BioFactorsPub Date : 2025-05-30DOI: 10.1002/biof.70026
Saba Nikanfar, Christiani A. Amorim
{"title":"The Potential Role of Matrix Metalloproteinase in Polycystic Ovary Syndrome: Implications for Extracellular Matrix Remodeling","authors":"Saba Nikanfar, Christiani A. Amorim","doi":"10.1002/biof.70026","DOIUrl":"https://doi.org/10.1002/biof.70026","url":null,"abstract":"<div>\u0000 \u0000 <p>Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder and a leading cause of infertility primarily due to impaired folliculogenesis and anovulation. Central to ovarian function and follicular development is the extracellular matrix (ECM), which undergoes significant remodeling facilitated by matrix metalloproteinases (MMPs). In PCOS, the ovarian cortex becomes thickened and collagen-rich, creating a rigid environment that disrupts normal follicular growth and oocyte maturation. Altered MMP activity further complicates this scenario by impairing ECM degradation, leading to the accumulation of small, quiescent follicles, and elevated androgen levels. This review aims to explore the intricate roles of ECM and MMP alterations in PCOS pathogenesis, highlighting their impact on folliculogenesis and steroidogenesis. Understanding MMP/TIMP dynamics offers insights into potential therapeutic targets to restore normal ovarian function and improve fertility outcomes for women with PCOS.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 3","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179353","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}
BioFactorsPub Date : 2025-05-24DOI: 10.1002/biof.70023
Li Shan, Guo-jian Gu, Cheng-Cheng Xiang, Er-Dong Zuo, Lian Lian, Xu Cheng
{"title":"The Immunotherapeutic Target ANLN Promotes Renal Clear Cell Carcinoma by Regulating PI3K/Akt and P53 Signaling Pathways","authors":"Li Shan, Guo-jian Gu, Cheng-Cheng Xiang, Er-Dong Zuo, Lian Lian, Xu Cheng","doi":"10.1002/biof.70023","DOIUrl":"https://doi.org/10.1002/biof.70023","url":null,"abstract":"<div>\u0000 \u0000 <p>The role of Anillin (ANLN) in clear cell renal cell carcinoma (ccRCC) is not well understood. This study aimed to investigate the possible function and mechanism of ANLN in ccRCC. By using data from the Cancer Genome Atlas (TCGA), we assessed ANLN expression in various cancers. Furthermore, the GEPIA database was used to analyze survival rates, pathway enrichment, and immune infiltration. Experiments were employed to study how ANLN expression affects tumor cell apoptosis, migration, invasion, and proliferation. Protein blotting was conducted to evaluate apoptosis, proliferation, epithelial mesenchymal transition (EMT), and the expression of proteins linked to the PI3K/AKT and P53 signaling pathways. mRNA levels of ANLN were notably increased in diverse cancer tissues, as shown in the TCGA database, a finding that was also observed in ccRCC patients. Remarkably, high ANLN levels were associated with lower pathologic grades and a worse survival prognosis in ccRCC patients. In vitro experiments revealed that knockdown of ANLN in ccRCC cells led to reduced proliferation, migration, invasion, and EMT. Additionally, ANLN seemed to impact immune evasion and increase the likelihood of distant metastasis based on immune infiltration analyses. The use of PI3K/AKT pathway inhibitors or P53 signaling pathway agonists was effective in reducing the invasive behavior of ccRCC and correcting immunosuppression. Overall, ANLN could be a valuable prognostic indicator for the survival of ccRCC patients.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 3","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126058","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}
BioFactorsPub Date : 2025-05-22DOI: 10.1002/biof.70019
{"title":"Correction to “Untargeted metabolomics reveals biomarkers for the diagnosis of coronary artery plaques as observed by coronary cardiac computed tomography”","authors":"","doi":"10.1002/biof.70019","DOIUrl":"https://doi.org/10.1002/biof.70019","url":null,"abstract":"<p>Shmet M, Amasha M, Khattib A, Schweitzer R, Khatib S, Hamudi J, Halabi M, Khatib S. Untargeted metabolomics reveals biomarkers for the diagnosis of coronary artery plaques as observed by coronary cardiac computed tomography. Biofactors 2025;51(1):e2156. https://doi.org/10.1002/biof.2156</p><p>In the originally published article, Figure 6 repeated parts A and B. The correct figure, which incudes parts A–D, is included below.</p><p>We apologize for this error.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 3","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108881","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}
BioFactorsPub Date : 2025-05-13DOI: 10.1002/biof.70021
Ilias Amtil-Ouahdi, Fabián Vergara, Carlos Rio, Coral González-Martínez, Andreas Jahn, María Antonia Forteza-Genestra, Antonio Gayá, Javier Calvo, Ernest Sala-Llinas, Bernardino Alcázar Navarrete, Ana Dolores Romero-Ortiz, Marta Monjo, Johana M. Ramis, Francisco G. Ortega
{"title":"EVs Biodistribution and Antifibrotic Impact in Aged Lung Fibrosis Model","authors":"Ilias Amtil-Ouahdi, Fabián Vergara, Carlos Rio, Coral González-Martínez, Andreas Jahn, María Antonia Forteza-Genestra, Antonio Gayá, Javier Calvo, Ernest Sala-Llinas, Bernardino Alcázar Navarrete, Ana Dolores Romero-Ortiz, Marta Monjo, Johana M. Ramis, Francisco G. Ortega","doi":"10.1002/biof.70021","DOIUrl":"https://doi.org/10.1002/biof.70021","url":null,"abstract":"<div>\u0000 \u0000 <p>Pulmonary fibrosis (PF) is a progressive, life-threatening disease marked by excessive scarring of lung tissue. Recently, extracellular vesicles (EVs) have emerged as a promising antifibrotic therapy due to their regenerative and anti-inflammatory properties. However, the success of EV-based therapies depends on the route of administration, which can significantly influence their biodistribution and therapeutic effects. Furthermore, in PF, aging is a significant risk factor for the disease and, until today, EV treatment efficacy has not been studied in aged tissues. Specifically, we studied EVs derived from human umbilical cord mesenchymal stem cells and compared the biodistribution of these vesicles delivered via three routes: intravenous (IV), intrapleural (IP), and intratracheal (IT). A protocol was developed to set EV staining and concentration, minimizing animal use while maximizing the accuracy of results. To evaluate therapeutic effects, we conducted three experimental setups: (i) to assess their ability to reverse established fibrosis; (ii) to evaluate their effect on fibrosis progression; and (iii) to study early inflammation and macrophage polarization. Lung fibrosis and inflammation were assessed by analyzing fibrotic markers, inflammatory cytokines, collagen deposition, and bronchoalveolar lavage (BAL) fluid cell analysis, providing insights into EVs therapeutic potential in aged, fibrotic lung tissue. In the biodistribution study, IV administration was identified as the most effective route, successfully delivering EVs to both normal and fibrotic lung tissues. In the therapeutic study, antifibrotic effects were observed only when EVs were administered prophylactically, before the establishment of fibrosis. Under this protocol, IV-administered EVs reduced fibrotic mRNA biomarkers, collagen deposition, inflammatory cell infiltration, and macrophage polarization in BAL, as well as altering cytokine. Our findings emphasize the critical importance of selecting the appropriate route of administration for EV-based therapies. Notably, our work with an aging model reveals that EV treatments primarily exhibit prophylactic effects, with a marked reduction in their regenerative potential compared to previous studies conducted in younger models.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 3","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944834","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}
BioFactorsPub Date : 2025-04-30DOI: 10.1002/biof.70020
Srija Roy, Gouranga Saha, Mrinal K. Ghosh
{"title":"UPS and Kinases—Gatekeepers of the G1/S Transition","authors":"Srija Roy, Gouranga Saha, Mrinal K. Ghosh","doi":"10.1002/biof.70020","DOIUrl":"https://doi.org/10.1002/biof.70020","url":null,"abstract":"<div>\u0000 \u0000 <p>The G1/S transition is a highly regulated and pivotal checkpoint in the cell cycle, where the cell decides whether to commit to DNA replication and subsequent division or enter a non-dividing state. This checkpoint serves as a critical control point for preventing uncontrolled cell proliferation and maintaining genomic stability. The major driving force underlying the G1/S transition is the sequential activation of Cyclin-dependent kinases (CDKs), which is regulated by the coordinated binding of Cyclin partners, as well as the phosphorylation and ubiquitin-mediated degradation of both Cyclin partners and Cyclin-dependent kinase inhibitors (CKIs). Various E3 ligase families govern the timely degradation of these regulatory proteins, with their activity intricately controlled by phosphorylation events. This coordination enables the cells to efficiently translate the environmental cues and molecular signaling inputs to determine their fate. We explore the evolution of three distinct models describing the G1/S transition, highlighting how the traditional linear model is being challenged by recent paradigm shifts and conflicting findings. These advances reveal emerging complexity and unresolved questions in the field, particularly regarding how the latest insights into coordinated phosphorylation and ubiquitination-dependent degradation integrate into contemporary models of the G1/S transition.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 3","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892961","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}
BioFactorsPub Date : 2025-04-18DOI: 10.1002/biof.70018
L. C. Erjavec, L. G. Parra, D. E. Sendyk, M. Recabarren, C. Herbón, N. O. Favale, S. Tulino, M. Carballo, M. López Nigro, N. Magnani, P. Evelson, C. I. Casali, María del Carmen Fernández Tome
{"title":"Non-beneficial effects of resveratrol on renal epithelial cell cultures: Implications in cell differentiation","authors":"L. C. Erjavec, L. G. Parra, D. E. Sendyk, M. Recabarren, C. Herbón, N. O. Favale, S. Tulino, M. Carballo, M. López Nigro, N. Magnani, P. Evelson, C. I. Casali, María del Carmen Fernández Tome","doi":"10.1002/biof.70018","DOIUrl":"https://doi.org/10.1002/biof.70018","url":null,"abstract":"<p>During the last three decades, resveratrol (RSV), a polyphenolic compound, has been proposed as a new panacea due to its all-potential beneficial actions. However, due to its hormetic properties, RSV has also been associated with toxic effects. In this work, we explored whether RSV affects osmoprotection and/or differentiation processes. Experiments were performed in Madin–Darby canine kidney (MDCK) cells subjected to high-NaCl hyperosmolar medium, a requisite for cell differentiation, in the absence or presence of RSV. Our results show that RSV does not affect osmoprotection but impedes epithelial cell differentiation by inducing oxidative stress, DNA damage, and impairing cell-cycle progression and motility. All these observations drive cells to stay in S phase and induce apoptosis. Our results warn about the possible harmful effects on tubular epithelial restitution processes or in postnatal kidney structures maturation when large quantities of this nutraceutical are ingested.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845798","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}
BioFactorsPub Date : 2025-04-18DOI: 10.1002/biof.70017
Liang Ke, Wanshi He, Chuyao Zong, Tiantian Wang, Jie Xiao, Yong Cao, Hang Xiao, Xiaojuan Liu
{"title":"A novel peptide derived from Haematococcus pluvialis residue balanced lipid metabolism through NHR-49/PPARα and AAK-2/AMPK pathways in Caenorhabditis elegans","authors":"Liang Ke, Wanshi He, Chuyao Zong, Tiantian Wang, Jie Xiao, Yong Cao, Hang Xiao, Xiaojuan Liu","doi":"10.1002/biof.70017","DOIUrl":"https://doi.org/10.1002/biof.70017","url":null,"abstract":"<p>To explore the potential value of <i>Haematococcus pluvialis</i> residue after astaxanthin extraction, a novel peptide (HPp) was identified as a bioactive component. However, the possible lipid-lowering effect in vivo remains unclear. Thus, the classic model of <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) was employed to evaluate the anti-obesity effects and underlying mechanism. The results showed that 100 μM HPp significantly reduced the overall fat and triglyceride contents, while also remarkably decreasing the lipid droplets size and promoting desaturation of C18:0 to C18:1n9. Subsequent analysis indicated that HPp increased energy expenditure and alleviated intestinal distension. Further molecular research revealed that HPp activated the gene expression of <i>fat-6</i>, <i>fat-7</i>, <i>nhr-49</i>, <i>acs-2</i>, <i>aak-2</i>, <i>atgl-1</i>. Notably, the lipid-lowering effects were abolished in <i>fat-6</i>, <i>fat-7</i>, <i>nhr-49</i> mutants, and further verified in GFP-tagged nematodes, indicating that HPp balanced lipid metabolism by activating NHR-49/PPARα and AAK-2/AMPK pathways in <i>C. elegans</i>. These findings highlight the high-value applications of marine microalgae.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845799","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}
BioFactorsPub Date : 2025-04-10DOI: 10.1002/biof.70013
Sara Salman, Virginie Paulet, Kévin Hardonnière, Saadia Kerdine-Römer
{"title":"The role of NRF2 transcription factor in inflammatory skin diseases","authors":"Sara Salman, Virginie Paulet, Kévin Hardonnière, Saadia Kerdine-Römer","doi":"10.1002/biof.70013","DOIUrl":"https://doi.org/10.1002/biof.70013","url":null,"abstract":"<p>The skin is the body's largest organ and performs several vital functions, such as controlling the movement of essential substances while protecting against external threats. Although mainly composed of keratinocytes (KCs), the skin also contains a complex network of immune cells that play a critical role in host defense and maintaining skin homeostasis. KCs proliferate in the basal layer of the epidermis and undergo differentiation, altering their functional and phenotypic characteristics. These differentiation steps are crucial for the stratification of the epidermis and the formation of the stratum corneum, ensuring the skin barrier's functions. Exposure to UV, environmental pollutants, or chemicals can lead to an overproduction of reactive species of oxygen (ROS), leading to oxidative stress. To ensure redox homeostasis and prevent damage resulting from the formation of ROS, the skin has an extensive network of antioxidant defense systems, mainly orchestrated by the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. Indeed, Nrf2 induces the expression of detoxification and antioxidant enzymes and suppresses inductions of pro-inflammatory cytokine genes. In this context, Nrf2 is critical in preserving skin functions such as epidermal differentiation, regulating skin immunity, and managing environmental stresses. Besides, this pathway plays an important role in the pathogenesis of common inflammatory skin diseases such as allergic contact dermatitis, atopic dermatitis, and psoriasis. Therefore, the present review highlights the crucial role of Nrf2 in KCs for maintaining skin homeostasis and regulating skin immunity, as well as its contribution to the pathophysiology of inflammatory skin diseases. Finally, a particular emphasis will be placed on the therapeutic potential of targeting the Nrf2 pathway to alleviate symptoms of these inflammatory skin disorders.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809848","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}
BioFactorsPub Date : 2025-04-09DOI: 10.1002/biof.70016
Zixuan Chen, Chengtao Han, Huiwen Xie, Xingyu Chen, Haojie Zhang, Zongrun Sun, Min Liu
{"title":"2-Undecanone induces ferroptosis via the STAT3/GPX4 pathway to enhance sensitivity of renal cell carcinoma to sunitinib","authors":"Zixuan Chen, Chengtao Han, Huiwen Xie, Xingyu Chen, Haojie Zhang, Zongrun Sun, Min Liu","doi":"10.1002/biof.70016","DOIUrl":"https://doi.org/10.1002/biof.70016","url":null,"abstract":"<p>The development of resistance significantly reduces the efficacy of targeted therapies, such as sunitinib, in renal cell carcinoma (RCC) patients, emphasizing the need for novel therapeutic agents. Natural products, known for their diverse chemical structures and mechanisms of action, offer promising anti-tumor potential with favorable safety profiles and lower toxicity compared to synthetic drugs. 2-Undecanone, a natural compound extracted from <i>Houttuynia cordata</i> Thunb., has demonstrated anti-tumor effects, but its specific role in RCC treatment remains unclear. In this study, we integrated network pharmacology with in vitro experiments to explore the mechanisms underlying 2-Undecanone's effects on RCC. Our results reveal that 2-Undecanone effectively inhibits RCC cell viability, proliferation, and migration. Mechanistically, we discovered that 2-Undecanone induces ferroptosis in RCC cells by promoting reactive oxygen species (ROS) generation, intracellular Fe<sup>2+</sup> accumulation, glutathione (GSH) production, lipid peroxidation, and modulation of the STAT3/GPX4 signaling pathway. Furthermore, 2-Undecanone lowers the IC50 value of sunitinib in RCC cells, enhancing their sensitivity to this targeted therapy. Additionally, 2-Undecanone potentiates sunitinib-induced ferroptosis. In summary, our research reveals that 2-Undecanone enhances the sensitivity of RCC cells to sunitinib through targeting the STAT3/GPX4 pathway, providing new insights into potential therapeutic strategies for RCC.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801746","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":"EPA and DHA acylcarnitines are less cardiotoxic than are saturated and monounsaturated long-chain acylcarnitines","authors":"Edgars Liepinsh, Baiba Gukalova, Kristaps Krims-Davis, Janis Kuka, Aiga Leduskrasta, Stanislava Korzh, Reinis Vilskersts, Marina Makrecka-Kuka, Ilze Konrade, Maija Dambrova","doi":"10.1002/biof.70014","DOIUrl":"https://doi.org/10.1002/biof.70014","url":null,"abstract":"<p>Elevated levels of fatty acid-derived long-chain acylcarnitines are detrimental to cardiac health, primarily because of their adverse effects on mitochondrial function and key metabolic pathways in the heart. While trans-fatty acids are considered harmful and omega-3 polyunsaturated fatty acids (PUFAs) are considered beneficial, the specific properties of acylcarnitines derived from these types of fatty acids are not characterized. This study aimed to compare the effects of saturated palmitoylcarnitine (PC), monounsaturated cis-oleoylcarnitine (cis-OC), trans-elaidoylcarnitine (trans-EC), and polyunsaturated eicosapentaenoylcarnitine (EPAC) and docosahexaenoylcarnitine (DHAC) on heart function, cardiac cell viability, mitochondrial functionality, and insulin signaling pathways. Saturated and monounsaturated acylcarnitines, particularly trans-EC, significantly reduced cardiac contractility at concentrations of 8–12 μM, and trans-EC was identified as the most cardiotoxic acylcarnitine. Conversely, the presence of EPAC and DHAC in the perfusion buffer did not impair heart functionality. Saturated and monounsaturated acylcarnitines also drastically reduced H9C2 cell viability and suppressed mitochondrial OXPHOS by up to 70% at 25 μM, whereas PUFA-derived acylcarnitines caused only a 20%–25% reduction in OXPHOS and did not decrease cell viability. Furthermore, PC, cis-OC, and trans-EC significantly inhibited Akt phosphorylation, whereas EPAC and DHAC had a much weaker effect on insulin signaling. In conclusion, saturated and monounsaturated acylcarnitines, particularly trans-EC, exert significant cardiotoxic effects, primarily through the impairment of cardiac mitochondrial function. The omega-3 PUFA-derived acylcarnitines EPAC and DHAC are safe and less likely to damage cardiac mitochondria, cardiac cells, and the heart than other acylcarnitines. PUFA intake might be safer than other long-chain fatty acid-containing lipid sources in patients with FAODs and cardiometabolic diseases.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 2","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793623","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}