1.Trehalose protects H9C2 cardiomyocytes against cardiac ischemia/reperfusion injury by activating Nrf2
Yanyu LU ; Lijuan ZHANG ; Yikun MAO ; Yu LI
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(8):954-959
Objective To investigate the effect of trehalose(Tre)H9C2 cardiomyocytes under oxy-gen-glucose deprivation/reoxygenation(OGD/R)injury and its mechanism of action with the cel-lular model simulating the process of myocardial ischemia/reperfusion injury.Methods H9C2 cells were divided control group,OGD/R group,Tre group(OGD/R+Tre),and combination group(OGD/R+Tre+ML385).MTT assay was used to observe cell proliferation,and lactate de-hydrogenase(LDH)release and Hoechst/propidium iodide staining were employed to evaluate cell membrane damage.Western blot analysis was utilized to detect the expression of nuclear fac-tor erythroid 2-related factor 2(Nrf2)and its downstream related proteins.The generation of re-active oxygen species(ROS)and mitochondrial membrane potential(MMP)were measured to quantify the level of oxidative stress.The expression of apoptosis-related proteins was determined by Western blot analysis.Results In comparison to the control group,the OGD/R group exhibi-ted a significantly reduced cell viability.When compared with the OGD/R group,the intervention of varying concentrations of Tre obviously improved cell viability in a dose-dependent manner(P<0.01),increased MMP,and up-regulated the expression of glutathione(GSH),Nrf2,hemeo-xygenase 1,and nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1(NQO1),Bcl-2,and cysteinyl aspartate specific proteinase 3(Caspase-3)(P<0.05,P<0.01),and decreased the production of ROS and MDA and the expression of responding element binding protein 1,Bax,Bax/Bcl-2,and cleaved Caspase-3(P<0.05,P<0.01).What's more,the combined group ex-hibited significantly higher production of ROS,MDA,increased mRNA levels of TNF-α,IL-1β,and IL-6,and reduced MMP and GSH levels(P<0.05,P<0.01),as well as,enhanced expression of Bax,Bax/Bcl-2,and cleaved Caspase-3(1.77±0.08 vs 1.20±0.20,3.41±1.45 vs 0.99±0.15,4.10±1.05 vs 1.79±0.52,P<0.01),and decreased expression of Bcl-2 and Caspase-3(0.58±0.21 vs 1.23±0.25,0.87±0.25 vs 1.45±0.31,P<0.01)in comparison with the Tre group.Conclusion Tre can be regarded as an Nrf2 activator that inhibits oxidative stress and apoptosis by activating Nrf2,and thereby ameliorates OGD/R-induced cardiomyocyte injury.
2.Effects of trehalose on oxygen-glucose deprivation and restoration injury in H9C2 cells and the role of SLC7A11-GPX4 signaling pathway
Lijuan ZHANG ; Ruyang TENG ; Xiuyun WU ; Qin ZHAO ; Yanyu LU ; Yikun MAO ; Yu LI
Chinese Journal of Anesthesiology 2024;44(11):1351-1355
Objective:To evaluate the effect of trehalose on oxygen-glucose deprivation and restoration (OGD/R) injury in H9C2 cells and the role of solute carrier family 7 member 11- (SLC7A11)-glutathione peroxidase 4 (GPX4) signaling pathway.Methods:Well-grown H9C2 cells were divided into 4 groups ( n=24 each) by the random number table method: control group (group C), OGD/R group (group O), OGD/R+ trehalose group (group OT) and OGD/R+ trehalose+ erastin group (group OTE). The cells were normally cultured in group C. In O, OT and OTE groups, the DMEM medium was replaced with EBSS medium, the cells were exposed to 5% CO 2-95% N 2 in an incubator at 37 ℃ for 6 h, and then the medium was replaced with DMEM medium supplemented with 6% fetal bovine serum to restore oxygen and glucose supply for 24 h. In group OT, trehalose at a final concentration of 50 mmol/L was added during restoration of oxygen and glucose supply. In group OTE, the SLC7A11 inhibitor erastin at a final concentration of 10 μmol/L was added at 8 h before oxygen-glucose deprivation, and trehalose at a final concentration of 50 mmol/L was added during restoration of oxygen and glucose supply. The cell viability, lactic dehydrogenase (LDH) activity, contents of glutathione (GSH), malondialdehyde (MDA) and iron, and reactive oxygen species (ROS) levels were measured at 24 h of restoration of oxygen and glucose supply. The expression of SLC7A11, GPX4, long-chain fatty acyl coenzyme A synthetase 4 (ACSL4), and ferritin heavy chain 1 (FTH1) was detected by Western blot. The structure of the mitochondrial morphology was observed with a transmission electron microscope. Results:Compared with group C, the cell viability and GSH content were significantly decreased, the LDH activity, contents of MDA and iron, and ROS level were increased, the expression of SLC7A11, GPX4 and FTH1 was down-regulated, and the expression of ACSL4 was up-regulated in group O ( P<0.05). Compared with group O, the cell viability and GSH content were significantly increased, the LDH activity, contents of MDA and iron, and ROS level were decreased, the expression of SLC7A11, GPX4 and FTH1 was up-regulated, and the expression of ACSL4 was down-regulated in group OT ( P<0.05). Compared with group OT, the cell viability and GSH content were significantly decreased, the LDH activity, contents of MDA and iron, and ROS levels were increased, the expression of SLC7A11, GPX4 and FTH1 was down-regulated, and the expression of ACSL4 was up-regulated in group OTE ( P<0.05). Conclusions:Trehalose can inhibit ferroptosis by activating the SLC7A11-GPX4 signaling pathway, thereby attenuating OGD/R injury in H9C2 cells.
3.Epidemiological characteristic and current status of surgical treatment for esophageal cancer by analysis of national registry database
Yousheng MAO ; Shugeng GAO ; Qun WANG ; Xiaotian SHI ; Yin LI ; Wenjun GAO ; Fushun GUAN ; Xiaofei LI ; Yongtao HAN ; Yongyu LIU ; Junfeng LIU ; Kang ZHANG ; Shuoyan LIU ; Xiangning FU ; Wentao FANG ; Longqi CHEN ; Qingchen WU ; Gaoming XIAO ; Keneng CHEN ; Guanggen JIAO ; Shijiang ZHANG ; Weimin MAO ; Tiehua RONG ; Jianhua FU ; Lijie TAN ; Chun CHEN ; Shidong XU ; Shiping GUO ; Zhentao YU ; Jian HU ; Zhendong HU ; Yikun YANG ; Ningning DING ; Ding YANG ; Jie HE
Chinese Journal of Oncology 2020;42(3):228-233
Objective:To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China.Methods:A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014.Results:Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively.Conclusions:The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.
4.Epidemiological characteristic and current status of surgical treatment for esophageal cancer by analysis of national registry database
Yousheng MAO ; Shugeng GAO ; Qun WANG ; Xiaotian SHI ; Yin LI ; Wenjun GAO ; Fushun GUAN ; Xiaofei LI ; Yongtao HAN ; Yongyu LIU ; Junfeng LIU ; Kang ZHANG ; Shuoyan LIU ; Xiangning FU ; Wentao FANG ; Longqi CHEN ; Qingchen WU ; Gaoming XIAO ; Keneng CHEN ; Guanggen JIAO ; Shijiang ZHANG ; Weimin MAO ; Tiehua RONG ; Jianhua FU ; Lijie TAN ; Chun CHEN ; Shidong XU ; Shiping GUO ; Zhentao YU ; Jian HU ; Zhendong HU ; Yikun YANG ; Ningning DING ; Ding YANG ; Jie HE
Chinese Journal of Oncology 2020;42(3):228-233
Objective:To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China.Methods:A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014.Results:Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively.Conclusions:The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.
5.Characterization of Distinct T Cell Receptor Repertoires in Tumor and Distant Non-tumor Tissues from Lung Cancer Patients.
Xiang WANG ; Botao ZHANG ; Yikun YANG ; Jiawei ZHU ; Shujun CHENG ; Yousheng MAO ; Lin FENG ; Ting XIAO
Genomics, Proteomics & Bioinformatics 2019;17(3):287-296
T cells and T cell receptors (TCRs) play pivotal roles in adaptive immune responses against tumors. The development of next-generation sequencing technologies has enabled the analysis of the TCRβ repertoire usage. Given the scarce investigations on the TCR repertoire in lung cancer tissues, in this study, we analyzed TCRβ repertoires in lung cancer tissues and the matched distant non-tumor lung tissues (normal lung tissues) from 15 lung cancer patients. Based on our results, the general distribution of T cell clones was similar between cancer tissues and normal lung tissues; however, the proportion of highly expanded clones was significantly higher in normal lung tissues than in cancer tissues (0.021% ± 0.002% vs. 0.016% ± 0.001%, P = 0.0054, Wilcoxon signed rank test). In addition, a significantly higher TCR diversity was observed in cancer tissues than in normal lung tissues (431.37 ± 305.96 vs. 166.20 ± 101.58, P = 0.0075, Mann-Whitney U test). Moreover, younger patients had a significantly higher TCR diversity than older patients (640.7 ± 295.3 vs. 291.8 ± 233.6, P = 0.036, Mann-Whitney U test), and the higher TCR diversity in tumors was significantly associated with worse cancer outcomes. Thus, we provided a comprehensive comparison of the TCR repertoires between cancer tissues and matched normal lung tissues and demonstrated the presence of distinct T cell immune microenvironments in lung cancer patients.