IF 3.7 3区生物学

IUBMB Life Pub Date : 2025-05-27 DOI: 10.1002/iub.70027

Davide Ricci, Ilenia Cruciata, Ignazio Fiduccia, Emanuele Vitale, Federica Corrao, Alessio Branchini, Pietro Salvatore Carollo, Ivana Pibiri, Laura Lentini

{"title":"Advancing Therapeutic Strategies for Nonsense-Related Diseases: From Small Molecules to Nucleic Acid-Based Innovations","authors":"Davide Ricci, Ilenia Cruciata, Ignazio Fiduccia, Emanuele Vitale, Federica Corrao, Alessio Branchini, Pietro Salvatore Carollo, Ivana Pibiri, Laura Lentini","doi":"10.1002/iub.70027","DOIUrl":"https://doi.org/10.1002/iub.70027","url":null,"abstract":"<p>Nonsense mutations in gene coding regions introduce an in-frame premature termination codon (PTC) in the mRNA transcript, resulting in the early termination of translation and the production of a truncated, nonfunctional protein. The absence of protein expression and the consequent loss of essential cellular functions are responsible for the severe phenotypes in the so-called genetic nonsense-related diseases (NRDs), such as cystic fibrosis, hemophilia, Duchenne muscular dystrophy, Fabry disease, Choroideremia, Usher syndrome, Shwachman–Diamond syndrome, and even certain types of cancer. Nonsense mutations pose a significant challenge in the treatment of NRDs, as a specific approach directly addressing this genetic defect is currently unavailable. Developing new therapeutic strategies for nonsense suppression is a crucial goal of precision medicine. This review describes some of the most promising therapeutic approaches and emerging strategies for treating NRDs. It considered both the use of small molecules to interfere with molecular mechanisms related to nonsense mutations, such as translational readthrough-inducing drugs (TRIDs) or inhibitors of the nonsense-mediated decay (NMD) pathway, and also innovative approaches involving nucleic acids, such as gene editing, anticodon engineered-tRNA (ACE-tRNA), or mRNA-based therapy. Future research should focus on refining these approaches and exploring integrated and personalized treatments to enhance therapeutic outcomes and ensure continuous improvement in the quality of care.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iub.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Blood Coagulation Factor IX: Structure, Function, and Regulation 凝血因子IX：结构、功能和调控

IF 3.7 3区生物学

IUBMB Life Pub Date : 2025-05-22 DOI: 10.1002/iub.70024

Lacramioara Ivanciu, Rodney M. Camire

引用次数: 0

Discovery and Validation of a New Biomarker Integrating Ferroptosis and Glycolysis-Related Genes in Bladder Cancer 整合铁质下垂和糖酵解相关基因的膀胱癌新生物标志物的发现和验证

IF 3.7 3区生物学

IUBMB Life Pub Date : 2025-05-22 DOI: 10.1002/iub.70028

Chenyang Wang, Yuncong Shu, Jiaqi Shan, Kunpeng Li, Shun Wan, Siyu Chen, Xiaoran Li, Jiping Niu, Li Yang

{"title":"Discovery and Validation of a New Biomarker Integrating Ferroptosis and Glycolysis-Related Genes in Bladder Cancer","authors":"Chenyang Wang, Yuncong Shu, Jiaqi Shan, Kunpeng Li, Shun Wan, Siyu Chen, Xiaoran Li, Jiping Niu, Li Yang","doi":"10.1002/iub.70028","DOIUrl":"https://doi.org/10.1002/iub.70028","url":null,"abstract":"<div>\u0000 \u0000 <p>Bladder cancer (BCa) is a highly invasive tumor with few successful therapies, and its unfavorable prognosis mainly stems from late diagnosis and resistance to treatment. Ferroptosis is a type of non-apoptotic cell death characterized by iron-dependent regulated necrosis due to extensive lipid peroxidation. Glycolysis is fundamental to cancer cell metabolism, with cancer cells developing various strategies to enhance this process. In this study, we combined ferroptosis and glycolysis gene sets, two biological processes closely related to tumorigenesis and development, and obtained ferroptosis and glycolysis-related gene sets (FGRGs). By leveraging both single-cell and bulk transcriptome data from BCa, we have investigated the presence and role of FGRGs in the onset and progression of BCa through various approaches. Using machine learning algorithms, we identified a feature gene set consisting of 13 genes in the TCGA data set to predict the prognosis of BCa and verified it in the GEO data set. After that, we explored FGRGs in depth using a variety of bioinformatics analyses, such as mutational landscape analysis, functional enrichment analysis, immune infiltration analysis, FGRGs-associated risk and clinical characterization, and drug susceptibility analysis. Finally, we validated the function of the core gene chondroitin polymerizing factor 2 (CHPF2) using CCK-8, clone formation, transwell, and wound healing assays. Our research innovatively combines ferroptosis with glycolytic genes and applies it as an independent prognostic factor in the study of BCa. It reveals new characteristic genes and therapeutic targets that can predict the prognosis of BCa patients and lays a foundation for the study of the occurrence and development mechanism of BCa and targeted data strategies.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proline- and Serine-Rich Coiled-Coil 1 Predicts an Unfavorable Prognosis and Exhibits Oncogenic Activities in Breast Cancer 富含脯氨酸和丝氨酸的卷曲卷曲1预测乳腺癌的不良预后并显示致癌活性

IF 3.7 3区生物学

IUBMB Life Pub Date : 2025-05-21 DOI: 10.1002/iub.70019

Xin Jin, Qingqing Zhao, Xiaowen Hao, Peicong Shi, Yan Wang, Pei Wang

{"title":"Proline- and Serine-Rich Coiled-Coil 1 Predicts an Unfavorable Prognosis and Exhibits Oncogenic Activities in Breast Cancer","authors":"Xin Jin, Qingqing Zhao, Xiaowen Hao, Peicong Shi, Yan Wang, Pei Wang","doi":"10.1002/iub.70019","DOIUrl":"https://doi.org/10.1002/iub.70019","url":null,"abstract":"<div>\u0000 \u0000 <p>Proline- and serine-rich coiled-coil 1 (PSRC1) has been implicated in various cancers, yet its role in breast cancer (BRCA) remains incompletely understood. Here, we employed the UALCAN database to explore PSRC1 expression in BRCA and obtained survival prognosis data from the Kaplan–Meier Plotter database. Additionally, PSRC1 expression was analyzed in 81 pairs of BRCA tissues and their corresponding adjacent noncancerous tissues through quantitative real-time PCR, western blotting, and immunohistochemistry. We observed PSRC1 was overexpressed in BRCA tissues, especially in triple negative breast cancer (TNBC). Higher PSRC1 levels correlated with poorer outcomes for BRCA patients. In 81 BRCA tumor tissues, PSRC1 protein levels were significantly associated with positive vessel tumor embolus. Subsequently, the clinical relevance of PSRC1 in BRCA was assessed using the chi-square test, the Kaplan–Meier model with a Log-rank test, as well as univariate and multivariate analyses. Patients with high PSRC1 had worse prognoses. Elevated PSRC1 expression served as an independent predictor of prognosis. Moreover, we investigated the effects of PSRC1 on BRCA cell phenotypes in MCF-7 and BT549 cells and used a mouse xenograft model with BT549 cells to determine its in vivo effect. Both in vitro and in vivo experiments demonstrated that silencing PSRC1 inhibited cell proliferation, migration, and tumor development. In summary, our results indicate that high PSRC1 expression is closely linked to BRCA patient survival and could be a valuable prognostic biomarker for this disease.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Contrast-Induced Acute Kidney Injury is Modulated by Circadian CLOCK/NRF2 Pathway 对比剂诱导的急性肾损伤受昼夜节律时钟/NRF2通路调控

IF 3.7 3区生物学

IUBMB Life Pub Date : 2025-05-20 DOI: 10.1002/iub.70022

Shuqing Yang, Xinxin Xu, Lulu Wang, Yi Fang, Yang Zhou, Chunsun Dai, Lei Jiang, Boqing Zhang, Jing Luo

{"title":"Contrast-Induced Acute Kidney Injury is Modulated by Circadian CLOCK/NRF2 Pathway","authors":"Shuqing Yang, Xinxin Xu, Lulu Wang, Yi Fang, Yang Zhou, Chunsun Dai, Lei Jiang, Boqing Zhang, Jing Luo","doi":"10.1002/iub.70022","DOIUrl":"https://doi.org/10.1002/iub.70022","url":null,"abstract":"<div>\u0000 \u0000 <p>Numerous kidney functions exhibit substantial circadian oscillations, such as renal blood flow, glomerular filtration rate, tubular reabsorption function, and erythropoietin production. The onset and the injury of acute kidney injury caused by ischemia or drugs also have a circadian rhythmicity. Contrast media are widely used in clinical diagnosis and treatment; however, whether contrast-induced kidney injury exhibits a time-of-day dependence is unknown. We retrospectively analyzed 33 patients who underwent percutaneous coronary angiography and found that contrast induced the increase of serum neutrophil gelatinase-associated lipocalin (NGAL) was more obvious in the group who underwent operation during 6:00 ~ 13:00 than the group who underwent operation between 13:00 ~ 20:00. In addition, C57BL/6J mice were injected with iohexol at different times. The kidney injury of mice injected with iohexol at ZT12 was more severe than that at ZT0, which was manifested in the increase of urinary KIM1 and NGAL, enhanced renal tubular lipid peroxidation, and increased tubular ferroptosis. Inhibition of ferroptosis could alleviate kidney injury induced by iohexol at ZT12. Mechanistically, we found that nuclear factor erythrocyte 2-associated factor 2 (NRF2) expression has a 24-h circadian rhythm and is directly regulated by CLOCK. Administration of 4-Octyl itaconate at ZT12 to increase NRF2 expression could attenuate iohexol-induced tubular ferroptosis. These findings provide a new insight into the pathology of contrast medium-induced kidney injury, in which oscillatory NRF2 expression regulated by CLOCK contributes to the susceptibility of contrast-induced kidney injury in a time-of-day–specific fashion.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hermansky-Pudlak Syndrome: From Molecular Pathogenesis to Targeted Therapies Hermansky-Pudlak综合征：从分子发病机制到靶向治疗

IF 3.7 3区生物学

IUBMB Life Pub Date : 2025-05-19 DOI: 10.1002/iub.70025

Francesca Tondi, Roberta Annamaria Cirsmaru, Chiara Conti, Antonia Follenzi, Paolo Gresele, Cristina Olgasi, Loredana Bury

{"title":"Hermansky-Pudlak Syndrome: From Molecular Pathogenesis to Targeted Therapies","authors":"Francesca Tondi, Roberta Annamaria Cirsmaru, Chiara Conti, Antonia Follenzi, Paolo Gresele, Cristina Olgasi, Loredana Bury","doi":"10.1002/iub.70025","DOIUrl":"https://doi.org/10.1002/iub.70025","url":null,"abstract":"<p>Hermansky-Pudlak syndrome (HPS) is a rare inherited disorder caused by defects in lysosome-related organelles (LROs) in various tissues, including platelets, melanocytes, and endothelial cells. Key features of HPS include oculocutaneous albinism, bleeding tendency, and, in some cases, pulmonary fibrosis, granulomatous colitis, and immunodeficiency. The condition is linked to mutations in 11 genes involved in the formation of LROs. Currently, treatment options for HPS are limited and often ineffective. Though cell and gene therapies have been explored for melanosomes and epithelial cells, there is limited knowledge about their application to platelets and endothelial cells. Understanding the detailed mechanisms of HPS pathogenesis is crucial, and using induced pluripotent stem cell (iPSC) models may provide valuable insights into the disease's molecular processes, aiding the development of new treatments. In this review, we will focus on the genetics and molecular mechanisms of HPS, on its clinical manifestations and current therapeutic approaches, highlighting the need for further research into the disease mechanisms and potential innovative therapies.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iub.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

The combination of midkine inhibitor with Lenvatinib amplifies the suppression of hepatocellular carcinoma midkine抑制剂联合Lenvatinib可增强对肝细胞癌的抑制作用

IF 3.7 3区生物学

IUBMB Life Pub Date : 2025-05-05 DOI: 10.1002/iub.70014

Xue Chen, Shujun Guo, Qilin Meng, Junye Xie, Yujie Xiao, Yuanmeng Sun, Jinchi Yao, Xinyi Jiang, An Hong, Xiaojia Chen

{"title":"The combination of midkine inhibitor with Lenvatinib amplifies the suppression of hepatocellular carcinoma","authors":"Xue Chen, Shujun Guo, Qilin Meng, Junye Xie, Yujie Xiao, Yuanmeng Sun, Jinchi Yao, Xinyi Jiang, An Hong, Xiaojia Chen","doi":"10.1002/iub.70014","DOIUrl":"https://doi.org/10.1002/iub.70014","url":null,"abstract":"<p>Hepatocellular carcinoma (HCC) accounts for 75%–85% of primary liver cancer cases globally. HCC patients have a poor prognosis because of tumor metastasis and medication resistance; thus, novel therapy targets and techniques are needed. By using the Kaplan–Meier plotter database, we identified a strong association between midkine (MDK) and HCC mortality and validated its high expression in numerous HCC cell lines. In vitro, MDK down-regulation decreased HCC cell growth and macrophage M2-type polarization, whereas the presence of the MDK factor led to an increase in these processes. Combined with the first-line chemotherapeutic agent for HCC, Lenvatinib, zebrafish experiments showed that the inhibitor iMDK inhibited the growth of intersegmental vessels and subintestinal vessels, while also mitigating the pericardial edema side effect. In a subcutaneous mouse model, the combination of iMDK with Lenvatinib inhibited HCC growth, angiogenesis, and M2-type macrophage infiltration. These results indicate that MDK represents a promising therapeutic target for HCC. Furthermore, the combination of iMDK with Lenvatinib enhances HCC inhibition, thereby presenting a novel therapy option.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modulation of Osteogenic Differentiation by CYBB in Osteoporotic Models CYBB对骨质疏松模型成骨分化的调节作用

IF 3.7 3区生物学

IUBMB Life Pub Date : 2025-05-02 DOI: 10.1002/iub.70023

Zhaodong Wang, Chen Xu, Yajun Liu, Keyou Duan, Zhonglian Zhu, Jianzhong Guan

{"title":"Modulation of Osteogenic Differentiation by CYBB in Osteoporotic Models","authors":"Zhaodong Wang, Chen Xu, Yajun Liu, Keyou Duan, Zhonglian Zhu, Jianzhong Guan","doi":"10.1002/iub.70023","DOIUrl":"https://doi.org/10.1002/iub.70023","url":null,"abstract":"<div>\u0000 \u0000 <p>Osteoporosis (OP) is a prevalent systemic skeletal disease characterized by increased bone fragility and fracture risk. Identifying factors that influence osteogenic differentiation in OP is crucial. We screened genes associated with OP from the Gene Expression Omnibus (GEO) database and constructed a weighted correlation network analysis (WGCNA) to identify hub genes, validating our findings in external and clinical cohorts. Various experiments assessed the proliferation, apoptosis, and osteogenic differentiation abilities of bone marrow mesenchymal stem cells (BMSCs) following CYBB knockdown. We established a postmenopausal OP model in rats through bilateral ovariectomy (OVX) and evaluated OP severity using three-dimensional computed tomography (3D-CT) and H&E staining. Differential gene expression analysis revealed that CYBB was significantly upregulated in OP, with the highest area under the curve (AUC) among differentially expressed genes (DEGs). Notably, CYBB expression in BMSCs decreased over time. Knockdown of CYBB promoted BMSC proliferation and reduced apoptosis, as demonstrated by Alizarin red and ALP staining, which indicated enhanced osteogenic differentiation. Markers such as RUNX1, RUNX2, ALP, secreted phosphoprotein 1 (SPP1), and bone sialoprotein (BSP) were upregulated post-knockdown. In vivo, CYBB knockdown improved bone mineral density (BMD), relative bone volume fraction (BV/TV), and trabecular number (Tb.N). In conclusion, CYBB influences OP progression by modulating bone formation.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to “Upstream Transcription Factor 1 Suppresses Laryngeal Squamous Cell Carcinoma Progression Through Transcriptional Activation of Junctional Adhesion Molecule 3” 更正“上游转录因子1通过连接粘附分子3的转录激活抑制喉部鳞状细胞癌的进展”

IF 3.7 3区生物学

IUBMB Life Pub Date : 2025-05-02 DOI: 10.1002/iub.70021

引用次数: 0

Therapeutic Potential of Translational Readthrough at Disease-Associated Premature Termination Codons From Tumor Suppressor Genes 肿瘤抑制基因中与疾病相关的过早终止密码子翻译读通的治疗潜力

IF 3.7 3区生物学

IUBMB Life Pub Date : 2025-05-02 DOI: 10.1002/iub.70018

Leire Torices, Caroline E. Nunes-Xavier, Rafael Pulido

引用次数: 0

IUBMB Life最新文献