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.Establishment of fingerprint ,content determination and chemical pattern recognition of decoction pieces and dispensing granules of Gardenia jasminoides
Chaofeng LIANG ; Xiaoke HAN ; Yadong QIN ; Bin XU ; Jun QI ; Juanjuan ZHOU
China Pharmacy 2022;33(14):1718-1723
OBJECTIVE To establish the fingerp rint of decoction pi eces and dispensing granules of Gardenia jasminoides ,to determine the contents of 6 components,so as to evaluate its quality combined with chemical pattern recognition. METHODS High performance liquid chromatography (HPLC)was used. Using geniposide as the reference ,Similarity Evaluation System for Chromatographic Fingerprint of TCM (2012 edition)was used to draw the fingerprints of 20 batches of G. jasminoides decoction pieces and 10 batches of G. jasminoides dispensing granules. Similarity evaluation and common peaks identification were conducted. The same HPLC method was adopted to determine the contents of deacetyl asperulosidic acid methyl ester ,geniposide, picrocrocin,rutin,crocin-Ⅰ and crocin- Ⅱ. ORIGIN 9.1 software was used for hierarchical clustering analysis ,and SIMCA 16.0 software was used for principal component analysis (PCA) and partial least squares-discriminant analysis. The differential components affecting the quality of decoction pieces and dispensing granules were screened by taking the variable importance in projection(VIP)value>1 as the standard. RESULTS There were 24 common peaks for both 20 batches of G. jasminoides decoction piece and 10 batches of G. jasminoides dispensing granules ;a total of 22 common peaks were found in the fingerprints of 30 batches of samples ,and the similarity was not lower than 0.96;six common peaks were identified ,i.e. deacetyl asperulosidic acid methyl ester (peak 2),geniposide(peak 6),picrocrocin(peak 9),rutin(peak 11),crocin-Ⅰ(peak 15),crocin-Ⅱ(peak 17). Average contents of above 6 components in G. jasminoides decoction pieces were 1.04,57.00,1.30,1.03,9.63 and 0.99 mg/g, respectively;those of G. jasmin oides dispensing granules were 0.96,17.04,0.37,0.27,0.73 and 0.04 mg/g,respectively. PCA results showed that G. jasminoides decoction pieces and G. jasminoides dispensing granules were clustered into respective one category ,which was consistent with results of cluster analysis. There were 9 common peaks with VIP value >1, which were 16,14,3,17(crocin-Ⅱ),15(crocin-Ⅰ),18, 22, 2 (deacetyl asperulosidic acid methyl ester) and 21. CONCLUSIONS The estab lished fingerprint and content determination method are simple and reproducible. Combined with chemical pattern recognition ,it can be used to evaluate the quality of decoction pieces and dispensing granules of G. jasminoides . Nine corresponding components represented by peak 16 and so on are the differential components that affect the quality of them.
5.Association Between Lipid Profiles and Left Ventricular Hypertrophy: New Evidence from a Retrospective Study
Huang XUEWEI ; Deng KEQIONG ; Qin JUANJUAN ; Lei FANG ; Zhang XINGYUAN ; Wang WENXIN ; Lin LIJIN ; Zheng YUMING ; Yao DONGAI ; Lu HUIMING ; Liu FENG ; Chen LIDONG ; Zhang GUILAN ; Liu YUEPING ; Yang QIONGYU ; Cai JINGJING ; She ZHIGANG ; Li HONGLIANG
Chinese Medical Sciences Journal 2022;37(2):103-117
Objective To explore the association between lipid profiles and left ventricular hypertrophy in a Chinese general population. Methods We conducted a retrospective observational study to investigate the relationship between lipid markers [including triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL-cholesterol, apolipoprotein A-I, apolipoprotein B, lipoprotein[a], and composite lipid profiles] and left ventricular hypertrophy. A total of 309,400 participants of two populations (one from Beijing and another from nationwide) who underwent physical examinations at different health management centers between 2009 and 2018 in China were included in the cross-sectional study. 7,475 participants who had multiple physical examinations and initially did not have left ventricular hypertrophy constituted a longitudinal cohort to analyze the association between lipid markers and the new-onset of left ventricular hypertrophy. Left ventricular hypertrophy was measured by echocardiography and defined as an end-diastolic thickness of the interventricular septum or left ventricle posterior wall > 11 mm. The Logistic regression model was used in the cross-sectional study. Cox model and Cox model with restricted cubic splines were used in the longitudinal cohort. Results In the cross-sectional study, for participants in the highest tertile of each lipid marker compared to the respective lowest, triglycerides [odds ratio (OR): 1.250, 95%CI: 1.060 to 1.474], HDL-cholesterol (OR: 0.780, 95%CI: 0.662 to 0.918), and lipoprotein(a) (OR: 1.311, 95%CI: 1.115 to 1.541) had an association with left ventricular hypertrophy. In the longitudinal cohort, for participants in the highest tertile of each lipid marker at the baseline compared to the respective lowest, triglycerides [hazard ratio (HR): 3.277, 95%CI: 1.720 to 6.244], HDL-cholesterol (HR: 0.516, 95%CI: 0.283 to 0.940), non-HDL-cholesterol (HR: 2.309, 95%CI: 1.296 to 4.112), apolipoprotein B (HR: 2.244, 95%CI: 1.251 to 4.032) showed an association with new-onset left ventricular hypertrophy. In the Cox model with forward stepwise selection, triglycerides were the only lipid markers entered into the final model. Conclusion Lipids levels, especially triglycerides, are associated with left ventricular hypertrophy. Controlling triglycerides level potentiate to be a strategy in harnessing cardiac remodeling but deserve to be further investigated.
6.Analysis of influencing factors of depression in patients with chronic heart failure: a systematic review and Meta-analysis
Jingwen QIN ; Juanjuan XIONG ; Kaizheng GONG
Chinese Journal of Modern Nursing 2021;27(32):4400-4406
Objective:To analyze the potential influencing factors of depression among chronic heart failure (CHF) patients systematically, so as to provide reference for effective intervention.Methods:We searched the databases of CNKI, WanFang Data, VIP, CBM, PubMed, Cochrane library, Web of Science, Embase, PsycINFO and PsyARTICLE database for relevant articles. The literature was screened according to the inclusion and exclusion criteria. The quality of the included literature was evaluated and the data was extracted by 2 researchers independently. Review Manager 5.3 was used to analyze the data.Results:A total of 25 articles were included. The combined effect size OR/ SD (95% CI) of each influencing factor in descending order were: sedentary behavior 2.75 (1.62 to 4.66) , long duration 2.58 (2.09 to 3.07) , EF values -2.29 (-3.44 to -1.13) , NYHAⅢ/Ⅳ 2.28 (1.70 to 3.08) , the combination of anemia 1.72 (1.30 to 2.28) , solitary 1.48 (1.16 to 1.88) , the combination of Chronic renal insufficiency 1.46 (1.16 to 1.85) and COPD 1.44 (1.04 to 2.00) , low BMI -1.13 (-1.64 to -0.98) , good knowledge of heart failure 0.67 (0.47 to 0.95) , male 0.63 (0.53 to 0.76) , married 0.57 (0.47 to 0.69) . Conclusions:The influencing factors of chronic heart failure combined with depression are diverse. Medical staff can identify the heart failure patients with high prevalence of depression early according to the related influencing factors, and can also intervene the controllable influencing factors to reduce the occurrence of depression.
7.Advances in gene editing of Corynebacterium glutamate.
Juanjuan YANG ; Xiaoyu MA ; Xiaorui WANG ; Zhaohui ZHANG ; Shan WANG ; Huimin QIN ; Shuhong MAO ; Fuping LU
Chinese Journal of Biotechnology 2020;36(5):820-828
Corynebacterium glutamicum, an important microorganism to produce amino acids and organic acids, has been widely applied in food and medicine fields. Therefore, using editing tools to study the function of unknown genes in C. glutamicum has great significance for systematic development of industrial strain with efficient and novel production capability. Recently, gene editing has been greatly developed. Traditional gene editing based on homologous recombination and gene editing mediated by nuclease are successfully applied in C. glutamicum. Among these, the CRISPR system has been developed to be a main tool used for gene knockout of C. glutamicum due to its advantages of efficiency, simplicity and good target specificity. However, more efficient and reliable knockout system is still urgently demanded, to help develop high-performing strains in industrial application.
CRISPR-Cas Systems
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Clustered Regularly Interspaced Short Palindromic Repeats
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Corynebacterium glutamicum
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genetics
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Gene Editing
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trends
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Glutamic Acid
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Industrial Microbiology
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trends
8.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.
9.Implementation effect of mixed teaching mode + formative evaluation in the course of normal human morphology
Wujin CHEN ; Yuxin ZHAO ; Wen QIN ; Wenqing YANG ; Aimaier MUSA ; Xiaotong MENG ; Juanjuan DONG ; Shengbin BAI
Chinese Journal of Medical Education Research 2018;17(3):244-247
The nursing students of Grade 2009 to Grade 2016 were selected.Their skills,midterm,usual and final performances as well as comprehensive scores of normal human morphology course were analyzed by one-way ANOVA in combination with different stages of curriculum integration in order to compare the teaching effect between traditional teaching mode + evaluation system and mixed teaching mode + formative evaluation in the course of normal human morphology.Statistical analysis by SPSS 17.0 showed that the average score of formation stage (traditional teaching mode) was 67.55 ± 12.72,the average score of integration stage (mixed teaching mode) was 72.79 ± 10.93 and the average score of development stage (formative evaluation +mixed teaching mode) was 83.94 ± 9.58.After making comparisons,the P values of ANOVA of the course of normal human body morphology in all stages were all less than 0.001,having statistical significance.The results showed that the overall development of the curriculum is becoming mature and the new teaching model can help students who usually do not like to review.
10.Simultaneous determination of liquiritin, glycyrrhizic acid and glycyrrhetinic acid in Xianlong-Jiedu Yin by HPCE
Juanjuan ZHOU ; Jun QI ; Yadong QIN
International Journal of Traditional Chinese Medicine 2017;39(2):144-147
Objective To simultaneously determine the quantify liquiritin, glycyrrhetinic acid and glycyrrhizic acid inXianlong-Jiedu Yin by high performance capillary electrophoresis (HPCE).Methods HPCE method was performed on a fused silica capillary coates 75μm×85 cm (effective column length 78.5 cm) using 50 mmol/L borax solution-acetonitrile (95:5), with adjusted pH=8.50 as running buffer, lytical 22 kV, and electrokinetic injection 10 s, detected wave length of 254 nm, and temprature maintaining 25℃.Results The liquiritin, glycyrrhetinic acid and glycyrrhizic acid were completely separated within 30 minutes, showing good linear relationship in the range of 12-120, 15-150, 8-160μg/ml (r>0.999 3). The average recoveries were 100.70%, 98.51%, 98.40% withRSD 2.49%, 2.79%, 0.40%, respectively.Conclusions The HPCE was suitable for the determination of liquiritin, glycyrrhetinic acid and glycyrrhizic acid inXianLong-JieDu Yin, which can be used for the quality control.

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