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. Advances in relationship between pyroptosis and pulmonary arterial hypertension and therapeutic drugs
Qian YAN ; Yang SUN ; Jun-Peng LONG ; Jiao YAO ; Yu-Ting LIN ; Song-Wei YANG ; Yan-Tao YANG ; Gang PEI ; Qi-Di AI ; Nai-Hong CHEN ; Qian YAN ; Yang SUN ; Jun-Peng LONG ; Jiao YAO ; Yu-Ting LIN ; Song-Wei YANG ; Yan-Tao YANG ; Gang PEI ; Qi-Di AI ; Nai-Hong CHEN ; Sha-Sha LIU ; Nai-Hong CHEN
Chinese Pharmacological Bulletin 2024;40(1):25-30
Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.
5.Diagnostic Value of Conventional Ultrasound Combined with Shear Wave Elastography for Sarcopenia in Patients with Chronic Kidney Disease
Xiaozhu ZHONG ; Jiachuan LIN ; Qirong SONG ; Sha FU ; Ting SHU ; Ying TANG ; Ping WANG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(6):912-922
[Objective]To explore the diagnostic value of conventional ultrasound combined with shear wave elastography (SWE) for sarcopenia in patients with chronic kidney disease (CKD).[Methods]The study included 94 CKD patients (34 with sarcopenia and 60 without). All patient underwent the Simplified Assessment Rating Questionnaire (SARC-CalF),Mini Nutritional Assessment (MNA),Short Physical Performance Battery (SPPB),grip strength test,bioelectrical impedance analysis (BIA),conventional muscle ultrasound and SWE of the thighs. We then compared the differences in indicators between the sarcopenia group and non-sarcopenia group,used Spearman correlation analysis to assess the relationship between the two examinations (conventional ultrasound and SWE) and other clinical indicators,identified the diagnostic markers for sarcopenia,created receiver operating characteristic (ROC) curves,calculated the area under the curve (AUC) and determined the diagnostic performance of conventional ultrasound,SWE and their combination. Binary logistic regression was used to analyze the influencing factors of sarcopenia in CKD patients and a combined diagnosis model was established.[Results]The sarcopenia group showed lower upper arm circumference,calf circumference,6-meter walking speed and handgrip strength than non-sarcopenia group,and the differences were statistically significant (P<0.05). The sarcopenia group exhibited lower SARC-CalF and SPBB scores,as well as more compromised nutritional status. Statistically significant differences were observed in the ultrasound parameters between the two groups,including thickness of the subcutaneous fat and rectus femoris,combined thickness of the rectus femoris and vastus intermedius,rectus femoris cross-sectional area,elastic modulus of the rectus femoris and vastus medialis (all P<0.05). The muscle mass index had a moderate positive correlation with muscle thickness and cross-sectional area of the rectus femoris (0.3
6.Research and evaluation on dynamic accumulation of dry matter and quality of Isatis indigotica in Longdong area
Fu-Hong YANG ; Xin ZHAO ; Dong LIU ; Meng-Sha SONG ; Pan WANG ; Tao DU
Chinese Traditional Patent Medicine 2024;46(1):149-155
AIM To explore the laws in accumulation of dry matter and medicinal ingredients of Isatis indigotica Fort.in Longdong area,and determine the best harvest time to obtain the high-quality and high-yield medicinal plant.METHODS The I.indigotica had its agronomic traits investigated regularly;the accumulation laws of its uridine,guanosine,(R,S)-geichan and adenosine measured by HPLC;and its comprehensive utilization value in different periods evaluated by grey correlation method.RESULTS There existed significant variations among the plant height,plant width,leaf length,leaf width,number of leaves,leaf weight,root length,root diameter,root weight,and the yields of uridine,guanosine,(R,S)-goitrin and adenosine at different growth stages,whose peak values appeared in different period.Additionally,there were also obvious differences in the aforementioned indexes levels among different strains.The highest weighted correlation degree of the comprehensive utilization value of Longde and 2008-6-2 on October 9,and of 2008-11 and 2016-2 on October 24.On the whole,the 2008-6-2 and 2016-2 were superior to 2008-11 and Longde.CONCLUSION It is suggested that the best harvest time of I.indigotica in Longdong area is in mid to late October.
7.The Spatial Differences and Dynamic Evolution of China's Healthcare Service Efficiency from 2012 to 2021
Sha-Sha SONG ; Lina SHAO ; Zhonghua SUO ; Jing WU ; Ying LANG
Chinese Health Economics 2024;43(9):70-74,96
Objective:To study the longitudinal trends and spatial clustering characteristics of healthcare service efficiency in China and in North,Northeast,East,Central,South,Southwest,and Northwest China.Methods:The Malmquist index model is used to measure China's healthcare service efficiency from 2012 to 2021,the Dagum Gini coefficient as well as the decomposition method are used to measure the magnitude and source of regional gaps in healthcare service efficiency,and the Kernel density estimation is used to study the longitudinal trend of change and spatial agglomeration characteristics of China's healthcare service efficiency.Results:China's overall healthcare service efficiency is growing,and the inter-regional gap is gradually narrowing,characterized by a concentration trend;the gap in the level of healthcare service efficiency between regions did not widen during the period under examination,but it was found that the gap within some regions was still significant.Conclusion:The national health service efficiency is growing slightly,and the regional gap is generally decreasing,but the Gini coefficient shows that the inter-regional contribution is still the main source of the gap.National health service efficiency is generally concentrated,but some regions are less efficient,with significant internal disparities.
8.The Spatial Differences and Dynamic Evolution of China's Healthcare Service Efficiency from 2012 to 2021
Sha-Sha SONG ; Lina SHAO ; Zhonghua SUO ; Jing WU ; Ying LANG
Chinese Health Economics 2024;43(9):70-74,96
Objective:To study the longitudinal trends and spatial clustering characteristics of healthcare service efficiency in China and in North,Northeast,East,Central,South,Southwest,and Northwest China.Methods:The Malmquist index model is used to measure China's healthcare service efficiency from 2012 to 2021,the Dagum Gini coefficient as well as the decomposition method are used to measure the magnitude and source of regional gaps in healthcare service efficiency,and the Kernel density estimation is used to study the longitudinal trend of change and spatial agglomeration characteristics of China's healthcare service efficiency.Results:China's overall healthcare service efficiency is growing,and the inter-regional gap is gradually narrowing,characterized by a concentration trend;the gap in the level of healthcare service efficiency between regions did not widen during the period under examination,but it was found that the gap within some regions was still significant.Conclusion:The national health service efficiency is growing slightly,and the regional gap is generally decreasing,but the Gini coefficient shows that the inter-regional contribution is still the main source of the gap.National health service efficiency is generally concentrated,but some regions are less efficient,with significant internal disparities.
9.The Spatial Differences and Dynamic Evolution of China's Healthcare Service Efficiency from 2012 to 2021
Sha-Sha SONG ; Lina SHAO ; Zhonghua SUO ; Jing WU ; Ying LANG
Chinese Health Economics 2024;43(9):70-74,96
Objective:To study the longitudinal trends and spatial clustering characteristics of healthcare service efficiency in China and in North,Northeast,East,Central,South,Southwest,and Northwest China.Methods:The Malmquist index model is used to measure China's healthcare service efficiency from 2012 to 2021,the Dagum Gini coefficient as well as the decomposition method are used to measure the magnitude and source of regional gaps in healthcare service efficiency,and the Kernel density estimation is used to study the longitudinal trend of change and spatial agglomeration characteristics of China's healthcare service efficiency.Results:China's overall healthcare service efficiency is growing,and the inter-regional gap is gradually narrowing,characterized by a concentration trend;the gap in the level of healthcare service efficiency between regions did not widen during the period under examination,but it was found that the gap within some regions was still significant.Conclusion:The national health service efficiency is growing slightly,and the regional gap is generally decreasing,but the Gini coefficient shows that the inter-regional contribution is still the main source of the gap.National health service efficiency is generally concentrated,but some regions are less efficient,with significant internal disparities.
10.The Spatial Differences and Dynamic Evolution of China's Healthcare Service Efficiency from 2012 to 2021
Sha-Sha SONG ; Lina SHAO ; Zhonghua SUO ; Jing WU ; Ying LANG
Chinese Health Economics 2024;43(9):70-74,96
Objective:To study the longitudinal trends and spatial clustering characteristics of healthcare service efficiency in China and in North,Northeast,East,Central,South,Southwest,and Northwest China.Methods:The Malmquist index model is used to measure China's healthcare service efficiency from 2012 to 2021,the Dagum Gini coefficient as well as the decomposition method are used to measure the magnitude and source of regional gaps in healthcare service efficiency,and the Kernel density estimation is used to study the longitudinal trend of change and spatial agglomeration characteristics of China's healthcare service efficiency.Results:China's overall healthcare service efficiency is growing,and the inter-regional gap is gradually narrowing,characterized by a concentration trend;the gap in the level of healthcare service efficiency between regions did not widen during the period under examination,but it was found that the gap within some regions was still significant.Conclusion:The national health service efficiency is growing slightly,and the regional gap is generally decreasing,but the Gini coefficient shows that the inter-regional contribution is still the main source of the gap.National health service efficiency is generally concentrated,but some regions are less efficient,with significant internal disparities.

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