Journal of Biochemical and Molecular Toxicology最新文献_第5页

Estrogen Promotes the Proliferation and Migration of Endometrial Cancer Through the GPER-Mediated NOTCH Pathway

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-01-29 DOI: 10.1002/jbt.70129

Meng Qi, Yuxi Jin, Lulu Si, Hanlin Fu, Xiaojing Shi, Yana Liu, Yifan Wang, Ruixia Guo

{"title":"Estrogen Promotes the Proliferation and Migration of Endometrial Cancer Through the GPER-Mediated NOTCH Pathway","authors":"Meng Qi, Yuxi Jin, Lulu Si, Hanlin Fu, Xiaojing Shi, Yana Liu, Yifan Wang, Ruixia Guo","doi":"10.1002/jbt.70129","DOIUrl":"10.1002/jbt.70129","url":null,"abstract":"<p>This study aims to investigate the expression of GPER in EC, assess the impact of estrogen on the proliferation and migration of EC via GPER, and examine the potential role of GPER in mediating the NOTCH pathway to influence EC proliferation and migration. The expression of GPER and its correlation with clinicopathological features were investigated using clinical data. Cell proliferation was assessed through MTT and EdU assays, while cell migration ability was evaluated using wound healing and transwell assays. Western blot analysis was conducted to detect proteins associated with the GPER and NOTCH signaling pathways. Additionally, xenograft tumor models were established to investigate the potential role of estrogen in mediating the NOTCH pathway via GPER. The results demonstrated a significant upregulation of GPER expression in EC, which was associated with clinical stage and metastasis. In vitro experiments provided evidence that estrogen promotes EC cell proliferation and metastasis by enhancing the expression levels of GPER, Notch1, and Hes-1 proteins. Conversely, knocking down or suppressing GPER effectively reverses these effects. Furthermore, treatment with JAG-1, an agonist for the NOTCH pathway, counteracts si-GPER's inhibitory impact on both proliferation and migration abilities of EC cells while increasing Notch1 and Hes-1 protein expression levels; however, it does not alter GPER expression. In vivo experiments have substantiated that estrogen facilitates EC proliferation via the GPER-mediated NOTCH pathway.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the Role of Epithelial–Mesenchymal Transition During Colorectal Cancer Peritoneal Metastasis: Update on Their Mechanisms

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-01-27 DOI: 10.1002/jbt.70166

Chenyan Long, Xiang Li, Jungang Liu, Xianwei Mo, Huage Zhong, Weizhong Tang, Junfeng Yu

引用次数: 0

Unlocking the Potential of miRNAs in Sepsis Diagnosis and Prognosis: From Pathophysiology to Precision Medicine 发掘 miRNA 在败血症诊断和预后中的潜力：从病理生理学到精准医学。

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-01-27 DOI: 10.1002/jbt.70156

Emad Gamil Khidr, Gharieb S. El-Sayyad, Ahmed I. Abulsoud, Nehal I. Rizk, Mohamed Bakr Zaki, Ahmed Amr Raouf, Mahmoud A. Elrebehy, Manal M. M. Abdel Hady, Mohammed S. Elballal, Osama A. Mohammed, Mustafa Ahmed Abdel-Reheim, Walaa A. El-Dakroury, Sherif S. Abdel Mageed, Tohada M. AL-Noshokaty, Ahmed S. Doghish

{"title":"Unlocking the Potential of miRNAs in Sepsis Diagnosis and Prognosis: From Pathophysiology to Precision Medicine","authors":"Emad Gamil Khidr, Gharieb S. El-Sayyad, Ahmed I. Abulsoud, Nehal I. Rizk, Mohamed Bakr Zaki, Ahmed Amr Raouf, Mahmoud A. Elrebehy, Manal M. M. Abdel Hady, Mohammed S. Elballal, Osama A. Mohammed, Mustafa Ahmed Abdel-Reheim, Walaa A. El-Dakroury, Sherif S. Abdel Mageed, Tohada M. AL-Noshokaty, Ahmed S. Doghish","doi":"10.1002/jbt.70156","DOIUrl":"10.1002/jbt.70156","url":null,"abstract":"<div>\u0000 \u0000 <p>The clinical syndrome appears as a dysregulated host response to infection that results in life-threatening organ dysfunction known as Sepsis. Sepsis is a serious public health concern where for every five deaths in ICU there is one patient who dies with sepsis worldwide. Sepsis is featured as unbalanced inflammation and immunosuppression which is sustained and profound, increasing patient susceptibility to secondary infections and mortality. microRNAs (miRNAs) play a central role in the control of many biological processes, and the deregulation of their expression has been linked to the development of oncological, cardiovascular, neurodegenerative, and metabolic diseases. In this review, we discuss the role of miRNAs in sepsis pathophysiology. Overall, miRNAs are seen as promising biomarkers, and it has been proposed to develop miRNA-based diagnosis and therapies for sepsis. Yet, the picture is not so straightforward because of miRNAs’ versatile and dynamic features. More research is needed to clarify the expression and role of miRNAs in sepsis and promote the use of miRNAs for sepsis management. This study provides an extensive, current, and thorough analysis of the involvement of miRNAs in sepsis. Its purpose is to encourage future research in this area, as tiny miRNAs have the potential to be used for rapid diagnosis, prognosis, and treatment of sepsis.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lycopene Ameliorates Polycystic Ovary Syndrome in Rats by Inhibiting Ovarian Ferroptosis Through Activation of the AMPK/Nrf2 Pathway

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-01-27 DOI: 10.1002/jbt.70158

Kexin Wang, Lin Wang, Chengyong Wu, Hongxiang Chen, Donghui Cai, Linglan Lu, Xuli Liu, Zhen Jiao

{"title":"Lycopene Ameliorates Polycystic Ovary Syndrome in Rats by Inhibiting Ovarian Ferroptosis Through Activation of the AMPK/Nrf2 Pathway","authors":"Kexin Wang, Lin Wang, Chengyong Wu, Hongxiang Chen, Donghui Cai, Linglan Lu, Xuli Liu, Zhen Jiao","doi":"10.1002/jbt.70158","DOIUrl":"10.1002/jbt.70158","url":null,"abstract":"<div>\u0000 \u0000 <p>Lycopene (LYC) is an extremely powerful antioxidant with the potential to treat a range of diseases and to inhibit ferroptosis. This research aims to elucidate how LYC impacts polycystic ovarian syndrome (PCOS) and the action mechanisms. A PCOS rat model was constructed by injecting DHEA. Different doses of LYC were injected intraperitoneally in PCOS rats, the estrous cycle was recorded. The histopathological damage of ovary in PCOS rats was observed by HE staining, testosterone (T), estradiol (E2), luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were examined by ELISA kits. Transmission electron microscopy, prussian blue staining, biochemical kits to determine ferroptosis. Immunohistochemistry and Western blot to assess the levels of ferroptosis-related and AMPK/Nrf2 pathway-related proteins to explore whether LYC affects ferroptosis in PCOS through this pathway. PCOS rats had significantly higher body weights, ovarian weights and ovarian indices, and disorganized estrous cycles, which were dose-dependently ameliorated by LYC. In addition, LYC significantly ameliorated the histopathological damage of ovary in PCOS rats and restored the normal secretion of T, E2, LH, and FSH. LYC attenuates iron deposition in PCOS ovarian tissues, reduces iron and ROS levels, and inhibits ferroptosis. Notably, LYC activated the AMPK/Nrf2 pathway, and AMPK inhibitor intervention attenuated the therapeutic effect of LYC in PCOS rats, suggesting that LYC acts through the AMPK/Nrf2 pathway. LYC attenuates estrous cycle disruption, ameliorates pathological impairments, and inhibits ferroptosis in PCOS rats by modulating the AMPK/Nrf2 pathway.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sirtuin 1 Suppresses Hydrogen Peroxide-Induced Senescence and Promotes Viability and Migration in Lens Epithelial Cells by Inhibiting Forkhead Box Protein O1/Toll-Like Receptor 4 Pathway

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-01-27 DOI: 10.1002/jbt.70150

Hongda Jiang, Yuting Liu, Yinggui Yu, Yu Yan

{"title":"Sirtuin 1 Suppresses Hydrogen Peroxide-Induced Senescence and Promotes Viability and Migration in Lens Epithelial Cells by Inhibiting Forkhead Box Protein O1/Toll-Like Receptor 4 Pathway","authors":"Hongda Jiang, Yuting Liu, Yinggui Yu, Yu Yan","doi":"10.1002/jbt.70150","DOIUrl":"10.1002/jbt.70150","url":null,"abstract":"<div>\u0000 \u0000 <p>Age-related cataracts (ARCs) are associated with increased oxidative stress and cellular senescence. Our objective is to investigate the function of Sirtuin 1 (SIRT1) within ARCs. In ARCs tissues and H<sub>2</sub>O<sub>2</sub>-treated lens epithelial cells (LECs), the expression levels of SIRT1 were examined. Senescence-associated β-galactosidase (SA-β-gal) staining was employed to evaluate cellular senescence. The Cell Counting Kit-8 assay was employed to measure viability. A wound healing assay was performed to assess migratory capacity in LECs. Oxidative stress-related indicators were determined by enzyme-linked immunosorbent assay kits. Additionally, the Coxpresdb and GeneCards databases were utilized to identify downstream pathways of SIRT1 in ARCs. The expression levels of protein and mRNA were detected using western blot and real-time quantitative polymerase chain reaction, respectively. The expression of SIRT1 was downregulated in ARCs tissues with an increase in reactive oxygen species. In H<sub>2</sub>O<sub>2</sub>-induced LECs, SIRT1 was downregulated and its overexpression inhibited oxidative stress and cellular senescence while promoting viability and migration. Furthermore, FoxO1/TLR4 pathway was screened out as the key pathway of SIRT1, which was activated in H<sub>2</sub>O<sub>2</sub>-induced LECs senescence. Overexpression of SIRT1 suppressed FoxO1/TLR4 pathway. Further research demonstrated that the activation of FoxO1/TLR4 pathway reversed the inhibitory role of SIRT1 in oxidative stress-induced cellular senescence and the promotion effect of SIRT1 on viability and migration in H<sub>2</sub>O<sub>2</sub>-induced LECs. SIRT1 inhibits oxidative stress-induced cellular senescence and promotes the viability and migration in H<sub>2</sub>O<sub>2</sub>-induced LECs via suppressing FoxO1/TLR4 pathway.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rutin Attenuates Pirarubicin-Induced Cardiomyocyte Injury by Knocking Down lncRNA Miat

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-01-26 DOI: 10.1002/jbt.70144

Peng Huang, Kaixu Yan, Wenqing Zhang, Jiahua Ji, Dexian Wei, Wentao Zheng, Lu Li, Liqun Ren

{"title":"Rutin Attenuates Pirarubicin-Induced Cardiomyocyte Injury by Knocking Down lncRNA Miat","authors":"Peng Huang, Kaixu Yan, Wenqing Zhang, Jiahua Ji, Dexian Wei, Wentao Zheng, Lu Li, Liqun Ren","doi":"10.1002/jbt.70144","DOIUrl":"https://doi.org/10.1002/jbt.70144","url":null,"abstract":"<div>\u0000 \u0000 <p>Pirarubicin (THP) is a widely used chemotherapeutic agent for breast cancer, but its clinical use is limited by its cardiotoxicity. In our previous study, we found that rutin (RUT), the main active ingredient in the traditional Chinese medicine Sophora japonica, could attenuate THP-induced cardiotoxicity. The aim of this study was to further investigate the potential role and mechanism of RUT in attenuating THP-induced cardiotoxicity. We examined the expression of lncRNA Miat in mouse cardiomyocytes (HL-1) under the intervention of THP/THP + RUT, respectively. Then we evaluated the protective effect of RUT on THP-induced HL-1 by CCK8, TUNEL, reactive oxygen species (ROS) assay and Western Blot. The mediating role of lncRNA Miat was verified by transfection of overexpression lncRNA Miat plasmid. The results showed that RUT increased cell viability, inhibited apoptosis, reduced ROS accumulation and decreased calcium overload in THP-induced HL-1. While overexpression of Miat significantly abrogated the therapeutic effect of rutin. In conclusion, RUT attenuates THP-induced myocardial injury by downregulating lncRNA Miat.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143119366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protective Effect of Fisetin on Subacute and Chronic Arsenic and Fluoride Co-Exposure Induced Hepatic, Renal and Cardiac Toxicities in Mice

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-01-26 DOI: 10.1002/jbt.70113

Sudipta Nayak, Debarati Rakshit, Vikas Yadav, Snehashis Kundu, Mohit Nema, Nilotpal Saharia, Awanish Mishra

{"title":"Protective Effect of Fisetin on Subacute and Chronic Arsenic and Fluoride Co-Exposure Induced Hepatic, Renal and Cardiac Toxicities in Mice","authors":"Sudipta Nayak, Debarati Rakshit, Vikas Yadav, Snehashis Kundu, Mohit Nema, Nilotpal Saharia, Awanish Mishra","doi":"10.1002/jbt.70113","DOIUrl":"https://doi.org/10.1002/jbt.70113","url":null,"abstract":"<div>\u0000 \u0000 <p>Arsenic and fluoride are potent toxicants frequently present in drinking water and food, posing severe health risks through toxic impacts on key organs, primarily by inducing oxidative stress. Combined exposure to these elements exacerbates oxidative damage, yet effective strategies for preventing and managing their toxicities remain elusive. Fisetin, a bioflavonoid known for its antioxidant and anti-inflammatory properties, has demonstrated protective effects in multiple toxicity studies. However, its effect on arsenic- and fluoride-induced toxicity in vital organs (particularly the liver, kidneys, and heart) remains unexplored. This study investigates the protective potential of fisetin against subacute and chronic co-exposure to arsenic and fluoride-induced organ toxicity in a murine model. Male mice were administered arsenic and fluoride through drinking water, while fisetin (5, 10, and 20 mg/kg/day, orally) was co-administered simultaneously. Animals were sacrificed at 4 weeks (subacute) and 24 weeks (chronic) for liver, kidney, and heart tissue analysis, assessing biochemical markers and arsenic accumulation. Spectrophotometry study revealed some degree of arsenic chelation with fisetin. The results of In Vivo studies showed that both subacute and chronic exposure led to significant increases in pro-oxidant levels (ROS, TBARS, and nitrite) and arsenic accumulation, along with reduced GSH content in these organs compared to control. Fisetin treatment dose-dependently reduced oxidative stress and arsenic content in vital organs of exposed animals. The findings highlight fisetin's antioxidant activity and its capacity to reduce arsenic burden as potential protective mechanisms. These results support fisetin or fisetin-rich fruit consumption as a therapeutic strategy to mitigate organ toxicity from arsenic and fluoride co-exposure.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143119365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protective Role of Oxycodone in Myocardial Oxidative Stress and Mitochondrial Dysfunction Induced by Ischemia-Reperfusion

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-01-26 DOI: 10.1002/jbt.70151

Yongzheng Jiang, Hua He, Xinwei Jia

{"title":"Protective Role of Oxycodone in Myocardial Oxidative Stress and Mitochondrial Dysfunction Induced by Ischemia-Reperfusion","authors":"Yongzheng Jiang, Hua He, Xinwei Jia","doi":"10.1002/jbt.70151","DOIUrl":"10.1002/jbt.70151","url":null,"abstract":"<p>Ischemia-reperfusion (I/R) injury is a significant clinical problem impacting the heart and other organs, such as the kidneys and liver. This study explores the protective effects of oxycodone on myocardial I/R injury and its underlying mechanisms. Using a myocardial I/R model in Sprague-Dawley (SD) rats and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in H9c2 cells, we administered oxycodone and inhibited AMP-activated protein kinase (AMPK) with Compound C (C.C). Our results showed that oxycodone significantly reduced lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) production while stabilizing mitochondrial membrane potential (MMP). Western blot and RT-qPCR analyzes confirmed that oxycodone enhances AMPK phosphorylation and upregulates the expression of Silent Information Regulator 1 (SIRT1) and Peroxisome Proliferator-Activated Receptor γ Coactivator 1α (PGC-1α), thereby protecting myocardial cells. These findings suggest that oxycodone exerts significant protective effects against I/R injury by activating the AMPK pathway, offering new potential therapeutic targets for myocardial protection.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanistic Insight of Pharmacological Aspects of Violacein: Recent Trends and Advancements

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-01-26 DOI: 10.1002/jbt.70114

Abhishek Chauhan, Darin Mansor Mathkor, Hemant Joshi, Ritu Chauhan, Ujjawal Sharma, Vikas Sharma, Manoj Kumar, Reena V. Saini, Adesh K. Saini, Hardeep Singh Tuli, Damandeep Kaur, Shafiul Haque

{"title":"Mechanistic Insight of Pharmacological Aspects of Violacein: Recent Trends and Advancements","authors":"Abhishek Chauhan, Darin Mansor Mathkor, Hemant Joshi, Ritu Chauhan, Ujjawal Sharma, Vikas Sharma, Manoj Kumar, Reena V. Saini, Adesh K. Saini, Hardeep Singh Tuli, Damandeep Kaur, Shafiul Haque","doi":"10.1002/jbt.70114","DOIUrl":"10.1002/jbt.70114","url":null,"abstract":"<div>\u0000 \u0000 <p>Since its discovery in the bacterium <i>Chromobacterium violaceum</i>, violacein—a striking purple pigment—has garnered significant interest due to its promising applications in the food and pharmaceutical industries. Violacein exhibits a range of pharmacological properties, including anti-inflammatory, anticancer, antibacterial, and antiparasitic effects, yet its complete molecular mechanisms are still being elucidated. Its mechanisms of action likely involve complex interactions with cellular receptors, signaling pathways, and specific molecular targets. Given violacein's unique properties and bioactive intermediates, future research holds substantial potential to advance its clinical and industrial applications. Upcoming studies will focus on deepening our understanding of violacein's molecular interactions, conducting clinical trials, and refining drug delivery systems to maximize its therapeutic value. Additionally, obtaining regulatory approval, conducting rigorous safety assessments, and developing efficient biosynthetic methods remain essential steps for violacein's successful integration into food biotechnology and medical applications.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of NLRP3 Inflammasome in Chronic Pain and Alzheimer's Disease—A Review

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-01-23 DOI: 10.1002/jbt.70071

Fatemeh Moradi, Tahmineh Mokhtari

{"title":"Role of NLRP3 Inflammasome in Chronic Pain and Alzheimer's Disease—A Review","authors":"Fatemeh Moradi, Tahmineh Mokhtari","doi":"10.1002/jbt.70071","DOIUrl":"10.1002/jbt.70071","url":null,"abstract":"<div>\u0000 \u0000 <p>The coexistence of Alzheimer's disease (AD) and chronic pain (CP) in the elderly population has been extensively documented, and a growing body of evidence supports the potential interconnections between these two conditions. This comprehensive review explores the mechanisms by which CP may contribute to the development and progression of AD, with a particular focus on neuroinflammatory pathways and the role of microglia, as well as the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. The review proposes that prolonged pain processing in critical brain regions can dysregulate the activity of the NLRP3 inflammasome within microglia, leading to the overproduction of pro-inflammatory cytokines and excessive oxidative stress in these regions. This aberrant microglial response also results in localized neuroinflammation in brain areas crucial for cognitive function. Additionally, CP as a persistent physiological and psychological stressor may be associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction, systemic inflammation, disruption of the blood–brain barrier (BBB), and neuroinflammation. These pathophysiological changes can cause morphological and functional impairments in brain regions responsible for cognition, memory, and neurotransmitter production, potentially contributing to the development and progression of CP-associated AD. Resultant neuroinflammation can further promote amyloid-beta (Aβ) plaque deposition, a hallmark of AD pathology. Potential therapeutic interventions targeting these neuroinflammatory pathways, particularly through the regulation of microglial NLRP3 activation, hold promise for improving outcomes in individuals with comorbid CP and AD. However, further research is required to fully elucidate the complex interplay between these conditions and develop effective treatment strategies.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0