Molecular & Cellular Toxicology最新文献

{"title":"A systematic review of the carcinogenicity of rats and mice by sex due to exposure to phenyl compounds","authors":"Kyung-Taek Rim","doi":"10.1007/s13273-024-00432-y","DOIUrl":"https://doi.org/10.1007/s13273-024-00432-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>Differences in cancer incidence between men and women are often explained by differences in environmental exposure, or the influence of sex hormones. However, there is little research on the intrinsic differences in sensitivity to chemical carcinogens.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>To predict and consider related in vivo carcinogenicity tests, changes in gene expression were examined in rats and mice (by gender and organ) due to exposure to carcinogenic chemicals such as phenyl compounds, which among chemicals are the main cause of carcinogenesis.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In the case of male SD rats, the genes IL1B, TNF, NOS2, IL6, and NGF were related, and the probability of carcinogenesis in the urinary bladder, kidney, and oral cavity was high. In female SD rats, the genes ADRB2, TNF, HMOX1, CYP1A1, PTGS2, ILB1, CASP3, POR, PRL, TSC22D1, ATEG, REG1, HRH2, NFE2L2, AKR1C2, ADRB2, NR3C1, IL6, ADRB1, ADRB3, and LPO showed high probability of carcinogenesis in the stomach, liver, and nasal cavity. In the male F344 rat, the genes ACACA, ACSL1, ALB, ALCAM, CYP19A1, PPARA, CYP4A1, ACAA1, and ACOX1 were related, and showed a high probability of carcinogenesis in the liver, kidney, stomach, and urinary bladder. In the female F344 rat, no related genes were found, but a high probability of carcinogenesis was shown in the kidney, ear, Zymbal’s gland, stomach, and liver. In male ICR mice, no related genes and organs with a high probability of carcinogenesis were found, while in female ICR mice, genes for KRAS, ACHE, CAT, CYP3A4, and GPT were involved, and carcinogenesis occurred in the stomach, thyroid gland, ovary, liver, etc. The probability was shown to be high. In BALBc mice, no related genes and organs with a high probability of carcinogenesis were found, while in female BALBc mice, the genes NR1I2, CYP3A4, ABCB1, CYP2B6, PRKDC, CYP2C9, and NCOA1 were related, and the liver, etc., had a high probability of carcinogenesis.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Differences in the epigenetics of each sex begin at the moment of fertilization due to differences in sex chromosome gene expression and metabolic profiles between XX and XY embryos. These fundamental sex differences in nutrient utilization and mitochondrial activity may contribute to sex differences in the metabolic reprogramming of cancer cells, which is important during cancer development, cancer progression, and response to anticancer treatment.</p><h3 data-test=\"abstract-sub-heading\">Purpose of review</h3><p>In this study, I compared and considered the degree of toxicity and genome expression in each male and female gender and organ due to exposure to phenyl compounds (PAH, etc.), which are the basis of benzene toxicity as aromatic hydrocarbons, and conducted future inhalation toxicity tests and related carcinogenicity tests.</p><h3 data-test=\"abstract-sub-heading","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"22 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140037159","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":"MicroRNA-34b-5p increases chemosensitivity of hepatocellular carcinoma cells","authors":"JinSuo Chen, LiNa Wang, XueMei Wu, ZhiJie Ding, WenXi Cao, LeiLei Yang, YongPing Zhou, Li Xia, Zhao Song","doi":"10.1007/s13273-024-00431-z","DOIUrl":"https://doi.org/10.1007/s13273-024-00431-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objective</h3><p>Increasing evidence shows that microRNA (miR) is related to drug resistance in hepatocellular carcinoma (HCC). miR-34b-5p could retard tumor development, but its function in HCC is still unclear.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>miR-34b-5p expression was determined in HCC tissues and cell lines. Analysis and verification of the binding between miR-34b-5p and metadherin (MTDH) was carried out. The actual action of miR-34b-5p and MTDH in the area of proliferation, apoptosis, invasion, and migration of cisplatin (DDP)-resistant HCC cells was monitored.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>miR-34b-5p was downregulated in HCC. Overexpression of miR-34b-5p enhanced the sensitivity of HCC cells to DDP, inhibiting proliferation, migration, and invasion and promoting apoptosis. MTDH was the direct target of miR-34b-5p. MTDH was upregulated in HCC tissues, which was negatively correlated with miR-34b-5p expression. Enhancement of MTDH can reverse the effect of upregulated miR-34b-5p on the chemosensitivity of HCC cells.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>miR-34b-5p targets MTDH and enhances the chemosensitivity of HCC cells.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"6 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140025585","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":"Prediction of herb–drug interaction between hyperforin and sedative hypnotics (zolpidem, alprazolam, and midazolam) using physiologically-based pharmacokinetic modeling","authors":"Anna Shin, Boyun Jang, Sunyoung Cho, Youngsoo Kim, Min Soo Park, Kwang-Il Park, Young Woo Kim, Choon Ok Kim","doi":"10.1007/s13273-024-00427-9","DOIUrl":"https://doi.org/10.1007/s13273-024-00427-9","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>This study investigates the interactions between various doses of hyperforin, a key compound in St. John’s Wort, and sedative hypnotics such as zolpidem, alprazolam, and midazolam. Since St John’s Wort is known to be an inducer of cytochrome P450 (CYP) 3A4, co-administration with drugs metabolized by CYP3A4 has been contraindicated.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>We studied the risks of combination use and the possibility of safe combination by simulating the interaction of hyperforin, a key compound in St. John’s Wort, with drugs metabolized by CYP3A4 that can be used to relieve various symptoms of depression. Understanding these interactions is crucial for optimizing the treatment of depression and associated symptoms.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The hyperforin physiologically based pharmacokinetic (PBPK) model was validated against clinical data, and PBPK models for zolpidem, alprazolam, and midazolam were used to predict herb–drug interactions. The simulations with a two-week co-administration scenario showed that hyperforin potentially acts as a weak inducer (hyperforin dose 2–20 mg, 3 times a day, AUC ratio 0.8–0.68) of 10 mg zolpidem metabolism, with sex-dependent interactions largely unaffected. However, the pharmacokinetics of alprazolam at doses of 0.25, 0.5, and 1 mg were minimally impacted (hyperforin dose 1–20 mg, 3 times a day, AUC ratio 0.96–0.87). In the case of 7.5 mg midazolam, hyperforin acted as a moderate to strong inducer (hyperforin dose 1–20 mg, 3 times a day, AUC ratio 0.26–0.20), even at low doses.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>These findings emphasize the importance of careful monitoring and dose adjustments when using hyperforin and sedative hypnotics together. This study provided insights into co-administration of hyperforin and sedative hypnotics, facilitating the safe and effective use of these medications. Based on these results, it is necessary to know the possibility of safer drug combination, and to conduct clinical research and verification on this.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"175 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139969015","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":"VD/VDR-mediated ATG16L1 activation reduces Alzheimer’s disease-like pathology and cognitive decline","authors":"Zhixiong Huang, Wei Ang, Hefei Huang, Yanyan Wang","doi":"10.1007/s13273-024-00429-7","DOIUrl":"https://doi.org/10.1007/s13273-024-00429-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Despite extensive global efforts, there is currently no effective remedy for Alzheimer’s disease (AD).</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>This investigation aimed to examine the impact of vitamin D/vitamin D receptor (VDR)/ATG16L1 signaling on memory in AD mice, as well as the levels of autophagy and inflammation in the hippocampus.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Administering cholecalciferol cholesterol emulsion (CCE), which serves as a precursor to 1,25-OH vitamin D3, through water feeding for a duration of 12 weeks demonstrated the ability to mitigate both short-term and long-term memory impairments in AD mice. CCE treatment reduced the deposition of TAU protein in the hippocampus, suppressed the phosphorylation of TAU Thr181 and 212, and significantly decreased Aβ (1–40) levels. Moreover, CCE heightened hippocampal autophagy in AD mice, upregulated the expression of ATG16L1 and LC3B, and inhibited P62 expression. In addition, CCE supplementation attenuated hippocampal inflammation in AD mice by decreasing the levels of IL1β and TNFα and restoring the TOM1/IL1R1 pathway. The Luciferase reporter assay verified that the knockdown of VDR could impede the activation of the ATG16L1 promoter by vitamin D, and ChIP analysis confirmed that VDR could bind to the ATG16L1 promoter and exert its function.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>CCE exhibits potential in safeguarding hippocampal neurons against AD-induced harm, stimulating autophagy, and suppressing inflammation. These effects may be regulated by VD/VDR/ATG16L1 signaling.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"97 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139945505","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":"Dual suppressive effect of p-coumaric acid on pigmentation in B16F10 cells","authors":"Sohee Jang, Chang-Woo Ha, Sung-Hyeok Kim, Jung Hun Choi, Seung Namkoong, Sungsil Hong, Hyun Jung Koo, Youn-Kyu Kim, Mediana Hadiwidjaja, Sung Ryul Lee, Eun-Hwa Sohn","doi":"10.1007/s13273-024-00430-0","DOIUrl":"https://doi.org/10.1007/s13273-024-00430-0","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Hyperpigmentation, frequently triggered by an excessive production of melanin, is a common issue within the realms of dermatology and cosmetology. In addition to regulating tyrosinase activity, the autophagy process plays a role in melanosome turnover, contributing to pigmentation control. <i>p</i>-Coumaric acid (PCA), a dietary phenolic compound with antioxidant and anti-inflammatory properties, was investigated for its dual suppressive effects on melanin production induced by alpha-melanocyte-stimulating hormone (α-MSH) and autophagy inhibitors in B16F10 cells.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>PCA (25–100 µg/mL) serves as a potent in vitro inhibitor of tyrosinase activity. In addition, PCA can effectively mitigate the upregulation of tyrosinase gene expression (<i>P</i> &lt; 0.01) and its cellular activities induced by α-MSH. In contrast to early-stage autophagy inhibitors like SBI0206965 (SBI) and spautin-1, treatment with 50 µM of chloroquine (CQ) and 20 nM of bafilomycin A1 (BFA), both of which inhibit the late stages of the autophagic process, results in an increase in melanin content within B16F10 cells, independent of cellular tyrosinase activity. Furthermore, PCA treatment could protect cells against CQ and BFA-induced lysosomal damage, ultimately leading to the promotion of autolysosome formation and the activation of the autophagic process, which results in melanin degradation.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>In summary, PCA exhibits dual suppressive effects on melanogenesis via inhibiting tyrosinase activity and melanin accumulation caused by lysosomal dysfunction. These effects offer an enhanced opportunity for the development of a safe and effective anti-melanogenesis agent.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"244 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139945397","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":"Bergenin ameliorates the progression of atherosclerosis by inhibiting oxidative stress, inflammation, and monocytes adhesion in human umbilical vein endothelial cells","authors":"Liyuan Liang, Wei Yang","doi":"10.1007/s13273-024-00428-8","DOIUrl":"https://doi.org/10.1007/s13273-024-00428-8","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Bergenin is a type of polyphenol derived from various medicinal plants and has multiple biological functions, including antioxidant, anti-cancerous, and anti-inflammatory activity. However, the role of bergenin in atherosclerosis (AS) development has not been detected yet. Here, human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of bergenin on TNF-α-induced oxidative stress, inflammation, and monocyte adhesion in vitro.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Cell viability of HUVECs was assessed by cell counting kit-8 (CCK-8) assay. Western blotting was performed to evaluate the levels of apoptosis- or signaling-related proteins. Intracellular oxidative stress levels were detected by evaluating reactive oxygen species (ROS) production, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity in HUVECs. The effects of bergenin on monocyte adhesion to HUVECs were detected by measuring the protein and expression levels of adhesion molecules.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Bergenin promoted the viability and inhibited the apoptosis in TNF-α-treated HUVECs. The increased oxidative stress induced by TNF-α was significantly suppressed by bergenin in a concentration-dependent manner. Bergenin reduced the protein and expression levels of adhesion molecules in TNF-α-treated HUVECs. Human leukemic monocyte (U973) adhesion to HUVECs was promoted by TNF-α treatment and significantly inhibited by bergenin. In addition, bergenin blocked the activation of NF-κB signaling in TNF-α-treated HUVECs.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Bergenin inhibited TNF-α-induced apoptosis and oxidative stress in HUVECs and suppressed monocyte adhesion to HUVECs by inactivating NF-κB signaling pathway.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"35 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139927894","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":"Mechanistic insight of mitochondrial dysfunctions in cardiovascular diseases with potential biomarkers","authors":"Md. Nazmul Islam, Vineet Kumar Mishra, Rina Munalisa, Farzana Parveen, Saieeda Fabia Ali, Khadiza Akter, Tanvir Ahmed, Tsung-Jung Ho, Chih-Yang Huang","doi":"10.1007/s13273-023-00424-4","DOIUrl":"https://doi.org/10.1007/s13273-023-00424-4","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Acceleration of atherogenesis is an aftermath of cardiovascular diseases (CVDs), which arise with mitochondrial dysfunction (MD). Endothelium restraint inflammation, repair and fluidic exchange with nearby tissues. Endothelium-mediated mitochondrial damage can trigger the molecular mechanisms of vasodilation, pro-inflammation and process of pro-thrombotic accumulation in microvascular endothelial layer. The oxidation of lipid particles generates modified lipoproteins. Modification of mitochondrial function recently emerged a great concern towards the atherosclerosis initiation and progression, because the powerhouse of energy production mitochondria mutation can release mtDNA into cytoplasm and it can be act as sensor for viral DNA or foreign DNA. Another cause is mitochondrial imbalance can lead to product excess amount of reactive oxygen species (ROS) which can cause cellular metabolism and respiration system.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>In previous some studies showed that mitochondrial dysfunction plays a vital role in term of cardiac diseases. However, very few studies provide evidence of endothelium-mediated mitochondrial imbalance. This study investigated the potential involvement of mitochondrial impairment in cardiotoxicity using a series of mechanistic endpoints, including mitochondrial respiration and endothelial suppression of inflammation, mitochondrial DNA. Our study provides some molecular mechanisms regarding mitochondrial role in endothelium function. In each section, we are trying to introduce key concepts and then analysis previous studies revealed the importance of that molecular mechanism regarding mitochondrial dysfunction.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The ultimate goal of our review is to find out the novel drug discovery or new approaches of therapy. Our review will target different aspects of mitochondrial protein function and their effect of endothelial and cause of atherosclerosis diseases. To evaluate the healthy lifestyle and better condition of mitochondrial balance nowadays it is urgent to utilize the proper function for therapeutical effect for future direction.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"14 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139927633","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 atypical protein kinase RIOK3 contributes to the phenotypic modulation of vascular smooth muscle cells in intracranial aneurysms","authors":"Jianzhu Wei, Yang Zhang, Bo Xie, Ziyi Zhu, Jingyu Qian, Yulin Tan","doi":"10.1007/s13273-023-00425-3","DOIUrl":"https://doi.org/10.1007/s13273-023-00425-3","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Previous studies manifested that abnormal proliferation, migration, apoptosis, and phenotypic conversion of vascular smooth muscle cells (VSMCs) are the main pathogenic basis of intracranial aneurysms (IAs).</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>The aim of this study was to explore a key gene associated with IA growth and rupture using bioinformatics analysis and validate it by exogenous overexpression into human brain VSMCs (HBVSMCs). Four IA-associated microarray datasets, GSE54083, GSE15629, GSE66238, and GSE13353, were obtained from Gene Expression Omnibus (GEO) and analyzed using GEO2R for differentially expressed genes (DEGs). HBVSMCs were infected with lentivirus containing RIO kinase 3 (RIOK3) to overexpress exogenous RIOK3, and then, CCK-8, EdU, cell scratch, Transwell, Western blotting, and ELISA were introduced to measure proliferation, migration, phenotypic conversion-related proteins, and proinflammatory cytokines in HBVSMCs. To simulate the abnormal hemodynamic environment in the late stages of IA formation, RIOK3-overexpressing HBVSMCs were cultured under wall shear stress (WSS)-loaded conditions and then subjected to apoptosis assessment.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>RIOK3 was defined as a key gene in the DEGs of IAs by bioinformatics analysis. RIOK3 overexpression could contribute to the abnormal proliferation, migration, secretion of proinflammatory factors, and the conversion of contractile phenotype to synthetic phenotype of HBVSMCs. Additionally, RIOK3 overexpression encouraged HBVSMC apoptosis after loading WSS in vitro to mimic advanced-IAs.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>RIOK3 in pre-IAs (without WSS loading) facilitates phenotypic conversion, abnormal proliferation, invasion, and inflammatory cytokine secretion of HBVSMCs; whereas in the advanced-IAs, RIOK3 accelerated the abnormal apoptosis of HBVSMCs in the setting of loaded-WSS.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"18 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139756675","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":"Lycopene mitigates DHT-induced apoptosis and oxidative stress in human granulosa cell line KGN by regulating the Nrf2 pathway","authors":"Yue Chen, Mengmeng Zhao, Xiaoqing Li, Yuanyuan Liu, Yuhong Shang","doi":"10.1007/s13273-023-00419-1","DOIUrl":"https://doi.org/10.1007/s13273-023-00419-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Recently, accumulating evidence has proved that apoptosis and oxidative stress exert essential roles in the development of polycystic ovarian syndrome (PCOS). Besides, multiple natural products have been identified to be related to the PCOS process.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>This investigation aimed to elucidate the effects and mechanisms of lycopene on granulosa-like tumor cell line (KGN) in the presence of dihydrotestosterone (DHT). KGN cells were treated using DHT or lycopene and cell survival rate was tested by cell counting kit 8 (CCK-8) assay. Also, flow cytometry, western blot as well as enzyme-linked immunosorbent assay (ELISA) were utilized to detect cell apoptosis, protein level and the marker of oxidative stress. ROS accumulation was observed with DCFH-DA dye. The nuclear factor-erythroid 2-related factor (Nrf2) expression in KGN cells was reduced via small interfering RNA (siRNA). The nuclear translocation of Nrf2 was determined through immunofluorescence (IF) analysis.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Lycopene effectively reversed DHT-induced apoptosis in addition to oxidative stress in KGN cells. Besides, lycopene treatment obviously activated Nrf2 signaling and accelerated nuclear translocation of Nrf2 in KGN cells. Nrf2 depletion partially counteracted the role of lycopene in DHT-mediated apoptosis as well as oxidative stress in KGN cells.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>In summary, this work revealed that lycopene alleviates oxidative stress and apoptosis in KGN cells in the presence of DHT, which at least partly by depending on the activation of Nrf2 cascade signal at the molecular level.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"1 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139756571","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":"CARD9 regulates myocardial inflammation, oxidative stress, and vascular dysfunction in hypertensive rats by activating MAPK/p38 pathway in combination with NOD2","authors":"","doi":"10.1007/s13273-023-00420-8","DOIUrl":"https://doi.org/10.1007/s13273-023-00420-8","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Objective</h3> <p>This study aimed to uncover the related mechanism of CARD9 in myocardial inflammation, oxidative stress, and vascular dysfunction following hypertension.</p> </span> <span> <h3>Methods</h3> <p>Spontaneous hypertension rats were injected with shRNA adenovirus vector or adenovirus overexpression vector. Blood pressure was measured. Cardiac tissue and aortic tissue were harvested to observe pathological damage by HE staining and apoptosis by TUNEL staining, as well as expression of α-SMA, Collagen I, and Collagen II by IHC staining. In addition, inflammatory response and oxidative stress in cardiac tissues were determined. CO-IP assay was employed to examine the binding of CARD9 to NOD2. Gene protein expression was measured by Western blot.</p> </span> <span> <h3>Results</h3> <p>CARD9 and NOD2 were overexpressed in the myocardium of hypertensive rats. Knocking down CARD9 improved myocardial inflammation, oxidative stress, and vascular dysfunction in hypertensive rats, whereas overexpressing NOD2 had the opposite result. CARD9 was bound to NOD2. NOD2 overexpression rescued the protective impacts of CARD9 knockdown. CARD9 activated the MAPK/p38 pathway by targeting NOD2.</p> </span> <span> <h3>Conclusion</h3> <p>CARD9 regulates myocardial inflammation, oxidative stress, and vascular dysfunction in hypertensive rats by activating the MAPK/p38 pathway in combination with NOD2.</p> </span>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"183 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139668056","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}