Experimental cell research最新文献

{"title":"USP7-mediated NUF2 deubiquitination accelerates ovarian cancer progression through regulating SLC7A11 expression","authors":"Yiyang Zhai ,&nbsp;Hongli Niu ,&nbsp;Junying Zhai ,&nbsp;Ran Yang ,&nbsp;Quanxiao Xu ,&nbsp;Pu Qiao","doi":"10.1016/j.yexcr.2025.114659","DOIUrl":"10.1016/j.yexcr.2025.114659","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer is highly lethal malignancy. Previous studies have indicated that Ndc80 kinetochore complex component (NUF2) exhibited oncogenic properties in ovarian cancer. This study aimed to investigate the underlying mechanisms by which NUF2 contributes to ovarian cancer progression.</div></div><div><h3>Methods</h3><div>Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was conducted to measure the mRNA expression levels of NUF2 and solute carrier family 7 member 11 (SLC7A11). The protein expression of NUF2, ubiquitin-specific protease 7 (USP7) and SLC7A11 was examined through Western blot. Cell proliferation was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide (MTT) and 5-ethynyl-2′-deoxyuridine (EdU) assays. Cell apoptosis and invasion were detected by flow cytometry and transwell invasion assay, respectively. Ferroptosis was assessed through detecting ferrous ion (Fe²⁺), reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Immunoprecipitation (IP) and ubiquitination assays were conducted to prove the relationship between NUF2 and USP7. <em>In vivo</em>, the role of NUF2 in ovarian cancer was examined using xenograft mouse models, followed by immunohistochemistry (IHC) analysis.</div></div><div><h3>Results</h3><div>NUF2 was significantly elevated in ovarian cancer cells. Knockdown of NUF2 markedly inhibited ovarian cancer cell proliferation and invasion while promoting apoptosis and ferroptosis. Mechanistically, USP7 stabilized NUF2 by mediating its deubiquitination. USP7 depletion inhibited cell proliferation and invasion, and promoted cell apoptosis and ferroptosis in ovarian cancer cells, effects that were mediated through NUF2 downregulation. Furthermore, SLC7A11 was overexpressed in ovarian cancer, and NUF2 positively regulated its expression. NUF2 depletion decreased SLC7A11 expression, thereby suppressing ovarian cancer progression. Additionally, SLC7A11 overexpression could reverse the inhibitory effects of USP7 knockdown on ovarian cancer progression.</div></div><div><h3>Conclusion</h3><div>USP7 stabilized NUF2 expression via deubiquitination to accelerate ovarian cancer progression through regulating SLC7A11 expression.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114659"},"PeriodicalIF":3.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527093","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}

{"title":"Vinculin and c-Cbl-associated protein (CAP) suppress Meflin expression to regulate stiffness-dependent osteogenic differentiation of mesenchymal stem cells","authors":"Moe Fujiwara ,&nbsp;Akihisa Ogawa ,&nbsp;Shinsuke Takahashi ,&nbsp;Takeshi Kobayashi ,&nbsp;Shuhei Tanabe ,&nbsp;Merisa Hosotani ,&nbsp;Yasuhisa Kimura ,&nbsp;Atsushi Enomoto ,&nbsp;Mito Kuroda ,&nbsp;Noriyuki Kioka","doi":"10.1016/j.yexcr.2025.114657","DOIUrl":"10.1016/j.yexcr.2025.114657","url":null,"abstract":"<div><div>Vinculin and c-Cbl-associated protein (CAP) mediate the regulation of mesenchymal stem cell (MSC) differentiation depending on the stiffness of the extracellular matrix (ECM); however, the molecular mechanism downstream of vinculin-CAP is not fully elucidated. Here, we demonstrated that vinculin and CAP suppress Meflin expression, a factor crucial for maintaining MSCs in an undifferentiated state. Depletion of vinculin and CAP increases Meflin expression, particularly on rigid ECM substrates. This regulation occurs through Yes-associated protein, a transcriptional co-activator that influences cellular differentiation. Furthermore, CAP-mediated suppression of Meflin promotes osteoblast differentiation on rigid ECM. Overall, this study demonstrates that the vinculin-CAP-Meflin axis is involved in a complex regulatory mechanism that controls MSC differentiation into osteoblasts depending on ECM stiffness.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114657"},"PeriodicalIF":3.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505276","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}

{"title":"Secreted phosphoprotein 1 promotes the activation of keloid fibroblasts via the CD44/TGF-β1/Smad pathway","authors":"Yemingzi Tu ,&nbsp;Yifeng Xiong ,&nbsp;Ougen Liu ,&nbsp;Yating Peng","doi":"10.1016/j.yexcr.2025.114658","DOIUrl":"10.1016/j.yexcr.2025.114658","url":null,"abstract":"<div><div>Keloids, characterized by pruritic and painful lesions, severely impact quality of life. Although Secreted Phosphoprotein 1 (SPP1) has been linked to fibrotic disorders, its role in keloid pathogenesis remains unclear. Bioinformatics analysis and Gene Expression Omnibus (GEO) datasets were utilized to identify key genes in keloid development. mRNA and protein expression levels were assessed using qRT-PCR and Western blot. Cellular proliferation was evaluated via CCK-8 and EdU assays, while cell motility was analyzed through scratch wound healing and migration/invasion assays. Mitochondrial network morphology was examined using MitoTracker staining. In vivo experiments were conducted using a mouse subcutaneous tumor model to validate the functional role of SPP1.SPP1 was identified as a critical gene in keloid fibrosis through bioinformatics and GEO dataset analysis. Human keloid fibroblasts (HKF) exhibited significantly higher SPP1 mRNA and protein expression compared to human skin fibroblasts (HSF). SPP1 inhibition reduced CD44 expression and suppressed HKF migration, invasion, proliferation, epithelial-mesenchymal transition (EMT), and the expression of TGF-β1, p-Smad2/3, Col1A1, and myofibroblast markers. Conversely, transfection of recombinant human SPP1 protein (rhSPP1) enhanced these cellular behaviors. CD44 inhibition attenuated the effects of rhSPP1 and downregulated TGF-β1 and p-Smad2/3 expression. In vivo, downregulation of SPP1 significantly reduced the volume and weight of subcutaneous tumors.SPP1 promotes HKF activity and fibrosis-related behaviors via the CD44/TGF-β1/Smad signaling axis and may inhibit apoptosis through the mitochondrial pathway. These findings highlight SPP1 as a potential therapeutic target for keloid treatment.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114658"},"PeriodicalIF":3.3,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505275","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}

{"title":"Constructing a co-culture model of cancer-associated fibroblasts and ovarian cancer organoids and studying mechanisms of drug resistance","authors":"Ying Ma ,&nbsp;Fengqin Xue ,&nbsp;Zhihua Pei ,&nbsp;Ye Zhao","doi":"10.1016/j.yexcr.2025.114656","DOIUrl":"10.1016/j.yexcr.2025.114656","url":null,"abstract":"<div><h3>Background</h3><div>Drug resistance contributes to the relatively low 5-year survival rate in ovarian cancer patients. Due to the complex cell-cell interactions in the tumor microenvironment, the mechanism of drug resistance is highly intricate. Here, we aim to establish 3-dimensional (3D) organotypic co-cultures of primary ovarian cancer-derived organoids with cancer-associated fibroblasts (CAFs) and to understand their interactions and the response to treatment.</div></div><div><h3>Methods</h3><div>CAFs and organoids were isolated from tissues of a patient with high-grade serous ovarian cancer, and a 3D co-culture model of organoids with CAFs was established in vitro. The organoid growth and drug sensitivity were compared with and without the presence of CAFs. Gene expression analysis was conducted to identify the key genes and pathways leading to the phenotypic changes.</div></div><div><h3>Results</h3><div>We successfully constructed a 3D co-culture model of human ovarian cancer organoids with CAFs. CAFs have been observed to promote organoids growth and protect them from paclitaxel and cisplatin treatment. Transcriptome analysis suggested that CAFs may mediate organoid growth and promote resistance through multiple pathways, including the PI3K-Akt signaling pathway and cytokine-cytokine receptor interaction. Additionally, patients with high ovarian CAF signature exhibited a poor prognosis in three public ovarian cancer cohorts.</div></div><div><h3>Conclusion</h3><div>In conclusion, this study demonstrates that the integration of CAFs into an ovarian cancer organoid culture model results in the promotion of tumor growth and the mediation of resistance through multiple signaling pathways. This provides a reliable research model for elucidating the mechanisms underlying drug resistance in ovarian cancer and the development of targeted therapies.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114656"},"PeriodicalIF":3.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470348","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}

{"title":"Tissue is the issue: overcoming limitations in lung cancer precision medicine through cryobiopsy-derived lung cancer organoids and organ-on-a-chip models","authors":"Yoonjoo Kim ,&nbsp;Dongil Park ,&nbsp;Dahye Lee,&nbsp;Chaeuk Chung","doi":"10.1016/j.yexcr.2025.114642","DOIUrl":"10.1016/j.yexcr.2025.114642","url":null,"abstract":"","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114642"},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293609","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}

{"title":"The Scribble-Rac1 signaling axis drives epithelial cell motility and contributes to diffuse adenomyosis pathogenesis","authors":"Xiaoping He ,&nbsp;Yaoming Peng ,&nbsp;Haiou Liu ,&nbsp;Congjian Xu","doi":"10.1016/j.yexcr.2025.114654","DOIUrl":"10.1016/j.yexcr.2025.114654","url":null,"abstract":"<div><h3>Purpose</h3><div>The study was designed to investigate whether estrogen regulates cell migration through cell polarity signaling and contributes to adenomyosis development.</div></div><div><h3>Methods</h3><div>In vitro study, Ishikawa cells received different treatments, Western Blot was used to detect the expression of adhesion factors and cytoskeletal proteins. Pseudopodia formation was assessed by cell immunofluorescence staining. Scratch test and transwell invasion test were used to detect the changes in Ishikawa cell migration and invasion.</div></div><div><h3>Results</h3><div>Scribble expression in Ishikawa cells is down-regulated by estrogen, leading to reduced expression of adhesion factors, increased expression of cytoskeletal proteins, enhanced pseudopodia formation, and elevated cell motility and invasion. Molecular mechanism research suggests that reduced Scribble expression may promote cell motility and invasion through activation of the Rac1-IRSp53-WAVE2 signaling pathway.</div></div><div><h3>Conclusions</h3><div>Scribble downregulation may serve as an indicator of adenomyosis severity. Its reduction alters cytoskeletal protein expression, enhancing cell motility. Mechanistically, Scribble downregulation likely activates Rac1, triggering the Rac1/IRSp53/WAVE2 pathway, which promotes pseudopodia formation and increases cell migration. These insights provide a theoretical basis for understanding the pathogenesis of adenomyosis.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114654"},"PeriodicalIF":3.3,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307892","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}

{"title":"Dysfunctional pericellular hyaluronan deposition contributes to attenuated CD44/EGFR co-localization and impaired myofibroblast differentiation in chronic wound fibroblasts","authors":"Nathaniel Glyn Morris ,&nbsp;Emma Louise Woods ,&nbsp;Jordanna Dally ,&nbsp;Adam Christopher Midgley ,&nbsp;Robert Steadman ,&nbsp;Ryan Moseley","doi":"10.1016/j.yexcr.2025.114646","DOIUrl":"10.1016/j.yexcr.2025.114646","url":null,"abstract":"<div><div>Non-healing chronic wounds, such as venous ulcers and pressure sores, represent significant causes of patient morbidity and financial burden to Healthcare Services worldwide. During normal healing, dermal fibroblasts (DFs) mediate numerous responses to promote wound closure. However, phenotypic changes induced within chronic wound environments lead to dysfunctional fibroblast functions, which facilitate non-healing. Although the processes underlying impaired proliferative and migratory responses in chronic wound fibroblasts (CWFs) are established, the mechanisms that mediate impaired CWF-myofibroblast differentiation remain poorly understood. Fibroblast-myofibroblast differentiation is induced by transforming growth factor-β₁ (TGF-β₁) and downstream classical Smad2/3 and non-classical epidermal growth factor receptor (EGFR)/ERK1/2 signaling, initiated through hyaluronan (HA) receptor (CD44) binding to EGFR and dependent on elevated HA synthesis and its pericellular accumulation. Here, we demonstrate that these signaling pathways are dysregulated in venous ulcer- and pressure sore-derived CWFs, compared to DFs. CWFs exhibit increased susceptibilities to cellular senescence and impaired myofibroblast differentiation, accompanied by defective lysosomal/endosomal activities and dysfunctional activation of the HA/CD44/EGFR pathway. Irrespective of wound source, CWFs exhibited increased HAS1 versus HAS2 expression, altered HAS1 and HAS2 intracellular localization, and deregulated hyaladherin (CD44, TSG-6, and IαI heavy chain motifs, HC3, HC4 and HC5) induction, following TGF-β₁ stimulation. These events attenuated HA pericellular coat formation and CD44/EGFR co-localization within membrane lipid rafts, essential for myofibroblast development. Our findings suggest that aberrant HAS1 and HAS2 expression and distributions cause reduced pericellular hyaluronan deposition, leading to attenuated CD44/EGFR co-localization and dysfunctional CWF-myofibroblast differentiation, which contributes to the impaired closure and healing of chronic wounds.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114646"},"PeriodicalIF":3.3,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309789","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}

{"title":"BMSC-derived exosomal CD73 mediated macrophage polarization promotes osteoblastic differentiation in diabetes","authors":"Yiping Dou ,&nbsp;Shujia Yu ,&nbsp;Shiyu Cao,&nbsp;Kang Gao,&nbsp;Menghao Lv,&nbsp;Yilin He,&nbsp;Ruihong Ma,&nbsp;Qian Zhu,&nbsp;Chenrui Li,&nbsp;Zhenhua Gao,&nbsp;Pan Ma","doi":"10.1016/j.yexcr.2025.114653","DOIUrl":"10.1016/j.yexcr.2025.114653","url":null,"abstract":"<div><div>Stem cell-derived exosomes have exhibited promise for applications in tissue regeneration. However, the osteogenic ability of exosomes derived from bone marrow mesenchymal stem cells(BMSCs) in diabetes is impaired. Exosomes play a role in intercellular communication and affect the functional status of many adjacent cells. The micro-inflammatory state in diabetes often leads to a higher proportion of M1/M2 macrophages in the tissue damage area than in non-diabetic individuals, which is unfavorable for tissue regeneration and delays wound healing. In the present study, we compared the macrophage polarization effect of exosomes secreted by BMSCs derived from type 2 diabetic rats(Exo(dm)) and derived from normal rats(Exo(wis)). The impact of Exo(dm) on regulating the polarization to M2 type in macrophages was weaker than that of Exo(wis), which brought less osteogenesis and was one of the reasons for poor regenerative repair of bone defects. To go a step further, Exo(dm) has lower expression of CD73, which could activate adenosine receptor A2b and cAMP/AKP pathway, leading to disorder of macrophage polarization in diabetes.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114653"},"PeriodicalIF":3.3,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309788","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}

{"title":"CLEC5A suppresses cell growth and metastasis via interfering with the calcineurin/NFATc1 signaling pathway in osteosarcoma","authors":"Bin Hu ,&nbsp;Ruifeng Shi ,&nbsp;Xiang-an Kong ,&nbsp;Li Li ,&nbsp;Jie Gao ,&nbsp;Tao Xie ,&nbsp;Yong Hu","doi":"10.1016/j.yexcr.2025.114650","DOIUrl":"10.1016/j.yexcr.2025.114650","url":null,"abstract":"<div><div>Osteosarcoma (OS) is a prevalent primary bone malignancy characterized by a poor prognosis due to its high metastatic potential. Although the dysregulation of C-type lectin domain family 5, member A (CLEC5A) has been reported in various cancers, its role in OS progression and molecular pathogenesis remains elusive. We leveraged a comprehensive gene expression dataset (GSE21257) to elucidate the key genes in OS, both with and without metastatic involvement. Bioinformation analyses, Western blot, and RT-qPCR assays consistently demonstrated significantly lower CLEC5A expression levels in human OS cell lines and tissues. Notably, OS tissues from patients with metastasis exhibited lower CLEC5A levels compared to those without metastasis. We generated stable CLEC5A-deficient MG-63 and 143B cells with short hairpin RNA. Our findings revealed that CLEC5A knockdown enhanced OS cell proliferation and metastasis. Additionally, CLEC5A-deficient cells displayed increased calcineurin activity, which promoted the nuclear translocation of NFATc1, leading to elevated expression of MMPs. Conversely, CLEC5A overexpression suppressed OS cells growth and invasion and concurrently inhibited calcineurin activity. In summary, our study uncovers a suppressive role for CLEC5A in OS tumorigenesis and metastasis through the modulation of the calcineurin/NFATc1 signaling pathway. The deregulation of this pathway significantly impacts OS progression, highlighting its potential as a predicted and therapeutic target for metastatic OS.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114650"},"PeriodicalIF":3.3,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279740","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}

{"title":"Medication targeting to subcellular organelles: Emphasizing mitochondria as a therapeutic marvel—Current situation and future prospects","authors":"Riyad F. Alzhrani ,&nbsp;Adel Ali Alhowyan ,&nbsp;Ehab I. Taha ,&nbsp;Sabry M. Attia ,&nbsp;Samir A. Salama ,&nbsp;Gamaleldin I. Harisa","doi":"10.1016/j.yexcr.2025.114647","DOIUrl":"10.1016/j.yexcr.2025.114647","url":null,"abstract":"<div><div>Subcellular disorders are linked with several diseases, specifically mitochondrial dysfunction linked to age, metabolic disorders, cancer, cardiovascular disease, and other mitochondrial diseases (MDs). Intracellular medication delivery is a promising option for effective therapy. This study aims to highlight subcellular delivery with focus on mitochondrial pharmacology, gene therapy, transplantation, and drug targeting. PubMed, Google Scholar, Scopus, and other scholarly sources were leveraged to prepare this narrative review. According to current studies, intermittent fasting, consistent exercise, well-balanced diets, and proper sleep can all help to increase mitochondrial quality. Molecular therapies improve mitochondrial bioenergetics, redox status, biogenesis, dynamics, mitophagy, bioenergetic, and sirtuins. The antioxidant supplementation restores endogenous antioxidants such as alpha-lipoic acid, tocopherols, L-carnitine, and coenzyme Q10 to prevent mitochondrial damage. Mdivi-1, melatonin, resveratrol, PGC-1α agonists, metformin, and Opa1 activators modify the dynamics and biogenesis of mitochondria. Bioactive phytochemicals, including curcumin, berberine, quercetin, and capsaicin, affect OXPHOS and mitochondrial sirtuins. These agents affect gene expression, antioxidant defenses, inflammation, and mitochondrion functions. Therefore, bioactive phytochemicals limit oxidative damage, increase insulin sensitivity, and improve extended cell longevity. Mitochondrial transplantation and gene therapy using mRNA and gene editing technologies are promising treatment options for MDs. Mitoquidone, triphenylphosphine, mitochondrial-targeting peptides, and nanocarriers localize medicines within mitochondrial compartments. In conclusion, a good lifestyle and bioactive materials, alongside mitochondrial medications, gene therapy, transplantation, and drug targeting, could restore overall cellular health.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"450 2","pages":"Article 114647"},"PeriodicalIF":3.3,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298479","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}