1.Targeting a novel inducible GPX4 alternative isoform to alleviate ferroptosis and treat metabolic-associated fatty liver disease.
Jie TONG ; Dongjie LI ; Hongbo MENG ; Diyang SUN ; Xiuting LAN ; Min NI ; Jiawei MA ; Feiyan ZENG ; Sijia SUN ; Jiangtao FU ; Guoqiang LI ; Qingxin JI ; Guoyan ZHANG ; Qirui SHEN ; Yuanyuan WANG ; Jiahui ZHU ; Yi ZHAO ; Xujie WANG ; Yi LIU ; Shenxi OUYANG ; Chunquan SHENG ; Fuming SHEN ; Pei WANG
Acta Pharmaceutica Sinica B 2022;12(9):3650-3666
Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.
2.Protective effect of sipunculusnudus polysaccharide on HUVEC cell damage induced by 137 Cs γ-ray
Chunli GAO ; Qingrong WANG ; Xianrong SHEN ; BAISHUANG ; Xiuting HU ; Ying HE
Chinese journal of nautical medicine and hyperbaric medicine 2019;26(2):91-96
Objective To investigate the protective effect of sipunculusnudus polysaccharide (SNP) on HUVEC cell damage induced by ionizing radiation.Methods The survival rate of HUVEC cells was detected by CCK-8,after irradiation with 137Cs γ-rays and pre-treatment with SNP,and optimal absorption dose rate of 137Cs γ-ray was 8 Gy and optimal concentration of SNP was confirmed to be 100 g/mL.The radiation sensitivity of HUVEC cells pretreated with SNP was detected by clone formation assay.Apoptosis rate of HUVEC cells was measured by Hoechst33342/PI staining and flow cytometry.Results The results indicated that the survival rate of HUVEC cells decreased significantly with the increase of irradiation dose (P < 0.01).When pretreated with SNP,the survival rate of HUVEC cells significantly increased,and it was positively correlated with the concentration of SNP.When the end concentration of SNP was as high as 100 μg/ml,the survival rate reached the highest (84.96%),and the survival rate after irradiation increased from 63.43% to 84.96% (P <0.01).The rate of clone formation in the SNP-treated group was also significantly higher as compared with that of the control group(P < 0.01).Compared with the irradiation model group,the apoptosis rate and intracellular reactive oxygen species (ROS) levels in the SNP-treated group decreased significantly,with the apoptosis rate decreasing from 15.6% to 6.8%,and ROS level decreasing from 47.10 × 104 to 41.77 × 104,with statistical signficance (P < 0.05 or P < 0.01).The blue fluorescence of the Hoechst 33342 coloring and red fluorescence of PI coloring also decreased signficantly in the SNP-treated group (P < 0.01).Conclusion The results suggested that SNP pretreatment could increase cell survival rate and cloning rate after irradiation,reduce radiation-induced apoptosis and intracellular ROS levels effectively,indicating that SNP treatment could exert a certain protective effect on HUVEC cell damage induced by ionizing radiation.
3.Protective effect of sipunculusnudus polysaccharide on HUVEC cell damage induced by 137 Cs γ-ray
Chunli GAO ; Qingrong WANG ; Xianrong SHEN ; BAISHUANG ; Xiuting HU ; Ying HE
Chinese journal of nautical medicine and hyperbaric medicine 2019;26(2):91-96
Objective To investigate the protective effect of sipunculusnudus polysaccharide (SNP) on HUVEC cell damage induced by ionizing radiation.Methods The survival rate of HUVEC cells was detected by CCK-8,after irradiation with 137Cs γ-rays and pre-treatment with SNP,and optimal absorption dose rate of 137Cs γ-ray was 8 Gy and optimal concentration of SNP was confirmed to be 100 g/mL.The radiation sensitivity of HUVEC cells pretreated with SNP was detected by clone formation assay.Apoptosis rate of HUVEC cells was measured by Hoechst33342/PI staining and flow cytometry.Results The results indicated that the survival rate of HUVEC cells decreased significantly with the increase of irradiation dose (P < 0.01).When pretreated with SNP,the survival rate of HUVEC cells significantly increased,and it was positively correlated with the concentration of SNP.When the end concentration of SNP was as high as 100 μg/ml,the survival rate reached the highest (84.96%),and the survival rate after irradiation increased from 63.43% to 84.96% (P <0.01).The rate of clone formation in the SNP-treated group was also significantly higher as compared with that of the control group(P < 0.01).Compared with the irradiation model group,the apoptosis rate and intracellular reactive oxygen species (ROS) levels in the SNP-treated group decreased significantly,with the apoptosis rate decreasing from 15.6% to 6.8%,and ROS level decreasing from 47.10 × 104 to 41.77 × 104,with statistical signficance (P < 0.05 or P < 0.01).The blue fluorescence of the Hoechst 33342 coloring and red fluorescence of PI coloring also decreased signficantly in the SNP-treated group (P < 0.01).Conclusion The results suggested that SNP pretreatment could increase cell survival rate and cloning rate after irradiation,reduce radiation-induced apoptosis and intracellular ROS levels effectively,indicating that SNP treatment could exert a certain protective effect on HUVEC cell damage induced by ionizing radiation.
4.Analysis of folic acid combined with vitamins on two primary prevention of stroke effect
Fen ZHANG ; Suzhi LIU ; Yashuang SHEN ; Xiuyun WANG ; Yan SHU ; Xiuting GUO
China Modern Doctor 2015;(3):95-97
Objective To study the analysis of folic acid combined with vitamin for level two ischemic stroke prevention effect. Methods From April 2013 to January 2014 in our hospital , selected the patients with stroke in 100 cases as the research object. In digital method were randomly divided into observation group (50 cases) and control group (50 cases). The patients in the observation group was taken folic acid combined with vitamin , the control group only was given vitamins, in all patients on admission and at discharge on the plasma levels of Hcy, D-two dimer, fibrinogen, three glycerol, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol level, the effect of folic acid combined with the vitamin was observed. Results No significant differences between the two groups before treatment, plasma Hcy levels (P>0.05) in different ways, the observation group after treatment, the plasma Hcy levels were significantly lower than the control group , with significant difference ( P<0 . 05 ) . Two groups by different ways of treatment, the observation group was best accounted for 70% (35/50), the excellent and good rate was as high as 98% (49/50), significantly higher than the control group 44% (22/50) and 74% (37/50), with significant difference (P<0.05). On two groups of different ways of treatment of cerebral was stroke recurrence and score in patients with SIAS were compared, the recurrence rate of the observation group was lower than the control group, with significant difference (P<0.05), the SIAS score was significantly higher than that of the control group, with significant difference (P<0.05). Conclusion For the patients with stroke, should the use of folic acid combine with vitamin two level of prevention. The combine uses of folic acid and vitamin , can effectively reduce the incidence of stroke and recurrence rate.
5.Effect of ultrasonic coupling agent on iodine disinfectant
Bingshu WANG ; Yuwen ZHONG ; Xiaoling ZHENG ; Huizhen CHEN ; Yajing WANG ; Xiuting SHEN ; Chunhua HAN ; Qin ZOU
Chinese Journal of Infection Control 2014;(12):717-719,723
Objective To investigate whether ultrasonic coupling agent (UCA)can produce shielding or antago-nistic effect on iodine disinfectant for preoperative skin disinfection.Methods Shielding or antagonistic effect of UCA on iodine disinfectant were detected by laboratory carrier immersion killing test and on-the-spot skin disinfec-tion test.Results Antagonistic effect:after the mixing of iodophor with UCA,the average killing rate of iodophor containing available iodine 2 500mg/L and 625 mg/L to Staphylococcus aureus decreased from 100.00% to 99.67%-99.78% and 96.85 % - 98.25 %,respectively;the average killing rate to Escherichia coli decreased from 100.00% to 99.71 %-99.82% and 95 .93 %-98.56%,respectively.Shielding effect:after smearing with UCA, the average killing rate of iodophor and iodine tincture + alcohol to Escherichia coli decreased from 100.00% to 30.76% and 100.00% to 94.48%,respectively;the average killing rate to Staphylococcus aureus decreased from 99.99% to 55 .55 % and 100.00% to 98.22%,respectively.On-the-spot skin disinfection test:the killing rate of io-dophor and iodine tincture +alcohol to natural bacteria on skin surface were both 99.99%,after skin was smeared with UCA,the killing rate decreased to 92.62% and 93 .57%,respectively.Conclusion UCA remained on the oper-ative field has shielding and antagonistic effect on iodine disinfectant.
6.Contamination status of dental unit waterlines in three general hospitals
Xiaoling ZHENG ; Yuwen ZHONG ; Huizhen CHEN ; Yajing WANG ; Bingshu WANG ; Chunhua HAN ; Xiuting SHEN ; Qin ZOU
Chinese Journal of Infection Control 2014;(12):720-723
Objective To realize the contamination status of dental unit waterlines (DUWL)in general hospitals, and provide scientific evidence for making preventive measures.Methods Three hospitals were selected for study, water source adopted by hospital A,B and C was running water,reservoir water,and filtered water through reverse osmosis filtration system respectively,specimens of dental handpiece spray water and flushing water of dental chair units were collected quarterly,total bacterial colony in water were detected.Results The qualified rate of source wa-ter,handpiece spray water,and flushing water in hospital A was 75.00%(3/4),0 (0/40)and 0 (0/40)respectively,col-ony count of handpiece spray water and flushing water was (1.20×103 -5.53×104 )CFU/mL(M=3.80×104 CFU/mL) and (2.11×104 -1.66×105 )CFU/mL(M=4.80×104 CFU/mL)respectively.The qualified rate of source water,hand-piece spray water,and flushing water in hospital B was 50.00%(2/4),60.00%(24/40)and 72.50%(29/40)respectively, colony count of handpiece spray water and flushing water was (0.00 -3.71 ×106 )CFU/mL(M=83.00 CFU/mL)and (0.00-2.39×106 )CFU/mL(M=72.00 CFU/mL)respectively.The qualified rate of source water,handpiece spray wa-ter,and flushing water in hospital C was 100.00%(4/4),55.00%(22/40)and 65.00%(26/40)respectively,colony count of handpiece spray water and flushing water was (0.00-6.20×103 )CFU/mL(M=96.00 CFU/mL)and(0.00-1.63×103 )CFU/mL(M=87.50 CFU/mL)respectively.Conclusion Water of DUWL in general hospitals is seriously con-taminated,disinfection and standardized management of source water and DUWL must be strengthened.
7.Application of CT perfusion imaging in evaluating interventional therapy for small hepatocellular carcinoma:preliminary experience in 12 cases
Xiuting CHI ; Jialin SHEN ; Jiejun CHENG ; Ji WANG ; Jianrong XU
Journal of Interventional Radiology 2014;(9):772-776
Objective To investigate the clinical application of CT perfusion imaging in assessing the hemodynamic changes in patients with small hepatocellular carcinoma (<5 cm) before and after transcatheter arterial chemoembolization (TACE). Methods Twelve patients with small hepatocellular carcinoma were enrolled in this study. CT perfusion imaging of the liver was performed 1 - 2 days before and 3 - 4 weeks after TACE. By using the perfusion parameters the hemodynamics of the preoperative and postoperative tumor tissue, the hemodynamics of the preoperative tumor tissue and the normal tissue, and the hemodynamics of the postoperative active tumor tissue and the normal tissue were determined , and the results were compared between each other. Results Before TACE, the blood flow (BF), hepatic arterial fraction (HAF), hepatic arterial perfusion (HAP) and permeability of surface (PS) in the tumor tissue were significantly higher than those in the normal tissue (P < 0.01), while after TACE all the perfusion parameters except blood volume (BV) were significantly decreased in the tumor tissue (P < 0.01). After TACE, BF, PS, HAF and HAP in the activity tumor tissue were increased more than those in the normal tissue (P < 0.05). Conclusion CT perfusion imaging is of great clinical value in diagnosing < 5 cm hepatocellular carcinoma , in evaluating the hemodynamic changes after TACE and in demonstrating the activity of the residual tumor tissue.

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