Advanced biology最新文献_第2页

Differential Responses of Amyloid-β 42 Aggregates to Resveratrol 淀粉样蛋白-β 42聚集体对白藜芦醇的差异反应。

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-03-04 DOI: 10.1002/adbi.202500586

Nghia D. Nguyen, Peter G. Vekilov

{"title":"Differential Responses of Amyloid-β 42 Aggregates to Resveratrol","authors":"Nghia D. Nguyen, Peter G. Vekilov","doi":"10.1002/adbi.202500586","DOIUrl":"10.1002/adbi.202500586","url":null,"abstract":"<div>\u0000 \u0000 <p>Amyloid-β (Aβ) aggregation is targeted with small molecules as a pathway toward developing potential Alzheimer's disease (AD) therapies. Resveratrol, a natural polyphenol, has been proposed as an inhibitor of Aβ aggregation, but its mechanistic effects across distinct Aβ42 aggregates remain unresolved. To better evaluate resveratrol's potential to treat AD, here we focus on molecular-level insights into the mechanisms that underlie its interaction with several distinct classes of Aβ42 aggregates. In contrast to published approaches that are based on monitoring the evolution of the total fibrillar mass, we employ time-resolved in situ atomic force microscopy to explore the effects of resveratrol on Aβ42 amyloid and non-amyloid assemblies. While data suggest a weak interaction between resveratrol and low-molecular-weight Aβ42 species, we also observe a concentration-dependent reduction in fibrillization. In the presence of resveratrol, we observe a decrease in fibril thickness and end-dependent slowing of elongation; furthermore, the fibrils exhibit reduced mechanical integrity and fragment under minimal scanning stress. Importantly, resveratrol does not affect the formation or morphology of oligomers and amorphous aggregates. These findings suggest that resveratrol selectively targets the fibril pathway while leaving oligomeric assemblies unaltered. The results provide mechanistic insights into the differential effects of small molecules on Aβ42 assemblies and establish a framework for evaluating inhibitors of aggregation with single-aggregate resolution.</p>\u0000 </div>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353491","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}

引用次数: 0

Transcriptional Activation of SBNO2 by KDM1A Drives Immune Escape in Lung Cancer. KDM1A转录激活SBNO2驱动肺癌免疫逃逸

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-03-01 DOI: 10.1002/adbi.202500639

Deguang Pan, Chong Zhang

{"title":"Transcriptional Activation of SBNO2 by KDM1A Drives Immune Escape in Lung Cancer.","authors":"Deguang Pan, Chong Zhang","doi":"10.1002/adbi.202500639","DOIUrl":"https://doi.org/10.1002/adbi.202500639","url":null,"abstract":"<p><p>KDM1A is a crucial epigenetic modulator in tumor immune escape. Nevertheless, its precise regulatory function within the immune microenvironment of lung cancer needs investigation. Using TCGA data, we analyzed KDM1A and SBNO2 expression, clinical correlation, and immune infiltration. Functional assays included co-culture of lung cancer cells with CD8<sup>+</sup> T cells, flow cytometry, Transwell migration, ChIP, and luciferase reporter assays. qPCR measured gene expression. KDM1A and SBNO2 were notably upregulated in lung cancer tissues, which correlated with poor patient prognosis and reduced CD8<sup>+</sup> T cell infiltration. Functional experiments demonstrated that knockdown of KDM1A enhanced T cell proliferation, chemotaxis, and cytokine production. Mechanistically, KDM1A acted as a transcription regulator binding to the SBNO2 promoter and positively regulated its mRNA expression in lung cancer cells. Importantly, rescue experiments confirmed that silencing SBNO2 expression abolished the pro-tumor immune escape effects induced by KDM1A overexpression. This study unveils a novel mechanism whereby KDM1A drives immune escape in lung cancer by transcriptionally activating SBNO2, which subsequently suppresses the anti-tumor role of CD8<sup>+</sup> T cells. These findings lend strong support to targeting the KDM1A-SBNO2 axis as a promising immunotherapeutic approach for lung cancer.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 3","pages":"e00639"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502820","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}

引用次数: 0

Dormancy and Recurrence in Breast Cancer Bone Metastasis: From Mechanisms to Clinical Translation 乳腺癌骨转移的休眠与复发：从机制到临床转化。

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-02-24 DOI: 10.1002/adbi.202500485

Ziqi Sun, Baohong Li, Zichao Chen, Zhen Zhang

{"title":"Dormancy and Recurrence in Breast Cancer Bone Metastasis: From Mechanisms to Clinical Translation","authors":"Ziqi Sun, Baohong Li, Zichao Chen, Zhen Zhang","doi":"10.1002/adbi.202500485","DOIUrl":"10.1002/adbi.202500485","url":null,"abstract":"<div>\u0000 \u0000 <p>Breast cancer bone metastasis often involves a prolonged dormancy phase, during which disseminated tumor cells (DTCs) remain undetectable and resistant to conventional therapies, posing a significant risk for late recurrence. Understanding the underlying mechanisms of tumor dormancy and reactivation is crucial for developing effective clinical interventions. However, current clinical translation faces multiple challenges, including limitations in detecting dormant tumor cells, insufficient biomarkers for dormancy, and difficulties in targeted drug delivery. Recent advances in elucidating the mechanisms of dormancy—such as the establishment of the pre-metastatic niche, intercellular communication in the bone marrow microenvironment, and signaling pathways regulating dormancy and reactivation—have provided novel therapeutic targets. Based on these mechanistic insights, nanotechnology-based drug delivery systems have emerged as promising strategies to precisely target dormant breast cancer cells in bone marrow niches. In this review, we summarize the current understanding of dormancy mechanisms in breast cancer bone metastasis, discuss the barriers hindering clinical translation, and highlight how mechanism-driven nanotherapeutic strategies may offer new opportunities to prevent recurrence by targeting dormant tumor cells.</p>\u0000 </div>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281628","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}

引用次数: 0

TWIST1 Activates CDCA3 to Promote EMT of Lung Adenocarcinoma and Expression of PD-L1 TWIST1激活CDCA3促进肺腺癌EMT及PD-L1表达

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-02-22 DOI: 10.1002/adbi.202500531

Jianyi Ding, Junjun Zhao, Jiandong Zhang, Linhai Fu, Zhupeng Li, Desheng Wei, Guangmao Yu, Haiyong Wang

{"title":"TWIST1 Activates CDCA3 to Promote EMT of Lung Adenocarcinoma and Expression of PD-L1","authors":"Jianyi Ding, Junjun Zhao, Jiandong Zhang, Linhai Fu, Zhupeng Li, Desheng Wei, Guangmao Yu, Haiyong Wang","doi":"10.1002/adbi.202500531","DOIUrl":"10.1002/adbi.202500531","url":null,"abstract":"<div>\u0000 \u0000 <p>CDCA3 and TWIST1 are implicated in cell-cycle control and transcriptional regulation, yet their combined role in lung adenocarcinoma (LUAD) remains unclear. Here, we investigated the impact of the TWIST1/CDCA3 axis on LUAD cell behavior. Leveraging TCGA and KnockTF v2.0, we pinpointed TWIST1 as an upstream driver of CDCA3 in LUAD and delineated associated survival outcomes. ChIP and dual-luciferase assays verified the interaction between CDCA3 and TWIST1. We also quantified CDCA3 and TWIST1 mRNA by qRT-PCR and determined CDCA3, the immune-therapy biomarker PD-L1, and EMT-related protein levels by Western blot. Furthermore, CCK-8, colony formation assays, wound healing, and Transwell assays were conducted to evaluate the malignant behaviors of cells. Bioinformatic and functional analyses revealed that both CDCA3 and TWIST1 were highly expressed in LUAD, and their elevated levels predicted poor prognosis. Further investigation identified TWIST1 as an upstream activator of CDCA3. Knockdown of TWIST1 attenuated the malignant phenotype and reduced PD-L1 expression in LUAD cells, whereas subsequent overexpression of CDCA3 fully reversed these suppressive effects. This study aims to validate that the TWIST1/CDCA3 axis promotes invasion, migration, proliferation, and PD-L1 expression of LUAD cells.</p>\u0000 </div>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269441","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}

引用次数: 0

Feiwei Mixture Exerts Antitumor Activity Against Non-Small Cell Lung Cancer via Regulating NR1D1-Mediated Immune Cell Infiltration 飞味合剂通过调节nr1d1介导的免疫细胞浸润对非小细胞肺癌具有抗肿瘤活性。

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-02-22 DOI: 10.1002/adbi.202500574

Haiyong Wang, Lingsun Guo, Yu Zhao, Jinshu Ye, Tong Zhao, Chufeng Zhang

{"title":"Feiwei Mixture Exerts Antitumor Activity Against Non-Small Cell Lung Cancer via Regulating NR1D1-Mediated Immune Cell Infiltration","authors":"Haiyong Wang, Lingsun Guo, Yu Zhao, Jinshu Ye, Tong Zhao, Chufeng Zhang","doi":"10.1002/adbi.202500574","DOIUrl":"10.1002/adbi.202500574","url":null,"abstract":"<div>\u0000 \u0000 <p>Feiwei Mixture (FWHJ), a hospital preparation for lung cancer, lacks a defined mechanism of action. Using Lewis lung carcinoma (LLC) tumor-bearing mice and an LLC-CD8<sup>+</sup> T cell co-culture model, we evaluated the effects of FWHJ on tumor growth, T cell infiltration, and apoptosis. Key signaling molecules (NR1D1, cGAS-STING, SOCS3-JAK-STAT3) and chemokines were analyzed using Western blot, flow cytometry, and immunoassays. Further knockout of NR1D1 confirmed its critical role in mediating the anti-tumor effects of FWHJ. FWHJ dose-dependently inhibited tumor growth in mice and enhanced CD4<sup>+</sup>/CD8<sup>+</sup> T cell infiltration. It upregulated NR1D1, SOCS3, and the cGAS-STING pathway, while suppressing JAK-STAT3 signaling, leading to increased CCL5, CXCL10, and IFN-α. In co-culture model, FWHJ-containing serum promoted LLC cell apoptosis and suppressed malignant progression, recapitulating the signaling alterations observed in vivo. Crucially, NR1D1 knockout abolished the therapeutic effects of FWHJ. FWHJ inhibits non-small cell lung cancer (NSCLC) by activating NR1D1 to stimulate the cGAS-STING pathway and suppress the JAK-STAT3 signaling axis, thereby enhancing anti-tumor immunity. This study provides a foundation for further investigation into the anti-tumor mechanisms of FWHJ and establishes a scientific basis for its potential application in lung cancer therapy.</p>\u0000 </div>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269422","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}

引用次数: 0

Mechanical Dialogues of Life and Death: How External Molecules Entry Triggers a Chromatin-Cytoskeleton Morphogenetic Duel in Cancer Cells 生与死的机械对话：外部分子进入如何触发癌细胞中染色质-细胞骨架形态发生的决斗。

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-02-19 DOI: 10.1002/adbi.202500716

Parama Dey, Anup Singhania, Ajaikumar B. Kunnumakkara, Subrata Ghosh, Anirban Bandyopadhyay

{"title":"Mechanical Dialogues of Life and Death: How External Molecules Entry Triggers a Chromatin-Cytoskeleton Morphogenetic Duel in Cancer Cells","authors":"Parama Dey, Anup Singhania, Ajaikumar B. Kunnumakkara, Subrata Ghosh, Anirban Bandyopadhyay","doi":"10.1002/adbi.202500716","DOIUrl":"10.1002/adbi.202500716","url":null,"abstract":"<div>\u0000 \u0000 <p>The next-generation anti-cancer therapeutics must disrupt intracellular mechanics, efficiently eradicating cancer cells, rather than simply intoxicating them. We evaluate the mechanism of action of PCMS, a PAMAM-based supramolecule that eradicates cancer cells by reorganizing their internal mechanics rather than their genes. Once internalized, PCMS self-assembles into a perinuclear ring that severs nucleus-cytoskeleton communication. We observed PCMS's dual-intelligent mechanisms of action: Cytoskeletal rescue, where actin-microtubule filaments move towards the PCMS ring, treating it as a surrogate plasma membrane, attempting to restore vesicular trafficking; Nuclear counter-expansion, where chromatin-lamina condensates undergo stepwise viscoelastic transitions that push the nuclear envelope outward to reestablish membrane contact. These contradictory forces amplify mechanical stress, driving super-critical strain and nuclear lysis without broad transcriptional modulations. By geometry alone, PCMS collapses the actin-microtubule-nucleus continuum and turns the cell's adaptive machinery into its own executioner. The discovery that life and death decisions can be reprogrammed through spatial conflict establishes a paradigm of mechanical deception, inaugurating a new class of cellular adaptive feedback-targeted mechanotherapeutics that overcome resistance by exploiting the cell's own morphogenetic logic.</p>\u0000 </div>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224833","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}

引用次数: 0

Mechanical Cues and Lineage Commitment Govern the Angiogenic Potential of Mesenchymal Cell-Derived Extracellular Vesicles 机械提示和谱系承诺控制间充质细胞衍生的细胞外囊泡的血管生成潜能。

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-02-19 DOI: 10.1002/adbi.202500544

Carolina S. Martins, Mimma Maggio, Cansu Gorgun, Mathieu Y. Brunet, Marko Dobricic, R. Almasri, Fergal J. O'Brien, Lorraine O'Driscoll, David A. Hoey

{"title":"Mechanical Cues and Lineage Commitment Govern the Angiogenic Potential of Mesenchymal Cell-Derived Extracellular Vesicles","authors":"Carolina S. Martins, Mimma Maggio, Cansu Gorgun, Mathieu Y. Brunet, Marko Dobricic, R. Almasri, Fergal J. O'Brien, Lorraine O'Driscoll, David A. Hoey","doi":"10.1002/adbi.202500544","DOIUrl":"10.1002/adbi.202500544","url":null,"abstract":"<p>Bone regeneration requires a finely tuned interplay between osteogenesis and angiogenesis. While current treatments, such as auto/allografts, provide support, they often fail to promote adequate vascularization necessary for complete repair. Extracellular vesicles (EVs), as mediators of intercellular communication, have emerged as promising acellular nanotechnologies for tissue regeneration due to their bioactive cargo and low immunogenicity. Mechanical stimulation, a known enhancer of bone cell function, can modulate EV cargo and potentially improve regenerative efficacy. In this study, we investigated how mechanical stimulation and the stage of mesenchymal lineage commitment influence the angiogenic potential of secretomes and EVs derived from mesenchymal stromal/stem cells, osteoblasts, and osteocytes. Our findings reveal that both cell mechanical stimulation and their differentiation stage significantly modulate the angiogenic properties of the resulting EVs. Among the tested conditions, mechanically-stimulated osteocyte-derived EVs demonstrate superior angiogenesis, promoting endothelial cell migration, tube formation, and CD31 expression. These effects were further validated in a pre-clinical ex ovo chick chorioallantoic membrane assay, where robust neovascularization was observed. This work highlights the critical role of both mechanical cues and cell differentiation stage in regulating the angiogenic capacity of EVs and proposes mechanically activated osteocyte-derived EVs as a novel pro-angiogenic nanotherapeutic for bone repair.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12921385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224868","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}

引用次数: 0

Bioelectronic Technology for Nutritional Research—a Novel In Vitro Platform for a Better Understanding of Human Gut Barrier Absorption 用于营养研究的生物电子技术——更好地了解人体肠道屏障吸收的新型体外平台。

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-02-18 DOI: 10.1002/adbi.202500409

Verena Stoeger, Magdalena Strauss, Kumar Thurimella, Shani Elias-Kirma, Izabella Niewczas, Etkin Parlar, Erika Schaudy, Chrysanthi-Maria Moysidou, Stephen Voong, Jory Lietard, Jonathan Clark, Christopher Gerner, Róisín M. Owens

{"title":"Bioelectronic Technology for Nutritional Research—a Novel In Vitro Platform for a Better Understanding of Human Gut Barrier Absorption","authors":"Verena Stoeger, Magdalena Strauss, Kumar Thurimella, Shani Elias-Kirma, Izabella Niewczas, Etkin Parlar, Erika Schaudy, Chrysanthi-Maria Moysidou, Stephen Voong, Jory Lietard, Jonathan Clark, Christopher Gerner, Róisín M. Owens","doi":"10.1002/adbi.202500409","DOIUrl":"10.1002/adbi.202500409","url":null,"abstract":"<p>The epithelial gut barrier and gut microbiota significantly contribute to human health by controlling molecule absorption, a regulated transport that dictates bioavailability. Effective public health strategies, like dietary reference values, require a complete understanding of nutrient absorption. However, the lack of internationally harmonized nutritional recommendations indicates that gut barrier mechanisms are not fully unraveled. The conventional in vitro model Caco-2/HT29-MTX cultured on cell culture inserts, established for drug development, is limited in representing complex human gut physiology. The new bioelectronic e-transmembrane platform leverages technological and biological advances to generate more meaningful in vitro predictions. The soft electroactive Poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) scaffold enables direct cell-electrode coupling for more sensitive barrier impedance measurements, especially required for testing commonly low physiological nutrient concentrations. Promoted epithelial-fibroblast interactions result in modulated protein signal transduction and expression of genes regulating gut barrier integrity. Overall, the e-transmembrane gut barrier more closely mimicked physiological effects for humans as demonstrated using the dietary compound butyrate.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adbi.202500409","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218303","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}

引用次数: 0

Emerging Therapeutic Targets and Signaling Networks in Ischemia–Reperfusion Injury 缺血再灌注损伤的新治疗靶点和信号网络。

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-02-18 DOI: 10.1002/adbi.202500673

Shreeya Bhujbal, Lokesh Kumar Bhatt

{"title":"Emerging Therapeutic Targets and Signaling Networks in Ischemia–Reperfusion Injury","authors":"Shreeya Bhujbal, Lokesh Kumar Bhatt","doi":"10.1002/adbi.202500673","DOIUrl":"10.1002/adbi.202500673","url":null,"abstract":"<div>\u0000 \u0000 <p>Ischemia–reperfusion injury remains a major challenge in modern regenerative medicine due to its complex mechanisms, lack of effective therapies, and persistent constrains to translating new interventions from bench to bedside. Currently, there are no FDA-approved drugs that directly target ischemia–reperfusion injury, highlighting a substantial therapeutic gap. While restoring blood flow is vital for salvaging ischemic tissue, the reperfusion process paradoxically triggers additional cellular damage. The clinical significance and complexity of ischemia–reperfusion injury underscore an urgent need for mechanistically targeted therapeutic approaches. Recent research has identified pivotal molecular targets—PHLDA1, SIRT6, PKM2, and ubiquitin-specific proteases (USPs)—that play key roles in modulating cellular responses such as oxidative stress, inflammation, metabolism, apoptosis, autophagy, ferroptosis, and blood-brain barrier dysfunction during ischemia reperfusion injury. Advances in understanding these mechanisms offer promising strategies for developing novel interventions to mitigate tissue damage and improve patient outcomes. This review critically examines these molecular targets, detailing recent advances and outlining future directions in ischemia reperfusion injury research.</p>\u0000 </div>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218314","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}

引用次数: 0

Notoginsenoside R1 as a Protector Against Gentamicin Ototoxicity: Targeting p62-NRF2-GPX4 Ferroptosis Axis 三七皂苷R1作为抗Gentamicin耳毒性的保护剂：靶向p62-NRF2-GPX4 Ferroptosis轴

IF 2.6 3区生物学

Advanced biology Pub Date : 2026-02-18 DOI: 10.1002/adbi.202500580

Xiaorui Chen, Ruoyu Jiang, Yunfeng Chu, Yan Sun, Zijiang Yuan, Yuhan Qian, Xiaolan Cheng, Hongjun Dong

{"title":"Notoginsenoside R1 as a Protector Against Gentamicin Ototoxicity: Targeting p62-NRF2-GPX4 Ferroptosis Axis","authors":"Xiaorui Chen, Ruoyu Jiang, Yunfeng Chu, Yan Sun, Zijiang Yuan, Yuhan Qian, Xiaolan Cheng, Hongjun Dong","doi":"10.1002/adbi.202500580","DOIUrl":"10.1002/adbi.202500580","url":null,"abstract":"<div>\u0000 \u0000 <p>Sudden sensorineural hearing loss (SSNHL) is a common auditory disorder, with oxidative stress and ferroptosis implicated in its pathogenesis. Notoginsenoside R1, a major component of Panax notoginseng, exhibits antioxidant and cytoprotective effects, but its role in ferroptosis regulation remains unclear. In this study, a mouse model of SSNHL and an oxygen-glucose deprivation/reoxygenation (OGD/R)-induced Ear Institute-Organ of Corti 1 (HEI-OC1) cell model were used to evaluate the effects of Notoginsenoside R1. Notoginsenoside R1 significantly reduced auditory brainstem response (ABR) thresholds, reduced cochlear hair cell apoptosis, and alleviated oxidative damage. It inhibited ferroptosis by decreasing Fe<sup>2</sup><sup>+</sup>, ROS, MDA, and LPO levels, while upregulating SOD, GSH, GCL, and GPX4. Mechanistically, nuclear factor erythroid 2-related factor 2 (NRF2) was identified as a key responsive target through target prediction and qPCR validation, while molecular docking and microscale thermophoresis (MST) assays demonstrated a direct interaction between Notoginsenoside R1 and SQSTM1 (p62). Besides, Notoginsenoside R1 enhanced p62 expression and promoted NRF2 nuclear translocation, restoring expression of GCLC, GCLM, and GPX4. Both p62 knockout and siRNA-mediated knockdown progressively attenuated these protective effects. These findings suggest that Notoginsenoside R1 protects against SSNHL by inhibiting ferroptosis and oxidative stress via activation of the p62-NRF2-GCL-GPX4 axis.</p>\u0000 </div>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"10 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218331","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}

引用次数: 0