International Journal of Biological Sciences最新文献

{"title":"Orchestration of Tumor-Associated Macrophages in the Tumor Cell-Macrophage-CD8⁺ T Cell Loop for Cancer Immunotherapy.","authors":"Lin He, Paul Kwong-Hang Tam, Chu-Xia Deng","doi":"10.7150/ijbs.115932","DOIUrl":"10.7150/ijbs.115932","url":null,"abstract":"<p><p>The tumor microenvironment is densely populated with tumor-associated macrophages (TAMs), which exhibit various phenotypes at different stages of tumor progression. TAMs are highly plastic and intricately linked to the antitumor activity and functionality of CD8⁺ T cells. Tumor cells, TAMs and CD8⁺ T cells constitute a feedback loop that monitors the tumor immune surveillance. Modulation of several chief signaling pathways within TAMs can steer them towards either an immunoinflammatory or immunosuppressive state. This can be achieved indirectly through cancer therapies or by directly targeting TAMs. New detailed insights into the immunostimulatory reprogramming of TAMs inspire the design of novel combinatory strategies that can be extrapolated to bolster cancer immunotherapy.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 9","pages":"4098-4116"},"PeriodicalIF":8.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apelin facilitates integrin αvβ3 production and enhances metastasis in prostate cancer by activating STAT3 and inhibiting miR-8070.","authors":"Tien-Huang Lin, Shan-Chi Liu, Yuan-Li Huang, Chao-Yang Lai, Xiu-Yuan He, Chun-Hao Tsai, Yi-Chin Fong, Hsi-Chin Wu, An-Chen Chang, Yen-You Lin, Chih-Hsueh Lin, Chih-Hsin Tang","doi":"10.7150/ijbs.113161","DOIUrl":"10.7150/ijbs.113161","url":null,"abstract":"<p><p>Prostate cancer is the most common cancer in men and is often associated with distant metastasis in its later stages. Cell surface receptors called integrins function as adhesion molecules that mediate both cell adhesion and motility. The adipokine apelin has been implicated in cancer progression and metastasis. However, the mechanisms by which apelin regulates integrin production and metastasis in prostate cancer remain unclear. Here, we found that apelin and integrin αvβ3 expression levels were elevated in prostate cancer samples compared to those in normal individuals. Apelin stimulation enhances integrin αvβ3-dependent prostate cancer migration. The activation of STAT3 and inhibition of miR-8070 via the MAPK pathway mediate apelin-facilitated integrin synthesis and cell motility. Importantly, our <i>in vivo</i> study indicated that inhibiting apelin reduces integrin αvβ3 expression and prostate cancer metastasis. Our results suggest that the apelin/integrin axis is a novel therapeutic target for treating metastatic prostate cancer.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 9","pages":"4117-4128"},"PeriodicalIF":8.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APT1-derived depalmitoylation of CD36 alleviates diabetes-induced lipotoxicity in podocytes.","authors":"Juan Wang, Jijia Hu, Hongtu Hu, Qian Guan, Zijing Zhu, Qian Yang, Guohua Ding","doi":"10.7150/ijbs.109220","DOIUrl":"10.7150/ijbs.109220","url":null,"abstract":"<p><p>Cluster of Differentiation 36 (CD36), also known as scavenger receptor B2, plays a critical role in controlling podocyte lipid metabolism, mediating the onset and progression of diabetic kidney disease (DKD). However, the post-translational regulation of CD36 and its exact role in lipid transport within podocytes remain unclear. In this study, we elucidate the mechanism by which acyl-protein thioesterase 1 (APT1) depalmitoylates CD36 in podocytes. We reveal that APT1 interacts with CD36 and reduces its palmitoylation at Cys466 specifically, thereby promoting its trafficking from the plasma membrane to lysosomes for degradation. Diabetes-induced downregulation of APT1 redirects palmitoylated CD36 into the recycling pathway. Consequently, enhanced lipid uptake in podocytes leads to lipotoxicity. Conversely, APT1 overexpression mitigates lipid accumulation by enhancing lysosomal degradation and reducing plasma membrane-associated CD36. Our findings indicate that diabetes-induced APT1 deficiency promotes palmitoylated CD36 enrichment on plasma membranes through decreased APT1 expression, driving lipid overload and podocyte injury.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 9","pages":"3852-3866"},"PeriodicalIF":8.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction of Nanomaterials with Nucleic Acids and Their Applications in Nucleic Acid Analysis.","authors":"Jiale Wang, Kai Li, Fukai Li, Xinran Li, Jian Zhou, Mengrui Yang, Xiao Zhang, Mengyu Wang, Liang Li","doi":"10.7150/ijbs.113309","DOIUrl":"10.7150/ijbs.113309","url":null,"abstract":"<p><p>Nucleic acid analysis technology is the key to cracking the genetic information of life, which is very important for insight into disease diagnosis, drug development, food safety and environmental monitoring. The successful implementation of nucleic acid analysis depends on efficient and accurate nucleic acid sample purification technology. Traditional nucleic acid extraction methods are not only time-consuming and difficult to handle but also require skilled operators. Nanotechnology is gradually innovating nucleic acid extraction, simplifying the process and promoting biological science into a new era. The interaction modes between nanomaterials and nucleic acid molecules are diverse, including electrostatic interaction, covalent binding (direct covalent bonding, biotin-avidin system, disulfide bond connection, coordination bond, azide-alkyne click reaction, EDC/NHS coupling), π-π stacking effect, hydrogen bond formation, hydrophobic interaction and ion exchange. Among them, electrostatic interaction and covalent binding are particularly common and widely used. In addition, integrating nanomaterials into advanced monitoring systems such as microfluidic chips and biosensors provides strong support for the innovation of nucleic acid detection technology. The purpose of this paper is to comprehensively explain the basic principles and related molecular mechanisms of the interaction between nucleic acids and nanomaterials and to demonstrate their effectiveness in practical applications through specific examples for each interaction mode. Finally, we will review the latest progress of nanomaterial application in nucleic acid analysis, aiming to provide valuable references and inspirations for future research and development in this field.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 9","pages":"4051-4068"},"PeriodicalIF":8.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signature-based repurposed drugs resemble the inhibition of TGFβ-induced NDRG1 as potential therapeutics for triple-negative breast cancer.","authors":"Araceli López-Tejada, Jose L Blaya-Cánovas, Francisca E Cara, Jesús Calahorra, César Ramírez-Tortosa, Isabel Blancas, Violeta Delgado-Almenta, Fabiola Muñoz-Parra, Marta Ávalos-Moreno, Ana Sánchez, Adrián González-González, Juan A Marchal, Carmen Griñán-Lisón, Sergio Granados-Principal","doi":"10.7150/ijbs.112645","DOIUrl":"10.7150/ijbs.112645","url":null,"abstract":"<p><p>There is an urgent need for new therapeutic strategies against aggressive triple-negative breast cancer (TNBC), and drug repurposing offers a promising, time- and cost-effective solution. We previously reported that TGFβ leads to the tumorigenic role of NDRG1 in TNBC. Here, we aimed to identify drugs that mimic the transcriptomic signature after the inhibition of TGFβ-induced NDRG1 and to determine their antitumor properties. The transcriptomic signature was obtained by RNA sequencing after gene silencing of TGFβ-induced <i>NDRG1</i> expression in TNBC cells. For the drug repositioning study, the transcriptome was further computationally analyzed by using the Connectivity Map tool. Efavirenz, ouabain, and vinburnine were selected as the repurposed drug candidates to evaluate their therapeutic potential in TNBC models as monotherapies and pairwise combinations. We determined that the candidate drugs significantly reduced tumor cell proliferation, cancer stem cells, self-renewal, clonogenic properties, and migration abilities in TNBC cell lines through the blockade of AKT. Importantly, we validated their translational potential in TNBC patient-derived xenograft organoids in combination with docetaxel. After validating that the drugs decreased p-AKT and Ki67, we demonstrated their antitumor activity in combination with docetaxel in organoids. In addition, drugs also showed efficacy in a docetaxel-resistant TNBC model, supporting their potential to overcome chemoresistance. In conclusion, these findings demonstrate the potential of efavirenz, ouabain, and vinburnine as repurposed agents capable of inhibiting TNBC cell proliferation, stemness, and migration. Their synergistic effects with docetaxel in organoid cultures further underscore their translational relevance and highlight a promising strategy for combination therapies to improve TNBC treatment.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 9","pages":"3949-3967"},"PeriodicalIF":8.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin Ameliorate neuroinflammation in activated microglia through the Aryl hydrocarbon-Nrf2 axis.","authors":"Meei-Ling Sheu, Cheng-Ning Yang, Liang-Yi Pan, Jason Sheehan, Liang-Yu Pan, Weir-Chiang You, Chien-Chia Wang, Ying Ju Chen, Hong-Shiu Chen, Hung-Chuan Pan","doi":"10.7150/ijbs.105081","DOIUrl":"10.7150/ijbs.105081","url":null,"abstract":"<p><p>Microglia-mediated neuroinflammation is central to many neurological disorders. The Aryl hydrocarbon receptor (AhR) is highly expressed in microglia and plays a key role in neuroinflammation. While melatonin has anti-inflammatory effects in neurodegenerative disorders, its connection to AhR in modulating neuroinflammation is unclear. This study found that melatonin inhibits NF-κB activity, reduces pro-inflammatory mediators, and promotes an M2 microglia profile. Melatonin also enhances phospho-AhR (Tyr239) activation, increases Nrf2 expression, and decreases LPS-induced ROS generation in microglia. Melatonin's effects are similar to those achieved by AhR activation. In contrast, AhR knockout worsens neurological deficits and microglial activation, while melatonin reverses these effects by restoring AhR expression. In conclusion, effects of melatonin on microglia-mediated neuroinflammation are closely linked to phospho-AhR (Tyr239) activation and its associated downstream gene, Nrf2, via the AhR/Nrf2/ARE pathway. Therefore, melatonin, in conjunction with AhR may offer promising therapeutic benefits in neuroinflammatory disorders.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 9","pages":"3917-3933"},"PeriodicalIF":8.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein Arginine Methyltransferase 1-mediated Histone H4R3 Dimethyl Asymmetric enhances Epidermal Growth Factor Receptor signaling to promote Peritoneal Fibrosis.","authors":"Hui Chen, Yingfeng Shi, Jinqing Li, Qin Zhong, Xiaoyan Ma, Yan Hu, Yishu Wang, Daofang Jiang, Xialin Li, Shasha Zhang, Shougang Zhuang, Na Liu","doi":"10.7150/ijbs.114037","DOIUrl":"10.7150/ijbs.114037","url":null,"abstract":"<p><p>Peritoneal fibrosis (PF) is regarded as one of the major complications of peritoneal dialysis (PD) and is still lack of efficacious clinical interventions to address this issue. Previous publications have indicated that protein arginine methyltransferase 1 (PRMT1) is involved in the pathological process of various diseases. However, the role of PRMT1 in the development of PF remains to be elucidated. In the present study, we demonstrate that PRMT1 is highly expressed in the peritoneum and dialysis effluent of long-term PD patients, and that there is a positive correlation between PRMT1 and the hallmarks of fibrosis in human peritoneal specimens. Our results further demonstrate that the genetic depletion or pharmacological inhibition of PRMT1 has the potential to reduce extracellular matrix deposition and alleviate PF caused by high-glucose peritoneal dialysis fluid (HG-PDF) in murine models. In addition, silencing or pharmacological inhibition of PRMT1 could also reduce the epithelial-to-mesenchymal (EMT) phenotypic change caused by TGF-β1 <i>in vitro</i>. The use of RNA sequencing facilitated the identification of the epidermal growth factor receptor (EGFR) as a target of PRMT1 in PF. Furthermore, the reduction of PRMT1 levels, achieved through either genetic depletion or pharmacological inhibition, results in the deactivation of EGFR downstream signaling pathways. Our findings uncover a novel mechanism by which PRMT1-mediated H4R3me2a activates the EGFR and its associated downstream signaling pathways in the context of PF. Consequently, these findings imply that PRMT1 may serve as a valuable diagnostic or therapeutic target for PF.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 9","pages":"4010-4026"},"PeriodicalIF":8.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon Regulatory Factor 4 Recruits Immature B Cells to Signal Tertiary Lymphoid Structure Immaturity and Progression of Clear Cell Renal Cell Carcinoma.","authors":"Siqi Zhou, Shiqi Ye, Liang Chen, Qintao Ge, Jiahe Lu, Aihetaimujiang Anwaier, Xi Tian, Zhongyuan Wang, Shuxuan Zhu, Kun Chang, Jianfeng Yang, Tian Li, Hailiang Zhang, Dingwei Ye, Jianfeng Xiang, Wenhao Xu","doi":"10.7150/ijbs.113737","DOIUrl":"10.7150/ijbs.113737","url":null,"abstract":"<p><p><b>Background:</b> Tertiary lymphoid structures (TLSs), organized clusters of immune cells within non-lymphoid tissues, significantly influence tumor progression and therapeutic response. However, their prognostic relevance and underlying regulatory mechanisms in clear cell renal cell carcinoma (ccRCC) remain insufficiently characterized. <b>Methods:</b> We integrated transcriptomic and clinical data from 928 ccRCC patients to construct a TLS-related prognostic RiskScore using machine learning algorithms. TLS maturation heterogeneity was characterized via immunohistochemistry and multiplex immunofluorescence analyses. The functional role of interferon regulatory factor 4 (IRF4), a key regulator within the TLS gene network, was investigated using <i>in vitro</i> assays. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics were employed to dissect the involvement of IRF4 in TLS formation and maturation. <b>Results:</b> The derived TLS-associated signature RiskScore, comprising <i>CCL22, LOXL1, LIPA, ADAM8, and SAA1,</i> effectively stratified patients into distinct prognostic groups and showed robust associations with clinical parameters, tumor microenvironment (TME) features, and predicted immunotherapy responses. Functional assays demonstrated that IRF4 significantly enhanced the malignant phenotype of 786-O and 769-P ccRCC cells. Clinically, elevated IRF4 expression independently predicted worse patient outcomes, characterized by a predominance of immature TLS phenotypes, reduced TLS density, and diminished CD8⁺ T cell infiltration. Mechanistically, scRNA-seq analyses revealed that active IRF4 signaling was predominantly confined to immature B cell states and was inversely associated with TLS maturation trajectories. Spatial transcriptomics further confirmed IRF4 enrichment within TLS regions, notably spatially segregated from high endothelial venules (HEVs) and mature TLS compartments. <b>Conclusion:</b> In conclusion, this study establishes a robust TLS-related prognostic signature for ccRCC and elucidates the mechanistic role of IRF4 in promoting TLS immaturity and immune dysfunction. By potentially recruiting immature B cells while impairing their maturation, IRF4 contributes to an ineffective anti-tumor immune landscape, offering a promising target for therapeutic intervention.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 9","pages":"3827-3851"},"PeriodicalIF":8.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polystyrene Nanoplastics Exacerbate HFD-induced MASLD by Reducing Cathepsin Activity and Triggering Large Vacuole Formation via Impaired Lysosomal Acidification.","authors":"Jiwon Ahn, Kajung Ryu, Hyerin Kim, Hwi Won Seo, Minsu Jang, Seung-Hyun Kim, Yunho Park, Myung Jin Son, Ho-Joon Lee, Ok-Seon Kwon, Kyung-Sook Chung","doi":"10.7150/ijbs.108268","DOIUrl":"10.7150/ijbs.108268","url":null,"abstract":"<p><p>Environmental nanoplastics (NPs) have harmful effects on health. This study investigated the effects of polystyrene (PS) NPs on steatosis and fatty liver disease. PS-NP oral administration, in conjunction with a high-fat diet (HFD), synergistically exacerbated the symptoms of steatosis in mice, leading to increased alanine transaminase, aspartate aminotransferase, and cholesterol levels; no effects were observed with PS-NPs on a normal chow diet. Transcriptome analysis unveiled that PS-NPs interfered with actin organization, cell-cell adhesion, PPAR signaling, and lipid metabolism. In HepaRG cells, PS-NPs rapidly entered by inducing actin rearrangement, resulting in the formation of numerous small cytoplasmic vesicles. This treatment led to an augmented number of acidic organelles, leading to development and buildup of large vacuoles, indicative of enlarged pre-lysosomal and lysosomal compartments. PS-NP exposure hampered p62 degradation, leading to LC3B accumulation and decreased cathepsin B and D activity. Additionally, PS-NP exposure resulted in accumulation of lipid droplets and elevated expression of lipogenesis-, transport-, and storage-related genes. These findings suggest that excessive endocytosis driven by PS-NPs worsens MASLD in HFD through accumulation of lysosomes and large vacuoles with reduced cathepsin activity.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 9","pages":"3867-3885"},"PeriodicalIF":8.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exogenous SPD inhibits trastuzumab-mediated cardiomyocyte pyroptosis through SIRT3-regulated mitochondrial quality control.","authors":"Xue Yu, Yan Yang, Tianzuo Chen, Qianbing Wang, Zitong Wang, Xi Gao, Qianxue Wang, Jinxiang Guo, Yuqin Wang, Yajie Zhao, Shilin Wang, Wei Lu, Xing Luo, Tielei Gao, Jiayuan Kou, Hong Li, Liming Yang","doi":"10.7150/ijbs.110580","DOIUrl":"10.7150/ijbs.110580","url":null,"abstract":"<p><p>Trastuzumab (TRZ) is an anti-HER2 monoclonal antibody associated with significant survival benefits; however, its clinical utility is restricted by trastuzumab-induced cardiotoxicity (TIC). While the inhibition of HER2 induces mitochondrial dysfunction in cardiomyocytes, it is unclear whether mitochondrial quality control participates in trastuzumab-mediated cardiomyocyte pyroptosis. This study demonstrated that TRZ leads to a reduction in left ventricular systolic function, myocardial pyroptosis, and mitochondrial oxidative stress; alterations in the mitochondrial membrane potential; changes in mitochondrial permeability; mitochondrial dysfunction; and a decrease in mitochondrial biosynthesis in the murine heart. Supplementation with exogenous spermidine inhibits myocardial oxidative stress and mitochondrial dysfunction, and promotes mitochondrial biosynthesis in mice, thereby protecting cardiac function. Additionally, SIRT3 plays a protective role in TRZ-induced myocardial injury. In SIRT3 knockout mice, TRZ-induced cardiac injury was exacerbated, and mitochondrial damage was aggravated. In conclusion, these findings reveal the pathogenic mechanism underlying trastuzumab-induced cardiomyopathy and suggest a novel therapeutic target for preventing cardiotoxicity in HER2+ breast cancer treatment.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 9","pages":"4027-4050"},"PeriodicalIF":8.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}