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Liver sinusoidal endothelial cells (LSECs) are the highest proportion of liver non-parenchymal cells with fenestrae structure and high endocytic ability maintaining liver homeostasis and playing an indispensable role in the physiology and patholo-gy of the liver.LSECs are involved in the regulation of patholog-ical process in nonalcoholic fatty liver disease(NAFLD),alco-holic fatty liver(AFL),hepatocellular carcinoma(HCC),liverregeneration and liver fibrosis mainly via antiinflammation,endocytosis,secretion of angiocrine signals and maintaining thequiescence phenotype of HSCs.This review highlights the physiological function of LSECs and the different roles in different pathological conditions,which aims to provide a new perspectivefor the treatment of liver diseases through targeting LSECs.
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Nicotinamide adenine dinucleotide phosphate oxidase ( NOXs) contributes to the production of reactive oxygen species ( ROS) in liver fibrosis, resulting in the activation of endoplas-mic reticulum stress ( ERS ) and IRE1α-XBP1 signaling path-way. ROS is a series of oxygen metabolites and its derivatives, produced by the single electron reduction of molecular oxygen ( O2 ) , including superoxide anion ( O2- ) , hydroxyl radical (-OH) , hydrogen peroxide ( H2 O2 ) , hypochlorite ion ( OCl-) and so on. They can interact with a large number of molecules, including small inorganic molecules, proteins, lipids, carbohy-drates and nucleic acids, resulting in lipid peroxidation of cell damaging molecules. And as a second messenger, ROS can also affect the proliferation and activation of HSC in liver fibrosis, and induce the hepatocyte apoptosis through a variety of cellular signal transduction. Here we review the current status of the study on the mechanism of NOXs in liver fibrosis.
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Aim To explore the inhibitory effect of li-gustrazine combined with paeonol on rat liver fibrosis induced by CCl4 and its mechanisms,so as to provide new treatment strategies for liver fibrosis in clinical. Methods Cleaning laboratory male SD rats were ran-domly divided into blank control group,model group (CCl4 ),ligustrazine group,paeonol group and combi-nation group (ligustrazine+paeonol).HE staining was used to observe the pathological change.Masson stai-ning and Sirius red staining was used to observe the collagen deposition.The levels of serum ALT,AST, ALP and hydroxyproline were detected by automatic bi-ochemistry analyzer.Western blot detected the markers of liver fibrosis.HSC-T6 cell was divided into model group,ligustrazine group,paeonol group and combina-tion group.The protein and gene expression of inflam-mation and apoptosis pathway was analyzed by Western blot and real time-PCR.Results Ligustrazine com-bined with paeonol could significantly improve liver tis-sue pathology changes caused by CCl4 .It could reduce serum ALT, AST, ALP and hydroxyproline levels. Moreover,it could also inhibit liver fibrosis marker protein expression,and thus reduce the deposition of collagen fibers.The effect was better than that in sin-gle intervention group.Combination group could inhib-it the inflammatory pathways related protein expression in HSC cells and promote the apoptosis of HSC cells. Conclusion Ligustrazine in combination with paeonol has significant anti-fibrosis effect,and the effect is bet-ter than both single intervention.The effect may be due to the interference with TNF-α/NF-κB pathway in the HSC cells,which promotes its apoptosis and inhib-its the generation of extracellular matrix.
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Farnesoid X receptor ( FXR) plays a key role in me-tabolism of substance, such as bile acid, lipid, glucose,( etc) . Newly published credible discoveries have claimed that as a reg-ulatory hub in metabolism, FXR is closely linked with diverse chronic liver diseases, including viral hepatitis, alcoholic fatty liver disease, nonalcoholic fatty liver disease, hepatic fibrosis and hepatocellular carcinoma. This review summarizes the roles and mechanisms of FXR during the courses of chronic liver dis-eases, aiming at providing novel insights and therapeutic target for antifibrotic research and drug development.
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Liver fibrosis is a major cause of morbidity and mor-tality worldwide which poses a great threat to public health. Con-siderable evidence suggests that the immune system is closely re-lated to the development of hepatic fibrosis especially the dendrit-ic cells ( DCs) . In recent years, many studies have showed that DCs play a key role in regulating the immune function of liver, which not only mediate the activation of the immune system and inflammation reaction in liver, but influence the occurrence and development of liver fibrosis. Further study has found that DCs exert different effects on liver fibrosis at different stages of the disease, and it exerts anti-fibrosis in early stages and recession period, while plays opposite effect in the middle of the disease. This article reviews the research progress of the role of DCs in liver fibrosis and discusses the underlying mechanisms of DCs in regulation of liver fibrosis, which may provide references for bas-ic and clinical studies of liver fibrosis.
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Tumor metastasis is one of the most important biologi-cal characteristics of malignant tumor, and it is also the main factors that cause treatment failure and poor prognosis. Clinical studies have shown that the number of platelets in patients with malignant tumor increased more significantly than that in benign tumor patients and healthy people, which indicate that platelet might be involved in the development process of tumor. Further study found that in the process of cancer spreading to blood, platelet could interact with tumor cells to form tumor emboli, helped tumor cells escape from immune surveillance, thus pro-moted the tumor metastasis. In recent years, related mechanisms on platelets in promoting tumor metastasis were revealed gradual-ly, and several targeted therapies based on platelets were also carried out. This paper reviews the role of platelet in mediating tumor metastasis by hematogenous spread and its mechanisms and discusses the therapy strategies that target platelet, which may provide references for follow-up research and clinical treat-ment.
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Liver fibrosis occurs as compensatory responses to tis-sue repairing process in a wide range of chronic liver injures.It is characterized by excessive deposition of extracellular matrix (ECM)in liver tissues.The new discovery shows that suppres-sor of cytokine signaling (SOCS-3)is strictly associated with fi-brogenic progression of chronic liver diseases.Recent basic and clinical investigations also demonstrate that liver fibrogenesis is accompanied by SOCS-3,which critically determines the patho- genesis and prognosis of liver fibrosis.This review summarizes current knowledge on SOCS-3 and the relationships between SOCS-3 and liver fibrosis.On the other hand,it also presents the different strategies that have been used in experimental mod-els to counteract excessive SOCS-3 and the role of SOCS-3 in the prevention and treatment of liver fibrosis.
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MTH1 (MutT Homolog1 )as MutT homologous en-zyme,is a nucleotide pyrophosphatase,mainly involved in DNA damage repair process,especially plays an important role in the process of DNA replication in tumor cells.Recent studies have found that MTH1’s function is responsible for the development of a variety of tumors.Studies have shown that,MTH1 can remove tumor cells’oxidative DNA elements detrimental to the function-al structure,protecting tumor cell division and proliferation, maintaining tumor cell survival,however,normal cells do not need MTH1.Therefore,MTH1 may be only closely associated with abnormal cell growth.This makes MTH1 as therapeutic tar-gets that have been paid much attention.This article reviewed the relationship of MTH1 and tumor,discussed the mechanisms of MTH1 in tumor growth MTH1 and tumor treatment,so as to provide reference for clinical research and treatment of tumor.
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Histone modification participates in the occurrence and development of the diseases though affecting gene transcrip-tion activity by acetylation,methylation,phosphorylation,and other forms.It is an important field in the study of epigenetics. Numerous studies have demonstrated that histone modification plays an important role in the occurrence and development of liv-er diseases.This paper reviews the recent progress in under-standing the role and mechanisms of histone modification in alco-holic liver disease,nonalcoholic fatty liver disease,viral hepati-tis,liver fibrosis and hepatocellular carcinoma,with an aim to provide a theoretical basis for the treatment of liver diseases and drug development.
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Hedgehog pathway is an osteogenesis-related signaling pathway . During embryonic development , it regulates the growth and proliferation of progenitor cells and tissue formation. This pathway can be activated during liver injury. Activated Hedge-hog signaling pathway is involved in many aspects of liver wound-healing responses, including hepatic progenitor cell pro-liferation, myofibroblast transdifferentiation, apoptosis of various types of liver cells, inflammatory reactions, and vascular remod-eling. This article reviews the research progress in the role of Hedgehog signaling pathway in liver injury and the underlying mechanisms. The potential drug targets are also discussed. This review is to provide novel insights into antifibrotic research and therapeutic targets.
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AngiotensinⅡ( AngⅡ) is the main functional bioac-tive peptide of the renin angiotensin system,and its basic function is to regulate salt-water homeostasis and blood pressure. Howev-er,recent studies have shown that AngⅡ plays a very important role in tumor formation and angiogenesis by acting on its type 1 receptor (AT1R) as a kind of potential growth factor. This arti-cle is a brief overview of the research on effects of AngⅡ-AT1R system in the process of tumor angiogenesis in recent years.
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Traditional 2D cell culture technology is widely used in cell culture field, but it lacks the formation of 3D matrix scaffold and lacks specific cytokines in vivo.Cells in 3D cell culture system are similar to cells in vivo for gene expression and cell activity. The article focuses on the application of three-dimensional cell culture technology in cancer research, including the construction of tumor microenvironment,tumor biological behavior, tumor angiogenesis, drug resistance and so on and provides a reference for cancer research workers.
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OBJECTIVE:To investigate the curriculum setting of clinical pharmacy in higher institution of traditional Chinese medicine.METHODS:Questionnaire survey was applied to investigate the work of clinical pharmacy in hospital of traditional Chinese medicine in Jiangsu province.The problems of clinical pharmacy were analyzed to explore training target and curriculum system of clinical pharmacy major with characteristics of traditional Chinese medicine.RESULTS:The curriculums of clinical pharmacy major in higher institution of traditional Chinese medicine were determined preliminary.CONCLUSION:Scientific and reasonable curriculum setting lay a strong foundation for the students to engage in the work of clinical pharmacy.
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Hepatic fibrosis is the most important pathologic course for chronic hepatic injury developing into hepatic cirrhosis. It is meaningful for treating liver disease by inhibiting the development of hepatic fibrosis. Recently, herbs of promoting blood circulation for removing blood stasis has their unique characteristics and exhibits great therapeutic effect on hepatic fibrosis. The review explains the function and mechanism of the promoting blood circulation for removing blood stasis herbs in treating hepatic fibrosis from the aspects of the monomer, effective constituent and compound recipe. It provides basis for application of promoting blood circulation for removing blood stasis herbs in study and treating hepatic fibrosis.