Lingya Wu, Yixuan Deng, Zhe Lei, Yuhong Wang, Shan Huang","doi":"10.1111/jcmm.70756","DOIUrl":"https://doi.org/10.1111/jcmm.70756","url":null,"abstract":"Synthetic lethality (SL) not only addresses the challenge of drug resistance associated with classical targeted therapies but also offers innovative therapeutic approaches for previously ‘undruggable’ targets, such as deletion mutations in tumour suppressor genes. Advances in technology have significantly enhanced our understanding of gene–gene interactions in cancer cells, enabling the identification of synthetic lethal targets and the development of drugs targeting these mechanisms. Following the extensive clinical application of PARP inhibitors—the first synthetic lethal targeted drugs approved for clinical use—emerging targets such as ATR, WEE1 and WRN have demonstrated promising clinical potential. This review examines the functions and molecular mechanisms underlying these targets and discusses recent advancements in the theory of synthetic lethality. Additionally, it emphasises the integration of synthetic lethal drugs with traditional cancer treatments, highlighting the clinical benefits of this combined strategy and its potential to facilitate more precise and individualised cancer treatment modalities in the future.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 16","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70756","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144905434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Survival Prediction in Allogeneic Haematopoietic Stem Cell Transplant Recipients Using Pre- and Post-Transplant Factors and Computational Intelligence 利用移植前和移植后因素和计算智能预测同种异体造血干细胞移植受者的生存

IF 4.2

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-08-27 DOI: 10.1111/jcmm.70672

Panagiotis G. Asteris, Danial J. Armaghani, Amir H. Gandomi, Ahmed Salih Mohammed, Zoi Bousiou, Ioannis Batsis, Nikolaos Spyridis, Georgios Karavalakis, Anna Vardi, Markos Z. Tsoukals, Leonidas Triantafyllidis, Evangelos I. Koutras, Nikos Zygouris, Georgios A. Drosopoulos, Leonidas Dritsas, Nikolaos A. Fountas, Nikolaos M. Vaxevanidis, Abidhan Bardhan, Pijush Samui, George D. Hatzigeorgiou, Jian Zhou, Konstantina V. Leontari, Paschalis Evangelidis, Nikolaos Kotsiou, Ioanna Sakellari, Eleni Gavriilaki

{"title":"Survival Prediction in Allogeneic Haematopoietic Stem Cell Transplant Recipients Using Pre- and Post-Transplant Factors and Computational Intelligence","authors":"Panagiotis G. Asteris, Danial J. Armaghani, Amir H. Gandomi, Ahmed Salih Mohammed, Zoi Bousiou, Ioannis Batsis, Nikolaos Spyridis, Georgios Karavalakis, Anna Vardi, Markos Z. Tsoukals, Leonidas Triantafyllidis, Evangelos I. Koutras, Nikos Zygouris, Georgios A. Drosopoulos, Leonidas Dritsas, Nikolaos A. Fountas, Nikolaos M. Vaxevanidis, Abidhan Bardhan, Pijush Samui, George D. Hatzigeorgiou, Jian Zhou, Konstantina V. Leontari, Paschalis Evangelidis, Nikolaos Kotsiou, Ioanna Sakellari, Eleni Gavriilaki","doi":"10.1111/jcmm.70672","DOIUrl":"https://doi.org/10.1111/jcmm.70672","url":null,"abstract":"Advancements in artificial intelligence (AI) predictive models have emerged as valuable tools for predicting survival outcomes in allogeneic haematopoietic stem cell transplantation (allo-HSCT). These models primarily focus on pre-transplant factors, while algorithms incorporating changes in patient's status post-allo-HSCT are lacking. The aim of this study was to develop a predictive soft computing model assessing survival outcomes in allo-HSCT recipients. In this study, we assembled a comprehensive database comprising of 564 consecutive adult patients who underwent allo-HSCT between 2015 and 2024. Our algorithm selectively considers critical parameters from the database, ranking and evaluating them based on their impact on patient outcomes. By utilising the Data Ensemble Refinement Greedy Algorithm, we developed an AI model with 93.26% accuracy in predicting survivorship status in allo-HSCT recipients. Our model used only seven parameters, including age, disease, disease phase, creatinine levels at day 2 post-allo-HSCT, platelet engraftment, acute graft-versus-host disease (GvHD) and chronic GvHD. External validation of our AI model is considered essential. Machine learning algorithms have the potential to improve the prediction of long-term survival outcomes for patients undergoing allo-HSCT.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 16","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70672","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144905433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hedgehog Signalling in Osteogenesis and Bone Metabolism: Molecular Mechanisms, Regulatory Networks and Implications for Skeletal Disease 刺猬信号在成骨和骨代谢中的作用：分子机制、调控网络和对骨骼疾病的影响

IF 4.2

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-08-26 DOI: 10.1111/jcmm.70813

Rohey Njie, Shihan Xu, Taofen Wu, Jiashun Pi, Sisi Lin, Pengxiang Zhang, Jiaqi Wang, Qi Dai, Hui Shen, Nenghua Zhang, Guiqian Chen

{"title":"Hedgehog Signalling in Osteogenesis and Bone Metabolism: Molecular Mechanisms, Regulatory Networks and Implications for Skeletal Disease","authors":"Rohey Njie, Shihan Xu, Taofen Wu, Jiashun Pi, Sisi Lin, Pengxiang Zhang, Jiaqi Wang, Qi Dai, Hui Shen, Nenghua Zhang, Guiqian Chen","doi":"10.1111/jcmm.70813","DOIUrl":"https://doi.org/10.1111/jcmm.70813","url":null,"abstract":"The Hedgehog (Hh) signalling pathway serves as a fundamental regulator in bone development and homeostasis, translating extracellular signals into precise transcriptional programmes that govern osteogenic differentiation and bone remodelling. Central to this process, ligand-dependent Hh activation induces the nuclear translocation of GLI transcription factors (GLI1/2/3), which orchestrate the expression of key osteogenic regulators, including RUNX2 and Osterix (OSX), thereby directing mesenchymal stem cell (MSC) fate commitment. Among Hh ligands, the Indian hedgehog (Ihh) plays a dominant role in endochondral ossification, spatiotemporally controlling osteoprogenitor differentiation and chondrocyte maturation. Notably, the Hh pathway engages in extensive, context-dependent crosstalk with Wnt/β-catenin, BMP, TGF-β, FGF and PTHrP signalling cascades, forming a highly interconnected regulatory network essential for skeletal patterning and morphogenesis. Dysregulation of this balanced system contributes to a spectrum of skeletal disorders, ranging from congenital defects to degenerative bone diseases, highlighting its critical role in maintaining bone integrity. This review synthesises recent advances in Hh-mediated osteogenesis, dissecting its multi-layered interactions within the skeletal gene regulatory framework. By unravelling the molecular logic of Hh-dependent signalling networks, we deepen our understanding of bone biology and illuminate novel therapeutic targets for skeletal pathologies through precision modulation of Hh pathway activity.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 16","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70813","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dihydromikanolide Inhibits ROS-Mediated NLRP3 Inflammation via Antioxidant Nrf2 Activation and Mitophagy Induction in LPS/ATP-Stimulated Macrophages 二氢甘油三酯通过抗氧化激活Nrf2和诱导LPS/ atp刺激的巨噬细胞自噬抑制ros介导的NLRP3炎症

IF 4.2

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-08-26 DOI: 10.1111/jcmm.70803

You-Cheng Hseu, Yu-Fang Tseng, Jhih Ke-Hseu, Sudhir Pandey, Siang-Jyun Chen, Kai-Yuan Lin, Hsueh-Wei Chang, Tzong-Der Way, Chuan-Chen Lee, Jhih-Hsuan Hseu, Hsin-Ling Yang

{"title":"Dihydromikanolide Inhibits ROS-Mediated NLRP3 Inflammation via Antioxidant Nrf2 Activation and Mitophagy Induction in LPS/ATP-Stimulated Macrophages","authors":"You-Cheng Hseu, Yu-Fang Tseng, Jhih Ke-Hseu, Sudhir Pandey, Siang-Jyun Chen, Kai-Yuan Lin, Hsueh-Wei Chang, Tzong-Der Way, Chuan-Chen Lee, Jhih-Hsuan Hseu, Hsin-Ling Yang","doi":"10.1111/jcmm.70803","DOIUrl":"https://doi.org/10.1111/jcmm.70803","url":null,"abstract":"Dihydromikanolide (DHK) is a natural product in Mikania species. We examined the anti-inflammatory molecular mechanisms of DHK employing in vitro RAW264.7 macrophages and in vivo BALB/c mice under LPS/ATP stimulation. We found that DHK suppressed NLRP3 inflammasome, procaspase-1 activation and then pro-inflammatory IL1β expression in LPS/ATP-stimulated RAW264.7 cells. Notably, DHK-triggered autophagy in RAW264.7 cells was demonstrated by increased LC3-II accumulation, p62/SQSTM1 expression, Beclin-1/Bcl-2 ratio and PI3K/AKT/mTOR phosphorylation. Besides, DHK increased Parkin and Pink-1 protein expressions implying mitophagy induction in RAW264.7 cells. Interestingly, DHK enhanced Nrf2 nuclear translocation and provoked antioxidant HO-1, NQO-1 and γ-GCLC expressions in RAW264.7 cells. Nrf2 knockdown reversed DHK-inhibited LPS/ATP-stimulated IL1β expression in RAW264.7 cells. Interestingly, LPS/ATP-stimulated NLRP3 inflammasome and IL1β expression were inhibited by DHK, Mito-TEMPO (a mitochondrial ROS inhibitor), or N-acetylcysteine (a ROS inhibitor). In vivo study revealed that DHK attenuated wet/dry weight ratio of lung tissue, lung neutrophil intrusions and pulmonary oedema, and reduced the increased total cells, neutrophils, TNFα and IL1β expression in bronchoalveolar lavage fluid (BALF) in LPS-stimulated BALB/c mice. DHK alleviated LPS-induced pathological alterations of lung through inhibiting NLRP3 inflammation, enhancing antioxidant Nrf2 pathway and inducing mitophagy in LPS-stimulated BALB/c mice. Dihydromikanolide may be a potential therapeutic agent for inflammatory diseases.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 16","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70803","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

KIFC1 Overexpression Promotes Pancreatic Carcinoma Progression via Stabilising BUB1B KIFC1过表达通过稳定BUB1B促进胰腺癌进展

IF 4.2

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-08-26 DOI: 10.1111/jcmm.70767

Ao Cui, Ying-Xue Yu, Mei-Xue Xiong, Ji-Yang Wang, Ye-Qing Zou, Ya-Qiong Zhu, Long-Jian Ran, Yu Zhang, Rui-Xiang Liu, Ming-Yi Dong, Hui Wang, Lu Fang, Xiao-Wei Fu

{"title":"KIFC1 Overexpression Promotes Pancreatic Carcinoma Progression via Stabilising BUB1B","authors":"Ao Cui, Ying-Xue Yu, Mei-Xue Xiong, Ji-Yang Wang, Ye-Qing Zou, Ya-Qiong Zhu, Long-Jian Ran, Yu Zhang, Rui-Xiang Liu, Ming-Yi Dong, Hui Wang, Lu Fang, Xiao-Wei Fu","doi":"10.1111/jcmm.70767","DOIUrl":"https://doi.org/10.1111/jcmm.70767","url":null,"abstract":"Pancreatic cancer (PC) is a highly lethal tumour of the gastrointestinal tract. New molecular targets are urgently needed for its treatment. Kinesin family member C1 (KIFC1) is implicated in the development and progression of several types of cancer. Previous studies from our group demonstrated that KIFC1 overexpression in hepatocellular carcinoma promotes malignant behaviours via the PI3K/AKT pathway. However, the molecular and functional mechanisms of KIFC1 in PC are not yet fully elaborated. In this study, KIFC1 and BUB1B were significantly upregulated in PC patient samples, and high KIFC1 expression was closely associated with the malignant phenotype and poorer overall survival (OS) in PC patients. Functional experiments showed that KIFC1 knockdown inhibited PC cell growth in vivo and in vitro, blocked cell cycle progression and hindered cell migration and invasion. In addition, rescue experiments showed that KIFC1 induced PC cell malignant behaviours dependent on BUB1B. Mechanistically, KIFC1 regulates BUB1B expression by competitively binding to BUB1B and reducing its ubiquitination and degradation. We have shown for the first time the molecular regulatory mechanism between KIFC1 and BUB1B on PC. Therefore, KIFC1 shows promise as an attractive therapeutic target for PC in the future.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 16","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70767","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-Cell and Bulk RNA Sequencing Highlights Intra-Tumoral Heterogeneity and Malignant Progression Mechanisms in Prostate Cancer 单细胞和大量RNA测序强调前列腺癌肿瘤内异质性和恶性进展机制

IF 4.2

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-08-26 DOI: 10.1111/jcmm.70806

Junchao Wu, Ziqi Chen, Wentian Wu, Jiaxuan Qin, Rongfang Zhong, Jialin Meng, Yu Yin, Peng Guo, Song Fan

{"title":"Single-Cell and Bulk RNA Sequencing Highlights Intra-Tumoral Heterogeneity and Malignant Progression Mechanisms in Prostate Cancer","authors":"Junchao Wu, Ziqi Chen, Wentian Wu, Jiaxuan Qin, Rongfang Zhong, Jialin Meng, Yu Yin, Peng Guo, Song Fan","doi":"10.1111/jcmm.70806","DOIUrl":"https://doi.org/10.1111/jcmm.70806","url":null,"abstract":"Prostate cancer (PCa) is an extremely heterogeneous cancer and is highly prevalent in the older male population. Since intra-tumour heterogeneity (ITH) commonly results in PCa chemotherapy resistance and recurrence, it is critical to explore its effects on tumour behaviour. Prognostic genes related to ITH were identified, and a signature was constructed using Cox regression analyses and multiple machine learning algorithms. Single-cell RNA sequencing data extracted from PCa and CRPC samples were analysed via sub-clustering, pseudotime, cell communication and drug sensitivity approaches to elucidate their function. The oncogenic potential of hub genes was confirmed by immunohistochemistry and cell proliferation assays. An 11-gene signature underlying a prostate cancer meta-program (PCMP) was generated by selecting an optimal combination of machine learning methods. Survival assays and multivariate Cox regression analyses conducted in multiple cohorts revealed the superior prognostic value of the PCMP signature. Functional enrichment analyses indicated that it dysregulates the cell cycle. Using trajectory and cell–cell communication analyses, we illustrated that PCMP genes exert oncogenic effects by enhancing the proliferation and oxidative phosphorylation of epithelial cells. Intra-cellular assays also demonstrated that CENPA and CKS1B had promising malignant potential. In summary, our research not only establishes the association between the PCMP signature and reveals its malignant characteristics, but also deepens our understanding of the mechanisms underlying PCa progression and ITH. It holds promise for the development of targeted therapeutic interventions, thereby offering clinical benefits to patients.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 16","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70806","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NLRP3 Inflammasome-Mediated Pyroptosis in Osteoporosis: Osteoimmune Mechanisms and Therapeutic Targeting 骨质疏松症中NLRP3炎性体介导的焦亡：骨免疫机制和治疗靶向

IF 4.2

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2025-08-25 DOI: 10.1111/jcmm.70798

Jiaxuan Fan, Guokai Du, Te Ba, HuiXin Sun

{"title":"NLRP3 Inflammasome-Mediated Pyroptosis in Osteoporosis: Osteoimmune Mechanisms and Therapeutic Targeting","authors":"Jiaxuan Fan, Guokai Du, Te Ba, HuiXin Sun","doi":"10.1111/jcmm.70798","DOIUrl":"https://doi.org/10.1111/jcmm.70798","url":null,"abstract":"Osteoporosis (OP) is a chronic, age-related skeletal disorder characterised by progressive bone loss and microstructural deterioration, which increases bone fragility and fracture risk. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a multi-subunit protein complex involved in bone homeostasis, mediates inflammatory cascades in response to external stimuli and pathological conditions. This process triggers pyroptosis in various bone-related cells, disrupting bone repair and remodelling. Oestrogen deficiency and aging lead to the overactivation of the NLRP3 inflammasome, stimulate bone immunity, metabolism and other abnormalities and disrupt angiogenesis–osteogenesis coupling. These factors contribute significantly to the pathological progression of OP. However, the precise mechanisms remain poorly understood and are lacking clinical validation. Therefore, this review summarises the mechanisms of NLRP3 inflammasome in response to bone immune signals, external stress and intercellular communication, as well as its role in metabolic regulation, including reprogramming and post-translational modification, thereby influencing pyroptosis in macrophages, endothelial cells, mesenchymal stem cells and osteoblasts. It explores potential therapeutic strategies that target NLRP3 activation, including exosome (Exos)-based interventions and traditional Chinese medicine components, which may modulate its differential expression and affect angiogenesis–osteogenesis differentiation. These approaches offer promising avenues for the prevention and treatment of OP.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 16","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70798","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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