1.Effects of phthalates on expressions of heme oxygenase-1(HO-1)in HepG2 cells and construction of a HO-1-based 3D-QSAR model
Huan LIU ; Kangxing LI ; Wenjie WENG ; Yujun SHI ; Chunhong LIU ; Zhenyi NONG
Chinese Journal of Pharmacology and Toxicology 2025;39(9):681-688
OBJECTIVE To evaluate the effects of phthalic acid esters(PAEs)on the expression of heme oxygenase-1(HO-1)in HepG2 cells,and to construct an HO-1-based three-dimensional quantita-tive structure-activity relationship(3D-QSAR)model.METHODS ① HepG2 cells were treated with seven types of PAEs:di-(2-ethylhexyl)phthalate(DEHP),di-n-octyl phthalate(DnOP),dimethyl phthalate(DMP),diethyl phthalate(DEP),dihexyl phthalate(DHXP),dimethylglycol phthalate(DMEP),and dibutyl phthalate(DBP),at final concentrations of 0(DMSO,solvent control),0.062 5,0.125,0.25,0.5 and 1 mmol·L-1(n=6)for 48 h at 37℃.The expression level of HO-1 was measured by Western blotting.② A 3D-QSAR model was constructed using comparative molecular similarity indices analysis(CoMSIA)based on the measured HO-1 levels.The applicability domain(AD)of the model was evaluated using the leverage method.Model fitting quality and predictive ability were evaluated via the KNIME Enalos+node to verify model stability.Additionally,molecular docking was performed to validate the binding interactions between PAEs and HO-1.RESULTS ① Compared with the solvent control group,48 h of exposure to 0.062 5 mmol·L-1 PAEs(DMP,DMEP,DEHP,DnOP and DEP)significantly increased HO-1 protein expressions,while 1 mmol·L-1 PAEs(DMP,DBP,DnOP,DEP and DHXP)significantly suppressed HO-1 expressions.② The 3D-QSAR model showed a non-cross-validated coefficient(R2)of 0.996 and a cross-validated coefficient(Q2)of 0.548.All the seven PAEs in the 3D-QSAR model were within the applicability domain(AD)and passed external validation.Molecular docking results indi-cated that DBP,DnOP,DEHP and DHXP exhibited stronger binding affinities to HO-1.CONCLUSION Forty-eight hours of exposure of HepG2 cells to 1 mmol·L-1 PAEs can significantly suppress HO-1 expres-sions.The 3D-QSAR model established in this study provides a potential tool for predicting the HO-1-related toxic effects of novel PAEs.
2.Effects of phthalates on expressions of heme oxygenase-1(HO-1)in HepG2 cells and construction of a HO-1-based 3D-QSAR model
Huan LIU ; Kangxing LI ; Wenjie WENG ; Yujun SHI ; Chunhong LIU ; Zhenyi NONG
Chinese Journal of Pharmacology and Toxicology 2025;39(9):681-688
OBJECTIVE To evaluate the effects of phthalic acid esters(PAEs)on the expression of heme oxygenase-1(HO-1)in HepG2 cells,and to construct an HO-1-based three-dimensional quantita-tive structure-activity relationship(3D-QSAR)model.METHODS ① HepG2 cells were treated with seven types of PAEs:di-(2-ethylhexyl)phthalate(DEHP),di-n-octyl phthalate(DnOP),dimethyl phthalate(DMP),diethyl phthalate(DEP),dihexyl phthalate(DHXP),dimethylglycol phthalate(DMEP),and dibutyl phthalate(DBP),at final concentrations of 0(DMSO,solvent control),0.062 5,0.125,0.25,0.5 and 1 mmol·L-1(n=6)for 48 h at 37℃.The expression level of HO-1 was measured by Western blotting.② A 3D-QSAR model was constructed using comparative molecular similarity indices analysis(CoMSIA)based on the measured HO-1 levels.The applicability domain(AD)of the model was evaluated using the leverage method.Model fitting quality and predictive ability were evaluated via the KNIME Enalos+node to verify model stability.Additionally,molecular docking was performed to validate the binding interactions between PAEs and HO-1.RESULTS ① Compared with the solvent control group,48 h of exposure to 0.062 5 mmol·L-1 PAEs(DMP,DMEP,DEHP,DnOP and DEP)significantly increased HO-1 protein expressions,while 1 mmol·L-1 PAEs(DMP,DBP,DnOP,DEP and DHXP)significantly suppressed HO-1 expressions.② The 3D-QSAR model showed a non-cross-validated coefficient(R2)of 0.996 and a cross-validated coefficient(Q2)of 0.548.All the seven PAEs in the 3D-QSAR model were within the applicability domain(AD)and passed external validation.Molecular docking results indi-cated that DBP,DnOP,DEHP and DHXP exhibited stronger binding affinities to HO-1.CONCLUSION Forty-eight hours of exposure of HepG2 cells to 1 mmol·L-1 PAEs can significantly suppress HO-1 expres-sions.The 3D-QSAR model established in this study provides a potential tool for predicting the HO-1-related toxic effects of novel PAEs.
3.Progress in association of RSK2 with malignancies and its inhibitors
Kangxing CHEN ; Ziyou WANG ; Yanxia HUANG ; Chengzhi ZHONG ; Kaiheng LI ; Zunnan HUANG
Chinese Journal of Pathophysiology 2015;(10):1772-1779
RibosomalS6kinase2(RSK2)isamemberofthep90Rsk,whichbelongstoSer/Thrkinasefami-ly.It is a downstream molecule of Ras/MAPK cascade and regulates a variety of cellular processes.RSK2 plays a key role in the cell proliferation, survival and transformation.Furthermore, the aberrant up-regulation of RSK2 was observed in dif-ferent malignancies.We here briefly review the structure and function of RSK2, the relationship between RSK2 and tumor, and the existing RSK2 inhibitors.
4.The current status and influential factors of uncertainty in illness in cardiac valvular surgery patients with cardiopulmonary bypass
Yajie LI ; Wenhong XIE ; Mei LI ; Yan YU ; Kangxing LIN ; Yongyi PAN ; Suhua ZHUANG
Chinese Journal of Behavioral Medicine and Brain Science 2014;23(2):148-151
Objective To investigate the current status of uncertainty in illness in cardiac valvular surgery patients with cardiopulmonary bypass and analyze its influential factor,and provide reference for effective intervention.Methods A total of 208 cardiac valvular surgery patients with cardiopulmonary bypass were recruited from 4 cardiovascular surgery in Guangdong and were investigated with the self-designed questionnaire,Mishel Uncertainty in Illness Scale (MUIS),Connor-Davidson Resilience Scale (CD-RISC),Medical Coping Modes Questionnaire (MCMQ),in the preoperative day and the day before discharge.The data were analyzed by single-factor and multiple-factor analysis.Results The average score of uncertainty in illness in cardiac valvular surgery patients with cardiopulmonary bypass was 99.09±11.41,and 92.3% of patients got a moderate uncertainty in illness level in the preoperative day.The average score of uncertainty in illness in the patients was 90.33± 10.32,and 91.8% of patients got a moderate uncertainty in illness level in the day before discharge.Multiple linear regression indicated that,age,cardiac valvular disease types,number of cardiac valvular surgery,optimism and yield were the protective factors of uncertainty in illness level.Average monthly household income,self-improvement,scores of resilience and confront coping were the risk factors of uncertainty in illness level.Conclusion The level of uncertainty in illness in cardiac valvular surgery patients with cardiopulmonary bypass is moderate.Age,average monthly household income,cardiac valvular disease types,number of cardiac valvular surgery,resilience and coping style are factors influencing uncertainty in illness level of patients.
5.Relationship between resilience and coping style of cardiac valvular postoperative patients with cardiopulmonary bypass
Wenhong XIE ; Yajie LI ; Yan YU ; Mei LI ; Yongyi PAN ; Kangxing LIN ; Suhua ZHUANG
Chinese Journal of Practical Nursing 2013;29(36):42-45
Objective To explore the relationship between resilience and coping style of cardiac valvular postoperative patients with cardiopulmonary bypass.Methods A total of 208 cardiac valvular postoperative patients with cardiopulmonary bypass were recruited from 4 cardiovascular surgery in Guangdong and were investigated with the self-designed questionnaire,Connor-Davidson Resilience Scale (CD-RISC),Medical Coping Modes Questionnaire (MCMQ).Results The average score of resilience in cardiac valvular postoperative patients with cardiopulmonary bypass was (55.38±10.63)points.The average score of tenacity,strength and optimism were (28.21 ±5.87)points,(18.21 ±4.02)and (8.96± 1.85)points respectively.The average score of coping style of confrontation,avoidance and acceptance-resignation were(18.13±3.38),(16.95±1.75)and (9.24±2.47)points respectively.All the sub-scores of the resilience were positively correlated with confrontation,and all the sub-scores of the resilience were negatively correlated with avoidance and acceptance-resignation.Conclusions There is a certain degree of correlation between resilience and copping style of cardiac valvular postoperative patients with cardiopulmonary bypass.Nurses should enhance resilience of the patients,guide the patients to adopt effective coping styles,to promote disease rehabilitation and improve the quality of life.
6.A survey on diseases suffering in 5 068 members of rescue teams in Weachuan earthquake
Kangxing SONG ; Qiang MA ; Yan TAN ; Hong SHEN ; Yong WANG ; Xue YANG ; Lijie FENG ; Xinya YU ; Baofeng XU ; Jigang ZHANG ; Li CHEN
Chinese Journal of Emergency Medicine 2008;17(8):797-799
Objective To investigate the incidence of diseases in member of rescue teams in the Wenchuan earthquake in Sichuan Province.Method Twenty days afer the Wenchuan earthquake in 2008,5 068 resucing staff of rescue learns as random and cluster sample were investigated and analyzed to find the factors impacting their fitness associated with their characters,diseases,work,and encampment styles.Results Members of rescue teams suffered from the following diseases:insect dermatitis (18.37%),tinea pedis (10.83%),acute upper respiratory infection (10.56%)and solar dermatitis (6.20%).Contrasted by work tasks,staff resucing on the front line had the highest incidence of acute upper-respiratory infection(11.04%) ,logistics workers had the highest incidence of tinea pedis(15.21% ),and more patients of acute gastroenteritis,insect dermatitis,gingivitis emerged from medical personnel group(P<0.05).The encampment sites were devided into three sorts:plain land,hillside and valley.The staff stayed at valley had higher incidence of acute upper respiratory infection (24.90%),insect dermatitis (36.50%) and tinca pedis (20.02%)than those worked at plain land and hillside (P<0.01).The incidence of acute gastroerrteritis(1.26%) ha staff resides hillside is lower than that in valley or plain land (P<0.05).Conclusions In the period of rescue actions in the guake-hit region,the members of rescue teams suffered from famihar diseases such as dermatitis and acute upper-respiratory infection,etc.The incidence of diseases is associated with their work tasks and the topography of cantonment.

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