Biochemical and biophysical research communications最新文献

{"title":"RFFL inhibition increases cell surface CFTR and reduces IL-8 production in airway epithelial cells upon COPD-associated environmental pathogen exposure","authors":"Daichi Hinata,&nbsp;Shiori Beppu,&nbsp;Yuka Kamada,&nbsp;Tsukasa Okiyoneda","doi":"10.1016/j.bbrc.2025.152251","DOIUrl":"10.1016/j.bbrc.2025.152251","url":null,"abstract":"<div><div>Chronic exposure to environmental pathogens and pollutants can impair CFTR chloride channel function, contributing to chronic obstructive pulmonary disease (COPD). Our previous study demonstrated that pyocyanin (PYO), a COPD-associated pathogen factor, significantly reduces the functional expression of R75Q- or M470V-CFTR, two CFTR polymorphisms found in COPD patients, leading to increased IL-8 production in airway epithelial cells (AEC). In this study, we report that inhibition of RFFL, a ubiquitin ligase that targets CFTR mutants for removal from the plasma membrane (PM), mitigates excessive IL-8 production in AECs expressing R75Q- or M470V-CFTR, even in the presence of PYO. RFFL knockdown (KD) enhanced the functional PM expression of R75Q- or M470V-CFTR under PYO exposure, although it did not prevent PYO-induced CFTR downregulation. Our results indicate that RFFL likely regulates constitutive IL-8 production independently of CFTR, while also modulating pathogen-induced IL-8 expression through a CFTR-dependent mechanism. This highlights the potential of RFFL inhibitors to enhance CFTR function and reduce IL-8 secretion, even amid chronic exposure to environmental pathogens and pollutants, underscoring RFFL inhibition as a promising therapeutic approach for COPD management.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"777 ","pages":"Article 152251"},"PeriodicalIF":2.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490190","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":"Metformin limits cerebral cavernous malformation development by targeting KLF4-mediated mitochondrial damage","authors":"Cong Yan ,&nbsp;Yongqing Ye ,&nbsp;Nan Liu ,&nbsp;Dongdong Zhang ,&nbsp;Wenzhong Du ,&nbsp;Ying Li ,&nbsp;GuoFu Li ,&nbsp;Chen Li ,&nbsp;Jingwei Li ,&nbsp;Shengji Ma ,&nbsp;Zifeng Dai ,&nbsp;ZiYu Xiong ,&nbsp;Yuwen Wang ,&nbsp;Chunyang Men ,&nbsp;Rui Bi ,&nbsp;Qianpeng Duan ,&nbsp;Weishi Xu ,&nbsp;Husilengtu ,&nbsp;Yuan Cao ,&nbsp;Jiapei Du ,&nbsp;Changbin Shi","doi":"10.1016/j.bbrc.2025.152241","DOIUrl":"10.1016/j.bbrc.2025.152241","url":null,"abstract":"<div><div>Cerebral cavernous malformations (CCM) present prevalent vascular diseases of the central nervous system, which can result in hemorrhage and seizures. Metformin, a first-line antidiabetic with established safety profiles, demonstrates pleiotropic effects, including the inhibition of cellular proliferation, inflammation, and angiogenesis, all of which are implicated in the pathogenesis of CCM. However, the therapeutic benefits of metformin in the realm of CCM remain unclear. This study aims to investigate the effect of metformin on the growth of CCM lesions in <em>Slco1c1</em> CreERT2; <em>Pdcd10</em> ^fl/fl (<em>Pdcd10</em>^BECKO) mice. Super-resolution confocal microscopy and transmission electron microscopy (TEM) were employed to evaluate mitochondrial structure. The results showed that metformin administration significantly attenuated CCM lesion burden, reduced iron deposition, and decreased collagen accumulation in <em>Pdcd10</em>^BECKO mice. Metformin also normalized the defects from PDCD10 deficiency, including disruption of tight junctions and excessive proliferation of endothelial cells. Moreover, metformin significantly improved mitochondrial structural anomalies and dysfunction associated with PDCD10 deficiency, characterized by the presence of mitochondrial puncta and the loss of cristae, followed by impaired mitochondrial membrane potential and increased mitoROS in endothelial cells with the mutation. Metformin provided these beneficial effects by downregulating KLF4. In conclusion, these findings indicate that metformin suppresses the development of CCM in <em>Pdcd10</em>^BECKO mice by targeting KLF4-mediated mitochondrial damage, thereby providing promising prospects as a novel therapeutic approach for CCM.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"777 ","pages":"Article 152241"},"PeriodicalIF":2.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471722","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":"Differential toxicity of radiation with different dose-rates between testis and bone marrow cells via the differential regulation of ROS, Ca2+, and mitochondria membrane potential","authors":"Jeong-Hwa Baek ,&nbsp;Min Ji Bae ,&nbsp;Hye Min Kim ,&nbsp;Eun Kyoung Shin ,&nbsp;Yong Uk Kye ,&nbsp;HyoJin Kim ,&nbsp;Yeong-Rok Kang ,&nbsp;Wol Soon Jo ,&nbsp;Joong Sun Kim ,&nbsp;Min Kook Kang ,&nbsp;Chang Geun Lee","doi":"10.1016/j.bbrc.2025.152248","DOIUrl":"10.1016/j.bbrc.2025.152248","url":null,"abstract":"<div><div>It is believed that there may be a proportional relationship between the dose-rate and adverse effects of radiation for a given dose. However, we have previously shown that low dose-rate (LDR) radiation induces greater toxicity in the testes than that induced by high-dose rate (HDR) radiation, in contrast to results for the thymic lymphoma induction rate. Since cell/organ toxicity and cancer induction rates may not be directly comparable, we compared toxicities following LDR and HDR radiation between testis/spermatogenesis and bone marrow/hematopoiesis, similar organs/cells in terms of continuously producing progenitor cells. The two organs showed opposite patterns of toxicity due to LDR and HDR radiation, supporting the differential dose-rate effect between the two organs. Furthermore, reactive oxygen species (ROS), Ca²⁺ and mitochondria membrane potential (MMP) were specifically regulated between the two organs by LDR and HDR. These results suggest that LDR radiation may enhance toxicity specifically in the testes but not in the bone marrow via the specific regulation of ROS, Ca²⁺, and MMP in single testis/spermatogonia. This report provides the evidence that radiation at different dose rates induces differential toxicity depending on the organ, accompanied by the differential regulation of key cellular parameters, such as ROS, Ca²⁺ and MMP.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"777 ","pages":"Article 152248"},"PeriodicalIF":2.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480307","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":"Biochemical characteristics of spacer amino acid determine phase-separating behavior and induction of nucleolar stress by arginine-rich dipeptide repeat proteins","authors":"Tamami Miyagi ,&nbsp;Mikiro Nawa ,&nbsp;Shinya Kusakari ,&nbsp;Rio Yamazaki ,&nbsp;Hiroshi Uji-i ,&nbsp;Yuhei Hayamizu ,&nbsp;Hiroaki Suzuki ,&nbsp;Kohsuke Kanekura","doi":"10.1016/j.bbrc.2025.152252","DOIUrl":"10.1016/j.bbrc.2025.152252","url":null,"abstract":"<div><div>Arginine-rich dipeptide repeat proteins (R-DPRs), produced from hexanucleotide repeat expansions via repeat-associated non-AUG translation, are linked to neurodegenerative disorders. While novel, potentially pathogenic R-DPRs have been identified, their intracellular signaling mechanisms remain unclear. To explore their biological roles, we examined R-DPR liquid–liquid phase separation behavior <em>in vitro</em> and their impact on nucleolar function. We found that the spacer hydrophobicity is a key determinant of R-DPR phase separation. Specifically, R-DPRs with hydrophobic spacers formed aggregates with RNA and recombinant nucleophosmin <em>in vitro,</em> inducing nucleolar stress and impairing ribosomal RNA synthesis in cells. These findings provide insights into the mechanisms by which R-DPRs exert nucleolar stress, advancing our understanding of their pathological roles.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"777 ","pages":"Article 152252"},"PeriodicalIF":2.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480265","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":"Structure of quercetin 3,4′-dimethyl ether in complex with tubulin provides a rationale for drug design","authors":"Yang Su ,&nbsp;Wei Yan ,&nbsp;Jianhong Yang ,&nbsp;Falong Yang","doi":"10.1016/j.bbrc.2025.152245","DOIUrl":"10.1016/j.bbrc.2025.152245","url":null,"abstract":"<div><div>Microtubules, composed of αβ-tubulin heterodimers, serve as key targets for anticancer therapeutics due to their critical role in cell division. Numerous compounds have been discovered to interact with tubulin and disrupt microtubule dynamics, particularly those targeting the colchicine-binding domain. Certain flavones, for instance, have demonstrated the ability to bind to this site and suppress microtubule polymerization. Despite their potential, progress in developing flavone-based drugs has been limited by insufficient structural data on tubulin-ligand complexes. Here, we present the high-resolution (1.92 Å) crystal structure of tubulin in complex with a flavone derivative, quercetin 3,4′-dimethyl ether (QU34), elucidating the specific molecular interactions at atomic detail. By analyzing this structure alongside other colchicine-site inhibitors, we clarify prior structure-activity relationship (SAR) findings and offer a framework for designing optimized flavone analogs targeting this site.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"777 ","pages":"Article 152245"},"PeriodicalIF":2.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480305","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":"Thermal study of plants in a dynamic environment using thermovision","authors":"Aleksandra Orzechowska ,&nbsp;Renata Szymańska ,&nbsp;Jakub Dymek ,&nbsp;Agnieszka Trela-Makowej ,&nbsp;Martin Trtílek","doi":"10.1016/j.bbrc.2025.152246","DOIUrl":"10.1016/j.bbrc.2025.152246","url":null,"abstract":"<div><div>We examined the effect of light-induced heating of leaves in wild-type (Col-0) and <em>tmm-1 Arabidopsis</em> plants. The results showed that the <em>tmm-1</em> mutant exhibits accelerated cooling of rosettes in response to changes in light intensity, as demonstrated by thermal imaging measurements. This is evident in the time constants determined for temperature kinetics, which were reduced during the transition from light to dark. Our findings indicate that these dynamics can be reliably assessed under various light conditions. Measurements of gas exchange showed that stomatal conductance, transpiration rate, and net CO₂ assimilation rate were increased in the <em>tmm-1</em> mutant. Furthermore, fluorescence analysis revealed that the <em>tmm-1</em> mutant exhibited an increased ratio of total energy dissipation to the number of active reaction centers, as well as higher average absorption. We also observed that the performance index (PI_ABS) was reduced compared to Col-0. Nevertheless, the clustering of stomata did not affect the maximum quantum yield of PSII. Our results demonstrate that the maintenance of lower leaf temperatures and the greater cooling capacity in plants with clustered stomata positively affects overall photosynthetic performance.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"777 ","pages":"Article 152246"},"PeriodicalIF":2.5,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471727","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":"Papain-like protease of SARS-CoV-2 inhibits dsRNA-induced type I interferon response partly by cleaving TBK1","authors":"Wei-Hua Zheng ,&nbsp;Run-Ze Ni ,&nbsp;Xiang-Hong Ran ,&nbsp;Dan Mu","doi":"10.1016/j.bbrc.2025.152244","DOIUrl":"10.1016/j.bbrc.2025.152244","url":null,"abstract":"<div><div>Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has claimed millions of lives and has been a global threat since its emergence. Multiple SARS-CoV-2-encoded proteins have been shown to exert interferon-I (IFN–I)-antagonizing effects, which contribute to severe pathogenesis. We previously reported that the papain-like protease (PLpro) of SARS-CoV-2 and SARS-CoV, a closely related highly pathogenic coronavirus, counteracts IFN production via its deubiquitinating (DUB) activity. In this study, we reveal a new mechanism by which SARS-CoV-2 negatively regulates host innate antiviral responses. Both PLpro proteins from SARS-CoV and SARS-CoV-2 mediated the proteolytic cleavage of TBK1, the hub kinase in the IFN-I signaling pathway. Using point mutants, we demonstrated that the catalytic triad, which is composed of C111, H272, and D286, and the enzyme activity regulatory site, W93, are essential for the ability of SARS-CoV-2 PLpro to cleave the TBK1 protein and for the inhibitory effect on TBK1-triggered IFN expression. However, the mutants failed to abrogate the suppressive effect of SARS-CoV PLpro on Sendai virus (SeV)-induced IFN-I promoter activation, indicating that PLpro inhibits the dsRNA-induced IFN response partly by cleaving TBK1. Collectively, our findings suggest a conserved mechanism through which highly pathogenic SARS-CoV and SARS-CoV-2 harness their PLpro proteins to suppress IFN expression at the level of TBK1, resulting in the evasion of the host innate antiviral response.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"777 ","pages":"Article 152244"},"PeriodicalIF":2.5,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471728","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":"Regulation of Notch signaling by miR-79 in Drosophila eye development","authors":"Cheng-Hsien Lee,&nbsp;Yun-Chen Hung,&nbsp;Kai-Hsin Huang,&nbsp;Yu-Chen Tsai","doi":"10.1016/j.bbrc.2025.152222","DOIUrl":"10.1016/j.bbrc.2025.152222","url":null,"abstract":"<div><div>The Notch signaling pathway is crucial for cell fate determination and tissue morphogenesis. In <em>Drosophila</em>, Notch signaling regulates eye size, but the mechanisms that fine-tune its activity during eye development remain unclear. Here, we established a Notch-sensitized <em>Drosophila</em> model to identify novel regulators of this pathway. Using the Gal4/UAS system, we overexpressed <em>fringe</em> (<em>fng</em>) under <em>ey-Gal4</em> control (<em>ey &gt; fng</em>) in <em>Drosophila</em> eyes, disrupting Notch signaling and resulting in a small-eye phenotype. In this sensitizing background, a genetic screening identified <em>miR-79</em> as a key modulator of Notch signaling. <em>miR-79</em> overexpression rescued <em>ey &gt; fng-</em>induced small-eye phenotype, whereas loss-of-function analysis using a <em>mir-79</em> sponge exacerbated the phenotype, confirming its regulatory role. Furthermore, co-expression of <em>miR-79</em> with the Notch ligands Delta or Serrate induced eye disc overgrowth near the equator, where Notch signaling is typically active, suggesting a strong genetic interaction between <em>miR-79</em> and the Notch pathway. Functional studies revealed that <em>miR-79</em> directly targets <em>Beaded (Brd</em>) by binding to specific Brd-Box motifs in its 3’ UTR. RNAi-mediated <em>Brd</em> knockdown phenocopied the rescue effect of <em>miR-79</em> overexpression, whereas <em>Brd</em> gain-of-function enhanced the <em>ey &gt; fng</em> phenotype. RNA <em>in situ</em> hybridization demonstrated complementary expression patterns of <em>miR-79</em> and <em>Brd</em> during eye development. Although <em>Tom</em>, another <em>Brd</em> family member, was identified as a potential <em>miR-79</em> target, luciferase assays confirmed that <em>Tom</em> is not directly regulated by <em>miR-79</em>. However, genetic interactions between <em>Tom</em> and <em>Notch</em> components suggest function redundancy with <em>Brd</em>. These findings establish <em>miR-79</em> as a novel activator of Notch signaling in <em>Drosophila</em> eye development, primary through <em>Brd</em> regulation. This study provides new insights into molecular mechanisms governing Notch-mediated development and highlights the regulatory role of <em>miR-79</em> in tissue growth and differentiation.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152222"},"PeriodicalIF":2.5,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365866","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":"Molecular mechanism of secretory protein EFNA1 in HNSCC and its value in early screening","authors":"Yanan Fu ,&nbsp;Mengqiao He ,&nbsp;Jiayi Li ,&nbsp;Jia Ji ,&nbsp;Zhen Xiao ,&nbsp;Yukun Ma ,&nbsp;Xuelin Chen","doi":"10.1016/j.bbrc.2025.152243","DOIUrl":"10.1016/j.bbrc.2025.152243","url":null,"abstract":"<div><h3>Background</h3><div>Head and neck squamous cell carcinomas (HNSCC) is an aggressive malignancy, necessitating early diagnostic biomarkers. This study explores EFNA1's role in HNSCC and its potential for early screening.</div></div><div><h3>Methods</h3><div>Data from TCGA, CCLE, and Depmap databases were analyzed. Serum samples from HNSCC patients and controls were tested using ELISA. Cell proliferation, apoptosis assays, and KEGG pathway analysis were conducted. Western blotting assessed EphA2pS898, EphA2, and EFNA1's impact on the AKT/ERK1/2 pathway.</div></div><div><h3>Results</h3><div>EFNA1 expression was significantly higher in HNSCC tissues compared to healthy tissues (P &lt; 0.05). ROC analysis showed an AUC of 0.924 for EFNA1 in predicting HNSCC, indicating its diagnostic potential. Serum EFNA1 levels were elevated pre-surgery and decreased post-surgery (P &lt; 0.05), correlating with poor prognosis (P = 0.021). EFNA1 knockdown in BICR78 and SNU46 cells induced apoptosis (P &lt; 0.05). EFNA1 overexpression increased proliferation, which was reversed by EFNA1 antibody. EFNA1 downregulated AKT/ERK1/2 pathway activity, with its interference preventing full pathway activation.</div></div><div><h3>Conclusion</h3><div>EFNA1 is a promising biomarker for early HNSCC screening and a potential therapeutic target.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"777 ","pages":"Article 152243"},"PeriodicalIF":2.5,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489802","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":"Modulation of NF-κB/NLRP3 inflammasome axis Nrf2/HO-1 signaling and attenuation of oxidative stress mediate the protective effect of ambroxol against cyclophosphamide cardiotoxicity","authors":"Reem S. Alruhaimi ,&nbsp;Emad H.M. Hassanein ,&nbsp;Sulaiman M. Alnasser ,&nbsp;Ahmad F. Ahmeda ,&nbsp;Hanan S. Althagafy ,&nbsp;Amr M.T. Allam ,&nbsp;Hamada S. Qebesy ,&nbsp;Ayman M. Mahmoud","doi":"10.1016/j.bbrc.2025.152242","DOIUrl":"10.1016/j.bbrc.2025.152242","url":null,"abstract":"<div><div>Despite its potent chemotherapeutic efficacy, cyclophosphamide (CP) is associated with severe cardiac complications, limiting its clinical utility. Recent evidence suggests that the mucolytic agent ambroxol (ABX) exhibits antioxidant and anti-inflammatory properties, making it a candidate for mitigating CP cardiotoxicity. This study explored the protective effects of ABX against CP-mediated cardiotoxicity, with emphasis on oxidative stress, NF-κB/NLRP3 inflamamsome axis and Nrf2/HO-1 signaling. Rats were administered ABX (20 mg/kg) for 7 days and received a single injection of CP (100 mg/kg) on day 5, and blood and heart samples were collected for analyses. CP administration induced significant cardiac dysfunction, marked by elevated LDH, CK-MB, and troponin-I, alongside histopathological evidence of myocardial injury. ABX alleviated cardiac biomarkers, prevented histopathological alterations, reduced lipid peroxidation, and restored antioxidant defenses. CP upregulated NF-κB p65, NLRP3, ASC1, caspase-1, gasdermin D, and IL-1β, and suppressed Nrf2 and HO-1 in the heart of rats. ABX suppressed the NF-κB/NLRP3 inflamamsome axis mediators and upregulated Nrf2 and HO-1. <em>In silico</em> data revealed the binding affinity of ABX towards NF-κB p65 and NLRP3 and ASC1 PYD domains. In conclusion, ABX confers significant protection against CP-induced cardiotoxicity through multifaceted mechanisms, including attenuation of oxidative stress, inhibition of NF-κB/NLRP3 inflamamsome axis, and upregulation of Nrf2/HO-1 signaling. These findings suggest that ABX could serve as an effective adjunct therapy to improve the safety profile of CP in clinical oncology.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"776 ","pages":"Article 152242"},"PeriodicalIF":2.5,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365311","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}