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.Herbal Textual Research on Moschus in Famous Classical Formulas
Juanjuan LIU ; Sini LI ; Jie JI ; Liping YANG ; Houkang CAO ; Xiaohui MA ; Ling JIN ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):194-202
In this paper, by consulting the ancient and modern literature, the name, origin, quality evaluation, harvesting and processing, and others of the original animal and medicinal materials of Moschus were systematically sorted out and verified, in order to provide the basis for the development and utilization of the famous classical formulas containing Moschus. According to the textual research, musk deer was first recorded in Shanhaijing. Shennong Bencaojing was recorded as Moschus and all generations were used as the correct name, but there were also aliases such as Shefu, Xiangzhang and Xiangqizi. In ancient times, Moschus berezovskii, M. sifanicus and M. moschiferus were the main sources of Moschus, and the quality of Moschus produced in northwest China was better than that produced in the Yangtze River basin. In modern times, Moschus of M. moschiferus produced in northeast China, M. sifanicus produced in Gansu, Sichuan and other places, and M. berezovskii produced in Ningxia, Shaanxi and other places are regarded as genuine. In ancient times, gunshots, lassoes, arrow shots and other methods were generally used to hunt live musk deer, and the sachets were immediately cut off. Those with high quality were called Xiangshanhuo, and dried in the shade after harvesting, which was known as Maoke Shexiang. Cut open the sachet, remove the shell and dry preservation, commonly known as Moschus kernel. In modern times, the method of taking Moschus from the living body of cultured musk deer is adopted, that is, Moschus kernel is directly taken from its sachet, dried in the shade or dried in a closed dryer. This method realizes the sustainable utilization of Chinese herbal medicine resources, but attention should be paid to the frequency and quality of Moschus. The harvesting time is mostly after the autumnal equinox every year, and before the next summer, it is better to gather sachet in winter. In recent times, it is believed that the shell Moschus is dry, full, thin, elastic, loose inside, many particles, strong and persistent aroma for the best, while the Moschus kernel is particle purple-black, powder yellow-brown, soft and oily texture, strong and persistent aroma for the best. The ancient processing method of Moschus was extracting kernels from the shell. After removing impurities, it is ground and used as medicine. Because its composition is not suitable for heating, the processing method is most common in preparations such as grinding into powder and putting into pills or powders, which has the effect of opening up the orifices and refreshing the mind, and it has continued to this day. Based on the research conclusions, it is suggested that the development of famous classical formulas containing Moschus, M. sifanicus, M. moschiferus and M. berezovskii should be used as the origins. According to the processing requirements specified in the original formula, it should be processed and used as medicine, while those without processing requirements should be used as raw products.
5.The effect of Ba Duan Jin on the balance of community-dwelling older adults: a cluster randomized control trial
Leilei DUAN ; Yubin ZHAO ; Yuliang ER ; Pengpeng YE ; Wei WANG ; Xin GAO ; Xiao DENG ; Ye JIN ; Yuan WANG ; Cuirong JI ; Xinyan MA ; Cong GAO ; Yuhong ZHAO ; Suqiu ZHU ; Shuzhen SU ; Xin'e GUO ; Juanjuan PENG ; Yan YU ; Chen YANG ; Yaya SU ; Ming ZHAO ; Lihua GUO ; Yiping WU ; Yangnu LUO ; Ruilin MENG ; Haofeng XU ; Huazhang LIU ; Huihong RUAN ; Bo XIE ; Huimin ZHANG ; Yuhua LIAO ; Yan CHEN ; Linhong WANG
Chinese Journal of Epidemiology 2024;45(2):250-256
Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.
6.The impact of nursing intervention based on the Information-Motivation-Behavioral Skills model on the psychological status and gastrointestinal motility of patients with functional dyspepsia
Yingying FAN ; Juan SUN ; Yuhong JIN ; Caifeng ZHANG ; Juanjuan JI ; Yongsheng CHANG
Journal of Clinical Medicine in Practice 2024;28(12):144-148
Objective To analyze the effect of nursing interventions based on the Information-Motivation-Behavioral Skills (IMB) model in patients with functional dyspepsia, in order to improve their psychological state and gastrointestinal motility, and provide reference for clinical nursing. Methods A total of 160 functional dyspepsia patients admitted to the First Affiliated Hospital of Xinxiang Medical College from December 2022 to June 2023 were chosen as the study subjects. They were randomly divided into control group and observation group, using a random number table method, with 80 cases in each group. Patients in control group were given routine nursing intervention, and patients in the observation group were treated nursing intervention based on IMB model. The psychological state, gastrointestinal motility andquality of life of the two groups were compared before and after intezrvention. Results After intervention, the scores of Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) in two groups were decreased, and the observation group was lower than that in the control group (
7.Interleukin-17A-mediated psoriasis and cardiovascular comorbidities
Ying ZHAO ; Juanjuan WANG ; Jiang JI ; Wenxing SU ; Yuqian WEI ; Hong LENG ; Yujie DING ; Xin SHI
Chinese Journal of Dermatology 2022;55(1):76-79
The interleukin (IL) -23/IL-17 axis is the main pathway in the pathogenesis of plaque-type psoriasis vulgaris, and IL-17A plays a key role in the relevant immune pathways. IL-17A mediates overlapping inflammatory pathways in atherosclerosis and psoriasis, promotes inflammation, coagulation and thrombosis, and plays an important role in the occurrence and development of cardiovascular comorbidities in patients with psoriasis. Inhibiting the inflammatory effect of IL-17A can reduce the incidence and mortality of cardiovascular comorbidities in patients with severe psoriasis. This review summarizes recent research progress in IL-17A-mediated systemic inflammation and cardiovascular comorbidities in patients with psoriasis, and provides a reference for prevention and reduction of cardiovascular comorbidities in patients with psoriasis in clinical practice.
8.Retrospective analysis of 67 cases of neurosyphilis with abnormal mental behaviors as the initial symptom
Juanjuan WANG ; Rong CHEN ; Jiang JI ; Wenxing SU ; Yuqian WEI ; Ying ZHAO ; Xingping YIN ; Yuhua SU ; Xin SHI
Chinese Journal of Dermatology 2022;55(3):231-234
Objective:To analyze clinical characteristics of neurosyphilis patients with abnormal mental behaviors as the initial symptom, and to provide a reference for clinical classification of, as well as outcome prediction and efficacy monitoring in neurosyphilis.Methods:Clinical data were collected from 67 HIV-negative neurosyphilis patients with abnormal mental behaviors as the initial symptom in the Second Affiliated Hospital of Soochow University from November 2012 to November 2019, and retrospectively analyzed. Statistical analysis was carried out by using t test. Results:Among the 67 patients, 52 (77.6%) were males, and 15 (22.4%) were females; there were 63 (94.0%) middle-aged and elderly patients and 4 (6.0%) adolescent patients; 38 (56.7%) patients were diagnosed with progressive general paresis, 21 (31.3%) with meningovascular neurosyphilis, 1 (1.5%) with meningeal neurosyphilis, 3 (4.5%) with tabes dorsalis, and 4 (6.0%) with mixed-type neurosyphilis. As laboratory examination showed, 67 patients all presented with positive serum rapid plasma reagin (RPR) test, serum Treponema pallidum particle agglutination (TPPA) test, and cerebrospinal fluid TPPA test, 55 (82.1%) had positive cerebrospinal fluid RPR test, 47 (70.1%) had elevated cerebrospinal fluid protein levels of > 0.45 g/L, 50 (74.6%) had increased white blood cell counts of > 8 ×10 6/L in cerebrospinal fluids, and 28 (41.8%) had elevated IgG levels in cerebrospinal fluids. Magnetic resonance imaging of the brain revealed multiple ischemic foci in 21 (31.3%) cases, multiple leukodystrophy in 17 (25.4%) , cerebral atrophy in 15 (22.4%) , infarction in 8 (11.9%) , and encephalitis-like changes in 2 (3.0%) . Of the 67 patients, 48 were treated with penicillin in aqueous solutions, 15 with ceftriaxone, and 4 with doxycycline. Six months later, the follow-up showed that 46 (68.7%) patients responded to the treatment, and the early course of disease was significantly shorter in the highly responsive group than in the poorly responsive group ( P < 0.05) . Conclusion:The middle-aged and elderly males were predominant in the neurosyphilis patients with abnormal mental behaviors as the initial symptom, magnetic resonance imaging is helpful for clinical classification and prognosis prediction of neurosyphilis, and early and standardized antisyphilitic treatment can markedly improve the prognosis of patients.
9.Influence of different virologic responses on the prognosis of patients with decompensated hepatitis B cirrhosis
Xiaoxiao JI ; Li LI ; Juanjuan FU
Journal of Clinical Hepatology 2020;36(5):1033-1037
ObjectiveTo investigate the influence of different virologic responses on long-term survival rate and incidence rate of liver cancer in patients with decompensated hepatitis B cirrhosis. MethodsA total of 378 patients with decompensated hepatitis B cirrhosis who were admitted to The Affiliated Hospital of Xuzhou Medical University from September 2010 to September 2016 were enrolled, and according to whether HBV DNA was continuously undetectable during antiviral therapy, they were divided into sustained virologic response group with 243 patients and non-sustained virologic response group with 135 patients. The patients were stratified according to the application of different antiviral drugs. Baseline data were recorded and the patients were followed up to the occurrence of end events or study endpoint to record death and hepatocellular carcinoma (HCC). The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used to compare survival rates between groups. ResultsCompared with the non-sustained virologic response group, the sustained virologic response group had a significantly lower 5-year cumulative incidence rate of HCC (7.4% vs 19.3%, χ2=10.627, P=0.001) and a significantly higher 5-year transplant-free survival rate (93.4% vs 80.7%, χ2=12.594, P<0.001). For the sustained virologic response group, there were no significant differences between the entecavir group and the non-entecavir group in the 5-year transplant-free survival rate (94.7% vs 90.2%, χ2=1.122, P=0.290) and the 5-year cumulative incidence rate of liver cancer (6.4 % vs 9.7%, χ2=0.552, P=0.458). For the non-sustained viral response group, there were also no significant differences between the entecavir group and the non-entecavir group in the 5-year transplant-free survival rate (78.4% vs 82.8%, χ2=1.526, P=0.217) and the 5-year cumulative incidence rate of liver cancer (21.5% vs 17.1%, χ2=1.844, P=0.174). ConclusionAntiviral therapy can improve the prognosis of patients with decompensated hepatitis B cirrhosis, and sustained virologic response can reduce the incidence rate of liver cancer and prolong survival time.
10.Na2CO3-responsive Photosynthetic and ROS Scavenging Mechanisms in Chloroplasts of Alkaligrass Revealed by Phosphoproteomics
Suo JINWEI ; Zhang HENG ; Zhao QI ; Zhang NAN ; Zhang YONGXUE ; Li YING ; Song BAOHUA ; Yu JUANJUAN ; Cao JIANGUO ; Wang TAI ; Luo JI ; Guo LIHAI ; Ma JUN ; Zhang XUMIN ; She YIMIN ; Peng LIANWEI ; Ma WEIMIN ; Guo SIYI ; Miao YUCHEN ; Chen SIXUE ; Qin ZHI ; Dai SHAOJUN
Genomics, Proteomics & Bioinformatics 2020;18(3):271-288
Alkali-salinity exerts severe osmotic, ionic, and high-pH stresses to plants. To under-stand the alkali-salinity responsive mechanisms underlying photosynthetic modulation and reactive oxygen species (ROS) homeostasis, physiological and diverse quantitative proteomics analyses of alkaligrass (Puccinellia tenuiflora) under Na2CO3 stress were conducted. In addition, Western blot,real-time PCR, and transgenic techniques were applied to validate the proteomic results and test the functions of the Na2CO3-responsive proteins. A total of 104 and 102 Na2CO3-responsive proteins were identified in leaves and chloroplasts, respectively. In addition, 84 Na2CO3-responsive phospho-proteins were identified, including 56 new phosphorylation sites in 56 phosphoproteins from chloro-plasts, which are crucial for the regulation of photosynthesis, ion transport, signal transduction, and energy homeostasis. A full-length PtFBA encoding an alkaligrass chloroplastic fructose-bisphosphate aldolase (FBA) was overexpressed in wild-type cells of cyanobacterium Synechocystis sp. Strain PCC 6803, leading to enhanced Na2CO3 tolerance. All these results indicate that thermal dissipation, state transition, cyclic electron transport, photorespiration, repair of pho-tosystem (PS) Ⅱ, PSI activity, and ROS homeostasis were altered in response to Na2CO3 stress, which help to improve our understanding of the Na2CO3-responsive mechanisms in halophytes.


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