Tissue & cell最新文献

{"title":"Altered lung inflammation and expression of endoplasmic reticulum stress markers in male mice aged-asthma model.","authors":"Farshad Armin, Hamdollah Panahpour, Ramin Salimnejad, Hakimeh Saadati, Ali Abedi, Mohammad Reza Aslani","doi":"10.1016/j.tice.2025.102938","DOIUrl":"https://doi.org/10.1016/j.tice.2025.102938","url":null,"abstract":"<p><p>Although there is a strong correlation between aging and asthma pathophysiology, the underlying mechanism has not been fully elucidated. The endoplasmic reticulum (ER) has been demonstrated to be a crucial intracellular organelle involved in the pathogenesis of numerous diseases. The aim of the current study was to investigate ER stress markers in the lung tissue of aged ovalbumin (OVA)-sensitized mice. Male BALB/C mice were randomly divided into the following four groups (10 in each): 1) control, 2) OVA-sensitized (OVA), 3) D-galactose-induced aging (D-gal), and 4) OVA-sensitized associated with D-galactose-induced aging (OVA+D-gal). Total WBCs and differential cells were counted using the bronchoalveolar lavage (BAL) fluid. Lung tissue was analyzed for ER stress markers (ATF4, ATF6, GRP78, CHOP, and XBP1) through Real Time-PCR technique as well as histopathological assessment. The data indicated a significant increase in both total WBCs and differential cells within the OVA, D-gal, and OVA+D-gal groups when compared to the control group, particularly evident in the OVA+D-gal group. Also, the results showed that the increased expression of ER stress markers (ATF4, ATF6, GRP78, CHOP, and XBP1) was significantly higher in the OVA, D-gal, and OVA+D-gal groups than in the control group. Interestingly, the increased expression of CHOP, ATF4, and XBP1 was observed in the OVA+D-gal group more than in other groups. In aged OVA-sensitized mice, the findings revealed a maladaptive ER stress response in their lung tissue, characterized by elevated levels of CHOP, ATF4, and XBP1 expression.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"95 ","pages":"102938"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise ameliorates cardiac injury induced by nandrolone decanoate through downregulation of osteopontin and mTOR expressions.","authors":"Mohamed Aref, Wesam Mr Ashour, Nanees F El-Malkey, Haifa A Alqahtani, Mohamed A Nassan, Noha Ali Abd-Almotaleb, Gamal A Salem","doi":"10.1016/j.tice.2025.102932","DOIUrl":"https://doi.org/10.1016/j.tice.2025.102932","url":null,"abstract":"<p><p>Nandrolone-decanoate (NA), a synthetic anabolic steroid, negatively impacts cardiac function. While exercise is known to benefit cardiovascular health, its effects on individuals misusing anabolic steroids require further study. Osteopontin (OPN) and mammalian target of rapamycin (m-TOR) are crucial in inflammation-related cardiovascular diseases and can be influenced by exercise, though results are inconclusive. This study aims to examine how exercise affects NA's cardiac adverse effects and the potential role of OPN and m-TOR. The study involved 52 male rats divided into four groups: control, exercise-only, NA-treated (15 mg/kg/day S.C for 8 W), and combined exercise and NA treatment. Researchers measured blood pressure, heart rate (HR), serum cardiac enzymes, CRP, IL-1B, IL-6, Brain Natriuretic Peptide (BNP) and conducted macro and micromorphological assessments. Additionally, immunohistochemical analysis of cardiac OPN and mTOR was performed. The NA-treated group showed significant increases in blood pressure, HR, weight, and cardiac enzymes compared to the control group. Exercise significantly improved these parameters in the combined exercise and NA treatment group, except for blood pressure. All groups exhibited an increase in cardiac weight relative to the control. The NA-treated group displayed marked hyaline degeneration and necrosis in cardiac tissues, with increased cell diameter and excess collagen deposition, which was less severe in the combined exercise (EX) and NA treatment group. NA treatment significantly elevated inflammatory mediators and the area percentage of OPN and m-TOR expression. These markers were significantly reduced in the combined exercise and NA treatment group. BNP was remarkably raised in EX+NA group compared to all other groups. Exercise mitigated NA-induced cardiac damage by reducing inflammation, possibly through the downregulation of cardiac OPN and m-TOR expression.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"95 ","pages":"102932"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impacts of type 1 diabetes mellitus on male fertility and embryo quality in superovulated mice.","authors":"Begum Alyürük, Yusufhan Yazir, Zeynep Ece Utkan Korun, Özcan Budak, Ender Yalçinkaya Kalyan, Kamil Can Kiliç","doi":"10.1016/j.tice.2025.102941","DOIUrl":"https://doi.org/10.1016/j.tice.2025.102941","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to compare embryo quality, sperm morphology, motility, and fertilization obtained from male mice with type 1 diabetes mellitus (T1DM) induced by streptozotocin (STZ) in control and diabetic mice undergoing in vitro fertilization (IVF).</p><p><strong>Methods: </strong>CD-1 male mice were divided into control and DM groups, with an i.p. injection of 100 mg/kg STZ to induce T1DM. One month later, the mice were euthanized to investigate the effects of STZ-induced T1DM on the reproductive system. Sperms were obtained from the epididymis and vas deferens. The morphology and motility of the cells were evaluated. Follicle development was stimulated by controlled ovarian stimulation, and oocytes were collected by extracting oviducts and ovaries from female mice housed under controlled environmental conditions with ad libitum access. Both groups underwent IVF with fertilized zygotes followed up until the third day before embryo quality was compared.</p><p><strong>Results: </strong>Female mice bred with diabetic males exhibited significantly lower fertilization rates than the controls (p < 0.05). Sperm from diabetic mice displayed abnormalities in shape and movement, with reduced motility and fertilization. Embryos from male diabetic mice exhibited a higher incidence of developmental arrest during early embryogenesis. Although no significant differences in oocyte quality were observed, embryos from diabetic mice exhibited higher growth rates. These findings highlighted the T1DM's detrimental effects on sperm morphology, motility, fertilization, and early embryonic development, thus contributing to our understanding of reproductive complications.</p><p><strong>Conclusion: </strong>In conclusion, our findings demonstrated that T1DM significantly impaired sperm morphology, motility, and fertilization capacity, leading to reduced embryo quality and increased developmental arrest. These results highlight the detrimental impact of DM on male reproductive potential and underscore the importance of glycemic control in optimizing outcomes in assisted reproductive techniques such as IVF.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"95 ","pages":"102941"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria transfer from mesenchymal stem cells into osteoarthritic chondrocytes ameliorate cellular functions and alleviate both inflammation and oxidative stress","authors":"Candan Altuntaş ,&nbsp;Gökhan Duruksu ,&nbsp;Fatih Hunç ,&nbsp;Yusufhan Yazir","doi":"10.1016/j.tice.2025.102990","DOIUrl":"10.1016/j.tice.2025.102990","url":null,"abstract":"<div><h3>Objective</h3><div>Osteoarthritis, a common age-related joint disease, causes cartilage degeneration, leading to pain and disability. While pain management exists, cartilage regeneration options are limited. Exogenous mitochondria transfer is a novel regenerative approach. This study aimed to investigate the effects of exogenous mitochondrial transfer on cellular function, oxidative stress, inflammation, and apoptosis in osteoarthritic chondrocytes.</div></div><div><h3>Methods</h3><div>Two inflammatory models using M1-macrophage conditioned medium or co-culture with synovial fluid mesenchymal stem cells (MSCs) were established. The study compared mitochondria from Wharton's jelly (WJ-) and bone marrow (BM-) MSCs by analyzing their transfer to these models. Transfer effects were evaluated by mitochondrial membrane potential, cell viability, apoptosis, gene expression, and oxidative state.</div></div><div><h3>Results</h3><div>Mitochondria tracking showed high transfer efficiencies (99.62 % for WJ-MSCs, 91.34 % for BM-MSCs). Late apoptosis was significantly reduced after transfer of WJ-MSCs mitochondria from 5.58 % to 2.93 % in the model with M1-macrophage conditioned medium. Expression of TNF-α and IL-1β was reduced after mitochondrial delivery. The expression of Ki67 was induced in parallel with increased ATP production and reduced HMOX-1 expression levels after the transfer. A decrease of 2.5- and 5-fold in ATP levels in cells after the inflammatory models were recovered after WJ-MSCs mitochondria transfer by 3.1- and 100-fold depending on the inflammatory model used. Although ROS levels remained unchanged, MDA levels decreased, and collagen type-2 expression increased.</div></div><div><h3>Conclusion</h3><div>Mitochondria transfer improved key aspects of chondrocyte dysfunction in inflammatory osteoarthritis models. These findings support its therapeutic potential for treating or slowing osteoarthritis by directly improving damaged chondrocyte health and function.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102990"},"PeriodicalIF":2.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144154695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing thrombospondin function through repositioning: Implications for injury and diabetic foot ulcer management","authors":"Juan Valentin Trujillo-Paez ,&nbsp;Yolanda M. Jacobo-Delgado ,&nbsp;Camelia Felix-Arellano ,&nbsp;Adrian Rodriguez-Carlos ,&nbsp;Irma Gonzalez-Curiel ,&nbsp;Oscar Gonzalez-Muñiz ,&nbsp;Bruno Rivas-Santiago","doi":"10.1016/j.tice.2025.102987","DOIUrl":"10.1016/j.tice.2025.102987","url":null,"abstract":"<div><div>Diabetic foot ulcer (DFU) is a common and challenging complication of diabetes, characterized by impaired wound healing, chronic inflammation, poor tissue remodeling, and chronic inflammation. Thrombospondin 1 (TSP1) and thrombospondin 4 (TSP4) are key extracellular matrix proteins involved in wound healing. This study aimed to assess the levels and propose inducers of TSP1, TSP4, and SOD3 in diabetic foot ulcer. In this study, we first evaluated the expression of TSP1, TSP4, and superoxide dismutase 3 (SOD3) in DFU tissues using real-time PCR and immunohistochemistry. In DFU tissues using real-time PCR we found that TSP-4 expression was significantly reduced and confirmed by immunohistochemistry. TSP1 expression did not show similar alterations. Additionally, while SOD3 expression was decreased at the mRNA level in the diabetic population, no changes were observed in the protein levels by immunohistochemistry. To explore potential therapeutic approaches, we performed pharmacological repositioning and identified three drugs riboflavin, desloratadine, and chenodeoxycholic acid that selectively increased TSP-4 expression. These findings suggest that riboflavin, desloratadine, and chenodeoxycholic acid may promote wound healing in DFU by specifically upregulating TSP4, potentially enhancing tissue remodeling and angiogenesis.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102987"},"PeriodicalIF":2.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preventing effects of anterior cruciate ligament reconstruction on the trabecular bone remodeling in the rat proximal tibial epiphysis","authors":"Akinori Kaneguchi ,&nbsp;Marina Kanehara ,&nbsp;Norikazu Nishida ,&nbsp;Kaoru Yamaoka ,&nbsp;Junya Ozawa","doi":"10.1016/j.tice.2025.102985","DOIUrl":"10.1016/j.tice.2025.102985","url":null,"abstract":"<div><div>A previous study reported that in patients with anterior cruciate ligament (ACL) injury, subchondral bone density in the proximal tibia was reduced in the antero-medial region, while it was increased in the postero-medial region. Anterior tibial instability due to ACL injury may be the cause of the remodeling in the proximal tibial epiphysis. The aim of this study was to determine whether re-stabilization of tibial instability by ACL reconstruction prevents remodeling in the rat proximal tibial epiphysis and if so, to find optimal timing of ACL reconstruction after ACL transection. ACL-transected rats were divided into immediate, early, and delayed ACL reconstruction (1, 14, and 28 days after ACL transection, respectively) groups. Some ACL-transected rats were reared without ligament reconstruction. Untreated rats were used as controls. At 56 days after ACL transection, trabecular bone mass in the proximal tibia was assessed histologically by measuring the trabecular bone area. ACL transection decreased the trabecular bone area in the antero-medial region of the proximal tibia, while it did not alter trabecular bone area in the postero-medial region. This trabecular bone loss in the antero-medial region was prevented when reconstruction was performed 1 day after ACL transection, but not prevented by ACL reconstruction performed in later period, 14 or 28 days after ACL transection. Our results suggest that ACL reconstruction surgery should be performed as early as possible to prevent trabecular bone loss in the antero-medial region of the proximal tibia.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102985"},"PeriodicalIF":2.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arbutin improves post-myocardial infarction cardiac dysfunction by inhibiting cardiac fibroblast activation","authors":"Yun Liu ,&nbsp;Xuemei Liu ,&nbsp;Xuan Zhang ,&nbsp;Hongwei Yue ,&nbsp;Chang Pan","doi":"10.1016/j.tice.2025.102986","DOIUrl":"10.1016/j.tice.2025.102986","url":null,"abstract":"<div><h3>Background</h3><div>Arbutin exhibits multiple effects, including anti-inflammatory, antioxidant, and scavenging of free radicals, yet its research within the cardiovascular system remains limited.</div></div><div><h3>Purpose</h3><div>This study aims to investigate the effects of arbutin on myocardial infarction induced by left anterior descending (LAD) ligation in mice.</div></div><div><h3>Methods</h3><div>The possible mechanism of arbutin's effect on myocardial infarction was predicted through network pharmacology studies. To evaluate the impact of arbutin on cardiac function in myocardial infarction, TTC staining of the heart was performed, and echocardiography was conducted on mice at different time points. Furthermore, Western blot analysis was utilized not only to detect αSMA, Collagen I, and Collagen III, aiming to investigate the impact of arbutin on myocardial fibrosis but also to detect the influence of arbutin on the phosphorylation level of ERK1/2, thereby elucidating its potential mechanism of action.</div></div><div><h3>Results</h3><div>Network pharmacology data suggest that arbutin may exert a beneficial effect on myocardial infarction by modulating the ERK1/2 signaling pathway. In vivo experimental results indicate that after myocardial infarction, arbutin can alleviate myocardial fibrosis and cardiac hypertrophy, significantly improving cardiac function. Further in vitro experiments confirm that arbutin markedly reduces fibrosis-related indicators, and this process is partially achieved through the regulation of ERK1/2 phosphorylation.</div></div><div><h3>Conclusion</h3><div>In conclusion, this study reveals that arbutin exerts a significant protective effect by acting on the ERK1/2 signaling pathway, effectively inhibiting myocardial fibrosis, and subsequently attenuating myocardial infarction induced by LAD ligation.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102986"},"PeriodicalIF":2.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promotion of skin regeneration in diabetic rats by collagen-based hydrogel incorporated with basic fibroblast growth factor: A histological, molecular, and tensiometrical study","authors":"Melody Omraninava ,&nbsp;Rafat Rezapour-Nasrabad ,&nbsp;Mojgan Hosseini ,&nbsp;Mohammad Armin Kasiri ,&nbsp;Shadman Shahzamani ,&nbsp;Maryam Bahrami ,&nbsp;Zahra Sadrzadeh-aghajani ,&nbsp;Mohamad Sedigh Mirzaie","doi":"10.1016/j.tice.2025.102983","DOIUrl":"10.1016/j.tice.2025.102983","url":null,"abstract":"<div><div>Diabetic wounds represent a major and costly challenge for diabetic patients, leading to significant morbidity and healthcare expenses. Consequently, extensive research has been dedicated to identifying effective treatments to enhance wound healing. Among these, biological hydrogels have emerged as promising candidates due to their superior properties over traditional materials. This study aimed to assess the efficacy of a bioactive and biodegradable collagen-based hydrogel derived from human amniotic membrane (CHA) combined with basic fibroblast growth factor (bFGF) in promoting wound healing in diabetic rats. A total of thirty diabetic rats were randomly divided into three groups (n = 10): control, CHA, and CHA incorporated with bFGF (CHA+bFGF). Wound evaluations were conducted on days 7 and 21. The findings revealed notable improvements in wound closure, fibroblast and blood vessel counts, collagen density, tensiometrical parameters, and the levels of VEGF in the treatment groups compared to the control group, with the most significant effects observed in the CHA+bFGF group. Moreover, the CHA+bFGF group demonstrated a greater reduction in inflammatory cells infiltration, along with lower concentration of TNF-α and IL-1β cytokines, compared to the other groups. In conclusion, the combination of CHA with bFGF proved to be highly effective in enhancing the healing process of diabetic wounds.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102983"},"PeriodicalIF":2.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of misoprostol in the prevention of amikacin-induced neuronal damage","authors":"Sebile Azırak ,&nbsp;İlkay Armağan","doi":"10.1016/j.tice.2025.102981","DOIUrl":"10.1016/j.tice.2025.102981","url":null,"abstract":"<div><div>Amikacin (AK) is an aminoglycoside widely used in the treatment of Gram-negative infections which are life-threatening. In the etiology of toxicity, AK has been shown to cause tissue damage through oxidative stress and apoptosis as a consequence of the reactive oxygen species (ROS) production. Misoprostol (MP) is a prostaglangin E1 (PGE1) analogue with antioxidant, antiapoptotic, cytoprotective properties used to prevent gastrointestinal disorders induced by nonsteroidal anti-inflammatory drug. This study aims to investigate the neuroprotective effects of MP on brain cells against the neurotoxicity of AK by gene expression and histopathological analyses. Twenty-four male Spraque-Dawley rats were randomly separated into four groups (group 1, control; group 2, AK; group 3, MP; group 4, AK + MP). According to our findings, AK treatment significantly increased brain weight, brain weight/body weight ratios, and CYP2B1 mRNA gene expression. This was accompanied by histopathological changes such as eosinophilic neurons, pyknotic nuclei, vacuolated neuropil, congestion and inflammation in blood vessels. On the other hand, while significant improvements were observed in brain weight and brain weight/body weight ratios in the AK + MP group, there was a significant decrease in CYP2B1 mRNA gene expression levels and histopathological changes. According to our results, MP may serve as a potential therapeutic candidate to reduce the severity of oxidative damage induced by AK in brain tissue.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102981"},"PeriodicalIF":2.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144154694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleolin alleviates endotoxemia-induced myocardial dysfunction via inhibiting Drp1-mediated mitochondrial fission","authors":"Ludong Yuan ,&nbsp;Yuting Tang ,&nbsp;Leijing Yin ,&nbsp;Xiaofang Lin ,&nbsp;Pengfei Liang ,&nbsp;Bimei Jiang","doi":"10.1016/j.tice.2025.102964","DOIUrl":"10.1016/j.tice.2025.102964","url":null,"abstract":"<div><h3>Background</h3><div>Our previous study found that nucleolin expression exerted anti-cardiac injury effects by promoting mitochondrial biogenesis; however, it could not explain the increase in mitochondrial fragmentation during myocardial injury. Mitochondrial fragmentation is associated with mitochondrial fission, but it is unknown whether nucleolin regulates mitochondrial fission. Therefore, this study aims to investigate the mechanism by which nucleolin regulates mitochondrial fission in endotoxemia-induced myocardial dysfunction.</div></div><div><h3>Methods</h3><div>Nucleolin myocardial-specific knockout mice were used to construct an endotoxemia-induced myocardial dysfunction model. Mitochondrial membrane potential (MMP), ATP production, Mitotracker Red, Transmission Electron Microscope were measured to assess mitochondrial function. Mitochondria were isolated to observe Drp1 translocation to mitochondria. The expression of pGSK-3β-Tyr216, GSK-3β, pDrp1-Ser637, nucleolin and dynamin-related protein 1 (DNM1L, Drp1) were detected using qRT-PCR and western blot.</div></div><div><h3>Results</h3><div>Following cecum ligation and puncture (CLP) model, cardiac function was impaired, myocardial mitochondrial function declined, mitochondrial morphology became disorganized and fragmented, nucleolin and Drp1 expression was elevated. Myocardial injury and mitochondrial dysfunction were further exacerbated after nucleolin myocardium-specific knockout. Meanwhile, after cellular-level nucleolin interference, it further led to LPS and TNF-α-induced mitochondrial dysfunction and cardiomyocyte damage. Mechanically, nucleolin interference inhibited Drp1 phosphorylation at Ser637 and promoted Drp1 translocation to mitochondria. Myocardial injury caused by nucleolin knockdown was alleviated by the use of P110, an inhibitor of Drp1 mitochondrial translocation.</div></div><div><h3>Conclusion</h3><div>Endotoxemia-induced myocardial dysfunction is accompanied by increased mitochondrial fragmentation. Nucleolin alleviates endotoxemia-induced myocardial dysfunction by enhancing Drp1 phosphorylation at Ser637, inhibiting Drp1 translocation to the mitochondria and mitochondrial fission.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 102964"},"PeriodicalIF":2.7,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}