Human & experimental toxicology最新文献_第7页

Punicalagin is cytotoxic to human colon cancer cells by modulating cell proliferation, apoptosis, and invasion. 普尼卡金通过调节细胞增殖、凋亡和侵袭，对人结肠癌细胞具有细胞毒性。

Human & experimental toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271231213979

Ding-Ping Sun, Hsuan-Yi Huang, Chia-Lin Chou, Li-Chin Cheng, Wen-Ching Wang, Yu-Feng Tian, Chia-Lang Fang, Kai-Yuan Lin

{"title":"Punicalagin is cytotoxic to human colon cancer cells by modulating cell proliferation, apoptosis, and invasion.","authors":"Ding-Ping Sun, Hsuan-Yi Huang, Chia-Lin Chou, Li-Chin Cheng, Wen-Ching Wang, Yu-Feng Tian, Chia-Lang Fang, Kai-Yuan Lin","doi":"10.1177/09603271231213979","DOIUrl":"https://doi.org/10.1177/09603271231213979","url":null,"abstract":"Purpose: The purpose of this study was to explore the anticancer effect of punicalagin, an abundant bioactive tannin compound isolated from Punica granatum L., on three colon cancer cell lines, namely, HCT 116, HT-29, and LoVo.Research Design: Normal and colon cancer cells were treated with different concentrations of punicalagin for different periods. Data Collection and Analysis: Cell viability was measured with a CCK-8 assay. Programmed cell death and invasion were analyzed using an annexin V and cell death kit and a cell invasion analysis kit. The expression of active caspase-3, MMP-2, MMP-9, Snail, and Slug were measured by Western blot.Results: The results of the cell viability analysis showed that punicalagin was cytotoxic to colon cancer cells, but it was not to normal cells in a dose- and time-dependent manner. Additionally, punicalagin induced apoptosis in colon cancer cells (shown by the cumulative percentage of colorectal cancer cells in early and late apoptosis). It was found that caspase-3 activity increased following punicalagin treatment. Western blot results also showed that punicalagin increased the expression of activated caspase-3. In contrast, punicalagin inhibited the invasion of colon cancer cells. Further, treatment of colon cancer cells with punicalagin suppressed the expression of MMP-2, MMP-9, Snail, and Slug. Conclusions: These results showed that the activation of caspase-3 and the inhibition of MMP-2, MMP-9, Snail and Slug were involved in the effects of punicalagin on colon cancer cells.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71490396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nrf2 attenuates methamphetamine-induced myocardial injury by regulating oxidative stress and apoptosis in mice. Nrf2通过调节氧化应激和细胞凋亡减轻甲基苯丙胺诱导的小鼠心肌损伤。

Human & experimental toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271231219488

Hao Yu, Yanxia Peng, Wenjuan Dong, Baoyu Shen, Genmeng Yang, Qianyun Nie, Yan Tian, Lixiang Qin, Chunhui Song, Bingzheng Chen, Yongna Zhao, Lihua Li, Shijun Hong

{"title":"Nrf2 attenuates methamphetamine-induced myocardial injury by regulating oxidative stress and apoptosis in mice.","authors":"Hao Yu, Yanxia Peng, Wenjuan Dong, Baoyu Shen, Genmeng Yang, Qianyun Nie, Yan Tian, Lixiang Qin, Chunhui Song, Bingzheng Chen, Yongna Zhao, Lihua Li, Shijun Hong","doi":"10.1177/09603271231219488","DOIUrl":"10.1177/09603271231219488","url":null,"abstract":"Objectives: Methamphetamine (MA) abuse is a serious social problem worldwide. Cardiovascular complications were the second leading cause of death among MA abusers. We aimed to clarify the effects of MA on myocardial injury, oxidative stress, and apoptosis in myocardial cells and to explore the potential mechanism of nuclear factor-erythroid factor 2-related factor 2 (Nrf2) in MA-induced oxidative stress and apoptosis.Methods: An acute cardiac toxicity model of MA was established by intraperitoneal injection of MA (2 mg/kg) for 5 days. Nrf2 activation (by sulforaphane (SFN) 1 h before MA injection) and Nrf2 gene knockout were performed to explore the regulatory effects of Nrf2 on cardiac toxicity.Results: The protein expressions of Nrf2 (p < .001) and heme oxygenase-1 (HO-1) were increased (p < .01), suggesting that MA activated the Nrf2/HO-1 pathway. In the MA group, cardiac injury score (p < .001) and cardiac troponin I (cTnI) protein expression increased (p < .01). Malondialdehyde (MDA) content increased (p < .001), superoxide dismutase (SOD) activity decreased (p < .05). Protein expressions of Caspase-3 (p < .001) and Bax (p < .001) increased, and Bcl-2 decreased (p < .001) as well. These changes were reversed by activation of Nrf2 but became more pronounced after Nrf2 knockout, suggested that the activation and knockout of Nrf2 attenuated and aggravated MA-induced myocardial injury, oxidative stress and apoptosis in myocardial cells, respectively.Conclusions: MA administration induced myocardial injury, oxidative stress, and apoptosis in mice. Nrf2 attenuated MA-induced myocardial injury by regulating oxidative stress and apoptosis, thus playing a protective role.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138465186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biological function of C-X-C Motif Chemokine Ligand 1 gene (CXCL1) in ovarian malignant tumors. C-X-C基序趋化因子配体1基因（CXCL1）在卵巢恶性肿瘤中的生物学功能。

Human & experimental toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271231203392

Zhuang Li, Ning Huang, Wei Zhang, Li Li

{"title":"Biological function of C-X-C Motif Chemokine Ligand 1 gene (CXCL1) in ovarian malignant tumors.","authors":"Zhuang Li, Ning Huang, Wei Zhang, Li Li","doi":"10.1177/09603271231203392","DOIUrl":"10.1177/09603271231203392","url":null,"abstract":"Objective: To determine the function of the chemokine (C-X-C motif) ligand 1 (CXCL1) gene in ovarian cancer cells and to investigate the relationship between CXCL1 gene mRNA expression and ovarian tumor clinical pathology.Methods: Using bioinformatics methods to identify common differentially expressed genes associated with ovarian cancer in the GEO database. Growth curves of A2780 cells with or without CXCL1 expression were plotted by MTT assay. Cell cycles were measured by flow cytometry. Cell colony formation was enumerated in Transwell chambers. Migration and invasion in vitro were investigated using Cell Counting Kit-8 (CCK8), wound healing and Transwell, respectively. The relationship between CXCL1 gene mRNA expression and ovarian tumor clinical pathology was analyzed.Results: CXCL1 was found to be one of the co-upregulated differentially expressed genes in the GEO database. The migration of A2780 cells expressing CXCL1 was significantly higher than that of A2780 cells without CXCL1 expression. CXCL1 mRNA expression in ovarian malignancy was significantly higher than those in benign lesions and the normal control (p < .01). In advanced ovarian cancer (Stages III-IV), CXCL1 mRNA expression was also significantly higher than that in patients with early-stage ovarian cancer (Stages I-II) (p = .005). Kaplan-Meier survival curve showed no correlation between CXCL1 mRNA expression and ovarian cancer prognosis. A Cox proportional hazard model also showed that CXCL1 expression was not an independent prognostic factor for ovarian cancer patients.Conclusions: CXCL1 gene could promotes ovarian cancer A2780 cell proliferation and invasion in vitro, and contributed theoretical knowledge for the target selection in molecular targeted therapy. CXCL1 mRNA over-expression may be correlated with the occurrence and development of ovarian malignancy. Level of plasma CXCL1 might serve as a biomarker for prognosis in ovarian carcinoma patients.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41175893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toxic mechanisms of cadmium and exposure as a risk factor for oral and gastrointestinal carcinomas. 镉的毒性机制和暴露作为口腔癌和胃肠道癌的危险因素。

Human & experimental toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271231210262

Ali Tavakoli Pirzaman, Pouyan Ebrahimi, Shokat Niknezhad, Turan Vahidi, Dariush Hosseinzadeh, Sousan Akrami, Arash M Ashrafi, Mohammad Moeen Velayatimehr, Rezvan Hosseinzadeh, Sohrab Kazemi

{"title":"Toxic mechanisms of cadmium and exposure as a risk factor for oral and gastrointestinal carcinomas.","authors":"Ali Tavakoli Pirzaman, Pouyan Ebrahimi, Shokat Niknezhad, Turan Vahidi, Dariush Hosseinzadeh, Sousan Akrami, Arash M Ashrafi, Mohammad Moeen Velayatimehr, Rezvan Hosseinzadeh, Sohrab Kazemi","doi":"10.1177/09603271231210262","DOIUrl":"10.1177/09603271231210262","url":null,"abstract":"Incidence and mortality rates of gastrointestinal (GI) and oral cancers are among the highest in the world, compared to other cancers. GI cancers include esophageal, gastric, colon, rectal, liver, and pancreatic cancers, with colorectal cancer being the most common. Oral cancer, which is included in the head and neck cancers category, is one of the most important causes of death in India. Cadmium (Cd) is a toxic element affecting humans and the environment, which has both natural and anthropogenic sources. Generally, water, soil, air, and food supplies are reported as some sources of Cd. It accumulates in organs, particularly in the kidneys and liver. Exposure to cadmium is associated with different types of health risks such as kidney dysfunction, cardiovascular disease, reproductive dysfunction, diabetes, cerebral infarction, and neurotoxic effects (Parkinson's disease (PD) and Alzheimer's disease (AD)). Exposure to Cd is also associated with various cancers, including lung, kidney, liver, stomach, hematopoietic system, gynecologic and breast cancer. In the present study, we have provided and summarized the association of Cd exposure with oral and GI cancers.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49695372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Development and validation of a novel poisoning agitation-sedation score for predicting the need for endotracheal intubation and mechanical ventilation in acutely poisoned patients with disturbed consciousness. 开发并验证用于预测意识障碍的急性中毒患者是否需要气管插管和机械通气的新型中毒躁动-镇静评分。

Human & experimental toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271231222253

Soha A Abd Elghany, Heba I Lashin, Ghada N El-Sarnagawy, Merfat M Oreby, Eman Soliman

{"title":"Development and validation of a novel poisoning agitation-sedation score for predicting the need for endotracheal intubation and mechanical ventilation in acutely poisoned patients with disturbed consciousness.","authors":"Soha A Abd Elghany, Heba I Lashin, Ghada N El-Sarnagawy, Merfat M Oreby, Eman Soliman","doi":"10.1177/09603271231222253","DOIUrl":"https://doi.org/10.1177/09603271231222253","url":null,"abstract":"Background: Accurate assessment of disturbed consciousness level (DCL) is crucial for predicting acutely poisoned patients' outcomes.Aim: Development of a novel Poisoning Agitation-Sedation Score (PASS) to predict the need for endotracheal intubation (ETI) and mechanical ventilation (MV) in acutely poisoned patients with DCL. Validation of the proposed score on a new set of acutely poisoned patients with DCL.Methods: This study was conducted on 187 acutely poisoned patients with DCL admitted to hospital from June 2020 to November 2021 (Derivation cohort). Patients' demographics, toxicological data, neurological examination, calculation of the Glasgow Coma Scale (GCS), Full Outline of Unresponsiveness (FOUR) score, Richmond Agitation-Sedation Scale (RASS), and outcomes were gathered for developing a new score. The proposed score was externally validated on 100 acutely poisoned patients with DCL (Validation cohort).Results: The PASS assessing sedation consists of FOUR (reflexes and respiration) and GCS (motor) and provides a significantly excellent predictive power (AUC = 0.975) at a cutoff ≤9 with 100% sensitivity and 92.11% specificity for predicting the need for ETI and MV in sedated patients. Additionally, adding RASS (agitation) to the previous model exhibits significantly good predictive power (AUC = 0.893), 90.32% sensitivity, and 73.68% specificity at a cutoff ≤14 for predicting the need for ETI and MV in disturbed consciousness patients with agitation.Conclusion: The proposed PASS could be an excellent, valid and feasible tool to predict the need for ETI and MV in acutely poisoned disturbed consciousness patients with or without agitation.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138814268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of methylphenidate on femoral bone growth in male rats. 哌甲酯对雄性大鼠股骨生长的影响。

Human & experimental toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271231210970

Gökçe Nur Say, Mehmet Emin Önger, Ferhat Say, Onur Yontar, Oktay Yapıcı

{"title":"Effects of methylphenidate on femoral bone growth in male rats.","authors":"Gökçe Nur Say, Mehmet Emin Önger, Ferhat Say, Onur Yontar, Oktay Yapıcı","doi":"10.1177/09603271231210970","DOIUrl":"10.1177/09603271231210970","url":null,"abstract":"The use of Methylphenidate (MP) can have adverse effects on bone growth and mineralization. This study aimed to investigate the underlying pathophysiology of MP-induced skeletal deficits in growing rats using stereological and immunohistochemical methods. Male rats, aged 4 weeks, were orally treated with MP through an 8-h/day water drinking protocol. The rats (n=30) were randomly divided into three groups: MP-High Dose (30/60 mg/kg/day MP), MP-Low Dose (4/10 mg/kg/day MP), and control (water only). After 13 weeks, the femoral bones were assessed using calliper measurements, dual-energy X-ray absorptiometry, and biomechanical evaluation. The total femur volume, cartilage volume, growth zone volume, and volume fractions were determined using the Cavalieri method. Immunohistochemical analyses were conducted using alkaline phosphatase and anti-calpain antibody staining. Rats exposed to MP exhibited significant reductions in weight gain, femoral growth, bone mineralization, and biomechanical integrity compared to the control group. The total femoral volume of MP-treated rats was significantly lower than that of the control group. The MP-High Dose group showed significantly higher ratios of total cartilage volume/total femoral volume and total growth zone volume/total femoral volume than the other groups. Immunohistochemical evaluation of the growth plate revealed reduced osteoblastic activity and decreased intracellular calcium deposition with chronic MP exposure. The possible mechanism of MP-induced skeletal growth retardation may involve the inhibition of intracellular calcium deposition in chondrocytes of the hypertrophic zone in the growth plate. In this way, MP may hinder the differentiation of cartilage tissue from bone tissue, resulting in reduced bone growth and mineralization.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71416363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

5-Flourouracil-induced toxicity in both male and female reproductive systems: A narrative review. 5-氟尿嘧啶对男性和女性生殖系统的毒性：叙述性综述。

Human & experimental toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271231217988

Ali Tavakoli Pirzaman, Pouyan Ebrahimi, Shahrbanoo Doostmohamadian, Bardia Karim, Darya Almasi, Fatemeh Madani, Ahmadreza Moghadamnia, Sohrab Kazemi

{"title":"5-Flourouracil-induced toxicity in both male and female reproductive systems: A narrative review.","authors":"Ali Tavakoli Pirzaman, Pouyan Ebrahimi, Shahrbanoo Doostmohamadian, Bardia Karim, Darya Almasi, Fatemeh Madani, Ahmadreza Moghadamnia, Sohrab Kazemi","doi":"10.1177/09603271231217988","DOIUrl":"10.1177/09603271231217988","url":null,"abstract":"The chemotherapeutic drug 5-flourouracil (5FU) is frequently used to treat a wide range of solid malignant tumors, such as colorectal, pancreatic, gastric, breast, and head and neck cancers. Its antitumoral effects are achieved by interfering with the synthesis of RNA and DNA and by inhibiting thymidylate synthase in both malignant and non-malignant cells. Therefore, it can be responsible for severe toxicities in crucial body organs, including heart, liver, kidney, and reproductive system. Given the fact that 5FU-induced reproductive toxicity may limit the clinical application of this drug, in this study, we aimed to discuss the main locations and mechanisms of the 5FU-induced reproductive toxicity. Initially, we discussed the impact of 5FU on the male reproductive system, which leads to damage of the seminiferous epithelial cells and the development of vacuoles in Sertoli cells. Although no noticeable changes occur at the histopathological level, there is a decrease in the weight of the prostate. Additionally, 5FU causes significant abnormalities in spermatogenesis, including germ cell shedding, spermatid halo formation, polynucleated giant cells, and decreased sperm count. Finally, in females, 5FU-induced reproductive toxicity is characterized by the presence of atretic secondary and antral follicles with reduced numbers of growing follicles, ovarian weight, and maturity impairment.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138814220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RNA-seq analysis revealed genes associated with neuropathic pain induced by chronic compressive injury in interferon regulatory factors 4 knockout mice. RNA-seq分析揭示了干扰素调节因子4基因敲除小鼠慢性压迫性损伤诱发神经病理性疼痛的相关基因。

Human & experimental toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271231221567

Jiayi Peng, Yunlin Wu, Qi E, Ziyin Zhou, Xianjie Wen

{"title":"RNA-seq analysis revealed genes associated with neuropathic pain induced by chronic compressive injury in interferon regulatory factors 4 knockout mice.","authors":"Jiayi Peng, Yunlin Wu, Qi E, Ziyin Zhou, Xianjie Wen","doi":"10.1177/09603271231221567","DOIUrl":"https://doi.org/10.1177/09603271231221567","url":null,"abstract":"Objective: To explore the differential expression of genes between wild-type chronic compressive injury (CCI) mice (WT-CCI) and interferon regulatory factors 4 (IRF4) knockout CCI mice (KO-CCI) by RNA-seq analysis of the mouse spinal cord.Methods: RNA-seq analysis of the spinal cord tissue of the chronic sciatic nerve ligation mice and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used.Results: A total of 104 genes were up-regulated and 116 genes were down-regulated in spinal cord of the mice in IRF4 knockout (KO-CCI) group compared with that in the wild-type CCI (WT-CCI) group. There were 1472 differentially expressed genes in the biological process group, 62 differentially expressed genes in the cellular component group, and 163 differentially expressed genes in the molecular function group in KO-CCI mice. A total of 14 genes related to inflammatory reactions were differentially expressed. Real-time PCR results confirmed that Pparg and Grpr mRNA expression was up-regulated and Arg 1 and Ccl11 mRNA expression was down-regulated in the KO-CCI group.Conclusion: IRF4 is involved in neuropathic pain in CCI mice, IRF4 may participate in neuropathic pain by regulating Grpr, Mas1, Galr3, Nos2, Arg1, Ccl11, Ptgs2, S100a8, Pparg, Cd40, Has2, Gpr151, Il123a, Capns2, Ankrd1, Ccnb1, and Nppb genes.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138814394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tanshinone I induces ferroptosis in gastric cancer cells via the KDM4D/p53 pathway. 丹参酮I通过KDM4D/p53通路诱导胃癌细胞铁下垂。

Human & experimental toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271231216963

Minming Xia, Yifeng Wu, Hui Zhu, Wenbiao Duan

{"title":"Tanshinone I induces ferroptosis in gastric cancer cells via the KDM4D/p53 pathway.","authors":"Minming Xia, Yifeng Wu, Hui Zhu, Wenbiao Duan","doi":"10.1177/09603271231216963","DOIUrl":"10.1177/09603271231216963","url":null,"abstract":"Introduction: Tanshinone I (Tan I) is one of the bioactive components of Salvia miltiorrhiza. Whether it inhibits gastric cancer through ferroptosis has not been reported. This study aimed to confirm the effect of Tan I on ferroptosis in gastric cancer cells.Methods: AGS and HGC27 cells were treated with Tan I. First, oxidative stress-related parameters and the expression of ferroptosis-related proteins were examined. Combined with a ferroptosis inhibitor, Tan I was found to inhibit gastric cancer cells via the ferroptosis pathway. Finally, with bioinformatics analysis, the target protein of Tan I was identified.Results: Tan I significantly inhibited the expression level of GPX4. This molecule also increased ROS, MDA, and Fe2+ contents and decreased GSH enzyme activity. Therefore, we hypothesized that Tan I may inhibit gastric cancer cells by inducing ferroptosis. Western blotting results showed that Tan I inhibited the expression levels of the ferroptosis resistance-related proteins GPX4, SLC7A11, and FTH1, while the pro-ferroptosis-related proteins TFR1 and ACSL4 were significantly upregulated. A ferroptosis inhibitor effectively reversed these regulatory effects of Tan I in gastric cancer. With these data combined with the bioinformatics analysis, KDM4D was identified as a key regulatory target of Tan I. Mechanistically, Tan I induced positive regulation of ferroptosis resistance-related indicators by inhibiting KDM4D to upregulate p53 protein expression. Overexpression of KDM4D significantly reversed the effect of Tan I-induced ferroptosis resistance in gastric cancer cells.Conclusions: Tan I induced ferroptosis inhibition in gastric cancer by regulating the KDM4D/p53 pathway.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138292641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrative analysis of renal microRNA and mRNA to identify hub genes and pivotal pathways associated with cyclosporine-induced acute kidney injury in mice. 肾脏microRNA和mRNA的整合分析，以确定环孢素诱导的小鼠急性肾损伤相关的枢纽基因和关键途径。

Human & experimental toxicology Pub Date : 2023-01-01 DOI: 10.1177/09603271231215499

Qiaoling Yang, Xunjiang Wang, Hongjing Li, Xuedong Yin, Hongxia Liu, Wenjuan Hu, Ying Qing, Lili Ding, Li Yang, Zhiling Li, Huajun Sun

{"title":"Integrative analysis of renal microRNA and mRNA to identify hub genes and pivotal pathways associated with cyclosporine-induced acute kidney injury in mice.","authors":"Qiaoling Yang, Xunjiang Wang, Hongjing Li, Xuedong Yin, Hongxia Liu, Wenjuan Hu, Ying Qing, Lili Ding, Li Yang, Zhiling Li, Huajun Sun","doi":"10.1177/09603271231215499","DOIUrl":"10.1177/09603271231215499","url":null,"abstract":"Cyclosporine (CsA) is an immunosuppressive agent that often causes acute kidney injury (AKI) in children. The specific mechanisms underlying CsA-induced AKI are currently unknown. This study used an integrated network analysis of microRNA (miRNA) and mRNA expression profiles, biochemical and pathological analyses to further investigate these potential mechanisms of CsA-induced AKI. Small RNA sequence analysis identified 25 differentially expressed miRNAs, RNA sequencing analysis identified 4,109 differentially expressed mRNAs. We obtained a total of 4,367 target genes from the 25 differentially expressed miRNAs based on three algorithms, including the Mirdb, Mirtarbase, and TargetScan. 971 target genes overlapped between the 4,367 target genes and 4,109 differentially expressed mRNAs were identified for further bioinformatics analysis. Finally, 30 hub genes and two main modules were recognized. Functional enrichment analysis of 30 hub genes indicated that inflammation and epithelial-mesenchymal transition (EMT) related genes were mainly concentrated together. Pathway analysis revealed that the PI3K-Akt signaling pathway plays an integral role in CsA-induced AKI. Network analysis identified 3 important miRNAs, mmu-miR-17b-5p, mmu-miR-19b-3p, and mmu-mir-423-5p that may further promote the development of inflammatory responses and EMT by mediating a complex network of factors. Our research provides a clearer understanding the molecular mechanism of this specific drug-induced AKI by CsA use, which is useful for discovering potential targets for gene therapies, and drug development in CsA-induced AKI.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89721360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0