Bioimpacts最新文献

{"title":"microRNAs shuttled by mesenchymal stromal cell-derived exosomes in coronary artery disease: A systematic review of preclinical studies.","authors":"Soroush Mostafavi, Amin Arasteh, Seyedeh Mina Mostafavi Montazeri, Seyyedeh Mina Hejazian, Farahnoosh Farnood, Sima Abediazar, Abolfazl Barzegari, Sepideh Zununi Vahed","doi":"10.34172/bi.30989","DOIUrl":"https://doi.org/10.34172/bi.30989","url":null,"abstract":"<p><strong>Introduction: </strong>Coronary artery disease (CAD) is a life-threatening cardiac condition with high morbidity and mortality worldwide. This systematic review article highlighted the therapeutic roles of mesenchymal stromal cells (MSCs)-derived exosomal microRNAs (exo-miRs) in preclinical models of CAD.</p><p><strong>Methods: </strong>A comprehensive search was conducted on PubMed, Web of Science, Scopus, and Google Scholar to identify relevant publications until 04 Apr 2025. The literature review focuses on the origin of MSCs, the technique employed for exosome extraction and identification, the route and frequency of exosomal administration, the mechanisms through which exo-miRs regulate paracrine activity, and their impact on cardiac outcome.</p><p><strong>Results: </strong>After meticulous evaluation, fifty-six studies were deemed eligible for inclusion in this systematic review. Bone marrow-derived MSCs were the most commonly utilized cell type in the preclinical studies. The majority of studies employed the ultracentrifugation method for exosome isolation from MSCs. The administration of exosomes was primarily achieved through a single intramyocardial injection, utilizing a wide range of exosome concentrations (ranging from 0.02-400 μg/μL).</p><p><strong>Conclusion: </strong>The included studies predominantly have reported the anti-inflammatory, anti-apoptotic, angiogenic, antifibrotic, and reparative effects of MSC-exo-miRs, especially under hypoxic conditions. These findings support the capacity of MSC-exo-miRs to regulate the immune system and facilitate cardiac recovery following an injury.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"30989"},"PeriodicalIF":2.2,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revolutionizing cancer therapy: Monoclonal antibodies in radiosensitization.","authors":"Abolfazl Bemidinezhad, Yasaman Abolhassani, Mojgan Noroozi-Karimabad, Arman Abroumand Gholami, Abbas Alalikhan, Ramin Roshani, Mohammad Parsa-Kondelaji, Fatemeh Gheybi","doi":"10.34172/bi.30996","DOIUrl":"https://doi.org/10.34172/bi.30996","url":null,"abstract":"<p><p>Cancer treatment has advanced significantly, yet traditional modalities such as radiotherapy still encounter challenges, including damage to healthy tissues and limited tumor specificity. Monoclonal antibodies (mAbs) have emerged as powerful tools in oncology, offering particular therapeutic options with reduced toxicity. Their capacity to enhance the efficacy of radiotherapy through radiosensitization presents a promising strategy for improving cancer outcomes. This review synthesizes findings from the past decade, providing an in-depth analysis of the diverse roles of mAbs in radiosensitization. Key mechanisms are discussed, including targeting molecular pathways, modulation of immune responses, and integration with novel platforms such as nanoparticles and antibody-drug conjugates (ADCs). The review also highlights the successes of preclinical and clinical studies while addressing ongoing challenges like delivery inefficiencies, tumor resistance, and antigen heterogeneity. Additionally, emerging alternatives including aptamers, nanobodies, and engineered proteins are explored as potential solutions to these barriers. Advancements in mAb-based delivery systems and combination therapies remain crucial for achieving more personalized and effective cancer treatments.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"30996"},"PeriodicalIF":2.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigate the co-culture effects of BM-mesenchymal stem cells on the promotion of apoptotic pathways of CD34⁺leukemic stem cells.","authors":"Mei Ding, Chuanhua Jia","doi":"10.34172/bi.31302","DOIUrl":"https://doi.org/10.34172/bi.31302","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>The potential clinical application of mesenchymal stem cells (MSCs) in cell-based treatment makes them particularly interesting. The use of MSC-engaged therapies in cancer treatment is becoming more and more promising. Although the specifics of their activity have not yet been conclusively established, a variety of growth factors released by these cells are known to provide such multifunctional qualities.</p><p><strong>Methods: </strong>Through the measurement of cytokine levels, Annexin-V, and possible signaling pathways linked to apoptosis, we have assessed the impact of MSCs on CD34⁺leukemic stem cells (LSCs) enriched from the KG1-a cell line. Additionally, culture medium was taken from the experimental and control groups for the IL-2 and IL-4 measurement following a 7-day co-culture.</p><p><strong>Results: </strong>Co-culture conditions were observed to promote early and late apoptosis, although this increase just was statistically significant in late apoptosis. The co-cultured conditioned media clearly showed a large amount of IL-2, but there was an insignificant rise in IL-4. Also, MSCs significantly increased the protein expression of P16, P21, and p-P38 and significantly decreased C-Myc, and TERC.</p><p><strong>Conclusion: </strong>It can be concluded that the mentioned effects of IL-2 cytokine released from MSCs on CD34⁺LSCs maybe were applied by the components of P16, P21, and p-P38, C-Myc signaling pathways.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"31302"},"PeriodicalIF":2.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent innovations in nanomedicine and nano-based techniques for the treatment of breast cancer.","authors":"Meena Bhandari, Seema Raj, Md Sabir Alam","doi":"10.34172/bi.30804","DOIUrl":"https://doi.org/10.34172/bi.30804","url":null,"abstract":"<p><p>Breast cancer (BC) is a persistent global health challenge, necessitating innovative therapeutic strategies. Recently, nanotechnology has appeared as a transformative methodology to treat BC, suggesting precise targeting, controlled drug delivery, and improved imaging capabilities. This review offers a current overview of the latest innovations around nanotechnology for BC therapy in the field of new nanomedicines and nano-based drug delivery methods by carefully examining the utilization of nanoparticles to enhance the effectiveness of both new and old medications and to enable targeted evaluation using disease markers. Key topics include early detection, targeted drug delivery, multimodal imaging, and combination therapies. The paper underscores the probability of using nanotechnology to reshape BC management landscape and outlines potential future directions.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"30804"},"PeriodicalIF":2.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic Treg-derived artificial vesicles: A promising therapeutic modality for multiple sclerosis.","authors":"Irina Alekseevna Ganeeva, Elvina Maratovna Gilyazova, Arthur Ajdarovich Khannanov, Mariia Eugenievna Nektorova, Alexey Michailovich Rogov, Timur Ildarovich Khaibullin, Ekaterina Anatolievna Zmievskaya, Emil Rafaelevich Bulatov","doi":"10.34172/bi.30880","DOIUrl":"10.34172/bi.30880","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS). CD4⁺ CD25^+hi Tregs, which normally suppress immune responses, exhibit impaired function in MS. Treg-derived extracellular vesicles (EVs) carry immunoregulatory proteins and miRNAs that modulate T-cell activity. However, EVs from MS patients show reduced suppressive capacity, suggesting their dysfunction contributes to MS pathogenesis. This highlights EVs' potential role in MS development and therapy.</p><p><strong>Methods: </strong>Tregs were differentiated from naïve T cells isolated from peripheral blood mononuclear cells (PBMCs) of healthy donor, then transduced with B2M-shRNA lentivirus to generate HLA class I-knockdown Tregs. Extracellular vesicles-including natural vesicles, cytochalasin B-induced artificial vesicles, and ultrasound-induced artificial vesicles-were isolated from Tregs and characterized by scanning electron microscopy (SEM), nanoparticle tracking analysis (NTA), flow cytometry, and Western blot. Their effects on healthy donor and MS patient PBMCs were evaluated via flow cytometry and ELISA (IL-6, IL-10, IFN-γ).</p><p><strong>Results: </strong>Ultrasonication yielded a higher number оf vesicles enriched with key immunosuppressive proteins, including PD-1 and Tim-3, compared to cytochalasin B. Functional assays demonstrated the ability оf ultrasonication-induced AVs to suppress inflammatory markers, such as IFNγ, and modulate the cytokine profile in both healthy and MS-derived PBMCs.</p><p><strong>Conclusion: </strong>Developing effective MS therapies remains challenging. While cellular therapies face limitations like Treg dysfunction and CNS delivery issues, allogeneic EVs offer a promising alternative due to their scalability, low immunogenicity, and blood-brain barrier penetration. We developed Treg-derived artificial vesicles (TrAVs) that maintain immunosuppressive properties and modulate PBMC responses, suggesting therapeutic potential for MS. Further research is needed to optimize production and validate efficacy in disease models.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"30880"},"PeriodicalIF":2.2,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-372-3p impairs fatty acid metabolism in hepatocellular carcinoma cells by targeting <i>CPT1A</i> and <i>ACSL4</i>.","authors":"Chinnatam Phetkong, Thammachanok Boonto, Pannathon Thamjamrassri, Chaiyaboot Ariyachet, Pisit Tangkijvanich","doi":"10.34172/bi.31075","DOIUrl":"10.34172/bi.31075","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Hepatocellular carcinoma (HCC) remains a major cause of cancer mortality, and effective therapeutic options are limited. MicroRNA‑372‑3p (miR‑372‑3p) has been implicated in HCC, yet its exact role is unclear.</p><p><strong>Methods: </strong>We established miR‑372‑3p‑overexpressing HCC cell lines (HepG2, SNU‑449, JHH‑4) via lentiviral transduction. Malignant phenotypes were assessed with MTT, transwell migration/invasion, and colony‑formation assays. Transcriptomic changes were analyzed by RNA‑sequencing followed by Gene Set Enrichment Analysis. Lipid metabolism was examined using BODIPY/Oil Red O staining, triglyceride quantification, FAOBlue assays, and organelle colocalization imaging. Candidate targets of miR‑372‑3p were computationally predicted and validated by dual‑luciferase reporter assays.</p><p><strong>Results: </strong>miR‑372‑3p overexpression significantly reduced cell proliferation by more than 50%, migration by over 30%, invasion by over 30%, and colony formation by more than 50%, supporting its tumor-suppressive role. Transcriptomic analysis identified 1,759 downregulated genes, significantly enriched in pathways associated with fatty acid oxidation (FAO). miR‑372‑3p‑overexpressing cells exhibited increased lipid droplet accumulation, with triglyceride levels elevated by more than 50% and an approximate 50% reduction in FAO activity, indicating defective use under glucose-deprived conditions. High-resolution organelle imaging further revealed diminished physical contacts between lipid droplets and mitochondria, as well as a similar disruption in lipid droplet-lysosome interactions. Dual-luciferase reporter assays confirmed <i>CPT1A</i> and <i>ACSL4</i> as direct targets of miR‑372‑3p.</p><p><strong>Conclusion: </strong>miR‑372‑3p functions as a tumor suppressor in HCC by directly downregulating <i>CPT1A</i> and <i>ACSL4</i>, thereby inhibiting FAO and disrupting lipid metabolism. Targeting this miRNA and FAO axis may offer a novel therapeutic strategy for HCC.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"31075"},"PeriodicalIF":2.2,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development, in vitro, and in vivo assessments of PCL-gelatin-βTCP fibrous scaffolds for cardiac regeneration.","authors":"Mahnaz Fathi, Nafiseh Baheiraei, Nahid Moradi, Majid Salehi, Sepehr Zamani, Mehdi Razavi, Hossein Eyni","doi":"10.34172/bi.31096","DOIUrl":"https://doi.org/10.34172/bi.31096","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Cardiovascular disease is a leading cause of death worldwide. Tissue engineering offers a promising solution for promoting tissue regeneration at the infarcted site. In this study, beta-tricalcium phosphate (βTCP) was incorporated into poly(ε-caprolactone) (PCL) and gelatin (Gel) fibers for cardiac patch applications.</p><p><strong>Methods: </strong>Electrospun scaffolds were prepared via electrospinning a 1:1 (w/w) mixture of PCL and Gel, embedding varying concentrations of βTCP at 0.25, 0.5, 1, and 3 wt.%. The scaffolds were analyzed through scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), tensile strength testing, hemolysis assays, toxicity testing, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) for marker gene expression. Furthermore, subcutaneous scaffold implantation was performed to assess in vivo angiogenesis in NMRI mice. Tissue samples were examined using hematoxylin and eosin (H&E) staining and immunohistochemistry.</p><p><strong>Results: </strong>According to the results, βTCP was uniformly distributed throughout the fiber scaffold, exhibiting a smooth, unbranched morphology with fiber diameters of approximately 75 μm. Specifically, the mean diameters for PCL-Gel and PCL-Gel-βTCP at 3 wt.% were 45.01 ± 2.82 μm and 100.91 ± 11.69 μm, respectively. Mechanical property assessments revealed that the elastic modulus of the scaffolds was suitable for usage as a tissue-engineered cardiac patch. Scaffolds containing βTCP exhibited favorable blood compatibility and indicated no cytotoxicity at the tested concentrations. Furthermore, the expression levels of cardiac marker genes (Actn4, Connexin43, and TrpT2) were elevated in the treatment groups in conjunction with the escalation of βTCP dosage. Fiber composites with 1% βTCP were selected as the optimal scaffold for <i>in vivo</i> examination. This scaffold demonstrated a significantly enhanced cell migration rate, with a growth in capillary formation observed in the immunohistochemistry analysis.</p><p><strong>Conclusion: </strong>The fibrous PCL-Gel-βTCP-1% scaffold showed optimal cell proliferation, blood compatibility and vascularization. These properties highlight its promise for cardiac tissue engineering.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"31096"},"PeriodicalIF":2.2,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers for colorectal cancer detection: An insight into colorectal cancer and FDA-approved biomarkers.","authors":"Mohammad Yasin Zamanian, Darmadi Darmadi, Razieh Darabi, Raed Fanoukh Aboqader Al-Aouadi, Mehraveh Sadeghi Ivraghi, Esra Küpeli Akkol","doi":"10.34172/bi.31211","DOIUrl":"10.34172/bi.31211","url":null,"abstract":"<p><p>Colorectal cancer (CRC) constitutes a significant global health challenge, accounting for a considerable proportion of cancer cases and associated mortality. Projections indicate a potential increase in new cases by 2040, attributed to demographic factors such as aging and population growth. Although advancements in the understanding of CRC pathophysiology have broadened treatment options, challenges such as drug resistance and adverse effects persist, highlighting the necessity for enhanced diagnostic methodologies. Timely detection markedly improves survival rates; however, colonoscopy, regarded as the gold standard for CRC screening, is constrained by its invasiveness and reliance on practitioner expertise. Consequently, the development of novel diagnostic approaches is imperative. Cancer biomarkers, which serve as indicators of cancer progression, show significant promise for improving diagnosis, prognosis, and treatment strategies. This study investigates molecular and cellular biomarkers, including proteins, DNA mutations, methylation markers, and microRNAs, that are pivotal in precision medicine and the monitoring of CRC progression. Additionally, emerging biomarkers such as circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) present opportunities for early detection. Current Food and Drug Administration (FDA)-approved CRC biomarkers reflect a shift towards personalized medicine, enhancing patient compliance and clinical outcomes. Nevertheless, further research is essential for the discovery of novel biomarkers and for deepening the understanding of CRC etiology, thereby advancing personalized care. Addressing standardization challenges will be crucial for ensuring global patient access to biomarker-based strategies.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"31211"},"PeriodicalIF":2.2,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photoplethysmography based non-invasive blood glucose estimation using systolic-diastolic framing MFCC features and machine learning regression.","authors":"Ali Kermani, Hossein Esmaeili","doi":"10.34172/bi.30589","DOIUrl":"10.34172/bi.30589","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Accurate and non-invasive blood glucose estimation is essential for effective health monitoring. Traditional methods are invasive and inconvenient, often leading to poor patient compliance. This study introduces a novel approach that leverages systolic-diastolic framing Mel-frequency cepstral coefficients (SDFMFCC) to enhance the accuracy and reliability of blood glucose estimation using photoplethysmography (PPG) signals.</p><p><strong>Methods: </strong>The proposed method employs SDFMFCC for feature extraction, incorporating systolic and diastolic frames. The systolic and diastolic points are identified using the Savitzky-Golay filter, followed by local extrema detection. Blood glucose levels are estimated using support vector regression (SVR). The evaluation is performed on a dataset comprising 67 raw PPG signal samples, along with labeled demographic and biometric data collected from 23 volunteers (aged 20 to 60 years) under informed consent and ethical guidelines.</p><p><strong>Results: </strong>The SDFMFCC-based approach demonstrates high accuracy (99.8%) and precision (0.996), with a competitive root mean square error (RMSE) of 26.01 mg/dL. The Clarke Error Grid analysis indicates that 99.273% of predictions fall within Zone A, suggesting clinically insignificant differences between estimated and actual glucose levels.</p><p><strong>Conclusion: </strong>The study validates the hypothesis that incorporating a new framing method in MFCC feature extraction significantly enhances the accuracy and reliability of non-invasive blood glucose estimation. The results highlight that the SDFMFCC method effectively captures critical physiological variations in PPG signals, offering a promising alternative to traditional invasive methods.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"30589"},"PeriodicalIF":2.2,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mtDNA copy number/<i>miR663/AATF</i> axis in invasive ductal carcinoma of the breast.","authors":"Farzaneh Dahi, Shirin Shahbazi, Loabat Geranpayeh","doi":"10.34172/bi.30792","DOIUrl":"10.34172/bi.30792","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Mitochondrial DNA (mtDNA) copy number variations have been reported in multiple human cancers. Previous studies indicate that mitochondrial retrograde signaling regulates <i>miR663</i>, which plays a key role in tumorigenesis, including regulating apoptosis antagonizing transcription factor (<i>AATF</i>). This study investigates the expression of <i>miR663</i> and <i>AATF</i> in relation to mtDNA copy number in invasive ductal carcinoma (IDC) of the breast.</p><p><strong>Methods: </strong>Paired primary tumors and adjacent non-tumor tissues were analyzed to assess changes in <i>miR663</i> and <i>AATF</i> expression using fold-change analysis. The mtDNA copy number was quantified using <i>COX1</i> as the mitochondrial gene and <i>COX4</i> as the nuclear control gene. To validate the findings, publicly available data from The Cancer Genome Atlas (TCGA) were also analyzed.</p><p><strong>Results: </strong>A significant reduction in tumor <i>miR663</i> expression was observed (fold change=0.139), with a strong correlation between <i>miR663</i> and <i>AATF</i> expression. A significant Z-score difference was also detected between <i>miR663</i> and mtDNA copy number. <i>miR663</i> was predominantly expressed in grade I tumors but significantly downregulated in higher-grade tumors, whereas <i>AATF</i> expression increased with tumor grade. In silico analysis of TCGA data confirmed elevated <i>AATF</i> expression, with notable variations across breast cancer subtypes.</p><p><strong>Conclusion: </strong>We observed reduced expression of <i>miR663</i> and mtDNA copy number in breast tumors, along with variations in <i>AATF</i> levels across subtypes. The decrease in <i>miR663</i> could be associated with lower mtDNA copy numbers and impaired retrograde signaling, impacting <i>AATF</i> expression and function. Our findings underscore the therapeutic promise of targeting the mtDNA/miR-663/AATF axis, which could lead to advancements in breast cancer treatment.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"30792"},"PeriodicalIF":2.2,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}