International Journal of Biological Sciences最新文献

{"title":"Emodin Inhibits NLRP3 Inflammasome Activation and Protects Against Sepsis via Promoting FUNDC1-Mediated Mitophagy.","authors":"Wei Fu, Shu-Chang Liu, Tong-Xiang Xu, Ying Liu, Teng Zhang, Dong-Jie Liu, Xiao Wang, Jian-Yao Wang, Yu-Xin He, Tao Ma","doi":"10.7150/ijbs.110904","DOIUrl":"10.7150/ijbs.110904","url":null,"abstract":"<p><p>Dysregulated activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome contributes to the pathogenesis of numerous inflammatory and infectious diseases; however, effective targeted therapies remain elusive. In this study, we identify emodin-a bioactive anthraquinone derived from <i>Rheum palmatum</i> (radix Rhei) and <i>Polygonum cuspidatum</i> (Polygonaceae)-as a potent and selective inhibitor of NLRP3 inflammasome activation. Notably, emodin disrupts the assembly of the NLRP3 complex without impairing inflammasome priming. Transcriptomic profiling via RNA sequencing reveals that emodin reprograms mitochondrial quality control pathways, markedly enhancing mitophagy flux. Mechanistically, emodin suppresses casein kinase II (CK2)-mediated phosphorylation of FUNDC1, a pivotal mitophagy receptor, thereby promoting mitochondrial clearance and preventing mitochondrial reactive oxygen species-induced NLRP3 inflammasome assembly. Both genetic silencing of FUNDC1 and pharmacological inhibition of mitophagy with 3-methyladenine abrogated abrogate the inhibitory effects of emodin, establishing a direct mechanistic link between FUNDC1-dependent mitophagy and NLRP3 regulation. <i>In vivo</i>, emodin confers significant protection in sepsis models, with these protective effects being lost in NLRP3-deficient mice or upon macrophage-specific deletion of FUNDC1. Collectively, our findings uncover a novel CK2-FUNDC1-mitophagy axis through which emodin inhibits NLRP3 inflammasome activation, highlighting its promise as a clinically translatable candidate for the treatment of NLRP3-driven inflammatory diseases.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 8","pages":"3631-3648"},"PeriodicalIF":8.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omics-based Approach Towards Macrophages: New Perspectives of Biology and Function in the Normal and Diseased Heart.","authors":"Chao Yang, Huajun Li, Yuxing Chen, Wei Zhu, Jian'an Wang","doi":"10.7150/ijbs.112061","DOIUrl":"10.7150/ijbs.112061","url":null,"abstract":"<p><p>Macrophages play a crucial role not only in maintaining homeostasis but also in initiating inflammatory responses to various forms of stress or injury, thereby contributing to tissue damage while concurrently promoting recovery. Furthermore, the diversity of macrophage subtypes, their spatial distribution, and distinct cellular functions are closely linked to the pathogenesis and severity of cardiovascular diseases such as myocardial infarction, atherosclerosis, heart failure, and myocarditis. This association underscores the importance of investigating macrophage heterogeneity in different pathological contexts. Recent advances in multi-omics technologies-including single-cell RNA sequencing, spatial transcriptomics, and metabolomics-have elucidated the heterogeneity of macrophages, their intercellular interactions, underlying functional mechanisms, and spatial organization. In this review, we systematically summarize the diverse phenotypes and functional plasticity of macrophages in the regulation of cardiovascular diseases, with particular emphasis on the novel insights afforded by multi-omics approaches. We focus on the characteristics of macrophages in both physiological and pathological states, thereby providing reference points for clinical macrophage-targeted strategies and their translational significance.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 8","pages":"3666-3688"},"PeriodicalIF":8.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin Alleviates Liver Metabolic Dysfunction in Polycystic Ovary Syndrome by Activating the Ethe1/Keap1/PINK1 Pathway.","authors":"Yuan Xie, Ying Tian, Junting Huang, Wanying Deng, Xiaohui Li, Yujia Liu, Hao Liu, Lei Gao, Qiu Xie, Qi Yu","doi":"10.7150/ijbs.104778","DOIUrl":"10.7150/ijbs.104778","url":null,"abstract":"<p><p><b>Background:</b> Polycystic ovary syndrome (PCOS) is a reproductive endocrine disease characterized by metabolic abnormalities, with 34-70% of patients with PCOS also presenting non-alcoholic fatty liver disease (NAFLD). Metformin is a first-line treatment for relieving insulin resistance in PCOS; however, the potential therapeutic application of metformin for preventing NAFLD/metabolic dysfunction-associated fatty liver disease (MAFLD) in PCOS remains under-explored. Here, we investigated the potential protective effects and the underlying mechanisms of metformin against hepatic lipid metabolic disorders in prenatal anti-Müllerian hormone (PAMH)-induced PCOS mice. <b>Methods:</b> First, we developed a prenatal AMH-induced PCOS-like model using pregnant C57BL/6N mice. Female offspring of mice were then subjected to the glucose tolerance test and insulin tolerance test pre- and post-treatment with metformin. H&E staining, serum hormone, and biochemical analyses were performed to determine the effects of metformin on metabolic abnormalities and liver damage in the PCOS-like model. To verify the specific mechanism of action of metformin, dehydroepiandrosterone (DHEA) and free fatty acids (FFAs; palmitic acid and oleic acid) induced alpha mouse liver 12 (AML-12) cells were used to establish a mouse liver cell model of adipose-like degeneration and lipid deposition. <b>Results:</b> Metformin effectively alleviated hepatic lipid accumulation in the PCOS mice. Furthermore, mitochondrial dysfunction and loss of redox homeostasis in the liver of PCOS mice were rescued upon metformin administration. Mechanistic insights reveal that metformin regulates mitochondrial autophagy in PCOS liver tissue via the activation of the Ethe1/Keap1/Nrf2/PINK1/Parkin pathway, thereby improving liver recovery in PCOS mice. <b>Conclusions:</b> Our findings highlight the role and mechanism of metformin in ameliorating abnormal mitophagy and lipid metabolic disorders in the PCOS mice livers and the potential of metformin for addressing NAFLD in PCOS mice.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 8","pages":"3505-3526"},"PeriodicalIF":8.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Lung-Brain Axis in Chronic Obstructive Pulmonary Disease-Associated Neurocognitive Dysfunction: Mechanistic Insights and Potential Therapeutic Options.","authors":"Xiao Yu, Hui Xiao, Yushan Liu, Zhiyong Dong, Xiaoting Meng, Fang Wang","doi":"10.7150/ijbs.109261","DOIUrl":"10.7150/ijbs.109261","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) ranks as the third leading cause of global mortality, affecting 210 million individuals worldwide. Notably, 60% of COPD patients experience comorbid neurocognitive disorders. Importantly, patients with neurocognitive dysfunction often exhibit poor adherence to therapeutic interventions and medications, exacerbating their COPD morbidity and increasing hospitalization rates and mortality risk. This review explores the potential lung-brain axis in COPD, emphasizing that oxidative stress and inflammatory responses in the lungs can spread to the systemic circulation, thereby regulating in the blood-brain barrier (BBB) permeability and contributing to brain dysfunction. In addition, the role of hormone-based hypothalamic-pituitary-adrenal (HPA) axis in COPD progression is discussed. These cascading events can lead to neuronal deficits, altered glial cell function, and subsequent cognitive dysfunction. Furthermore, we provide a comprehensive overview of potential medications for treating COPD and its associated cognitive deficits, with a specific focus on anti-inflammatory and antioxidant therapies. This compilation serves as a pivotal foundation for the prevention and management of cognitive dysfunction in COPD.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 8","pages":"3461-3477"},"PeriodicalIF":8.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenesis and treatment strategies of sepsis-induced myocardial injury: modern and traditional medical perspectives.","authors":"Wenwen Yang, Yanting Cao, Jiayan Li, Xin Zhang, Xiaoyi Liu, Ye Tian, Liang Shan, Yang Yang","doi":"10.7150/ijbs.111288","DOIUrl":"10.7150/ijbs.111288","url":null,"abstract":"<p><p>Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Myocardial injury is a common complication in sepsis patients, which accelerates the progression of sepsis, leading to multiple organ dysfunction and poor prognosis. However, there are still many uncertainties about the characteristics, pathogenesis, treatment, and prognosis of sepsis-induced myocardial injury. While modern medical approaches dominate current clinical management of sepsis-induced myocardial injury, emerging evidence highlights the growing therapeutic potential of traditional Chinese medicine in this field, driven by advances in biomedical research. The integration of these two paradigms holds promise for elucidating the pathophysiological mechanisms and identifying novel therapeutic targets for sepsis-induced myocardial injury, which may accelerate the development of innovative treatment strategies. Therefore, this review comprehensively summarizes the pathogenesis and therapeutic interventions of sepsis-induced myocardial injury from both modern medicine and traditional Chinese medicine perspectives, and critically analyzes the two aiming to provide a valuable reference for researchers' understanding of sepsis-induced myocardial injury.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 8","pages":"3478-3504"},"PeriodicalIF":8.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial SIRT3 deficiency predisposes brown adipose tissue to whitening in diet-induced obesity.","authors":"Qing Zhou, Zongshi Lu, Bowen Wang, Yuyan Wang, Li Li, Mei You, Lijuan Wang, Tingbing Cao, Dan Tong, Jie Xiang, Yu Zhao, Qiang Li, Aidi Mou, Wentao Shu, Hongbo He, Zhigang Zhao, Daoyan Liu, Zhiming Zhu, Peng Gao, Zhencheng Yan","doi":"10.7150/ijbs.110741","DOIUrl":"10.7150/ijbs.110741","url":null,"abstract":"<p><p>Endothelial dysfunction and vascular rarefaction are supposed to be secondary to metabolic diseases, while recent evidence has revealed the primary roles of endothelium in initiating and accelerating metabolic disorders. Here, the effects and underlying mechanisms of endothelial SIRT3 in modulating the whitening of BAT during obesity progression were explored. Therefore, mice with global or BAT regional endothelium-specific Sirt3 knockout were constructed and fed with high-fat diet (HFD). The results showed that both global and BAT regional endothelium-specific Sirt3 knockout accelerated diet-induced weight gain, accompanied by glucose intolerance, insulin resistance, and BAT whitening. In vitro results revealed that the inhibition or knockdown of endothelial Sirt3 impeded palmitic acid-induced angiogenesis deficiency, while the overexpression of Sirt3 exhibited the opposite effects. Furtherly, endothelial Sirt3 overexpression ameliorated palmitic acid-induced adipocyte dysfunction and proinflammatory macrophages polarization in a paracrine way. Mechanistically, endothelial SIRT3 deficiency increased the acetylation of fatty acid synthase (FASN), which disturbed the fatty acid metabolism and thus, leading to angiogenesis insufficiency. Moreover, loss of SIRT3 promoted adipocytes dysfunction and proinflammatory macrophage polarization via CASP1-mediated pyroptosis. Endothelial SIRT3 loss contributed to diet-induced BAT whitening and obesity progression and thus, could be a therapeutic target in treating obesity and associated metabolic diseases.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 8","pages":"3444-3460"},"PeriodicalIF":8.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Negative Feedback Mechanisms in the PTEN-ACE Axis: Application of Electrosorb Hydrogel-Based Gene Delivery for Intervertebral Disc Regeneration.","authors":"Youfeng Guo, Feng Wang, Yu Zhou, Bijun Wang, Chao Wang, Tao Hu, Desheng Wu","doi":"10.7150/ijbs.111898","DOIUrl":"10.7150/ijbs.111898","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IDD), along with associated low back pain, stands as a primary cause of disability. The renin-angiotensin-aldosterone system has been linked to IDD; however, the mechanisms underlying this relationship have not been determined. In this study, the role of angiotensin-converting enzyme (ACE), a key synthetase in the system, in IDD and its regulatory mechanism were evaluated. Our findings revealed that downregulating ACE alleviates IDD. Additionally, phosphatase and tensin homolog (PTEN) regulated ACE through tripartite motif-containing 63 (TRIM63)-mediated K48-linked ubiquitination. PTEN dephosphorylated TRIM63, while polo-like kinase 1 (PLK1) phosphorylated TRIM63 at Ser67 and Ser69, two crucial sites for the interaction between ACE and TRIM63. Importantly, this regulatory axis also influenced endoplasmic reticulum autophagy by modulating O-GlcNAc modification, highlighting its significant role in the regulation of IDD. Furthermore, we developed a chitosan-virus electrosorb hydrogel for IDD repair therapy using lentivirus-mediated gene editing. The hydrogel exhibited excellent swelling, degradation, release rates, and biocompatibility. Specific gene editing by the chitosan-virus electrosorb hydrogel could reduce IDD in rats. These findings support the efficacy of modulating the PTEN-ACE pathway and O-GlcNAc modification and the therapeutic value of chitosan-virus electrosorb hydrogels for IDD.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 8","pages":"3416-3443"},"PeriodicalIF":8.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Luteolin improves precancerous conditions of the gastric mucosa by binding STAT3 and inhibiting LCN2 expression.","authors":"Xinyu Hao, Shouli Yuan, Jing Ning, Yuanfei Zhou, Yanfei Lang, Xiurui Han, Qiao Meng, Ying Xiong, Rongli Cui, Yueqing Gong, Chao Ma, Weichao Xu, Yangang Wang, Xiaohuan Guo, Chu Wang, Jing Zhang, Weiwei Fu, Shigang Ding","doi":"10.7150/ijbs.111636","DOIUrl":"10.7150/ijbs.111636","url":null,"abstract":"<p><p>Inhibition of malignant transformation from the precancerous stage has important clinical value for the prevention of gastric cancer. Here, we report a strategy to inhibit precancerous gastric conditions by Luteolin (Lut). Lut treatment resulted in remarkable resistance to oxyntic atrophy, spasmolytic polypeptide-expressing metaplasia (SPEM), and gastric mucosal injury in tamoxifen (TAM)-treated mice, chenodeoxycholic acid-treated rats, and human organoids. Mechanism study suggested that LCN2 expression was upregulated in the SPEM mucosa and downregulated after Lut treatment. LCN2 blocking suppressed TAM-induced oxyntic atrophy and metaplasia and partially counteracted the effect of Lut. Quantitative chemoproteomics identified that Lut bound to STAT3 and inhibited its phosphorylation. Functional experiments using STAT3 inhibitors and epithelial cell-specific <i>Stat3</i> deficient mice showed that STAT3 inhibition and deletion attenuated the beneficial effects of Lut. Our data supported that Lut might be a therapeutic candidate for the treatment of gastric mucosal injury by binding to STAT3 and thereby inhibiting the STAT3/LCN2 axis.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 8","pages":"3397-3415"},"PeriodicalIF":8.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pterostilbene Induces Apoptosis in Awakening Quiescent Prostate Cancer Cells by Upregulating C/EBP-β-Mediated SOD2 Transcription.","authors":"Zhichao Xi, Mengfan Liu, Xue Jiang, Jiling Feng, Rongchen Dai, Wan Najbah Nik Nabil, Xueyang Sun, Jiayi Chen, Hangui Ren, Juan Zhang, Qihan Dong, Man Yuan, Yang Li, Hongxi Xu","doi":"10.7150/ijbs.106219","DOIUrl":"10.7150/ijbs.106219","url":null,"abstract":"<p><p>Quiescent cancer cells (QCCs) are known to resist chemoradiotherapy, evade immune surveillance and have the potential to drive recurrence years after initial treatment. However, the key regulators of QCC survival during reactivation remain unclear. This study revealed that superoxide dismutase 2 (SOD2) levels are significantly greater in quiescent prostate cancer (PCa) cells than in proliferative cells. SOD2 overexpression induces apoptosis in awakening quiescent PCa cells, whereas its knockdown promotes reactivation. Elevated SOD2 also suppresses recurrent tumor growth by quiescent PCa cells and prolongs survival. Pterostilbene (PTE), a natural compound, preferentially induces apoptosis in quiescent PCa cells during awakening and reduces their long-term proliferative capacity by upregulating SOD2. Additionally, PTE inhibits tumorigenesis and significantly reduces the growth of quiescent PCa cells without apparent toxicity. Further mechanistic studies revealed that CCAAT/enhancer-binding protein beta (C/EBP-β) is critical for PTE-mediated SOD2 upregulation by enhancing SOD2 transcription. C/EBP-β knockdown significantly reduces PTE-induced apoptosis in awakening quiescent PCa cells. Clinical analysis revealed a positive correlation between <i>CEBPB</i> and <i>SOD2</i>, with low C/EBP-β expression linked to poor prognosis. Overall, the C/EBP-β-SOD2 pathway is crucial for eliminating awakening quiescent PCa cells and highlights PTE as a promising agent for preventing PCa recurrence.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 8","pages":"3379-3396"},"PeriodicalIF":8.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocytes Lingering at a Crossroads: Neuroprotection and Neurodegeneration in Neurocognitive Dysfunction.","authors":"Xiaoxia Xu, Bin Mei, Yue Yang, Junxiong Li, Juntao Weng, Yueyue Yang, Qianyun Zhu, Honghai Zhang, Xuesheng Liu","doi":"10.7150/ijbs.109315","DOIUrl":"10.7150/ijbs.109315","url":null,"abstract":"<p><p>Astrocytes, a major class of glial cells in the central nervous system, play a fundamental role in maintaining homeostasis, supporting neuronal function, and regulating synaptic activity. Recent studies have increasingly highlighted the pivotal role of astrocytes in the initiation and progression of neurocognitive dysfunction. Alterations in astrocytic morphology and functionality have been strongly associated with the onset of cognitive impairments, positioning astrocytes as key regulators in neurocognitive processes. Astrocytes influence neurocognitive function through their involvement in the uptake and release of gliotransmitters, modulation of inflammatory mediators, and metabolic regulation. These processes have been implicated in various neurodegenerative and neurocognitive disorders, including epilepsy, Alzheimer's disease, postoperative cognitive dysfunction, and sepsis-associated encephalopathy. Given the emerging role of astrocytes in these conditions, understanding the mechanisms by which they modulate neurocognitive function is essential for identifying potential therapeutic targets. This review provides an overview of the current understanding of astrocytic contributions to neurocognitive dysfunction and explores the therapeutic opportunities provided by the targeting of astrocyte-mediated pathways.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 7","pages":"3122-3143"},"PeriodicalIF":8.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}