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.Effect of tumor-stromal fibroblasts on the biological behavior of salivary gland pleomorphic adenoma cells in vitro.
Yali HOU ; Hexiang LI ; Peng SONG ; Yanxiao YANG ; Yali HAO ; Huijuan LIU
West China Journal of Stomatology 2023;41(2):149-156
OBJECTIVES:
This study aims to investigate the effects of tumor-stromal fibroblasts (TSFs) on the proliferation, invasion, and migration of salivary gland pleomorphic adenoma (SPA) cells in vitro.
METHODS:
Salivary gland pleomorphic adenoma cells (SPACs), TSFs, and peri-tumorous normal fibroblasts (NFs) were obtained by tissue primary culture and identified by immunocytochemical staining. The conditioned medium was obtained from TSF and NF in logarithmic phase. SPACs were cultured by conditioned medium and treated by TSF (group TSF-SPAC) and NF (group NF-SPAC). SPACs were used as the control group. The proliferation, invasion, and migration of the three groups of cells were detected by MTT, transwell, and scratch assays, respectively. The expression of vascular endothelial growth factor (VEGF) in the three groups was tested by enzyme linked immunosorbent assay (ELISA).
RESULTS:
Immunocytochemical staining showed positive vimentin expression in NF and TSF. Results also indicated the weak positive expression of α-smooth muscle actin (SMA) and fibroblast activation protein (FAP) in TSFs and the negative expression of α-SMA and FAP in NFs. MTT assay showed that cell proliferation in the TSF-SPAC group was significantly different from that in the NF-SPAC and SPAC groups (P<0.05). Cell proliferation was not different between the NF-SPAC and SPAC groups (P>0.05). Transwell and scratch assays showed no difference in cell invasion and migration among the groups (P>0.05). ELISA showed that no significant difference in VEGF expression among the three groups (P>0.05).
CONCLUSIONS
TSFs may be involved in SPA biological behavior by promoting the proliferation of SPACs but has no effect on the invasion and migration of SPACs in vitro. Hence, TSF may be a new therapeutic target in SPA treatment.
Humans
;
Adenoma, Pleomorphic/metabolism*
;
Vascular Endothelial Growth Factor A
;
Culture Media, Conditioned/metabolism*
;
Fibroblasts/metabolism*
;
Salivary Glands/metabolism*
5.Identification and expression pattern analysis of RcACA gene family in castor under abiotic stresses.
Yanxiao LI ; Chunlan ZHANG ; Liuting GENG ; Yanqiu CHEN ; Li ZHANG ; Dianjun XIANG ; Peng LIU
Chinese Journal of Biotechnology 2023;39(7):2861-2873
Auto-inhibited Ca2+-ATPase (ACA) is one of the Ca2+-ATPase subfamilies that plays an important role in maintaining Ca2+ concentration balance in plant cells. To explore the function and gene expression pattern of the RcACA gene family in castor, bioinformatics analysis was used to identify the members of the RcACA gene family in castor. The basic physical and chemical properties, subcellular location, protein secondary and tertiary structure, conserved domain, conserved motif, gene structure, chromosome location and collinear relationship, as well as the evolutionary characteristics and promoter cis-acting elements were predicted and analyzed. The expression pattern of the RcACA gene under abiotic stress was analyzed by expression (fragments per kilobase of exon model per million mapped fragments, FPKM) in castor transcriptome data. The results showed that 8 RcACA gene family members were identified in castor, acidic proteins located in the plasma membrane. In the secondary structure of all proteins, the α-helix and random coil is more; the RcACA genes were clustered into three categories, and the design of the genes in the same category was similar to the conserved motif. Both of them had four typical domains, RcACA3-RcACA8 had a Ca2+-ATPase N-terminal autoinhibitory domain. The RcACA gene is mostly located on the long arm of the chromosome and has 2 pairs of collinear relationships. There are more light response elements but fewer hormone-induced elements located upstream of the RcACA coding region. Interspecific clustering showed that the evolution of ACA genes among species was conservative. Tissue expression pattern analysis showed that RcACA genes showed apparent tissue expression specificity, and most of the genes showed the highest expression level in male flowers. Expression analysis under abiotic stress showed that RcACA2-RcACA8 were up-regulated under high salt and drought stress, and RcACA1 was up-regulated at 0-24 h under low-temperature stress, indicating that RcACA genes positively responded to abiotic stresses. The above results provide a theoretical basis for exploring the role of the RcACA gene in castor growth, development and stress response.
Genome, Plant
;
Stress, Physiological/genetics*
;
Transcriptome
;
Promoter Regions, Genetic
;
Phylogeny
;
Plant Proteins/metabolism*
;
Gene Expression Regulation, Plant
6.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.
7.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.
8.Relationship between serum claudin-1 level and papillary thyroid carcinoma
Weidong HOU ; Linhu HOU ; Xiaoyan QIN ; Yuanyuan YU ; Jin LI ; Yanxiao LIU
Chinese Journal of Endocrinology and Metabolism 2021;37(11):979-984
Objective:To analyze the correlation between serum claudin-1(Cla-1) level and the risk of papillary thyroid carcinoma(PTC) in patients with thyroid nodules.Methods:The clinical data of 345 patients with thyroid nodules were retrospectively analyzed. According to the pathological results, they were divided into PTC group and benign thyroid nodule(BTN) group. The difference of serum Cla-1 level between 2 groups and its correlation with the risk of PTC were analyzed.Results:In groups of PTC( n=225) and BTN( n=120), the median value of serum Cla-1 level was 14.03(10.30, 20.40) ng/mL. The differences in the median value[17.90(14.00, 22.93)ng/mL vs 9.40(8.15, 11.20) ng/mL] of serum Cla-1 level in the PTC and BTN were statistically significant by Wilcoxon signed-rank test. The prevalence of PTC in thyroid nodules increased gradually with increasing of serum Cla-1 level. Receiver operated characteristic curve analysis showed that the best diagnostic cut-off value of the PTC was 13.02 ng/ml of which the sensitivity was 81.8%, the specificity was 89.2%, and the area under curve(AUC) was the largest(AUC=0.944, P<0.01, 95% CI 0.922-0.965). Logistic regression analysis showed that elevated serum Cla-1 level increased the risk of PTC, and it was statistically significant( OR=4.334, 95% CI 1.662-11.303, P=0.003). There was a significant correlation among the serum Cla-1 level and gender, age, location of involvement, number and diameter of cancer nodules, extracapsular invasion of thyroid, lymph node metastasis, tumor stage and combined with Hashimoto′s thyroiditis( P<0.01). Conclusion:The serum level of Cla-1 may be one of risk factors to predict PTC, and it is related to the total amount of PTC tumor cells in vivo, but it was not related to the aggressive behavior of tumor.
9.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.
10.A survey on the willingness of college students majoring in public health to work in their majors
Bowen LIANG ; Yuewei ZHAN ; Anping FENG ; Yanxiao GAO ; Peiyang LI ; Yuelong SHU ; Huachun ZOU
Chinese Journal of Epidemiology 2021;42(3):562-568
Objective:To understand the basic qualities, practitioners will and related influences, of undergraduate, master, and doctoral students majoring in public health (hereinafter referred to as public health students), and explore the influencing factors of practitioners will.Methods:Through the online questionnaire survey, we collected information on the basic qualities of the public health students, their practitioners will and related influencing factors, and their opinions on the current state of public health in China. χ 2 test and multi-factor logistic regression were used to analyze the influencing factors of public health students' willingness to engage in public health related work, and word frequency analysis was used to conduct a descriptive analysis of public health students' views on public health in China. Results:A total of 2 081 pieces of valid information were collected, of which 86.54% (1 801/2 081) of the students in the school chose to engage in public health related work in the future. For public health students, the higher the target after-tax monthly income ( OR=0.345, 95% CI: 0.158-0.751), the lower the willingness to engage in public health related work in the future; Very satisfied with school employment guidance work ( OR=4.072, 95% CI: 1.234-13.436) compared with very dissatisfied, the willingness to engage in public health related work in the future is higher. Conclusion:The willingness of students in public health related majors to engage in public health related majors in China is mainly affected by three factors: payment levels, employment guidance and professional post recognition. It is recommended to appropriately raise the salaries of public health related positions. Strengthening school employment guidance training and professional identity training is conducive to enhancing the willingness of public health students to engage in relevant work in their profession.

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