Molecular & Cellular Toxicology最新文献

{"title":"Zearalenone activates GnRH neurons related to central precocious puberty by regulating microRNA-384/GPER signaling","authors":"Yan Sun","doi":"10.1007/s13273-024-00470-6","DOIUrl":"https://doi.org/10.1007/s13273-024-00470-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Central precocious puberty (CPP) is an important issue, characterized as the same physical features as normally timed puberty occurs at an early age. Non-steroidal mycotoxins such as zearalenone (ZEA) are the important triggering factors for CPP development in girls; however, the detailed mechanism responsible for the effect of ZEA is still unclear.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>In this study, the effect as well as the underlying mechanism of ZEA on cell proliferation and GnRH secretion in the mouse GnRH (gonadotropin-releasing hormone)-producing hypothalamic cell line GT1-7 were investigated.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The in vitro experiments revealed that ZEA treatment up-regulated cell proliferation as well as the expressions of GnRH and GPER (G protein-coupled estrogen receptor) in GT1-7 cells by down-regulating the expression of microRNA-384 (miR-384). However, such effects were attenuated by GPER inhibitor G15 pre-treatment. In addition, clinical samples analysis revealed that urinary ZEA in CPP patients significantly correlated to blood expressions of GPER and miR-384.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>In conclusion, this study reveals a novel mechanism of ZEA on CPP using in vitro model and clinical samples, and which may provide a potential therapeutic target as well as the diagnostic biomarker for CPP.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"38 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141524903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing circRUFY1 protects retinal ganglion cell injury in acute intraocular hypertension by activating the ERK pathway through miR-196a-5p/CALM3 axis","authors":"BinBin Li, ShaoJun Li, Wei Tang, Min Zeng","doi":"10.1007/s13273-024-00469-z","DOIUrl":"https://doi.org/10.1007/s13273-024-00469-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Neuroinflammation has been recognized as a key pathological event in acute glaucoma. Medical treatment of acute glaucoma has mainly focused on lowering intraocular pressure, yet the majority of patients still experience deterioration. Aberrant expression or activity of circular RNAs in the retina has been described in various ophthalmic diseases.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>This study surveyed the mechanism of circRUFY1 in acute ocular hypertension (AOH)-induced retinal ganglion cell (RGC) injury.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>AOH rats expressed high circRUFY1 and CALM3, and low miR-196a-5p in the retina tissue. CircRUFY1 silencing in AOH-induced rats reduced the severity of retinal damage and RGC damage. CircRUFY1, as a ceRNA of miR-196a-5p, upregulated CALM3, and CALM3 overexpression could further activate the ERK pathway signaling in RGCs.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Silence of circRUFY1 protects RGCs from AOH injury mainly by inhibiting the ERK signaling pathway by regulating the miR-196a-5p/CALM3 axis. Overall, targeted intervention of circRUFY1 expression is a promising therapeutic strategy for treating RGC damage in acute glaucoma.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"11 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The therapeutic potential of Laggera alata in alleviating inflammation and oxidative stress: insights into the miR-150-5p/TRIM8 axis","authors":"JiangCun Wei, Sen Liang, Peng Yang, Bing Qing, JiaBao Ma, LeiMin Jiang, QingMei Deng, Wen Zhong, MingGang Wang, ZuJie Qin","doi":"10.1007/s13273-024-00468-0","DOIUrl":"https://doi.org/10.1007/s13273-024-00468-0","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objective</h3><p>This research was conducted to study the protective effect of <i>Laggera alata</i> (TPLA) on sepsis-induced liver injury (SLI).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The SLI model was established in rats by cecal ligation and puncture (CLP), and human liver THLE-3 cells were induced by LPS to establish a cellular SLI model. HE staining and TUNEL staining were performed on the liver tissue of SLI rats treated with TPLA. The effects of TPLA on THLE-3 cells were studied using CCK-8, flow cytometry, ELISA, and biochemical analysis. The functional mechanism of TPLA, miR-150-5p, and TRIM8 in SLI was studied.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>TPLA treatment improved SLI in CLP rats and LPS-induced human liver THLE-3 cell injury was manifested by liver tissue injury recovery and decreased apoptosis of liver cells. At the same time, inflammation and oxidative stress were also alleviated. miR-150-5p level was reduced in SLI rats and cells, while TPLA pretreatment restored miR-150-5p level. miR-150-5p inhibitors could impair the therapeutic effect of TPLA in THLE-3 cell damage. TRIM8 was a direct target of miR-150-5p, and there was a negative regulatory relationship between the miR-150-5p and TRIM8 mRNA levels. Overexpressing TRIM8 also weakened the therapeutic effect of TPLA on THLE-3 cell damage.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>TPLA reduces TRIM8 expression by upregulating miR-150-5p, thereby reducing inflammatory response and oxidative stress, and thus significantly alleviating SLI.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"89 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hesperidin protects C2C12 myoblasts from oxidative damage by reducing ROS-mediated mitochondrial damage and endoplasmic reticulum stress","authors":"Yung Hyun Choi","doi":"10.1007/s13273-024-00446-6","DOIUrl":"https://doi.org/10.1007/s13273-024-00446-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Hesperidin, a flavanone glycoside found primarily in the peel of citrus fruits, has benefits as a natural compound for preventing various diseases, but its inhibitory effect against oxidative injury in muscle cells has not been reported.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>The current study aimed to investigate whether hesperidin can prevent oxidative damage in C2C12 murine myoblasts.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Hesperidin was able to inhibit cytotoxicity while blocking hydrogen peroxide (H₂O₂) H₂O₂-induced DNA damage and apoptosis. Hesperidin also significantly improved the antioxidant capacity of C2C12 cells exposed to H₂O₂ by suppressing cellular reactive oxygen species production and increasing glutathione level. Additionally, H₂O₂-induced mitochondrial dysfunction and endoplasmic reticulum (ER) stress were effectively attenuated in the presence of hesperidin. Moreover, hesperidin neutralized H₂O₂-induced calcium ion (Ca²⁺) overload in mitochondria and mitigated the expression of cytosolic Ca²⁺-dependent proteases.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>These results imply that hesperidin protects against mitochondrial impairment and Ca²⁺-mediated ER stress by minimizing oxidative stress, thereby suppressing H₂O₂-induced cytotoxicity in C2C12 myoblasts.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"32 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear translocation of β-catenin and migration of arecoline-induced oral cancer cells reduced by Taiwanin E via p-GSK3β downregulation","authors":"Chi-Cheng Li, Marthandam Asokan Shibu, Wei-Wen Kuo, Yueh-Hsiung Kuo, Yun-Peng Chao, Chun-Hsu Yao, Da-Tian Bau, Pei-Jei Lio, Chung-Jen Chiang, Chih-Yang Huang","doi":"10.1007/s13273-024-00464-4","DOIUrl":"https://doi.org/10.1007/s13273-024-00464-4","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Oral squamous cell carcinomas (OSCCs) accounts for 90% of the total oral cancers and is a major public health issue worldwide. It is the most prevalent malignant epithelial neoplasm of the oral cavity.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>In this study, we analyzed the effect of Taiwanin E, a bioactive compound derived from Taiwania (<i>Taiwania cryptomerioides</i> Hayata), on metastasis and migration and further checked the mechanism particularly by Wnt signaling which is one of the key cascades involved in cancer.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Taiwanin E considerably attenuated the cell migratory potential of oral cancer cells in a dose-dependent manner. At the molecular level, it was found that Taiwanin E interfered with nuclear translocation of β-catenin via p-GSK3β specifically in tumor derived cells (T28) and not in non-tumor (N28) cells. Moreover, Taiwanin E significantly downregulated the downstream metastatic protein c-myc and TBX3.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The present study demonstrates that Taiwanin E inhibits the elevated expression levels from the baseline β-catenin levels and thereby potentially inhibits the migratory effects of T28 cells.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"57 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"hsa_circ_0002454 controls cervical cancer cell growth and metastasis by targeting SDC4 through miR-654-3p","authors":"Yanmei Li, Yuzhen Zhang, Fuqiang Xu, Nan Wang, Qing Liu","doi":"10.1007/s13273-024-00467-1","DOIUrl":"https://doi.org/10.1007/s13273-024-00467-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Circular RNAs (circRNAs) are involved in tumor growth and metastasis. The aim of this study was to elucidate the possible role of has_circ_0002454 in cervical cancer (CC) and its potential molecular mechanism.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>has_circ_0002454, miR-654-3p, and SDC4 mRNA levels were determined by RT-qPCR, and SDC4 protein was by Western Blot. Cell proliferation was detected by MTT, colony formation, and wound healing. Invasion and migration capacities of cells were assessed by Transwell assays. The targeting relationship between miR-654-3p and has_circ_0002454 or SDC4 was confirmed by dual-luciferase reporter gene and RIP assay. Xenograft tumor model was constructed to determine the role of has_circ_0002454 in CC.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In CC tissues and cell lines, has_circ_0002454 was associated with significantly higher SDC4 levels and significantly lower miR-654-3p expression. Down-regulation of has_circ_0002454 promoted miR-654-3p expression while decreasing SDC4 expression levels. has_circ_0002454 competitively bound miR-654-3p, and elevated miR-654-3p expression rescued the effects of has_circ_0002454 silencing on cancer cell proliferation, apoptosis, migration, and invasion. miR-654-3p directly targeted SDC4, and overexpression of SDC4 reversed the effect of has_circ_0002454 knockdown on cancer cell function. In addition, down-regulation of has_circ_0002454 effectively suppressed tumor growth in vivo.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>has_circ_0002454 reduction weakens the cancer phenotype of CC cells by modulating the miR-654-3p/SDC4 axis.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"63 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long intergenic non-protein coding RNA 1436 accelerates cell proliferation, migration and adhesion properties of the MUM-2B cell line via microRNA-513a-5p/CUG Triplet repeat-binding protein 1 axis to activate the phosphatidylinositol 3-kinase/Akt signaling pathway","authors":"XinCheng Sun, ZhaoDong Chu, XiaoYan Zhao, MengJiao Wang, YaNan Kong, GuoHua Lu","doi":"10.1007/s13273-024-00466-2","DOIUrl":"https://doi.org/10.1007/s13273-024-00466-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objective</h3><p>Long intergenic non-protein coding RNA 1436 (LINC01436) has been reported as a critical regulator of tumor occurrence, but the association between LINC01436 and choroidal melanoma (CM) has hardly been explored. The study was to uncover the precise association of LINC01436 with CM.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>CM tissues and their corresponding adjacent normal tissues were collected, normal chorocytes UM96 and CM cell lines (C918, MUM-2B, OCM-1, MUM-2C) were cultured. LINC01436, microRNA (miR)-513a-5p, and CUG Triplet repeat-binding protein 1 (CELF1) expression in CM tissues and cells were detected. The screened MUM-2B cell line was transfected with LINC01436, miR-513a-5p or CELF1-related sequences or plasmids to explore their biological effects on cells with the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. The expressions of PI3K/Akt pathway-related protein were measured after transfection, same as the proliferation, cell cycle distribution, apoptosis, adhesion, migration, and invasion of MUM-2B cells. The binding of LINC01436 with miR-513a-5p and the targeting of miR-513a-5p with CELF1 were verified.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>LINC01436 and CELF1 were upregulated in CM tissues and cells, while miR-513a-5p was reduced. LINC01436 adsorbed miR-513a-5p as a sponge, which targeted CELF1. Silenced LINC01436 suppressed the activation of PI3K/Akt pathway in MUM-2B cells as well as cell proliferation, adhesion, and metastasis. Meanwhile, elevated LINC01436 showed the opposite effect on MUM-2B cells. Restoring miR-513a-5p reversed the influence of augmented LINC01436 on MUM-2B cells. MiR-513a-5p restrained the activation of PI3K/Akt pathway and malignant behaviors of MUM-2B cells via targeting CELF1.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>LINC01436 promotes cell proliferation, migration, and adhesion properties of the MUM-2B cell line via miR-513a-5p/CELF1 axis, which may be related to the PI3K/Akt pathway.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"63 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the toxicological impact of yeast vacuoles in Daphnia","authors":"Taehwan Kim, Hyo Jin Choi, Woo-Ri Shin, Uyen Le Ngoc Phuong, Dae-Young Park, Ji-Young Ahn, Yang Hoon Kim, Jiho Min","doi":"10.1007/s13273-024-00462-6","DOIUrl":"https://doi.org/10.1007/s13273-024-00462-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>The spread of introduced species necessitates effective management strategies. However, the current methods have proven ineffective, thus calling for alternative solutions.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>In this study, we investigated the impact of yeast vacuoles on <i>Daphnia</i> as a potential agent for managing adult organisms, focusing on morphological analysis, cellular damage assessment, reproductive outcomes, birthing duration, and molting behaviors. By evaluating the ecological impact of vacuoles isolated from yeast, a beneficial microorganism, we discovered a new function of vacuoles as versatile nanomaterials.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Although vacuoles have been extensively studied in various fields, their effects on aquatic ecosystems are not fully understood. Our findings revealed a significant influence of vacuoles on the ecology of <i>Daphnia</i>. The morphological characteristics of yeast vacuoles were revealed by FE-SEM and NTA analysis. Treating vacuoles and vacuolar enzymes to <i>Daphnia</i> resulted in observable internal damage, as evidenced by increased red fluorescence indicative of cell death. Higher concentrations of vacuoles correlated with decreased green fluorescence, suggesting greater internal damage. Furthermore, <i>Daphnia</i> treated with vacuoles exhibited different birth rates and birthing duration. Additionally, increasing vacuole concentrations correlated with increased foreign materials on <i>Daphnia</i> shells after molting, suggesting external adherence of vacuoles.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>In summary, this study provides a comprehensive understanding of toxicology and microbial ecology by revealing the influence of yeast vacuoles on <i>Daphnia</i> physiology and behavior. It also informs environmental management and conservation strategies in aquatic ecosystems and demonstrates the potential of vacuoles as useful agents in controlling harmful fish populations.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"44 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Terrestrosin D inhibits invasion and induces apoptosis through inhibition of STAT3 in anaplastic thyroid carcinoma","authors":"Honglai Zhang, Dawei Sun, Peijie Lei, Jingjing Cheng","doi":"10.1007/s13273-024-00457-3","DOIUrl":"https://doi.org/10.1007/s13273-024-00457-3","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>The prognosis with current management approach of anaplastic thyroid carcinoma (ATC) remains poor, and new effective treatments are greatly needed. Terrestrosin D (TED) is active component of traditional Chinese medicine (TCM) <i>Tribulus terrestris L.</i> with anti-tumor and anti-inflammatory activities. However, it remains unclear about the activity and mechanisms of TED in ATC.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>In this study, the experimental groups included control, DMSO, TED (2.5 μM), and TED (5 μM). We detected cell viability, invasion, migration, and apoptosis to assess the effects of TED on ATC cells in vitro. Next, we performed western blot to determine apoptosis-related proteins and STAT3 protein expression. In addition, the possible mechanism of TED anti-cancer effects on ATC was preliminarily investigated through network pharmacology.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>These results showed that TED groups could significantly inhibit cell viability, invasion, migration, and colony formation ability, and promote the cell apoptosis, compared with the DMSO group. Besides, TED obviously downregulated the levels of Bcl-2, and STAT3 protein, increased level of Bax and caspase-3 protein. Network pharmacological analysis showed that 27 intersecting genes were obtained by intersecting TED and ATC target gene sets, of which STAT3 had the best correlation.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>We found that TED has strong anti-cancer activities on ATC, which could induce cell apoptosis through the regulation of STAT3. This study provides a new idea to treat ATC.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"70 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141252898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary flavonoids protect human brain microvascular endothelial cell from oxidative stress-induced dysfunction","authors":"Qian Tan, Xiaoqiong Yan, Lizhu Chen, Kun Jiang, Zhenli Guo","doi":"10.1007/s13273-024-00461-7","DOIUrl":"https://doi.org/10.1007/s13273-024-00461-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>The BBB plays a crucial role in the development of numerous neurological diseases and is especially vulnerable to oxidative stress. Human brain microvascular endothelial cells (HBMECs), the principal constituents of the BBB, significantly contribute to its formation and preservation. Increasing evidence indicates a potential inverse correlation between the consumption of dietary flavonoids and cardiovascular risk, which could be attributed to their antioxidative properties.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>To explore the impact of four prevalent and abundant flavonoids on HBMECs within a microenvironment characterized by oxidative stress.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Quercetin, apigenin, and genistein notably mitigated the adverse effects of H₂O₂-induced dysfunctions observed in various HBMEC events, including capillary network differentiation, growth, and survival. Moreover, these compounds reversed the oxidative stress provoked by H₂O₂, alongside reducing oxidative damage to lipids and DNA. Conversely, myricetin failed to reverse the H₂O₂-induced oxidative stress and did not exhibit any protective effects on HBMEC. Intriguingly, quercetin and apigenin elevated NRF2 and NQO1 levels in HBMEC, while genistein did not have the same effect.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Our research offers preclinical evidence indicating that certain flavonoids exhibit antioxidant effects, effectively reducing the dysfunction induced by oxidative stress in brain endothelial cells. This underscores the beneficial impact of flavonoids on the blood–brain barrier (BBB). Additionally, our findings propose potential strategies utilizing flavonoids for the treatment of neurological diseases.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"53 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141191882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}