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1.
Journal of Clinical Hepatology ; (12): 682-687, 2022.
Article in Chinese | WPRIM | ID: wpr-922980

ABSTRACT

Lysyl oxidase (LOX) family is a group of copper-containing amine oxidases composed of LOX and LOX-like proteins (LOXL1, LOXL2, LOXL3, and LOXL4). It is overexpressed in tumor tissue and promotes tumor metastasis through covalent cross-linking of extracellular matrix, with the functions of cell growth control, tumor inhibition, senescence, and chemotaxis. In recent years, more and more evidence has shown that LOX family members play a key role in the pathogenesis of hepatocellular carcinoma (HCC), suggesting that they have great potential as therapeutic targets. This article reviews the role of LOX family members in the development and progression of HCC and the intervention effect of traditional Chinese medicine extracts on HCC by regulating LOX family, in order to provide a reference for further research on the prevention and treatment of HCC.

2.
China Pharmacy ; (12): 2224-2229, 2022.
Article in Chinese | WPRIM | ID: wpr-943062

ABSTRACT

OBJECTIVE To study the protective effect and mechanism of Shiyifang medicinal wine (SYF) on knee osteoarthritis(KOA)of rabbit induced by papain . METHODS Thirty-five rabbits were randomly divided into blank group ,model group,positive group (Diclofenac diethylamine emulsion 200 mg/kg),SYF high -dose group (386 mg/kg)and SYF low -dose group(97 mg/kg),with 7 rabbits in each group (all had 4 males and 3 females). Except for the blank group ,the other groups ’ rabbits were injected 0.5 mL papain mixture (containing 2% papain and 0.03 mol/L L -cysteine)into the right knee cavity on day 1, 4 and 7,to replicate KOA model . Blank group was given constant volume of normal saline . From the 15th day ,drugs were applied to right hind knee joints of rabbits in each group ,twice a day for 20 days. At the same time ,the diameter of right knee joints of rabbits was measured by vernier calipers at day 0,8,14 and 35 to calculate swelling degree . After the experiment ,the levels of IL-1β,TNF-α and PGE 2 in synovial tissue were determined by enzyme -linked immunosorbent assay . Hematoxylin-eosin(HE) staining was used to prepare the sections of synovial tissue ,and the pathological changes were observed . The relative mRNA expressions of TLR 4,MyD88 and NF - кB p 65 in the TLR 4/MyD88/NF- кB signaling pathway were detected by real -time quantitative polymerase chain reaction . The relative protein expressions of TLR 4,MyD88,NF-кB p 65 and p -NF-кB p 65 were detect by Western blot . RESULTS Compared with blank group,the degree of knee swelling could be increased in model group ,the pathological damage of synovial tissue was more serious ,and the levels of IL -1β,TNF-α and PGE 2 were increased significantly in synovial tissue (P<0.05). The relative expression levels of TLR 4,MyD88,NF-кB p 65 mRNAs and TLR 4,MyD88,p-NF-кB p 65 proteins were significantly increased(P<0.05). Compared with model group ,swelling degree of right hind knee and the pathological injury degree of synovial tissue were significantly improved in each treatment group ,while the levels of IL -1β,TNF-α and PGE 2 in synovial tissue were significantly decreased (P<0.05). The relative mRNA expressions of TLR 4,MyD88 and NF -кB p 65 and relative protein expressions of TLR 4,MyD88(except for SYF low -dose group )and p -NF-кB p 65 were all significantly decreased (P<0.05). CONCLUSIONS SYF shows protective effect on KOA induced by papain ,the mechanism of which is associated with decreasing the levels of IL -1β,TNF-α and PGE 2 and down -regulating TLR 4/MyD88/NF-кB signaling pathway .

3.
Journal of Clinical Hepatology ; (12): 2182-2187, 2022.
Article in Chinese | WPRIM | ID: wpr-942684

ABSTRACT

The cytochrome P450 (CYP) family is the most important drug-metabolizing enzyme in human body and is responsible for the metabolism of endogenous and exogenous compounds. As the main site of the expression of the CYP family, the liver is the metabolic center of drugs, and in recent years, the role of the CYP family in the liver has attracted wide attention from the scholars in China and globally. This article reviews the distribution differences of the CYP family from the aspects of anatomy, genetics, and genomics, changes in the expression of the CYP family in the pathological processes such as non-alcoholic fatty liver disease, alcoholic liver disease, liver fibrosis, liver cirrhosis, and hepatocellular carcinoma, and the effect of CYP family-mediated enzyme activity on the treatment effect of pharmacotherapy for metabolic-associated liver diseases, in order to provide important enlightenment for identifying key drug intervention targets in diseases and enhancing clinical efficacy and safety.

4.
Journal of Clinical Hepatology ; (12): 1931-1936, 2022.
Article in Chinese | WPRIM | ID: wpr-941566

ABSTRACT

Glycolysis plays an important role in the development and progression of liver diseases and shows varying degrees of enhancement in different liver diseases, and it is closely associated with mitochondrial dysfunction (oxidative phosphorylation deficiency and reactive oxygen species production), which helps to fill energy production deficiency caused by impaired oxidative phosphorylation. Therefore, it might be possible to search for potential new therapies for liver diseases through targeted regulation of the key factors in aerobic glycolysis, such as hexokinase 2, pyruvate kinase M2, and other regulatory pathways. From the perspective of the association between glycolysis and liver diseases, this article elaborates on the therapeutic significance and potential value of glycolysis in liver diseases, in order to provide new ideas for the diagnosis and treatment of liver diseases.

5.
Journal of Clinical Hepatology ; (12): 461-465, 2022.
Article in Chinese | WPRIM | ID: wpr-920913

ABSTRACT

Sphingomyelinases (SMase) are the main enzymes that regulate the signaling pathway of sphingomyelin and the metabolism of related products, and they are involved in the key steps of the complex metabolic process of sphingomyelin. In recent years, many studies have shown that SMase is involved in the biological processes such as cell cycle arrest, cell migration, and inflammation and promotes the development and progression of hepatocellular carcinoma by regulating the apoptosis and proliferation of tumor stem cells. SMase has an important potential biological value in the development, progression, diagnosis, and treatment of hepatocellular carcinoma. This article summarizes the exact role of SMase in the development and progression of hepatocellular carcinoma, in order to provide new ideas and strategies for the clinical treatment of hepatocellular carcinoma and the development of new drugs.

6.
Journal of Clinical Hepatology ; (12): 480-484, 2021.
Article in Chinese | WPRIM | ID: wpr-873426

ABSTRACT

Liver failure is a common critical medical disease, and extensive liver cell necrosis within a short period of time exceeds the regeneration capacity of liver cells and thus results in an extremely high fatality rate. Promotion of effective liver regeneration is the key to antagonizing liver failure. Recent studies have shown that bile acid, farnesoid X receptor (FXR), and intestinal microecology play an important role in liver failure and liver regeneration. This article reviews the association between bile acid, FXR, and intestinal microecology and their role in liver failure and liver regeneration, so as to provide new ideas for the treatment of liver failure in clinical practice.

7.
Journal of Clinical Hepatology ; (12): 444-447, 2021.
Article in Chinese | WPRIM | ID: wpr-873419

ABSTRACT

Liver cancer has always been a threat to national health since liver disease has a high incidence rate in China. At present, methods for the prevention and treatment of liver cancer have unsatisfactory effects in clinical practice, and with in-depth studies, scholars have changed their focus to cancer-associated fibroblasts (CAFs) in tumor microenvironment. More and more evidence has shown that CAFs may provide a new target for the prevention and treatment of liver cancer. This article summarizes the role of CAFs in the development and progression of liver cancer and the potential of CAFs in the treatment of liver cancer.

8.
Journal of Clinical Hepatology ; (12): 2696-2700, 2021.
Article in Chinese | WPRIM | ID: wpr-905024

ABSTRACT

Acute-on-chronic liver failure (ACLF) is a life-threatening disease with a high risk of multiple organ failure, sepsis, and death. ACLF activates innate and acquired immune responses in human body and thus leads to the progression of persistent systemic inflammatory response syndrome and multiple organ dysfunction, leading to the high mortality rate of this disease. Dysregulated immune response plays a key role in disease progression, and immunotherapy may help to target immune-mediated organ damage and inhibit the progression of liver failure. This article reviews the role and mechanism of drugs and means with a potential immune regulatory effect in ACLF, in order to provide a reference for immunotherapy for ACLF.

9.
Journal of Clinical Hepatology ; (12): 2676-2679, 2021.
Article in Chinese | WPRIM | ID: wpr-905019

ABSTRACT

The incidence rate of nonalcoholic fatty liver disease (NAFLD) is increasing. Diet is considered one of the main driving forces regulating the composition of intestinal microbiota, and the intestine and the liver are closely linked through the portal vein, so changes in gut microbiota may affect liver function and promote inflammation, insulin resistance, and steatosis, thereby causing NAFLD. This article elaborates on the relationship between diet, gut microbiota, and the liver and the research advances in how this axis promotes the progression of NAFLD, as well as the change in potential mechanism due to intestinal dysbacteriosis and related treatment methods.

10.
Journal of Clinical Hepatology ; (12): 2488-2492, 2021.
Article in Chinese | WPRIM | ID: wpr-904977

ABSTRACT

Absent in melanoma 2 (AIM2) is a cytoplasmic double-stranded DNA (dsDNA) sensing protein that can recognize the dsDNA released during cell disturbance and pathogen invasion and trigger the activation of inflammasome cascade. Activation of inflammasomes leads to the maturation and release of inflammatory cytokines (interleukin-1β and interleukin-18), induces pyroptosis, and initiate innate immune response. Among these inflammasomes, AIM2 and its mechanism of action and clinical significance in liver diseases has become a research hotspot at present. This article summarizes and discusses the importance of AIM2 in the pathogenesis of various liver diseases including nonalcoholic fatty liver disease, hepatitis B virus infection, liver fibrosis, liver cirrhosis, and hepatocellular carcinoma, so as to provide new ideas and a reference for clinical treatment.

11.
Journal of Clinical Hepatology ; (12): 2308-2315, 2021.
Article in Chinese | WPRIM | ID: wpr-904938

ABSTRACT

Objective To investigate the mechanism of action of Xiaochaihu decoction in the treatment of hepatitis B based on network pharmacology. Methods The TCMSP database was used to obtain the main chemical components and action targets of the seven traditional Chinese medicines in Xiaochaihu decoction; the GeneCards and OMIM databases were used to obtain the targets associated with hepatitis B; the STRING online platform was used to construct a PPI network of potential targets, and R language was used to perform gene ontology (GO) functional enrichment analysis and KEGG pathway analysis; Cytoscape 3.7.2 was used to construct an "active component-core target" network and perform a topology analysis of this network; AutoDock vina and related software were used to perform molecular docking and visualized analysis of the active components with high value and the core targets in the network. Results A total of 193 main chemical components (including quercetin, kaempferol, wogonin, and naringenin) and 247 related targets were screened out, among which the key targets included RELA, MAPK1, TP53, ESR1, EGFR, and AKT1. A total of 2612 enrichment items were obtained by GO functional enrichment analysis, which were mainly involved in regulating the biological processes such as cell response to chemical stress, response to drugs, oxidative stress response, and lipopolysaccharide response. A total of 174 pathways were obtained by the KEGG pathway analysis, mainly involving hepatitis B, PI3K-AKT signaling pathway, and MAPK signaling pathway. Molecular docking results showed that the main active components had strong binding force to core targets, and the protein crystal complex had a stable conformation. Conclusion This study preliminarily shows that Xiaochaihu decoction exerts a therapeutic effect on hepatitis B through multiple components, targets, and pathways.

12.
Journal of Clinical Hepatology ; (12): 2488-2492, 2021.
Article in Chinese | WPRIM | ID: wpr-904927

ABSTRACT

Absent in melanoma 2 (AIM2) is a cytoplasmic double-stranded DNA (dsDNA) sensing protein that can recognize the dsDNA released during cell disturbance and pathogen invasion and trigger the activation of inflammasome cascade. Activation of inflammasomes leads to the maturation and release of inflammatory cytokines (interleukin-1β and interleukin-18), induces pyroptosis, and initiate innate immune response. Among these inflammasomes, AIM2 and its mechanism of action and clinical significance in liver diseases has become a research hotspot at present. This article summarizes and discusses the importance of AIM2 in the pathogenesis of various liver diseases including nonalcoholic fatty liver disease, hepatitis B virus infection, liver fibrosis, liver cirrhosis, and hepatocellular carcinoma, so as to provide new ideas and a reference for clinical treatment.

13.
Journal of Clinical Hepatology ; (12): 2308-2315, 2021.
Article in Chinese | WPRIM | ID: wpr-904888

ABSTRACT

Objective To investigate the mechanism of action of Xiaochaihu decoction in the treatment of hepatitis B based on network pharmacology. Methods The TCMSP database was used to obtain the main chemical components and action targets of the seven traditional Chinese medicines in Xiaochaihu decoction; the GeneCards and OMIM databases were used to obtain the targets associated with hepatitis B; the STRING online platform was used to construct a PPI network of potential targets, and R language was used to perform gene ontology (GO) functional enrichment analysis and KEGG pathway analysis; Cytoscape 3.7.2 was used to construct an "active component-core target" network and perform a topology analysis of this network; AutoDock vina and related software were used to perform molecular docking and visualized analysis of the active components with high value and the core targets in the network. Results A total of 193 main chemical components (including quercetin, kaempferol, wogonin, and naringenin) and 247 related targets were screened out, among which the key targets included RELA, MAPK1, TP53, ESR1, EGFR, and AKT1. A total of 2612 enrichment items were obtained by GO functional enrichment analysis, which were mainly involved in regulating the biological processes such as cell response to chemical stress, response to drugs, oxidative stress response, and lipopolysaccharide response. A total of 174 pathways were obtained by the KEGG pathway analysis, mainly involving hepatitis B, PI3K-AKT signaling pathway, and MAPK signaling pathway. Molecular docking results showed that the main active components had strong binding force to core targets, and the protein crystal complex had a stable conformation. Conclusion This study preliminarily shows that Xiaochaihu decoction exerts a therapeutic effect on hepatitis B through multiple components, targets, and pathways.

14.
Journal of Clinical Hepatology ; (12): 204-208, 2021.
Article in Chinese | WPRIM | ID: wpr-862571

ABSTRACT

Acute liver failure is a serious and complex liver disease with a high short-term mortality rate. Its pathogenesis remains unknown and there is still a lack of effective drugs. Animal models play an important role in further revealing the pathogenesis of acute liver failure and the therapeutic mechanism of drugs, and the selection of experimental animals and preparation methods is the key to the effective implementation of research. This article summarizes the commonly used and new animal models of acute liver failure in recent years and the corresponding preparation methods and divides the animal models of acute liver failure into following four categories: chemical drug model, surgical model, infection model, and other models. Meanwhile, the above models are evaluated based on Terblanche and Hickman evaluation criteria for liver failure models, hoping to provide a reference for model selection and evaluation in basic research on this disease.

15.
Journal of Clinical Hepatology ; (12): 2617-2620, 2020.
Article in Chinese | WPRIM | ID: wpr-829654

ABSTRACT

Bile acids (BAs) are produced in the liver and are the final product of cholesterol catabolism, with a wide range of biological effects. This article reviews the research advances in the synthesis, transport, and metabolism of BAs and the role of BAs in regulating hepatocytes and immunity via enterohepatic circulation, as well as the current research on traditional Chinese medicine in the regulation of BAs, in order to further understand the mechanism of action of BAs in affecting intestinal flora and liver function, expand the knowledge of its regulatory mechanism, explore the mechanism of action of traditional Chinese medicine and related pathways in regulating BAs, and provide new ideas for the prevention and treatment of liver-related systemic diseases by regulating BAs.

16.
Journal of Clinical Hepatology ; (12): 2375-2379, 2020.
Article in Chinese | WPRIM | ID: wpr-829422

ABSTRACT

At present, hepatic encephalopathy has a relatively high mortality and thus greatly affects patients’ quality of life. This article describes the changes of intestinal flora in patients with hepatic encephalopathy and analyzes the mechanism of action of intestinal flora in hepatic encephalopathy and related treatment methods. It is pointed out that the development of hepatic encephalopathy is closely associated with intestinal flora, and clinical treatment by regulating intestinal flora has achieved a marked effect in patients with hepatic encephalopathy. In the future, the research on intestinal flora in patients with hepatic encephalopathy can be deepened to provide better regimens for the treatment of hepatic encephalopathy.

17.
Journal of Clinical Hepatology ; (12): 2847-2850, 2020.
Article in Chinese | WPRIM | ID: wpr-837663

ABSTRACT

As a novel form of programmed cell death different from cell necrosis, apoptosis, and autophagy discovered in recent years, pyroptosis is characterized by cell membrane rupture and release of cell contents and proinflammatory factors mediated by gasdermin, thus leading to cell death. Pyroptosis signaling pathways can be classified into classical pathways dependent on caspase-1 and non-classical pathways dependent on caspase-4/5/11; the activation of caspase-1 in classical pathways depends on the function of inflammasome, while the direct activation of caspase-4/5/11 is observed in non-classical pathways, which leads to the lysis of gasdermin D and induce the formation of membrane pores, the maturation and release of interleukin-1β and interleukin-18, and the rupture of cell membrane to cause pyroptosis. Latest research has shown that pyroptosis plays an important role in the development and progression of chronic liver diseases. This article introduces the mechanism of pyroptosis and summarizes the role of pyroptosis in the development and progression of nonalcoholic fatty liver disease, alcoholic liver disease, viral hepatitis, liver cirrhosis, and hepatocellular carcinoma, in order to provide new ideas and methods for the prevention and treatment of liver diseases in clinical practice.

18.
Journal of Clinical Hepatology ; (12): 1874-1879, 2020.
Article in Chinese | WPRIM | ID: wpr-825048

ABSTRACT

The development and progression of nonalcoholic fatty liver disease (NAFLD) have complex potential mechanisms. The traditional “two-hit” pathophysiological theory has been challenged, and in recent years, an increasing number of studies have been performed to investigate the interaction between insulin resistance, adipokines, and other unknown pathogenic factors in various organs. This article summarizes the factors of the liver, intestinal tract, hypothalamus, and extracellular cysts, as well as genetic factors, with an emphasis on the synergistic mechanism of action of the liver and extrahepatic organs in the pathogenesis of NAFLD, in order to provide a reference for obtaining new insights into NAFLD regulatory network and determining new targets for the prevention and treatment of NAFLD.

19.
Journal of Clinical Hepatology ; (12): 1415-1419, 2020.
Article in Chinese | WPRIM | ID: wpr-822204

ABSTRACT

Liver failure is a syndrome of severe liver diseases commonly seen in clinical practice, and it has a high mortality rate and thus becomes one of the critical diseases in internal medicine. Massive hepatocyte death and the extent of hepatocyte death exceeding the liver’s regenerative capacity are considered the core events in the development and progression of liver failure, and direct injury and immune-mediated inflammatory injury are the two main factors in this process. An increasing number of evidence has shown that host immune response and inflammatory cascade play an important role in the pathogenesis of liver failure. This article reviews the mechanism of action of immunoregulation (congenital and adaptive) and inflammatory injury (inflammation inducers, receptor cells, and inflammatory mediators) in the process of hepatic failure, as well as the interactions between immune response and immune cells and between inflammatory response and inflammatory factors, in order to help understand the pathogenesis of liver failure and provide new ideas for the diagnosis and treatment of liver failure and drug research and development.

20.
Journal of Clinical Hepatology ; (12): 2346-2350, 2019.
Article in Chinese | WPRIM | ID: wpr-778749

ABSTRACT

Immune cascade due to inflammasome has become a research hotspot in recent years, and the role of NLRP3 inflammasome in the development and progression of liver diseases has attracted more and more attention. This article analyzes the action characteristics and regulatory mechanism of NLRP3 inflammasome in liver diseases, such as viral hepatitis, liver fibrosis, nonalcoholic fatty liver disease, liver failure, and liver cancer, and establishes targeted therapy based on NLRP3 inflammasome to regulate immune response triggered by inflammasome, in order to provide new ideas for the prevention and treatment of liver diseases.

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