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.Role and mechanism of caffeic acid phenethyl ester in hepatic stellate cell
Ning YANG ; Jiang DENG ; Yikai WANG ; Sha CHANG ; Ning GAO ; Wenjun WANG ; Shuangsuo DANG ; Juanjuan SHI
Journal of Clinical Hepatology 2022;38(10):2273-2278
Objective To assess the effect and underlying molecular events of caffeic acid phenethyl ester (CAPE) on rat hepatic stellate HSC-T6 cells. Methods HSC-T6 cells were grown and treated with different concentrations of CAPE (5, 10, or 15 μmol/L), transfected with or without LC3-GFP plasmid, and then treated with or without an autophagy inducer rapamycin or the autophagy inhibitor 3-methyladenine (3-MA). The changed cell viability and morphology were assessed by using cell viability MTT assay and Transmission electron microscope, respectively. The expression of LC3 protein in HSC-T6 cells was detected by immunofluorescence assay, the autophagy-related genes expression of ATG5, ATG7, ATG12, Beclin1 and LC3 were detected by qRT-PCR, and the expression of ATG7, Beclin1, LC3I/Ⅱ, p-AKT/AKT, p-mTOR protein was detected by Western-blot. Comparison between multiple groups was analyzed by one-way ANOVA with Dunnett t -test. Results Compared with the control, CAPE treatment significantly reduced cell viability but induced formation of lipid droplets and roulette-shaped autophagosomes. Compared with the control (13.34%±2.59), LC3 protein was significantly induced in HSC-T6 cells after CAPE treatment (5 μmol/L, 23.68%±3.76, t =-5.553, P < 0.001; 10 μmol/L, 43.47%±3.83, t =-15.958, P < 0.001; 15 μM, 57.25%±2.78, t =-28.334, P < 0.001), while levels of ATG5, ATG7, ATG12, Beclin 1, and LC3 mRNAs were all significantly increased in 10 μm and 15 μm CAPE treated cells vs the control (all P < 0.05). After LC3 overexpression in HSC-T6 cells, LC3 protein was induced vs the vector control (79.01%±6.69% vs 67.06%±6.74%, t =-3.083, P =0.012), while rapamycin treatment further increased LC3 expression (86.88%±5.42%, t =-2.239, P =0.049); however, 3-MA treatment significantly decreased LC3 expression in cells (71.22%±4.29%, t =-2.404, P =0.037). In addition, levels of ATG7, Beclin1, and LC3 Ⅰ/Ⅱ proteins were increased, whereas levels of AKT/p-AKT and p-mTOR were decreased in the CAPE and rapamycin groups vs controls. However, the 3-MA treatment had an opposite result, indicating that 3-MA reversed CAPE-induced effects in HSC-T6 cells. Conclusion Caffeic acid phenethyl ester may induce autophagy to reduce cell viability in hepatic stellate cells by inhibition of the AKT/mTOR signaling.
5.Research progress in the molecular epidemiology of gastric cancer
Sha HUANG ; Jin DAI ; Juanjuan GAO ; Weicheng YOU ; Kaifeng PAN ; Wenqing LI
Chinese Journal of Clinical Oncology 2019;46(1):16-21
Gastric cancer is a malignant tumor characterized by high morbidity and mortality. With the development of molecular biol-ogy technology and the emergence of various new omics detection techniques in recent years, molecular epidemiologists of gastric cancer have conducted extensive studies on the genetic and host factors, as well as gene-environment interactions associated with ex-posure to environmental factors in gastric cancer. In addition, epidemiologists have studied the evolution of precancerous gastric le-sions, the development of gastric cancer, and explored relevant biomarkers to provide major evidence for the prevention and control of gastric cancer. This review summarizes the latest advances in the molecular epidemiology of gastric cancer, including existing evi-dence in studies for candidate-approach-based serum/plasma biomarkers, genome-wide association, whole-exome sequencing, tissue microarrays, as well as studies on metabolomics and microbiomes. We expect to provide insights into the future of molecular epidemi-ology studies in gastric cancer, promoting etiologic research, and the precise prevention and control of gastric cancer.
6.Comparative analysis of effect of atorvastatin calcium with different doses on inflammatory cytokine and carotid atherosclerotic plaque of patients with cerebral infarction
Bei REN ; Aixiang ZHANG ; Juanjuan SHA ; Peihong HOU
Drug Evaluation Research 2017;40(6):812-815
Objective To investigate the effect of atorvastatin calcium with different doses on inflammatory cytokine and carotid atherosclerotic plaque of patients with cerebral infarction.Methods One hundred and seventy-eight patients with cerebral infarction admitted into our hospital from January 2014 to June 2015 were divided into low dose (LD) group and high dose (HD) group.Ninety patients in LD group were treated with atorvastatin calcium in a dose of 10 mg/d,and eighty-seven patients in HD group were treated with atorvastatin calcium in a dose of 20 mg/d.The serum levels of lipid including TC,TG,LDL-C,HDL-C,inflammatory cytokine including hs-CRP,IL-6,TNF-α,and carotid atherosclerotic plaque of both groups were analyzed and compared before and after treatment.Results After six months of treatment,the serum levels and inflammatory cytokine of patients in both groups showed remarkable improvement (P < 0.05),and those in HD group were significantly better than those of LD group (P < 0.05).Additionally,compared with those before treatment,changes in carotid atherosclerotic plaque of patients in LD group were not obvious,while those in HD group markedly decreased,and which were significantly lower than those of LD group (P < 0.05).Conclusion Atorvastatin calcium with HD of 20 mg/d showed a better capability on improving serum levels of lipid,inflammatory cytokine,and carotid atherosclerotic plaque of patients with cerebral infarction than those with LD of 10 mg/d.
7.Values of recombinant tissue type plasminogen activator in the treatment of acute cerebral infarction complicated with atrial fibrillation
Juanjuan SHA ; Peihong HOU ; Bei REN ; Aixiang ZHANG
Drug Evaluation Research 2017;40(4):525-528
Objective To investigate the values of recombinant tissue type plasminogen activator (rt-PA)) in the treatment of acute cerebral infarction complicated with atrial fibrillation.Methods Used the prospective research methods,74 patients of acerebral infarction complicated with atrial fibrillation in Xi'an XD Group Hospital from February 2015 to August 2016 were selected and were equally divided into the observation group and the control group accorded to the principle of random envelope drawing.The control group was treated with urokinase intravenous thrombolytic therapy,the observation group was treated with rt-PA intravenous thrombolytic therapy,and the prognosis of the two groups were observed.Results There were no significant differences in gender,age,time window,disease,systolic blood pressure and diastolic blood pressure compared between the two groups.The treatment efficiency in the observation group and control group were 94.6% and 75.7%,the observation group was significantly higher than that of the control group (P < 0.05).After treatment,the mRS scores in the observation group and the control group were (5.22± 1.83) points and (7.29± 1.45) points,were significantly lower than those before treatment of (10.24± 1.31) points and (10.19 ± 1.52) points (P < 0.05),and the observation group was significantly lower than the control group (P < 0.05).In the observation group,the symptomatic intracerebral hemorrhage and non symptomatic cerebral hemorrhage were 5.4% and 2.7% respectively,so that were 18.9% and 16.2% in the control group that the observation group were significantly lower than those of the control group (P < 0.05).Conclusion Intravenous thrombolysis with recombinant tissue type plasminogen activator of patients with acute cerebral infarction combined with atrial fibrillation is safe and effective,it can promote the improvement of neurological function,and has good application value.
8.Study on the classification of periodontal phenotype based on crown forms and gingival characteristics
Sha SU ; Lu LIN ; Juanjuan ZONG
Journal of Practical Stomatology 2017;33(5):710-711
87 periodontally healthy young volunteers paticipated in the study.4 clinical parameters were measured:Gingival thickness (GT),gingival width (GW),papilla height (PH) and crown width/crown length ratio (CW/CL).Cluster analysis was employed to identify the periodontal phenotypes.As a result,the periodontal phenotype of maxillary anterior tooth was classified as thin fan type (Ⅰ,n =31),thick and wide type(Ⅲ,n =8) and intermediate type(Ⅱ,n =48) in Han Chinese.
9.Relationship between gingival thickness and the underlying bone thickness in maxillary anterior tooth area
Lu LIN ; Pinghua HE ; Sha SU ; Juanjuan ZONG
Journal of Practical Stomatology 2016;32(4):569-572
Objective:To study the relationship between gingival thickness(GT)and the underlying alveolar bone thickness(BT)in maxillary anterior region and the distance from cemento-enamel junction(CEJ)to alveolar crest.Methods:30 young volunteers with healthy gingiva were included.GT was measured at 2mm below the CEJ,buccal BT were measured at 3 locations:2,4 and 6 mm below the alveolar crest respectively,the distance from CEJ to alveolar crest were measured by CBCT and clinical direct measure respectively. Results:The correlation coefficient (r)values between GT and BT at 2,4 and 6 mm below alveolar crest were 0.493,0.383 and 0.342 (P <0.001 )respectively,the r value between GT and the distance from CEJ to alveolar crest was -0.21 3(P <0.01 ).No statistically significant difference was observed between CBCT and clinical measurements(t =-0.521 ,P =0.603).Conclusion:There is positive correlation between GT and BT at 2,4 and 6 mm below alveolar crest and negative relation between GT and the distance from CEJ to alveolar crest.
10.The Effect of Dezocine Analgesia on Cognitive Function of Patients after Gynecological Laparoscopic Surgery
Minli ZHANG ; Zhongming SHENG ; Sha ZHU ; Juanjuan ZHANG
Journal of Kunming Medical University 2016;37(12):107-110
Objective To discuss the application of Mini Mental State Scale (the mini-mental state examination MMSE) test in assess the effect of dezocine analgesia therapy on the cognitive function of patients with agitation in recovery period of general anesthesia after gynecological laparoscopic surgery.Methods We observed 210 cases of elective gynecologic laparoscopic surgery in our hospital from January 2015 to December 2015,ASA grade Ⅰ or Ⅱ.All patients were transrered to PACU (ICU) after extubation,and were divided into three groups:A,B,C group,each with 70 cases in each group.Patients with severe agitation in A group were timely given 10mg of dezocine,patients with mild agitation in B group were given 10mg of dezocine after a delay of 5 ~ 10 minutes,and patients without agitation in C group were not given dezocine.Then the MMSE test was performed to evaluate the cognition scores of patients in the three groups.The MMSE scores immediately,15 minutes,30 minutes,60 minutes after given dezocine and 24 hours after operation were recorded.Results The statistical results showed that there were significant differences in the MMSE scores of patients immediately and at 30 minutes after given dezocine between three groups (P<0.05);and there was no significant difference in the MMSE scores of patients at 60 minutes after given dezocine and 24 hours after operation between three groups (P >0.05).Conclusion Dezocine analgesia therapy has no effect on the cognitive function of patients with agitation in recovery period of general anesthesia after gynecological laparoscopic surgery.Dezocine can be safely used for analgesia and sedation treatment for patients with agitation in recovery period of general anesthesia after gynecological laparoscopic surgery analgesia,sedation agitation.

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