1.Current status of research on the mechanism of action of emodin in the prevention and treatment of chronic liver diseases
Yajie CHEN ; Xin WANG ; Yunjuan WU ; Ying SU ; Yuhan WANG ; Jinxue ZHANG ; Ning YAO ; Ying QIN ; Xiaoning ZUO
Journal of Clinical Hepatology 2026;42(1):228-234
Chronic liver diseases are a group of diseases in which the liver is subjected to a variety of injuries over a long period of time, resulting in irreversible pathological changes that last longer than 6 months. Emodin (EMO) is a natural anthraquinone derivative derived from Rheum officinale, and its pharmacological effect has been extensively studied, exhibiting a variety of biological properties and involving multiple signaling molecules and pathways. Western medicine or surgical treatment is currently the main treatment regimen for chronic liver diseases, and the advance in treatment is limited by various reasons such as side effects and high costs. Due to its natural origin and efficacy, EMO has unique advantages in the treatment of chronic liver diseases and has now become a research hotspot. This article summarizes the therapeutic effect of EMO on chronic liver diseases and its mechanism, in order to provide a certain scientific basis for the traditional Chinese medicine treatment of chronic liver diseases and the development of drugs in clinical practice.
2.Mining of key genes for xylose metabolism and cloning, expression, and enzymatic characterization of XylA in Bacillus coagulans.
Yiwen ZHANG ; Yajie ZHANG ; Manxin CHEN ; Xiaojun GUO ; Baocheng ZHU ; Yuming ZHANG
Chinese Journal of Biotechnology 2025;41(10):3876-3890
Bacillus coagulans can utilize the hydrolyzed carbon source of agricultural waste to produce lactic acid via a homofermentative pathway. However, a significant carbon source metabolic repression effect was observed when the strain metabolized mixed sugars (glucose and xylose), reducing the productivity of lactic acid. In this study, we obtained the fermentation conditions for the simultaneous utilization of the mixed sugars by B. coagulans by changing the ratio of glucose to xylose in the medium. Through transcriptome sequencing, several key genes responsible for xylose utilization were identified. The critical role of xylose isomerase (XylA, EC 5.3.1.5) in the synchronous utilization of glucose/xylose in B. coagulans was investigated via qRT-PCR (quantitative real-time polymerase chain reaction). Subsequently, the heterologous expression and characterization of the XylA-encoding gene (XylA) were conducted. It was determined that the gene encoded a protein composed of 440 amino acid residues. The secondary structure of the encoded protein was predominantly composed of α-helixes and random coils, while the higher structure of the protein was identified as a homotetramer. Then, XylA was cloned and expressed in Escherichia coli BL21(DE3), and the recombinant protein Bc-XlyA was obtained with a molecular weight of approximately 50 kDa. The optimal pH and temperature of Bc-XylA were 8.0 and 60 ℃, respectively, and Mn2+, Mg2+, and Co2+ had positive effects on the activity of Bc-XlyA. The present study provides scientific data on the molecular modification of B. coagulans, offering theoretical support for the efficient utilization of xylose in the strain.
Xylose/metabolism*
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Cloning, Molecular
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Bacillus coagulans/enzymology*
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Aldose-Ketose Isomerases/metabolism*
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Fermentation
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Bacterial Proteins/metabolism*
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Glucose/metabolism*
3.Influence of NOD-like receptor protein 3 inflammasome on the development and progression of nonalcoholic steatohepatitis and the interventional effect of traditional Chinese medicine
Jinxue ZHANG ; Junhong LIU ; Jiale CHEN ; Dan WANG ; Lining SU ; Yajie CHEN ; Xueqian LAI ; Miaolei WANG ; Yajing LI
Journal of Clinical Hepatology 2025;41(11):2365-2371
Nonalcoholic steatohepatitis (NASH) is a chronic liver disease with the main pathological features of hepatic steatosis, inflammatory cell infiltration, and interstitial fibroplasia, and it is an important risk factor for liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. NOD-like receptor protein 3 (NLRP3) inflammasome is the core of innate immunity, and the abnormal activation of NLRP3 inflammasome is closely associated with the development and progression of NASH, which involves multiple links such as inflammatory response and oxidative stress. A large number of studies have shown that the active ingredients of traditional Chinese medicine (TCM) and TCM compound prescriptions can improve oxidative stress, regulate lipid metabolism, and alleviate liver inflammation by regulating NLRP3 inflammasome. TCM treatment applied in clinical practice has achieved a good therapeutic effect, while inflammasome is one of the key pathways or targets for TCM in improving NASH. This article reviews the mechanism of action of NLRP3 inflammasome in NASH and the research advances in TCM intervention of NLRP3 inflammasome, in order to provide ideas for the clinical TCM treatment of NASH, as well as reference targets and research directions for the research and development of new TCM drugs.
4.Effects of Jiaohong Pills and Its Prescription on Scopolamine-induced Alzheimer's Disease Mice
Lijinchan DONG ; Weiyan CAI ; Li FENG ; Qing YANG ; Mengting LI ; Yanli WANG ; Hong ZHANG ; Qi LI ; Xiaogang WENG ; Yajie WANG ; Xiaoxin ZHU ; Xiaoru HU ; Ying CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):37-45
ObjectiveTo investigate the effects of Jiaohong pills (JHP) and its prescription, Pericarpium Zanthoxyli (PZ) and Rehmanniae Radix (RR) cognitive dysfunction in scopolamine-induced Alzheimer's disease (AD) mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ, RG and JHP, respectively. The effects of JHP and its formulations were investigated by open field test, water maze test, object recognition test, avoidance test, cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry (UPLC Q-Exactive Orbitrap MS). ResultThe behavioral data showed that, compared with the model group, the discrimination indexes of the high dose of JHP, PZ and RR groups was significantly increased (P<0.05). The staging rate of Morris water maze test in the PZ, RR, high and low dose groups of JHP was significantly increased (P<0.05, P<0.01), the crossing numbers in the PZ, JHP high and low dose groups were significantly increased (P<0.05, P<0.01); the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups (P<0.01), and the error latencies were significantly increased in the JHP and its prescription drug groups (P<0.01). Compared with the model group, the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased (P<0.05, P<0.01), and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased (P<0.05), and the level of acetylcholine was significantly increased (P<0.01). At the same time, the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly (P<0.05, P<0.01). The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group, which were involved in neurotransmitter metabolism, energy metabolism, oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction, regulate cholinergic system, and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter, energy, amino acid metabolism, and improvement of oxidative stress.
5.Effect of Compatibility of Wujiwan on Pharmacokinetics and Tissue Distribution of Representative Components
Yu DONG ; Ying CHEN ; Zipeng GONG ; Qing YANG ; Xiaogang WENG ; Yajie WANG ; Xiaoxin ZHU ; Chenhao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):105-113
ObjectiveTo study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan, and to illustrate the difference of metabolism and tissue distribution before and after compatibility. MethodHealthy male SD rats were divided into four groups, including Wujiwan group(A group, 62.96 g·L-1), Coptidis Rhizoma group(B group, 38.4 g·L-1), processed Euodiae Fructus group(C group, 5.88 g·L-1) and fried Paeoniae Radix Alba group(D group, 18.68 g·L-1), with 65 rats in each group, and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts. Then plasma, liver, small intestine and brain were taken at pharmacokinetic set time in each group after administration. Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components[berberine(Ber), palmatine(Pal), evodiamine(Evo), rutecarpine(Rut) and paeoniflorin(Pae)] in Wujiwan, their concentrations in plasma, liver, small intestine and brain were detected at different time, plasma samples were processed by protein precipitation, and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction. Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component, and the parameters of each group were compared. ResultPharmacokinetic results of A group showed that area under the curve(AUC0-t) of the five representative components were ranked as follows:Ber and Pal were small intestine>liver>blood, Evo and Rut were liver>small intestine>plasma, Pae was small intestine>plasma, which was not detected in the liver, no other components were detected in brain except for Ber. In comparison with plasma and other tissues, peak concentration(Cmax) of Ber, Pal, Evo, and Rut were the highest and time to peak(tmax) were the lowest in the liver of A group. In plasma, the AUC0-t and Cmax of Evo and Rut were increased in A group compared with C group, tmax of Pea was elevated and its Cmax was decreased in A group compared with D group. In the liver, compared with B-D groups, Cmax values of 5 representative components except Pae were elevated, AUC0-t of Pae was decreased and AUC0-t of Evo and Rut were increased in the A group. In the small intestine, half-life(t1/2) of each representative components in A group was elevated and tmax was decreased, and Cmax of each representative ingredient except Pal was decreased, AUC0-t values of Ber and Pal were increased, whereas the AUC0-t values of Evo and Rut were decreased. ConclusionThe small intestine, as the effector organ, is the most distributed, followed by the liver. The pharmacokinetic parameters of the representative components in Wujiwan are changed before and after compatibility, which is more favorable to the exertion of its pharmacodynamic effects.
6.Strategies and advances in laboratory tests for primary liver cancer
Yuan CHEN ; Jing LIANG ; Yunhui LI ; Yajie WANG
Chinese Journal of Preventive Medicine 2024;58(1):128-135
Primary liver cancer is one of the leading causes of cancer-related deaths worldwide, its early diagnosis and early treatment are of great clinical importance. The main detection tools for liver cancer include serological indicators, imaging tests and risk assessment models. With the advancement of technology and research, the sensitivity and specificity of laboratory tests for liver cancer have been substantially improved, but there are still false negatives and low rates of early diagnosis. For different causes and prevalence regions, each country has developed its clinical practice guidelines to guide risk groups for effective prevention, early diagnosis and standardized treatment. It is important to establish a liver cancer diagnosis strategy that is suitable for China′s national conditions, concerning the guidelines for the vigilance and prevention of liver cancer. In this article, the advantages and disadvantages of liver cancer-related tests and the impact of future development trends on laboratory strategies are explained from the perspective of laboratory testing strategies, to provide theoretical support for the practical application of liver cancer diagnostic strategies.
7.Dendrobium Officinale Polysaccharide Alleviates Hepatic Fibrosis via Epithelial-Mesenchymal Transition
Liuqing YANG ; Qin FAN ; Yajie BAI ; Ying XU ; Jina LUO ; Jiamao CHENG ; Haiyan CHEN
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(1):76-84
ObjectiveTo investigate the effect of Dendrobium officinale polysaccharide (DOP)on CCl4-induced hepatic fibrosis(HF)and its mechanism. MethodsA total of 56 male SD rats were randomly divided into seven groups: normal group(NG),model group(MG),colchicine group(CG, 0.1 mg/kg), Fuzheng Huayu group(FG, 0.45 g/kg),low-dose DOP group(LDG, 0.05 g/kg),middle-dose DOP group(MDG, 0.1 g/kg)and high-dose DOP group(HDG,0.2 g/kg),with 8 rats in each group. HF rat model was established by subcutaneous injection with 40% CCl4 olive oil mixture, every 3-day for 10 weeks. At the end of the sixth week, the drug groups were treated with colchicine, Fuzheng Huayu and DOP solution by gavage respectively, once a day for 4 weeks. NG and MG groups were similarly handled with an equal amount of 0.9 % normal saline. Liver histopathology was detected using hematoxylin-eosin (HE), Masson and Sirius red staining; blood biochemistry was tested for liver function and four indicators of HF; RT-qPCR and Western Blot were used to measure the expression of α-SMA, Col-I, E-cadherin, and ZEB1 genes and proteins in the liver tissues of rats, respectively. ResultsHE, Masson, and Sirius red staining showed that the liver tissue of MG rats had typical pathologic features of HF, and the degree of HF was alleviated in LDG, MDG, and HDG rats, respectively. Liver function test results showed that the serum AST, TBIL, and AKP levels were significantly lower in LDG, MDG, and HDG, compared with those of the MG (P < 0.05 or < 0.01). Meanwhile, ALT levels in serum deceased remarkably except in LDG (P < 0.05 or < 0.01). The four results of HF showed that the serum HA, LN, PC-Ⅲ, and COL-Ⅳ levels in LDG, MDG, and HDG rats were significantly decreased compared with those of the MG (P < 0.05 or < 0.01). The relative expressions of α-SMA, COL-I, and ZEB1 genes and proteins were significantly decreased in the liver tissues of LDG, MDG, and HDG (P < 0.05 or < 0.01), and the relative expression of E-cadherin gene and protein increased (P < 0.05 or < 0.01). In addition, the expressions of HA, α-SMA, COL-I, ZEB1 and E-cadherin were dependent on the dose of DOP. ConclusionDOP alleviated the degree of CCl4 induced HF in rats by inhibiting the epithelial-mesenchymal transition in liver tissue.
8.Exploratory study on the role of tumor microenvironment-related gene CCR7 in Cuproptosis and its potential as a prognostic marker for liver cancer
Yuan CHEN ; Yunhui LI ; Jing LIANG ; Li WANG ; Renlong ZHU ; Jiayue MA ; Yajie WANG
Chinese Journal of Laboratory Medicine 2024;47(10):1169-1177
Objective:To explore the interplay between tumor microenvironment (TME)-associated genes, cuproptosis, and the prognosis of liver cancer through transcriptome sequencing and functional genomics analysis.Methods:Employing a hybrid approach that integrates bioinformatics with fundamental experimental research, we utilized the TCGA database to acquireexpression profiles and clinical-pathological information from 424 liver hepatocellular carcinoma patients. We evaluated ImmuneScore and StromalScore to categorize patients into high and low groups, subsequently identifying differentially expressed genes (DEG) at the intersection of these groups. Core DEG were identified through univariate Cox regression analysis and protein-protein interaction (PPI) network analysis. The association between the expression levels of core genes and the survival time of liver cancer patients was analyzed using the R language and Kaplan-Meier analysis, and verified using the Kaplan-Meier Plotter online database. We established a cuproptosis cell model and performed RNA-seq to examine gene expression alterations during copper-induced cell death, followed by in vitro cell experiments for verification.Results:A total of 1 701 and 2 041 DEG were llinked t ImmuneScore and StromalScore, respectively, encompassing 1 134 commonly upregulated genes and 60 commonly downregulated genes. The top 30 core genes from the PPI network's dominant nodes were cross-referenced with univariate Cox regression results, leading to the identification of the pivotal immune gene CCR7. CCR7 mRNA expression levels were higher in hepatocellular carcinoma tissues than in normal tissues ( P<0.05). Patients with high expression of CCR7 in liver cancer had a longer overall survival compared to those with low expression ( P=0.003). Treatment with elesclomol-CuCl2significantly curtailed the survival of hepatocellular carcinoma cel ( P<0.001). RNA-seq data from the cuproptosis model indicated a downregulation of CCR7 expression during the onset of cuproptosis [|log 2(FC)|=2.27, P<0.001], and downregulation of CCR7 expression enhanced the sensitivity of hepatocellular carcinoma cells to cuproptosis inducers. Conclusion:The TME-related gene CCR7 is implicated in cuproptosis, and its downregulation might facilitate the process in liver cancer.CCR7 holds potential as a biomarker for liver cancer prognosis.
9.Remyelination Regulated by microRNAs in Neurodegenerative Diseases: A Review
Manjing LI ; Qi LI ; Qingsen RAN ; Kunni CHEN ; Xinke DU ; Lina YANG ; Chunxia NIE ; Qing YANG ; Yujie LI ; Ying CHEN ; Yajie WANG ; Xiaogang WENG ; Weiyan CAI ; Xiaoxin ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):223-231
Demyelination of the central nervous system often occurs in neurodegenerative diseases, such as multiple sclerosis (MS). The myelin sheath, a layer of myelin membrane wrapping the axon, plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio, and further neuronal degeneration, which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath, remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes (OLs) derived from oligodendrocyte progenitor cells (OPCs) which are differentiated from neural stem cells (NSCs). The process of myelin regeneration, i.e., remyelination, is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs, as important regulators of neurodegenerative diseases, form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.
10.Analysis of Influencing Factors and Mechanism Model of Defensive Medicine based on Grounded Theory
Xinle YIN ; Huanyu ZHANG ; Juan ZHAO ; Chen WANG ; Yajie FENG ; Xinru LIU ; Yue ZHOU ; Libo LIANG
Chinese Hospital Management 2024;44(7):6-10,15
Objective To clarify the influencing factors of defensive medicine and provide ideas for preventing and re-solving defensive medicine.Methods Literature related to defensive medicine was searched,personnel related to de-fensive medicine were interviewed,and literature and interview data were coded with the method of grounded theo-ry,and related concepts and categories were summarized.Results After three levels of coding,52 initial concepts,23 initial categories,7 sub-categories and 3 main categories were sorted out,and the correlation among influencing factors was analyzed to build a three-dimensional model of"doctor-patient relationship-institutional system-social environment"influencing factors and their mechanism of action.Conclusion The influencing factors of defensive medi-cine mainly include doctor-patient relationship,institutional system and social environment.The three factors have an impact on defensive medicine through different mechanisms of action,which provides qualitative evidence for comprehensive analysis of factors in related studies of defensive medicine.

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