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Macropinocytosis, an evolutionarily conserved, actin-dependent form of endocytosis, is involved in various physiological processes, including nutrient absorption, antigen presentation, and cell signaling transduction and migration. Oncogene activation and tumor suppressor inactivation induce macropinocytosis in tumors in the digestive system, involved in tumorigenesis and progression, whereas the inhibition of macropinocytosis slows the aggressive phenotype of digestive system tumors and improves the efficacy of anti-tumor drugs. Macropinocytosis can also be used as a delivery route for anti-tumor drugs. Therefore, macropinocytosis has been widely studied to develop new methods for the treatment of digestive system tumors.This paper reviews the role of macropinocytosis in the body, the regulation of macropinocytosis-related signaling pathway, as well as the mechanism of macropinocytosis in colorectal cancer, pancreatic ductal adenocarcinoma, liver cancer and other digestive system tumors, to provide reference for related researches.
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Hepatocellular carcinoma (HCC) is the most common pathological type of primary liver cancer, with high fatality rate. The pathogenesis of HCC is complex, and the specific occurrence and development mechanism is still in the exploratory stage. CircRNA is a special endogenous noncoding RNA and mainly participates in the regulation of gene expression at the transcriptional and posttranscriptional levels. By regulating gene transcription, it acts as a molecular sponge of miRNA, participates in protein translation, and interacts with RNA binding protein (RBP). CircRNA is involved in the occurrence and development of HCC. Its abnormal expression in HCC cells is related to the pathological characteristics of HCC tissue, regulates the expression of downstream target genes, miRNA and proteins, participates in the proliferation, migration, invasion and apoptosis of HCC cells, and regulates tumor microenvironment and signal pathways, suggesting that circRNA may be a potential novel biomarker and therapeutic target for the diagnosis and prognosis of HCC. This paper reviews the biological mechanism of circRNA, its role in HCC, and research progress in diagnosis and treatment.
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Autophagy can regulate liver physiology and balance liver metabolism. Autophagy activation has a double-sided and complex effect on liver injury, and it is regulated by many factors and is associated with many protein pathways. This article summarizes the role of mTOR in the regulation of autophagy, which can inhibit or enhance autophagy through the PI3K/Akt upstream signaling pathway and participate in the physiological and pathological changes of related liver diseases. Therefore, this article reviews the research advances in the mTOR/PI3K/Akt autophagy pathway in liver injury, in order to provide new therapeutic targets for related liver diseases.
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Excessive lipid deposition, liver injury, and insulin resistance are hallmarks in the development and progression of nonalcoholic fatty liver disease (NAFLD). Liver X receptor (LXR) is a transcriptional regulator, and its two cell subtypes, LXRα and LXRβ, play a key role in regulating cholesterol metabolism, inducing anti-inflammation, and reducing insulin resistance. This article reviews the structure and function of LXR and its association with the pathogenesis of NAFLD, in order to provide new ideas and methods for the prevention and treatment of NAFLD.
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The development and progression of liver cancer have the stages of hepatitis, liver cirrhosis, precancerous lesion, and liver cancer, among which the malignant transformation of precancerous lesions of liver cancer is closely associated with the activation of hepatic stellate cells (HSC). By describing the activation of HSC, the generation of precancerous cells of liver cancer, the formation of inflammatory fibrotic microenvironment, and the association between HSC activation and precancerous lesion, this article points out that microRNAs can affect the malignant transformation of precancerous lesion of liver cancer by regulating the expression of related target genes and HSC activation, and the research in this field is expected to provide new ideas and targets for the prevention and treatment of liver cancer.
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The mitochondria in liver tissue not only provides energy for substance metabolism in hepatocytes, but also participates in hepatocellular injury and even apoptosis. It also plays an important role in several pathological processes closely associated with hepatocellular injury and apoptosis, such as hepatitis, hepatic fibrosis, precancerous lesion, and liver cancer. This article elaborates on the association between mitochondria and hepatocellular injury from the following aspects: the important role of the change in mitochondrial membrane permeability in hepatocellular injury, hepatocellular injury accelerated by ATP synthesis disorder and consumption, and the association of abnormal Ca2+ homeostasis in hepatocellular mitochondria with hepatocellular injury, in order to provide a theoretical basis for mitochondria-targeted prevention and treatment of chronic liver diseases due to hepatocellular injury.
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OBJECTIVE： To study the mechanism of wound healing promotion of Panax notoginseng-Bletilla striata gum sponge on diabetic foot ulcer （DFU） model rats. METHODS： Healthy SD rats were selected and given high-lipid and high-glucose diet， intraperitoneal injection of streptozotocin once to establish diabetes model. Neodymium-iron-boron magnet was used to press the back of rats to make ulcer wound then established DFU model. Totally 60 DFU model rats were randomly divided into group A（blank group， i.e. normal saline gauze group）， group B（vaseline gauze group），group C （gelatin sponge group） and group D （P. notoginseng-B. striata gum sponge group）， with 15 rats in each group. The rats were given corresponding gauze/sponge to cover the wound for intervention treatment， changing dressing once every 1-2 days. On the 3rd and 7th day after intervention， the wound healing of rats in each group was observed with naked eyes， and the wound healing rate was calculated. The wound margin tissue was collected to obtain HE staining section， and histopathological observation was conducted under microscope. mRNA expression of β-catenin， GSK-3β and Rspo3 in wound tissue were determined by RT-PCR. RESULTS： On the 3rd and 7th day after intervention， compared with group A， B， C， healing rate of group D was increased significantly （P＜0.05）； inflammatory cell infiltration， collagen deposition， capillary and granulation tissue growth in wound tissue increased significantly. The mRNA expression levels of β-catenin and Rspo3 all increased， and those of GSK-3β all decreased； except for the difference of β-catenin at the 3rd day and GSK-3β at the 7th day after intervention between group D and group C were not significant， the difference of other indicators was statistically significant （P＜0.05）. CONCLUSIONS： P. notoginseng-B. striata gum sponge can effectively promote the wound healing in DFU model rats， the mechanism of which may be associated with up-regulating the expression of β-catenin and Rspo3 mRNA and down-regulating the expression of GSK-3β mRNA.
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Ulcerative colitis is an intestinal inflammatory disease characterized by diarrhea, abdominal pain and purulent stool. Uncontrolled inflammation caused by macrophage hyper-activation is an important cause of ulcerative colitis. Therefore, inhibiting macrophage hyper-activation is an effective way to treat ulcerative colitis. Notch signaling pathway is involved in regulating the immune response of macrophages and promoting inflammation. NF-κB signaling pathway is the "star pathway" involved in inflammation. NLRP3 inflammatory body is involved in the activation of macrophages. Notch, NF-κB and NLRP3 inflammatory bodies constitute the upstream and downstream signal pathways in the existing immune inflammatory diseases. Notch signal pathway can regulate the activation of macrophage via NF-κB/NLRP3 inflammatory body signaling pathway.
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Humans , Colitis, Ulcerative , Cytokines , Macrophage Activation , NF-kappa B , NLR Family, Pyrin Domain-Containing 3 Protein , Receptors, Notch , Signal TransductionABSTRACT
Objective To investigate the distribution of femoro-popliteal artery chronic totally occlusions (CTO) and to analyze the influence of different risk factors on the distribution of lesions. Methods A total of 47 patients with CTA and DSA proved femoro-popliteal artery CTO, who were admitted to the Affiliated Beijing Shijitan Hospital of Capital Medical University during the period from January 2013 and May 2015, were enrolled in this study. In order to make a clear description about the distribution characteristics of the lesions, the superficial femoral artery was averagely divided into three segments (F1-F3), and the popliteal artery was also divided into three segments (P1-P3) according to the bony landmarks. Based on the CTA images (including 3D reconstruction images) and DSA images, the distribution of CTO lesions was determined. The factors that might influence the distribution of CTO lesions were collected, and the results were analyzed using multivariable logistic regression analysis. Results A total of 59 femoro-popliteal artery CTO lesions detected in 47 patients were included in this study. The average length of lesion segment was (12.91 ± 10.13) cm. According to the 6-section division method of femoro-popliteal artery, the lesions involved F1 (n=23), F2(n=34), F3(n=48), P1(n=18), P2(n=6) as well as P3(n=5) segments. Multivariable logistic regression analysis reveals that F1 segment was most prone to be affected by CTO lesions in patients with hypertension (RR=3.21) and in patients who had cigarette smoking habit (RR=1.76). In male patients, P1segment was more easil y involved by CTO lesions (RR=1.98). In patients with diabetes mellitus, the RR value was gradually increased from the proximal to the distal end of the blood vessel, indicating that the lesion was more likely to involve distal vessels. Conclusion The distributions of femoro-popliteal artery CTO lesions have certain characteristics, which are closely associated with femoro-popliteal artery hemodynamics and atherosclerosis risk factors.
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Objective To investigate the diagnostic values of direct lymphangiography for the thoracic duct outlet obstruction.Methods The image data of direct lymphangiography were retrospectively analyzed in 124 patients with lymphedema,Chylothorax,chylous ascites,chyluria and intestinal lymphangiectasis,and compared with the results of neck thoracic duct surgical exploration,2 radiologists reviewed DLG DSA images in a double blind manner.The number of neck stem,subclavian stem,bronchialmediastinal stem and TD terminal into blood obstruction on the operation side showed by DLG were assessed using Kappa analysis.Results Of 124 patients,80 patients had the left cervical lymphatic stem reflux on DLG,75 patients with the left subclavian lymphatic stem reflux,30 patients with the left bronchial-mediastinal lymphatie stem reflux,118 patients showed the thoracic duct outlet barrier into the blood.The consistency rate of DLG were 89.9％ (80/89),92.6％ (75/81),90.9％ (30/33) and 95.2％ (118/124) compared with the neck thoracic duct surgical exploration.Tow radiologists had a high degree of diagnostic consistency (K =0.82,P ＜ 0.05).In addition,114 patients (91.9％) had tortuous,dilated waist lymphatic stem,only 10 patients (8.1％) were normal.The cisterna chyli reflux were found in 92 patients (74.2％),intestinal stem reflux in 16 patients (12.9％),reflux to the kidney area in 11 patients (8.9％),to the pericardium reflux in 5 patients (4.0％),vaginal lymphatic leakage in 7 patients (5.6％),retroperitoneal lymph leakage in 2 patients (1.6％),pleural lymphatic leakage in 3 patients (2.4％),tracheal lymph leakage in 1 patient (0.8％).Conclusion Direct lymphangiography has a high consistency with the cervical thoracic duct surgical exploration in displaying thoracic duct outlet obstruction.
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Objective To evaluate the correlating clinical factors of coronary artery calcification score(CACS).Methods 141 patients suspected of coronary artery disease were included.They underwent multi-slice row computed tomography,pulse wave velocity ( PWV ),UCG and blood biochemistry within a period of 3 months.The subjects were divided into three groups according to CAC score:A(CACS =0-10),B ( CACS = 11-400),C ( CACS > 400).Results CACS was significantly associated with age,history of hypertension and diabetes mellitus.It was also associated with the presence of mitral annular calcification and aortic valve calcification,low ankel brachial pressure index(ABI) and high mean artery pressure(MAP) as well as high values of brachial ankel PWV (baPWV) and Upstroke time (UT).Muhifactorial logistic regression analysis showed that the presence of aortic valve calcification and mitral annular calcification,the history of diabetes mellitus and high value of UT were independently correlated with severe coronary artery calcification.Conclusions Aortic valve calcification,mitral annular calcification,history of diabetes mellitus,high value of UT were independently correlated with severe coronary artery calcification.Measurement of PWV and UCG should be performed before muhi-slicerow computed tomography,because the assessment of coronary artery lumen narrowing with multi-slice row computed tomography can not be carried out accurately in the presence of severe coronary artery calcification.
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The mitochondria in liver tissue not only provides energy for substance metabolism in hepatocytes, but also participates in hepatocellular injury and even apoptosis. It also plays an important role in several pathological processes closely associated with hepatocellular injury and apoptosis, such as hepatitis, hepatic fibrosis, precancerous lesion, and liver cancer. This article elaborates on the association between mitochondria and hepatocellular injury from the following aspects: the important role of the change in mitochondrial membrane permeability in hepatocellular injury, hepatocellular injury accelerated by ATP synthesis disorder and consumption, and the association of abnormal Ca2+ homeostasis in hepatocellular mitochondria with hepatocellular injury, in order to provide a theoretical basis for mitochondria-targeted prevention and treatment of chronic liver diseases due to hepatocellular injury.