1.Temozolomide Drives Ferroptosis via a DMT1-Dependent Pathway in Glioblastoma Cells
Qingxin SONG ; Shanxin PENG ; Zhiqing SUN ; Xueyuan HENG ; Xiaosong ZHU
Yonsei Medical Journal 2021;62(9):843-849
Purpose:
Temozolomide is used in first-line treatment for glioblastoma. However, chemoresistance to temozolomide is common in glioma patients. In addition, mechanisms for the anti-tumor effects of temozolomide are largely unknown. Ferroptosis is a form of programmed cell death triggered by disturbed redox homeostasis, overloaded iron, and increased lipid peroxidation. The present study was performed to elucidate the involvement of ferroptosis in the anti-tumor mechanisms of temozolomide.
Materials and Methods:
We utilized the CCK8 assay to evaluate cytotoxicity. Levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), iron, and glutathione (GSH) were measured. Flow cytometry and fluorescence microscope were used to detect the production of reactive oxygen species (ROS). Western blotting, RT-PCR and siRNA transfection were used to investigate molecular mechanisms.
Results:
Temozolomide increased the levels of LDH, MDA, and iron and reduced GSH levels in TG905 cells. Furthermore, we found that ROS levels and DMT1 expression were elevated in TG905 cells treated with temozolomide and were accompanied by a decrease in the expression of glutathione peroxidase 4, indicating an iron-dependent cell death, ferroptosis. Our results also showed that temozolomide-induced ferroptosis is associated with regulation of the Nrf2/HO-1 pathway. Conversely, DMT1 knockdown by siRNA evidently blocked temozolomide-induced ferroptosis in TG905 cells.
Conclusion
Taken together, our findings indicate that temozolomide may suppress cell growth partly by inducing ferroptosis by targeting DMT1 expression in glioblastoma cells.
2.Temozolomide Drives Ferroptosis via a DMT1-Dependent Pathway in Glioblastoma Cells
Qingxin SONG ; Shanxin PENG ; Zhiqing SUN ; Xueyuan HENG ; Xiaosong ZHU
Yonsei Medical Journal 2021;62(9):843-849
Purpose:
Temozolomide is used in first-line treatment for glioblastoma. However, chemoresistance to temozolomide is common in glioma patients. In addition, mechanisms for the anti-tumor effects of temozolomide are largely unknown. Ferroptosis is a form of programmed cell death triggered by disturbed redox homeostasis, overloaded iron, and increased lipid peroxidation. The present study was performed to elucidate the involvement of ferroptosis in the anti-tumor mechanisms of temozolomide.
Materials and Methods:
We utilized the CCK8 assay to evaluate cytotoxicity. Levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), iron, and glutathione (GSH) were measured. Flow cytometry and fluorescence microscope were used to detect the production of reactive oxygen species (ROS). Western blotting, RT-PCR and siRNA transfection were used to investigate molecular mechanisms.
Results:
Temozolomide increased the levels of LDH, MDA, and iron and reduced GSH levels in TG905 cells. Furthermore, we found that ROS levels and DMT1 expression were elevated in TG905 cells treated with temozolomide and were accompanied by a decrease in the expression of glutathione peroxidase 4, indicating an iron-dependent cell death, ferroptosis. Our results also showed that temozolomide-induced ferroptosis is associated with regulation of the Nrf2/HO-1 pathway. Conversely, DMT1 knockdown by siRNA evidently blocked temozolomide-induced ferroptosis in TG905 cells.
Conclusion
Taken together, our findings indicate that temozolomide may suppress cell growth partly by inducing ferroptosis by targeting DMT1 expression in glioblastoma cells.
3.Comparison of static intensity-modulated radiation therapy and volumetric modulated arc therapy in early-stage primary mediastinal B-cell lymphoma
Liming XU ; Minglei KANG ; Bo JIANG ; Hui FANG ; Jing JIN ; Weihu WANG ; Shulian WANG ; Yueping LIU ; Yongwen SONG ; Qingfeng LIU ; Qingxin WANG ; Jianrong DAI ; Yexiong LI
Chinese Journal of Radiation Oncology 2015;(6):638-643
Objective To compare target dosimetric distribution and normal tissue radiation between different static intensity?modulated radiation therapy ( IMRT) plans and volumetric modulated arc therapy ( VMAT) and to identify the best IMRT plan for patients with primary mediastinal B?cell lymphoma ( PMBCL) . Methods A total of 16 patients ( 8 males and 8 females) with early?stage ( Ann?Arbor stageⅠ) PMBCL were enrolled in this study,with doses of 45 Gy for primary gross tumor volume ( PGTV) and 40 Gy for planning target volume (PTV).Four plans were designed for each patient,consisting of static IMRT (5F?IMRT,7F?IMRT,9F?IMRT) and VMAT,and the target dosimetric distribution,normal tissue radiation dose,and efficiency of each plan were evaluated. The difference of dose was analyzed by analysis of variance. Results The mean conformity index ( CI) and homogeneity index ( HI) for PGTV in 5F?,7F?,9F?IMRT and VMAT were 1. 01 and 1. 10, 1. 01 and 1. 10, 1. 01 and 1. 10, and 1. 01 and 1. 11 ( P= 0. 963 and 0. 843) ,respectively,while these two indices for PTV were 1. 04 and 1. 22,1. 03 and 1. 19,1. 03 and 1. 17, and 1. 08 and 1. 14( P=0. 964 and 0. 969) ,respectively. The parameters of volume and dose were similar on normal tissue ( P= 0. 192?1. 000 ) . The treatment time and number of monitor units in 9F?IMRT were significantly higher than those in other static IMRT plans and VMAT ( P=0. 000,0. 000) ,and among these plans,VMAT had the lowest number of monitor units ( 13 345. 0 MU) and the shortest treatment time ( 5. 9 min) . Conclusions The target volume coverage of 7F?and 9F?IMRT is better than that of 5F?IMRT and VMAT.For early?stage PMBCL,VMAT is not superior to IMRT in terms of dosimetry,especially with a larger area of low?dose radiation to the breast,but it is highly efficient in practice.
4.Construction and Validation of a Predictive Model for the Risk of Concomitant Hemorrhage in Patients with Ruptured Tubal Pregnancy
Yanyi HUANG ; Yongmei ZHANG ; Qing MA ; Qingxin MAI ; Xingshan LIANG ; Jingyi HU ; Qunying LIANG ; Yongge GUAN ; Yang SONG
Journal of Practical Obstetrics and Gynecology 2023;39(12):923-928
Objective:To construct and validate a predictive model for the risk of excessive blood loss in pa-tients with ruptured tubal pregnancy,and to provide a basis and tool for the assessment of changes in the condi-tion of patients with ruptured tubal pregnancy.Methods:Clinical data of inpatients with ruptured tubal pregnancy from January 2014 to July 2021 were retrospectively analyzed,who underwent surgical treatment in the Depart-ment of Gynecology,Dongguan Maternal and Child Health Hospital.The pelvic blood volume was categorized into excessive blood loss and non-excessive blood loss groups based on whether the amount of pelvic blood was found to be≥750 ml intraoperatively.Factors influencing the occurrence of excessive blood loss were screened and modeled by univariate analysis,Lasso regression,and multi-factor Logistic stepwise regression.The area un-der the subject working characteristic curve(AUC)was used to evaluate the discrimination of the predictive mod-el,the model's consistency was evaluated by calibration curve and goodness-of-fit test,and the clinical utility of the model was evaluated and validated by the decision analysis curve.Finally,column line plots were drawn.Results:①A total of 386 patients with ruptured tubal pregnancy were included,of whom 124(32.12%)had blood loss≥750 ml.②The optimal predictors for predicting concomitant blood loss in patients with ruptured tubal preg-nancy were screened,including:days of abdominal pain,dizziness,pallor,fatigue,the maximum diameter of para-metrial mass,human chorionic gonadotropin(β-hCG),and hemoglobin(Hb)and the model and the column line graphswere constructed accordingly.③The prediction model AUC was 0.827(95%CI 0.781-0.873);the cut-off value was 0.391,at which point the specificity and sensitivity were 68.55%and 84.35%,respectively,and the AUC validated within the model by resampling was 0.804.Clinical decision curves showed that the threshold probability intervals for the maximum net benefit values ranged from 8.5%-97%,respectively.Conclusions:The constructed prediction model was validated to suggest good discriminatory efficacy and degree of consistency.As a tool,it has clinical application value in predicting the risk of hemorrhage in patients with ruptured tubal pregnan-cy.It can help to determine the occurrence of adverse events such as hemorrhagic shock at an early stage and improve the success rate of rescue treatment.
5.Expression of IQGAP1 in esophageal squamous cell carcinoma and its effect on malignant biologic behaviors of TE-2 cells
CHEN Yu ; SONG Wei ; CUI Facai ; WANG Jiaqi ; XIA Qingxin
Chinese Journal of Cancer Biotherapy 2019;26(1):73-78
Objective: To explore the expression of IQGAP1 (Ras GTPase-activating-like protein containing IQ domain) in esophageal squamous cell carcinoma (ESCC) tissues and cell lines and its effect on the proliferation and invasion of TE-2 cell. Methods: Totally 125 pairs of cancer tissues and para-cancerous tissues from ESCC patients, who underwent surgical resection inAffiliated Tumor Hospital of Zhengzhou University from January 2015 to December 2016, were included in this study; in addition, ESCC cell lines (TE-2, TE3, ECA109) and normal esophageal epithelial cell line Het-1A were also collected. The expression of IQGAP1 was detected by immunohistochemical staining and its relationship with cliniopathological features was also analyzed. IQGAP1 mRNA and protein expressions in ESCC cell lines were detected by Real-time quantitative PCR (qPCR) and Western blotting, respectively. TE-2 cells were transfected with si-IQGAP1 (positive transfection group) and si-CTRL (negative control group) plasmids, and the effects of IQGAP1 silencing on the proliferation and invasion of TE-2 cells were detected by MTT and Transwell assay. The expressions of E-cadherin and Ncadherin were detected by Western blotting. Results: The positive expression rate of IQGAP1 in ESCC tissues was significantly higher than that in para-cancerous tissues (P<0.05), which was closely related to tumor stage and histologic grade (all P<0.05). The mRNAand protein expressions of IQGAP1 in TE-2, TE-3 and ECA109 cells were significantly higher than those in Het-1Acells (all P<0.05).After IQGAP1 was silenced, compared with the negative control group and the blank group, the expression of IQGAP1 mRNAand protein in the positive transfection group significantly decreased (all P<0.05); the proliferation and invasiveness of TE-2 cells significantly decreased (all P<0.05); E-cardherin was up-regulated while N-cardherin was down-regulated (all P<0.05) in the positive interference group. Conclusion: IQGAP1 is highly expressed in ESCC tissues, and si-IQGAP1 can inhibit the proliferation and invasion of TE-2 cells, which plays an important role in the occurrence and development of ESCC.
6.Clinical treatment guideline for pulmonary blast injury (version 2023)
Zhiming SONG ; Junhua GUO ; Jianming CHEN ; Jing ZHONG ; Yan DOU ; Jiarong MENG ; Guomin ZHANG ; Guodong LIU ; Huaping LIANG ; Hezhong CHEN ; Shuogui XU ; Yufeng ZHANG ; Zhinong WANG ; Daixing ZHONG ; Tao JIANG ; Zhiqiang XUE ; Feihu ZHOU ; Zhixin LIANG ; Yang LIU ; Xu WU ; Kaican CAI ; Yi SHEN ; Yong SONG ; Xiaoli YUAN ; Enwu XU ; Yifeng ZHENG ; Shumin WANG ; Erping XI ; Shengsheng YANG ; Wenke CAI ; Yu CHEN ; Qingxin LI ; Zhiqiang ZOU ; Chang SU ; Hongwei SHANG ; Jiangxing XU ; Yongjing LIU ; Qianjin WANG ; Xiaodong WEI ; Guoan XU ; Gaofeng LIU ; Junhui LUO ; Qinghua LI ; Bin SONG ; Ming GUO ; Chen HUANG ; Xunyu XU ; Yuanrong TU ; Liling ZHENG ; Mingke DUAN ; Renping WAN ; Tengbo YU ; Hai YU ; Yanmei ZHAO ; Yuping WEI ; Jin ZHANG ; Hua GUO ; Jianxin JIANG ; Lianyang ZHANG ; Yunfeng YI
Chinese Journal of Trauma 2023;39(12):1057-1069
Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.
7.Role of Oxidative Stress in Ulcerative Colitis and Traditional Chinese Medicine Prevention and Treatment: A Review
Bo CHEN ; Xitong SUN ; Xinqian DONG ; Wei WANG ; Hongquan SONG ; Jiting ZHAO ; Ya ZHENG ; Honghao ZHANG ; Qingxin LUAN ; Kangning ZHAO ; Hualiang DENG ; Zhen SUN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(16):264-273
Ulcerative colitis (UC) is a commonly seen digestive system disease with unclear pathogenesis. The condition is complex and variable, often chronic, and has a long treatment period with no specific cure. Currently, the treatment of UC often involves the use of corticosteroids, aminosalicylates, and biologics in western medicine, which provide fast-acting and definite efficacy in the short term. However, with prolonged medication, some patients may develop drug resistance and worsening of the disease, leading to the occurrence of colon cancer. Research has found that oxidative stress is one of the important pathogenic factors in UC and influences its onset and development. Oxidative stress is a state of imbalance between oxidative products and the antioxidant system in the body, characterized by overexpression of oxidative products such as malondialdehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO), or deficiency of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). It is worth noting that traditional Chinese medicine (TCM), as a unique characteristic medicine of China, has achieved significant efficacy in the treatment of UC. Studies have shown that TCM effectively inhibits the occurrence of UC by suppressing the accumulation of metabolites and antagonizes the development of UC by enhancing the antioxidant system. Therefore, using TCM to regulate the oxidative balance as a diagnostic and therapeutic approach may be a new method and direction for the treatment of UC in the future. Based on the above research, this article summarized the mechanisms of key pathogenic proteins in oxidative stress and the occurrence and development of UC, and compiled the effective ingredients of Chinese medicine, single drugs, prescriptions, and acupuncture and moxibustion in regulating upstream and downstream target proteins of oxidative stress. These interventions can reduce pathological damage to the intestinal mucosa, lower the colon injury index, enrich the intestinal microbiota, increase colon length, and improve clinical symptoms of UC. The article is expected to expand the application of TCM in the treatment of UC and provide a reliable scientific theoretical basis.