Molecular & Cellular Toxicology最新文献

{"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}

{"title":"Evaluation of the antinociceptive effect and standardization of Platycladus orientalis (L.) Franco extract","authors":"","doi":"10.1007/s13273-023-00413-7","DOIUrl":"https://doi.org/10.1007/s13273-023-00413-7","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Background</h3> <p><em>Platycladus orientalis</em> (L.) Franco (PO) has been used in Oriental medicine to treat rheumatism and diarrhea; however, its antinociceptive effects remain unclear.</p> </span> <span> <h3>Objective</h3> <p>This study aimed to reveal the antinociceptive effect of the PO extract and standardize this extract in RAW 264.7 cells and mice with monosodium uric acid (MSU)-induced pain.</p> </span> <span> <h3>Results</h3> <p>PO extracts were prepared using different ethanol (EtOH) concentrations (0–100%). Thereafter, groups were determined based on the results of the MSU-induced pain model in mice and nitric oxide (NO) assay using lipopolysaccharide (LPS)-induced RAW 264.7 cells. As the methylene chloride (CH₂Cl₂) and ethyl acetate (EtOAc) layers exhibited increasing effects with time, these layers were selected to isolate the major components. The PO extract was standardized using a highly efficient HPLC method, and its antinociceptive effects in a mouse model of MSU-induced gout pain were determined using the von Frey test. The PO extract was found to exhibit antinociceptive effects. Moreover, sample standardization was successfully achieved based on the validation of these compounds.</p> </span> <span> <h3>Conclusion</h3> <p>The PO extract exhibited potent dose- and time-dependent antinociceptive effects in an animal model of gout pain; these effects might be mediated by the major compounds of this extract. Collectively, these results suggest that PO can be used as a herbal drug to treat gout-related pain.</p> </span>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"3 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139587884","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":"Bone marrow mesenchymal stem cell transplantation protects rats from myocardial infarction by regulating TXNIP/NLRP3 pathway-mediated inflammation and fibrosis","authors":"JianNan Bai, Cong Wang, HongQiang Yu, QingChao Wang, JinFeng Zhang, DanDan Shao, ZhiQiang Yu, Bo Meng, You Li","doi":"10.1007/s13273-023-00422-6","DOIUrl":"https://doi.org/10.1007/s13273-023-00422-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Bone marrow mesenchymal stem cells (BMSCs) may be a promising target in the treatment of myocardial infarction (MI). However, the underlying molecular mechanisms of BMSC therapy remain unclear.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>This study sought to evaluate the efficacy of direct intramyocardial transplantation of BMSCs in a mouse model of MI.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Mouse BMSCs were transfected with small interfering RNA or overexpression plasmid targeting TXNIP. The viability, proliferation, and apoptosis of BMSCs after hypoxia treatment were detected by MTT method, EdU analysis, and flow cytometry, respectively. A mouse model of MI was constructed, after which BSMCs were injected intramyocardially immediately. Cardiac ultrasound, HE staining, TUNEL staining and ELISA, IHC analysis, and Western blot were adopted to evaluate the effects of BSMC therapy on cardiac function, myocardial inflammation, and fibrosis in mice.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In vitro experiments reported that ablating TXNIP increased viability and inhibited apoptosis of hypoxia-treated BMSCs while overexpressing TXNIP did the opposite. In vivo results stated that BSMCs improved cardiac function, myocardial inflammation, and fibrosis after MI, which was further improved by silencing TXNIP but reversed by overexpressing TXNIP. Meanwhile, in vivo cell tracking experiments showed that the retained BMSCs in the myocardium decreased after transplantation, and TXNIP depletion promoted the survival of BMSCs in MI mice, whereas TXNIP overexpression did the opposite.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>In conclusion, BMSC transplantation improves cardiac function, myocardial inflammation, and fibrosis after MI by regulating the TXNIP/NLRP3 pathway.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"89 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139588001","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":"Olaparib synergically exacerbates the radiation-induced intestinal apoptosis in mice","authors":"","doi":"10.1007/s13273-023-00421-7","DOIUrl":"https://doi.org/10.1007/s13273-023-00421-7","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Background</h3> <p>Olaparib, a poly [ADP-ribose] polymerase (PARP) inhibitor, is used in cancer treatment and in other diseases and achieves local cancer control in combination with radiotherapy.</p> </span> <span> <h3>Objectives</h3> <p>We investigated the effects of olaparib on irradiation-induced intestinal damage using both in vitro and in vivo model systems. In particular, we evaluated how olaparib affects irradiation-induced cytotoxicity in intestinal epithelial (IEC-6) cell line and intestinal damage in mice subjected to abdominal radiation.</p> </span> <span> <h3>Results</h3> <p>Using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays to evaluate radiation-induced cytotoxicity and the loss of cell viability, we found that olaparib pretreatment significantly exacerbated radiation-induced effects. Olaparib therapy increased protein expression related to radiation-induced DNA damage. Administering per oral olaparib (100 mg/kg) to adult mice from − 2 to 0 days before radiation exposure (10 or 15 Gy) significantly accelerated intestinal damage. Measurements of the small intestinal villi length and number of crypts were collected through histological investigations. The irradiation group showed shorter crypt survival and jejunal villi height than the sham-irradiated group. In addition, through the TUNEL assay, we were able to confirm an increased apoptotic rate of enterocytes in the group pretreated with olaparib before 10 Gy of irradiation compared with the dose-matched irradiation group.</p> </span> <span> <h3>Conclusion</h3> <p>In radiation-exposed mice, olaparib therapy significantly reduced indicators such as the length of the small intestinal villi and number of crypts. Administering olaparib before radiation aggravated the radiation-induced damage to the jejunum and exacerbated intestinal apoptosis. Olaparib in combination with radiotherapy should be used cautiously in patients with cancer.</p> </span>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"30 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139510219","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":"Genotoxicity evaluation of collagen peptide derived from skate (Raja kenojei) skin: In vitro and in vivo studies","authors":"Heung-Sik Seo, Ji-Soo Kim, Myeong-Kyu Park, Nak-Won Seong, Geun-Hee Kang, Sang-Ho Kim, Joong-Sun Kim, Sung-Ho Kim, Jong-Choon Kim, Changjong Moon","doi":"10.1007/s13273-023-00423-5","DOIUrl":"https://doi.org/10.1007/s13273-023-00423-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>The medicinal properties and benefits of collagen peptides (CPs) are widely recognized and utilized. However, the potential genotoxicity of CPs remains elusive.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>The objective of this study was to assess the potential genotoxicity of CP derived from skate (<i>Raja kenojei</i>) skin (CPSS). To achieve this, we conducted a comprehensive study using three standard battery systems in accordance with the test guidelines provided by the Organisation for Economic Cooperation and Development and the Korean Ministry of Food and Drug Safety, as well as the principles of Good Laboratory Practice.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>We performed a bacterial reverse mutation (Ames) test using the pre-incubation method, with or without a metabolic activation system (S9 mixture). The Ames test, conducted on <i>Salmonella typhimurium</i> strains TA98, TA100, TA1535, and TA1537, as well as <i>Escherichia coli</i> strain WP2<i>uvr</i>A, demonstrated that CPSS did not cause gene mutations in any of the tested strains, regardless of the dose level. In addition, we performed an in vitro chromosome aberration test using cultured Chinese hamster lung fibroblast cells, with and without the S9 mixture, and an in vivo mouse bone marrow micronucleus test on specific pathogen-free male ICR mice. Both the in vitro chromosomal aberration test and the in vivo micronucleus test revealed no chromosomal aberrations resulting from CPSS treatment.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Our findings demonstrate that CPSS does not exhibit mutagenic or clastogenic activity in either in vitro or in vivo test systems, supporting its potential as a safe material for medical use.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"7 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139497867","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":"Phenotypic and functional alterations of bone marrow MSCs exposed to multiple myeloma cells","authors":"","doi":"10.1007/s13273-023-00415-5","DOIUrl":"https://doi.org/10.1007/s13273-023-00415-5","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Backgrounds</h3> <p>The direct and indirect interactions between multiple myeloma (MM) cells and bone marrow mesenchymal stromal cells (MSCs) play crucial roles in the formation of the bone marrow environment, disease progression, and drug resistance development. However, it remains unclear how MM cells and MSCs individually influence each other to induce these phenomena.</p> </span> <span> <h3>Objective</h3> <p>In this study, we focused on observing changes in MSCs induced by MM cells. Changes in MSCs due to exposure to MM cells were observed by assessing cell proliferation, apoptosis, cell cycle, and morphology. Furthermore, the unique abilities of MSCs were confirmed through differentiation potential and MSC marker expression, along with the demonstration of senescence. Gene profiling was performed to elucidate the mechanisms underlying these changes.</p> </span> <span> <h3>Results</h3> <p>Co-culturing MM cells with MSCs did not alter the morphology or proliferation of MSCs but increased apoptosis. As apoptosis increased, damaged deoxyribonucleic acid (DNA) was repaired, leading to the activation of the cell cycle with an increase in the S phase, resulting in no significant changes in cell proliferation and morphology. Osteogenesis and adipogenesis generally decreased by co-culturing with MM cells, and senescence increased. Significant differences were observed in the expression of MSC marker genes. Gene profiling revealed changes in gene expression following osteogenic differentiation.</p> </span> <span> <h3>Conclusion</h3> <p>Based on these results, MSCs exposed to MM cells exhibited an increase in the S phase of the cell cycle, leading to the recovery of cells undergoing apoptosis. Osteogenesis and adipogenesis decreased, whereas senescence increased, suggesting that these changes were attributed to the overall MSC characteristics and genetic mechanisms.</p> </span>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"30 1 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138685097","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":"Maslinic acid induces apoptosis in thyroid cancer cells via endoplasmic reticulum stress","authors":"Jing Zhu, Pinghui Tu, Yu Yang, Dandan Zhang, Fengling Chen","doi":"10.1007/s13273-023-00406-6","DOIUrl":"https://doi.org/10.1007/s13273-023-00406-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Thyroid cancer is one of the most common malignant tumors of the endocrine system. Studies have demonstrated that maslinic acid (MA) has a wide range of antitumor activities via multiple cellular pathways. However, the role of MA in thyroid cancer remains poorly investigated.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>To investigate the effects and underlying mechanisms of MA on thyroid cancer cells.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>MA inhibited cell viability and increased apoptosis in TPC1 and Cal62 cells. MA promoted apoptosis in TPC1 and Cal62 cells in a dose-dependent manner evidenced by flow cytometry and Western blotting. In addition, treatment with MA increased the expression of endoplasmic reticulum (ER) stress markers, such as Binding-immunoglobulin protein (BIP) and C/EBP homologous protein 10 (CHOP), in thyroid cancer cells. In cells treated with 4-phenylbutyric acid, an inhibitor of ER stress, MA-induced apoptosis was partially reversed. Finally, treatment with MA inhibited thyroid cancer growth in a TPC1 cell xenograft model.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Results indicated that MA promoted apoptosis in thyroid cancer cells via ER stress. These findings may provide new insights into novel therapeutic strategies for thyroid cancer.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"73 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138573965","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 mechanism of 5-aminolevulinic acid-photodynamic therapy pretreatment repressing keloid fibroblast proliferation and invasion by mediating forkhead box protein O6 (FoxO6) antioxidant stress","authors":"Qiong Wang, Weihui Zeng, Shuang Wang, Songmei Geng, Chen Tu","doi":"10.1007/s13273-023-00417-3","DOIUrl":"https://doi.org/10.1007/s13273-023-00417-3","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objective</h3><p>Keloid is a kind of disfiguring pathological scarring specific to human skin. For various cutaneous and internal tumours, 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT) is a curative choice, and we explored its mechanism on keloid fibroblast (KFB) proliferation and invasion via regulating forkhead box protein O6 (FoxO6) antioxidant stress.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Human keloid fibroblasts (HKFs) were cultured in vitro, treated with 5-ALA-PDT and simultaneously transfected with overexpression plasmid (oe-FoxO6). HKF proliferation, invasion, apoptosis and cell cycle were assessed by CCK-8/Transwell/TUNEL/flow cytometry assays. The protein levels of Bax, Bcl-2, FoxO6, Cyclin D1, Cyclin A1 and Cyclin B1 were determined by Western blot. SOD and CAT activities, and MDA and ROS levels were examined using the kits.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Pretreatment of 5-ALA-PDT prominently inhibited the proliferation of HKFs, up-regulated Bax level, down-regulated Bcl-2 level, promoted HKF apoptosis, and notably inhibited HKF invasion. 5-ALA-PDT treatment decreased the expression of FoxO6 protein, promoted oxidative stress in HKFs, up-regulated ROS and MDA levels in HKFs and reduced SOD and CAT antioxidant enzyme activities. In addition, 5-ALA-PDT pretreatment increased the level of cell cycle-associated protein Cyclin D1, decreased the levels of Cyclin A1 and Cyclin B1, and accelerated cell cycle arrest in the G₀/G₁ phase of HKFs. Overexpression of FoxO6 partially annulled the promoting effects of 5-ALA-PDT on G₀/G₁ phase cell cycle arrest and oxidative stress in HKFs and enhanced cell proliferation and invasion.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>5-ALA-PDT limited HKF proliferation and invasion by down-regulating the expression of FoxO6.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"13 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138560003","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}