1.Angiotensin Ⅱ activates p53/SAT1 signaling pathway to induce ferroptosis in white adipocytes
Wei DENG ; Xiyan LIU ; Liyuan GUO ; Qian XU ; Kun ZHOU ; Yuanqin ZHAO ; Zhaoyue WANG ; Xiang LI ; Xin-mei DENG ; Xinyi QIN ; Zhong REN ; Zhisheng JIANG
Chinese Journal of Arteriosclerosis 2025;33(5):385-394
Aim To investigate the effect and mechanism of angiotensin Ⅱ(Ang Ⅱ)on ferroptosis in white adi-pocytes.Methods The 3T3-L1 preadipocytes were differentiated into white adipocytes by inducer stimulation.The experiment was divided into control group,Ang Ⅱ group,Ang Ⅱ+Fer-1(ferroptosis inhibitor)group and Ang Ⅱ+PFT-α(p53 inhibitor)group.Ang Ⅱ was used to treat cells.RT-qPCR and Western blot were used to detect the expression levels of ferroptosis factors and adipokines.JC-1 kit was used to detect mitochondrial membrane potential(MMP)level.Iron ion kit was used to detect intracellular iron content.Glutathione(GSH)kit was used to detect GSH content.Fer-1 and Ang Ⅱ were added to treat cells to detect the the changes of ferroptosis level.The expression of p53 and spermidine/spermine N1-acetyltransferase 1(SAT1)protein was detected.Subsequently,PFT-α and Ang Ⅱ were added to co-treat cells to detect the changes of p53 and SAT1 protein expression,and to observe the effect of inhibiting p53 expression on the expression levels of ferroptosis factors and adipokines.Results 3T3-L1 cells were successfully differentiated into white adipocytes by stimulator-induced differentiation.Ang Ⅱ induced ferroptosis in white adipocytes.RT-qPCR results showed that compared with control group,the mRNA expression of anti-ferroptosis factor glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11)and iron regulatory protein 1(IRP-1)was down-regulated in Ang Ⅱ group,and the mRNA expression of pro-ferroptosis factor acyl-CoA synthetase of long-chain family member 4(ACSL4)was up-regulated.Western blot results showed that compared with control group,the protein expression of SLC7A11 and GPX4 was down-regulated in Ang Ⅱ group,and the protein expression of ACSL4 was up-regulated.Ang Ⅱ treatment increased the content of intracellular iron ions and decreased the levels of GSH and MMP.Compared with Ang Ⅱ group,the mRNA expression of IRP-1 and SLC7A11 was up-regulated in Ang Ⅱ+Fer-1 group.Ang Ⅱ induced changes in the expression profile of adipokines in white adipocytes.Western blot results showed that compared with control group,the protein ex-pression of pro-inflammatory adipokine leptin(LEP),resistin(RETN),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)was up-regulated in Ang Ⅱ group,and the protein expression of anti-inflammatory adipokine adiponectin(AD-PN)and omentin 1(ITLN1)was down-regulated.In addition,Ang Ⅱ increased the protein expression of p53 and SAT1.Inhibition of p53 expression can improve the level of ferroptosis and adipokine expression in white adipocytes trea-ted with Ang Ⅱ.Western blot results showed that compared with Ang Ⅱ group,the protein expression of p53 and SAT1 was down-regulated in Ang Ⅱ+PFT-α group,the protein expression of SLC7A11 and GPX4 was up-regulated,and the protein expression of ACSL4 was down-regulated.The protein expression of ADPN was up-regulated in Ang Ⅱ+PFT-αgroup,and the protein expression of TNF-α,LEP and RETN was down-regulated.Conclusion Ang Ⅱ induces fer-roptosis in white adipocytes through activating the p53/SAT1 signaling pathway.
2.Angiotensin Ⅱ activates p53/SAT1 signaling pathway to induce ferroptosis in white adipocytes
Wei DENG ; Xiyan LIU ; Liyuan GUO ; Qian XU ; Kun ZHOU ; Yuanqin ZHAO ; Zhaoyue WANG ; Xiang LI ; Xin-mei DENG ; Xinyi QIN ; Zhong REN ; Zhisheng JIANG
Chinese Journal of Arteriosclerosis 2025;33(5):385-394
Aim To investigate the effect and mechanism of angiotensin Ⅱ(Ang Ⅱ)on ferroptosis in white adi-pocytes.Methods The 3T3-L1 preadipocytes were differentiated into white adipocytes by inducer stimulation.The experiment was divided into control group,Ang Ⅱ group,Ang Ⅱ+Fer-1(ferroptosis inhibitor)group and Ang Ⅱ+PFT-α(p53 inhibitor)group.Ang Ⅱ was used to treat cells.RT-qPCR and Western blot were used to detect the expression levels of ferroptosis factors and adipokines.JC-1 kit was used to detect mitochondrial membrane potential(MMP)level.Iron ion kit was used to detect intracellular iron content.Glutathione(GSH)kit was used to detect GSH content.Fer-1 and Ang Ⅱ were added to treat cells to detect the the changes of ferroptosis level.The expression of p53 and spermidine/spermine N1-acetyltransferase 1(SAT1)protein was detected.Subsequently,PFT-α and Ang Ⅱ were added to co-treat cells to detect the changes of p53 and SAT1 protein expression,and to observe the effect of inhibiting p53 expression on the expression levels of ferroptosis factors and adipokines.Results 3T3-L1 cells were successfully differentiated into white adipocytes by stimulator-induced differentiation.Ang Ⅱ induced ferroptosis in white adipocytes.RT-qPCR results showed that compared with control group,the mRNA expression of anti-ferroptosis factor glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11)and iron regulatory protein 1(IRP-1)was down-regulated in Ang Ⅱ group,and the mRNA expression of pro-ferroptosis factor acyl-CoA synthetase of long-chain family member 4(ACSL4)was up-regulated.Western blot results showed that compared with control group,the protein expression of SLC7A11 and GPX4 was down-regulated in Ang Ⅱ group,and the protein expression of ACSL4 was up-regulated.Ang Ⅱ treatment increased the content of intracellular iron ions and decreased the levels of GSH and MMP.Compared with Ang Ⅱ group,the mRNA expression of IRP-1 and SLC7A11 was up-regulated in Ang Ⅱ+Fer-1 group.Ang Ⅱ induced changes in the expression profile of adipokines in white adipocytes.Western blot results showed that compared with control group,the protein ex-pression of pro-inflammatory adipokine leptin(LEP),resistin(RETN),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)was up-regulated in Ang Ⅱ group,and the protein expression of anti-inflammatory adipokine adiponectin(AD-PN)and omentin 1(ITLN1)was down-regulated.In addition,Ang Ⅱ increased the protein expression of p53 and SAT1.Inhibition of p53 expression can improve the level of ferroptosis and adipokine expression in white adipocytes trea-ted with Ang Ⅱ.Western blot results showed that compared with Ang Ⅱ group,the protein expression of p53 and SAT1 was down-regulated in Ang Ⅱ+PFT-α group,the protein expression of SLC7A11 and GPX4 was up-regulated,and the protein expression of ACSL4 was down-regulated.The protein expression of ADPN was up-regulated in Ang Ⅱ+PFT-αgroup,and the protein expression of TNF-α,LEP and RETN was down-regulated.Conclusion Ang Ⅱ induces fer-roptosis in white adipocytes through activating the p53/SAT1 signaling pathway.
3.Two cases of delayed puberty caused by intracranial germ cell tumors and literature review
Lingbo XU ; Xiaotong SUN ; Xiyan HE ; Ruiyang PU ; Jingran ZHEN
Chinese Journal of Reproduction and Contraception 2024;44(7):739-741
Intracranial germ cell tumors (iGCT) is a common cause of delayed puberty (DP). A retrospective analysis was conducted on the clinical data of two patients with DP caused by iGCT. The disease characteristics of the two patients included DP, primary amenorrhea, growth retardation, short stature, subclinical hypothyroidism, etc. They were diagnosed as DP through imaging and related biochemical tests, and some sex hormone drugs were given on the basis of active treatment of the primary disease. Two patients had varying degrees of development in height, weight and secondary sexual characteristics, and further treatment condition is being tracking by us. Early identification and appropriate clinical intervention are of great significance to the reproductive endocrine function, bone health and long-term health such as terminal height of DP patients.
4.Two cases of delayed puberty caused by intracranial germ cell tumors and literature review
Lingbo XU ; Xiaotong SUN ; Xiyan HE ; Ruiyang PU ; Jingran ZHEN
Chinese Journal of Reproduction and Contraception 2024;44(7):739-741
Intracranial germ cell tumors (iGCT) is a common cause of delayed puberty (DP). A retrospective analysis was conducted on the clinical data of two patients with DP caused by iGCT. The disease characteristics of the two patients included DP, primary amenorrhea, growth retardation, short stature, subclinical hypothyroidism, etc. They were diagnosed as DP through imaging and related biochemical tests, and some sex hormone drugs were given on the basis of active treatment of the primary disease. Two patients had varying degrees of development in height, weight and secondary sexual characteristics, and further treatment condition is being tracking by us. Early identification and appropriate clinical intervention are of great significance to the reproductive endocrine function, bone health and long-term health such as terminal height of DP patients.
5.Effectiveness of online and offline health education myopia intervention on primary school students
Chinese Journal of School Health 2023;44(11):1720-1723
Objective:
To assess the effectiveness of online and offline myopia prevention and control health education interventions using wearable behavior monitoring tools for non myopic elementary school students,so as to provide evidence based medical support for public health practices.
Methods:
From May to June in 2021, two schools were selected within the same county in Jiangsu Province. School 1 conducted online and offline parental health education ( n =111), while school 2 exclusively conducted offline health education activities, representing the traditional intervention group ( n =122). Students from both schools underwent monitoring through wearable behavior tracking tools, with feedback reports provided (eye distance, eye duration, ambient light, and outdoor exposure time). Both schools relied on activities to carry out health education interventions, and organized the distribution of promotional materials and display boards. The intervention group also established WeChat groups to conduct online "Healthy Parents Action" (answering and providing feedback on health knowledge related to myopia prevention and control, myopia prevention and control, science popularization, etc. raised by parents). Evaluation criteria included myopia rates, post dilation refractive error, and axial length, with a tracking period of two years (from 2021 to 2023). Additionally, the study collected refractive parameters from non myopic students who did not participate in wearable tool monitoring in the 12 classes across the two schools.
Results:
The baseline results indicated that there were no significant differences between the two groups in terms of refractive parameters and wearable tool monitoring results (including screen time, viewing distance, outdoor exposure time, and homework light exposure)( t/Z/χ 2=1.94,1.17,0.58,0.40,0.80,0.69,0.32, P >0.05). After a two-year follow up, in the first and second year, the myopia rate of the online Healthy Parents Action group (11.4%, 29.7%) were lower than that of the traditional group (26.2%, 50.9%), and the degree of refractive change in the intervention group [0.63(0.38,1.19)D] was lower than that of the traditional group [0.91(0.40,1.50)D], and all the differences were statistically significant( χ 2/ Z =4.93,10.37,2.29, P <0.05). However, there were no significant differences ( P >0.05) in axial length changes between the two groups over the twoyear intervention period. Nevertheless, in the second year, the axial length change in the traditional group [0.35(0.20,0.65)mm] was lower than that in the natural observation group [0.55(0.30,0.75)mm], and this difference was statistically significant ( Z =1.92, P <0.05).
Conclusions
Online and offline myopia prevention and control health education can effectively reduce myopia rates. The intervention mode combining wearable behavior monitoring tools with online health education may have better effects, but further large sample and multi center studies are needed to provide additional evidence and confirmation.
6.Application Value of Conventional Ultrasound Classification and Contrast-Enhanced Ultrasound in Non-Mass Breast-Like Lesions
Yuerui CHI ; Li LIU ; Xiyan LIU ; Jing LIU ; Xun LIU ; Wengui XU
Cancer Research on Prevention and Treatment 2022;49(10):1048-1053
Objective To investigate the application value of conventional ultrasound typing and contrast-enhanced ultrasound (CEUS) in non-mass breast like lesions (NMLs). Methods A total of 50 patients (50 lesions) who were pathologically confirmed to have breast NMLs in Tianjin Fifth Central Hospital. The corresponding relationship between conventional ultrasound typing of NMLs and BI-RADS classification was analyzed, and CEUS was performed on breast NMLs to compare the diagnostic value of combined BI-RADS and CEUS. Results The NMLs conventional ultrasound classified Ⅰa and Ⅱa lesions corresponded to BI-RADS classification 4a; Ⅲ and Ⅳ lesions corresponded to BI-RADS classification 4b; Ⅰb and Ⅱb lesions corresponded to BI-RADS classification 4c. A statistically significant correlation was observed between the expansion of lesion range and the presence of "crab foot sign" in benign and malignant lesions after the enhancement (
7.Two year follow up of myopia cohort in central Jiangsu Province
Chinese Journal of School Health 2022;43(9):1298-1300
Objective:
Based on observational, longitudinal and intervention study of common diseases among students in Jiangsu Province, this paper presents the current progress of two year follow up of myopia cohort regarding the association between growth parameters with progression of myopia among children and adolescents in areas with rapid economic growth.
Methods:
This survey adopted the stratified cluster sampling method for school selection. The full automatic computer optometry (TOPCON RM800) was used to track myopia related parameters for all participants from 2019 to 2020 under the condition of mydriasis (compound topicamide eye drops). Relationship between growth parameters of children and adolescents and the incidence and progression of myopia was analyzed by using Cox regression multiple statistical model.
Results:
The myopia rates of students from grade 1 to grade 3 in 2019 were 5.4%, 21.5% and 37.3% respectively. After one year, the myopia rates of all school stages increased to 25.3%, 43.3% and 58.1% respectively( χ 2=53.59, 49.63, 32.52, P <0.01). The mean diopter of right eye and left eye after mydriasis were ( 0.30± 1.24/0.39±1.26)D in 2019 and (-0.33±1.54/-0.19±1.55)D in 2020, respectively based on Cox multiple regression results, age ( HR =1.21, 95% CI =1.09-1.34), naked eye vision ( HR =0.08, 95% CI =0.07-0.11), height ( HR =0.98, 95% CI =0.97-0.99) showed a strong correlation with the incidence and progression of myopia( P <0.05).
Conclusion
Myopia is growing rapidly in the central region of Jiangsu Province. It is suggested that diopter, axial length, naked eye vision, age, height and other indicators should be included in the refractive archives of children and adolescents in the region.
8.Characteristics of HA, NA genes and antigenicity of two strains of Eurasian avian H1N1 swine influenza virus from two human cases in Gansu province
Hongyu LI ; Ping WANG ; Baodi LI ; Zi LI ; Xiyan LI ; Lei YANG ; Jia LIU ; Minju TAN ; Zixuan LIANG ; Congshan XU ; Minghui MA ; Hua WANG ; Miao WANG ; Deshan YU ; Dayan WANG
Chinese Journal of Experimental and Clinical Virology 2022;36(2):166-171
Objective:To analyze the antigenicity and genetic characteristics of two strains of Eurasian avian H1N1 swine influenza virus (EAS-H1N1) isolated from 2 human cases found in Gansu province to provide scientific reference for disease prevention and control.Methods:Two cases of human infection with EAS-H1N1 discovered in Gansu province since February 2021 were analyzed for antigenicity and genome comparison, and their genome characteristics were analyzed using software such as Mega7.0.Results:Two human infections with EAS-H1N1 had related environmental exposure history. Two strains were obtained: A/Gansu-Xifeng/1143/2021 and A/Gansu-Xifeng/1194/2021. The two strains of HA, NA genes were all from the Eurasian avian H1N1 swine influenza virus, and are closely related to the human infection EAS-H1N1 virus in Hebei and Tianjin and the EAS-H1N1 virus isolated from the mink in Shandong; the HA receptor binding sites of 2 strains E190D and D225E mutations occurred in all spots, and there were no H274Y and N294S mutations in NA protein.Conclusions:Some important molecular mutations occurred in the genome of people infected with EAS-H1N1 virus in Gansu province, which may lead to increased virulence and potential human-to-human transmission. Strengthening the research and analysis of EAS-H1N1 gene characteristics will help to monitor the mutation and mutation of the virus at the molecular level and scientifically prevent and control the epidemic.
9.Risk factors of thyroid nodule in diabetic patients and the correlation with Traditional Chinese Medicine constitution
Huan HE ; Yanwen PENG ; Ying LIU ; Jing XUE ; Xiyan ZHAO ; Xinyao XU ; Mingdi LI
International Journal of Traditional Chinese Medicine 2021;43(4):329-334
Objective:To explore the risk factors of thyroid nodules in diabetic patients and its correlation with Traditional Chinese Medicine (TCM) constitution.Methods:A Total of 213 cases of diabetic patients in Guang’anmen Hospital and Tangshan Hospital from January 2019 to August 2020 were choosen to do the questionnaire, with containly symptom and constitution. The patients were divided into diabetes with thyroid nodules group and diabetes without thyroid nodules group according to whether thyroid nodules were combined. We compared the clinical data characteristics of 2 groups, and used multi-factor logistic regression model to analyze the risk factors of diabetic patients with thyroid nodules and their correlation with TCM constitutions. Results:Diabetes patients aged from 50-80 years old [ OR=2.949, 95% CI (1.266-6.714)], females [ OR=3.736, 95% CI (1.823-1.541)], diabetes duration≥15 years [ OR=1.558, 95% CI (1.623-1.585)], elevated HbA1c [ OR=5.862, 95% CI (1.418-23.629)], elevated VLDL [ OR=2.851, 95% CI (1.597-6.824)], frequent insomnia [ OR=1.970, 95% CI (1.315-3.395)], Qi stagnation [ OR=4.357, 95% CI (2.634-8.377)], blood stasis [ OR=4.420, 95% CI (1.874-15.258)] are more likely to suffer from thyroid nodules ( P<0.05). Conclusion:Diabetic patients aged from 50-80 years old, females, diabetes duration≥15 years, elevated HbA1c, family history of thyroid nodules, frequent insomnia, and mood swings are more likely to develop thyroid nodules; qi stagnation and blood stasis are dangerous constitutions for diabetic patients with thyroid nodules.
10.Biomechanical Response of Macrophages/Microglia Cells to Blast Shock Injury in Mice
Nu ZHANG ; Dasen XU ; Xiyan ZHU ; Yidan ZHOU ; Sijie WANG ; Mingliang JIN ; Liangliang DAI ; Sufang WANG ; Hui ZHAO ; Yulong LI ; Hui YANG
Journal of Medical Biomechanics 2021;36(4):E596-E603
Objective To establish a blast injury experimental model using a shock tube at lateral lying position of C57BL/6 mice, investigate biomechanical responses of macrophages/microglia cells in the heart, lung and brain tissues to mechanical damage by shock wave within 24 hours. Methods Shock tube was employed to generate a shock wave to C57BL/6 mice. Firstly, the weight changes of mice were measured at different time points after the shock. Then the cardiac, pulmonary and whole brain tissue samples were dissected after anesthesia. Pathological sections were stained with HE staining to detect structural damage; the TUNEL staining method was used to mark and count the proportion of dead cells in each tissue. Microglial cells were labeled with fluorescent antibody, while responses and changes of macrophages/microglia after shock loading were analyzed. Results The shock tube exerted 179 kPa overpressure shock wave upon sideway of the mouse, and lethal rate of the mouse was 3.33%. Compared with normal control group, the mice in experimental group had a significant weight loss within 24 hours after loading shock. Pathological sections showed rupture of lung tissues after shock, accompanied by alveolar protein deposition, pulmonary bulla and other diseases. Fluorescence staining showed that lung tissue was recruited and activated in a large amount within 24 hours. The proportion of dead cells cleared rebounded to normal level within 24 hours. The heart was highly tolerant to shock, and macrophages appeared near the large blood vessels. The brain showed unilateral aggregation of microglia due to the impact posture, mainly due to prolonged inflammation and a higher proportion of dead cells at the junction of gray and white matter. Conclusions A blast shock model at lateral lying position of the mouse was established. Within 24 hours, macrophages/microglia were recruited quickly to the injury site after being impacted, which mediated strong immune stress, and might participate in the immune response to trigger a second long-term inflammatory injury. The results of the study provide experimental basis for the evaluation of primary impact injury, such as dose-effect relationship and tissue damage difference.


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