1.USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination
Sha HU ; Zhouxiang WANG ; Kun ZHU ; Hongjie SHI ; Fang QIN ; Tuo ZHANG ; Song TIAN ; Yanxiao JI ; Jianqing ZHANG ; Juanjuan QIN ; Zhigang SHE ; Xiaojing ZHANG ; Peng ZHANG ; Hongliang LI
Clinical and Molecular Hepatology 2025;31(1):147-165
Background/Aims:
Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression.
Methods:
USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes.
Results:
USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5.
Conclusions
USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.
2.USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination
Sha HU ; Zhouxiang WANG ; Kun ZHU ; Hongjie SHI ; Fang QIN ; Tuo ZHANG ; Song TIAN ; Yanxiao JI ; Jianqing ZHANG ; Juanjuan QIN ; Zhigang SHE ; Xiaojing ZHANG ; Peng ZHANG ; Hongliang LI
Clinical and Molecular Hepatology 2025;31(1):147-165
Background/Aims:
Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression.
Methods:
USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes.
Results:
USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5.
Conclusions
USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.
3.USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination
Sha HU ; Zhouxiang WANG ; Kun ZHU ; Hongjie SHI ; Fang QIN ; Tuo ZHANG ; Song TIAN ; Yanxiao JI ; Jianqing ZHANG ; Juanjuan QIN ; Zhigang SHE ; Xiaojing ZHANG ; Peng ZHANG ; Hongliang LI
Clinical and Molecular Hepatology 2025;31(1):147-165
Background/Aims:
Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression.
Methods:
USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes.
Results:
USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5.
Conclusions
USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.
4.Application of gelatin sponge-hemocoagulase plugging agent in patients with pulmonary puncture bleeding
Hao LIANG ; Jie ZHANG ; Longxiang LAI ; Yanxiao YUE ; Qian WANG ; Xian LIU ; Jingqin CAO
Journal of Interventional Radiology 2024;33(2):146-149
Objective To discuss the application of gelatin sponge-hemocoagulase plugging agent in patients with pulmonary puncture bleeding.Methods The clinical data of 43 patients with hemorrhage caused by DSA-guided lung puncture biopsy,who received gelatin sponge-hemocoagulase plugging agent treatment at the Jining Municipal First People's Hospital of China between September 2021 and May 2023,were collected,and the hemostatic effect of gelatin sponge-hemocoagulase plugging agent was analyzed.Results Successful lung puncture needle biopsy was achieved in all the 43 patients.The puncture needle channel occlusion was accomplished by using gelatin sponge-hemocoagulase plugging agent.Five minutes after occlusion treatment,in one patient,whose moderate hemoptysis with moderate bleeding shadow before puncture needle biopsy changed to bloody sputum,the intrapulmonary bleeding shadow displayed on image became slightly enlarged when compared the size five minutes ago,while in all the remaining patients successful hemostasis was achieved,the hemoptysis disappeared and the pulmonary hemorrhage shadow was similar to that five minutes ago.No occlusion-related complications occurred in all patients.Conclusion For the treatment of pulmonary hemorrhage caused by DSA-guided lung puncture biopsy,gelatin sponge-hemocoagulase plugging agent is clinically safe and effective.
5.Application of chain pain management model in perioperative nursing of children with traumatic fractures
Yanxiao HUA ; Lingling HU ; Keming SUN ; Lingling WANG ; Zhen LEI ; Danshao CHANG ; Lin LIU ; Jianli WANG ; Zheng WEI ; Zhiwei LI
Chinese Journal of Modern Nursing 2022;28(20):2746-2750
Objective:To explore the application effect of chain pain management model in perioperative nursing of children with traumatic fractures.Methods:Using the convenient sampling method, a total of 174 children with traumatic fractures and 174 caregivers who were treated in Henan Children's Hospital from May 2020 to May 2021 and underwent surgical treatment were selected as the research subjects. Among them, 85 children and 85 caregivers from May to November 2020 were used as the control group, and they were given the conventional pain management model for intervention. A total of 89 children and 89 caregivers from December 2020 to May 2021 were selected as the experimental group, and they were given chain pain management model for intervention. The perioperative pain, psychological stress status and nursing satisfaction of caregivers were compared between the two groups.Results:At 24 hours after admission and 24 hours after operation, score of FLACC Pain Assessment Scale of the experimental group was lower than that of the control group, and the difference was statistically significant ( P<0.05) . At discharge, the Short-term Response Scale of Stress Disorder in the experimental group was lower than that in the control group, and the satisfaction score of caregivers in the experimental group was higher than that in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The application of chain pain management model in perioperative nursing of children with traumatic fractures can reduce perioperative pain, improve the psychological stress state of children and improve satisfaction of caregivers with nursing work, which has certain clinical application value.
6.Protective effects of hypoxia inducible factor-1α on myocardial ischemia postconditioning in rats
Yanxiao LIANG ; Jianfen LI ; Wensheng WANG ; Dongyu LI
Chinese Pediatric Emergency Medicine 2021;28(6):499-504
Objective:To investigate the protective role and mechanism of hypoxia inducible factor(HIF)-1α in myocardial ischemia postconditioning.Methods:Forty healthy adult SD rats were randomly divided into four groups with 10 rats in each group.The control group(group A)was sham operation group, and the rats underwent the same surgical procedures except that the suture passed under the left anterior descending branch(LAD)of the coronary artery was not tightened for 225 minutes.In the ischemia-reperfusion group(group B), the LAD was blocked for 45 minutes, and then reperfusion for 3 hours.In the ischemic postconditioning group(group C), 45 minutes after blocking the LAD, reperfusion was performed for 10 seconds-ischemia for 10 seconds at the beginning of reperfusion, a total of 3 cycles of intervention, and reperfusion for 3 hours.Ischemic postconditioning + HIF-1α inhibitor group(group D): 45 minutes after blocking the LAD, HIF-1α inhibitor AG490 (3 μg/g) was injected intraperitoneally, and reperfusion was performed for 10 seconds-ischemia 10 seconds at the moment of reperfusion.A total of 3 cycles of intervention, reperfusion for 3 hours.Blood samples were harvested from femoral vein at three time points(before ligation of the LAD, 45 minutes after ischemia, 3 hours after reperfusion)to analyze the serum levels of creatine kinase and cardiac troponin respectively.After 3 hours of reperfusion, myocardial tissue was used to measure the infarction size through 2, 3, 5-triphenyltetrazolium chloride staining method; and Western blot method was used to detect the expression of HIF-1α in each group.Results:(1) There were no significant differences in the serum levels of creatine kinase and cardiac troponin among four groups before ligation( P>0.05); 45 minutes after ischemia, there were significant differences between group B, group C, and group D compared with group A ( P<0.01). After 3 hours of reperfusion, there were significant differences between group B, group C, and group D compared with group A (all P<0.01), and group B, group D were significantly higher than that in group C ( P<0.05). (2)Compared with group A[(2.46±1.13)%], the area of myocardial infarction in group B was (45.81±5.96)%, in group C was (37.17±4.99)%, and group D was (45.00±3.29) %, and the differences were statistically significant ( P<0.01). (3)The HIF-1α protein in myocardial tissue in group A was slightly expressed; the expression of HIF-1α protein in group B was higher than that in group A( P<0.05); and group C was significantly higher than that in group B ( P<0.05); HIF-1α protein was almost not expressed in group D. Conclusion:After ischemic postconditioning, HIF-1α increased in myocardium; the increased expression of HIF-1α may be involved in the protective process of myocardial ischemic postconditioning in rats.
7.Clinical characteristics of nine asymptomatic patients with 2019-nCoV infection
Erhei DAI ; Lei ZHAO ; Jian XUE ; Yanxiao RONG ; Huixia GAO ; Huanwei ZHENG ; Yanan LI ; Yuling WANG ; Zungui XU
Chinese Journal of Experimental and Clinical Virology 2021;35(1):7-10
Objective:To investigate the clinical data of asymptomatic patients with 2019 novel Coronavirus (2019-nCoV) infection in Shijiazhuang and provide scientific evidence for prevention and treatment of Coronavirus Disease 2019(COVID-19).Methods:Retrospective study was conducted to analyze the clinical features and laboratory data of 9 asymptomatic 2019-nCoV infected patients, admitted to the Fifth Hospital of Shijiazhuang from January 21, 2020 to February 21, 2020.Results:Asymptomatic infection was found in all age groups, including 5 males and 4 females. On the first day of admission, the detection result of leukocytes, lymphocytes and neutrophils in asymptomatic patients were at normal levels. On the third day after admission, the results increased and continued to stabilize on the twelfth day. The levels of alanine aminotransferase and lactate dehydrogenase were at normal levels during hospitalization, without transient increase or decrease. The level of C-reactive protein reached the highest level on the third day after admission, but it was always in the normal range. D-dimer level was relatively stable during hospitalization. The absolute value of T cell subsets showed that the levels of CD 3+ , CD 4+ , CD 8+ T cells in asymptomatic infection patients were higher than those determined before admission. The average duration of pharyngeal nucleic acid positive detection in asymptomatic patients was 11.88 days. The average cycle threshold of ORF1ab gene and N gene was 36.94 and 35.43 respectively. Conclusions:The inflammatory reaction in patients with asymptomatic 2019-nCoV infection was mild, and the immune function was relatively good.
8.Employment, turnover intention and the associated factors among public health graduates in China
Yuewei ZHAN ; Anping FENG ; Bowen LIANG ; Yanxiao GAO ; Yong LU ; Zhenyu WANG ; Yuelong SHU ; Huachun ZOU
Chinese Journal of Preventive Medicine 2021;55(7):910-915
Objective:To understand the employment situation of graduates of public health-related majors and explore the associated factors of turnover intention among public health practitioners in China.Methods:In April 2020, the convenient sampling method was used to recruit public health related graduates from 98 universities with public health-related majors from 31 provinces in China (excluding Hong Kong, Macao and Taiwan) and from Chinese Center for Disease Control and Prevention (only including working or unemployed status, no requirement for graduation years). A total of 1 322 questionnaires were collected, of which 1 165 (88.1%) were valid. Through the network questionnaire survey, the information of public health graduates′ work situation, job satisfaction and turnover intention were collected. Multivariate logistic regression model was used to analyze the associated factors of turnover intention, and structural equation model was constructed to explore the correlation between turnover intention and job satisfaction.Results:The age of 1 165 graduates was (28.1 ±4.8) years. Among them, 719 (61.7%) were female and 856 (73.5%) graduates were engaged in public health-related work after graduation. The results of multivariate logistic regression analysis showed that compared with those over 30 years old, graduates under 30 years old had higher turnover intention ( OR=2.531, 95% CI: 1.549-4.155). Compared with those with junior or no title, graduates with senior title had higher turnover intention ( OR=2.310, 95% CI: 1.047-5.162). The results of structural equation model analysis showed that the four factors of job satisfaction, ‘salary and welfare’, ‘promotion development’, ‘work itself’, and ‘internal and external environment’, were negatively correlated with turnover intention. The internal and external environment had the greatest impact on turnover intention (total effect =-0.539). Conclusion:Most graduates of public health-related majors are engaged in public health-related work in China. Age, professional title and job satisfaction are the associated factors of turnover intention.
9.Employment, turnover intention and the associated factors among public health graduates in China
Yuewei ZHAN ; Anping FENG ; Bowen LIANG ; Yanxiao GAO ; Yong LU ; Zhenyu WANG ; Yuelong SHU ; Huachun ZOU
Chinese Journal of Preventive Medicine 2021;55(7):910-915
Objective:To understand the employment situation of graduates of public health-related majors and explore the associated factors of turnover intention among public health practitioners in China.Methods:In April 2020, the convenient sampling method was used to recruit public health related graduates from 98 universities with public health-related majors from 31 provinces in China (excluding Hong Kong, Macao and Taiwan) and from Chinese Center for Disease Control and Prevention (only including working or unemployed status, no requirement for graduation years). A total of 1 322 questionnaires were collected, of which 1 165 (88.1%) were valid. Through the network questionnaire survey, the information of public health graduates′ work situation, job satisfaction and turnover intention were collected. Multivariate logistic regression model was used to analyze the associated factors of turnover intention, and structural equation model was constructed to explore the correlation between turnover intention and job satisfaction.Results:The age of 1 165 graduates was (28.1 ±4.8) years. Among them, 719 (61.7%) were female and 856 (73.5%) graduates were engaged in public health-related work after graduation. The results of multivariate logistic regression analysis showed that compared with those over 30 years old, graduates under 30 years old had higher turnover intention ( OR=2.531, 95% CI: 1.549-4.155). Compared with those with junior or no title, graduates with senior title had higher turnover intention ( OR=2.310, 95% CI: 1.047-5.162). The results of structural equation model analysis showed that the four factors of job satisfaction, ‘salary and welfare’, ‘promotion development’, ‘work itself’, and ‘internal and external environment’, were negatively correlated with turnover intention. The internal and external environment had the greatest impact on turnover intention (total effect =-0.539). Conclusion:Most graduates of public health-related majors are engaged in public health-related work in China. Age, professional title and job satisfaction are the associated factors of turnover intention.
10.Erythropoietin pretreatment for myocardial protection in perioperative period of infant congenital heart disease operation
Yanxiao LIANG ; Wensheng WANG ; Dongyu LI
Chinese Pediatric Emergency Medicine 2018;25(1):37-42
Objective To study the effect of erythropoietin( EPO) pretreatment on myocardial pro-tection in perioperative period of infant congenital heart disease operation and explore its underlying mecha-nism. Methods All the 80 patients who were suffered from non-cyanotic congenital heart disease undergone cardiopulmonary bypass in open heart operation were selected from Shengjing Hospital of China Medical Uni-versity cardiac surgery ward from April 2014 to January 2017. The patients were randomly divided into A,B, C three groups according to blocked randomization method. Group A patients were treated with subcutaneous injection of EPO 150 IU/kg 12 hours before operation,group B patients were treated with subcutaneous injec-tion of EPO 300 IU/kg 12 hours before operation,patients in group C( control group) had no treatment. All patients were detected myocardial zymetology after admission to hospital as well as 24 h,48 h,72 h after oper-ation. HSP70,ERK1/2 mRNA and protein expression in right auricle were detected by qRT-PCR and Western blot method,respectively. Results At each time point after operation,myocardial zymetology were signifi-cantly lower in group A and B compared with group C,the index of myocardial zymetology in group A were lower than that in group B(P<0. 05). The expressions of HSP70,ERK1/2 mRNA and protein were signifi-cantly up-regulated in group A and B compared to the control group(P<0. 05). The expressions of HSP70, ERK1/2 mRNA and protein in group A were significantly higher than those in group B ( P < 0. 05 ) . Conclusion EPO pretreatment has a positive effect on the myocardial protection during cardiopulmonary bypass. EPO may act a role of endogenous myocardial protection through up-regulation of the expressions of HSP70 and ERK1/2. The dosage of 150 IU/kg EPO is more significant on the effect of myocardial protection.

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