摘要
ObjectiveTo investigate the effect of modified Weijingtang on the pyroptosis of RAW264.7 macrophages via the cysteinyl aspartate-specific protease-1 （Caspase-1）/gasdermin D （GSDMD） pathway. MethodLipopolysaccharide （LPS） was used to induce pyroptosis of RAW264.7 cells. The blank group was treated with the blank serum， and the intervention groups were treated with the sera containing different doses of modified Weijingtang. After 24 h， the viability of cells in different groups was examined by the cell counting kit-8 （CCK-8）. The pyroptosis and morphology of cells in each group were observed by a scanning electron microscope and a phase-contrast microscope， respectively. The mRNA and protein levels of nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3）， Caspase-1， and GSDMD in each group were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The levels of interleukin （IL）-18 and IL-1β in each group were measured by enzyme-linked immunosorbent assay. ResultUnder the electron microscope， RAW264.7 cells presented the best morphology and structure in the blank group and obvious pyroptosis and leakage of cell contents in the model （LPS） group. Compared with the model group， the intervention groups showed reduced pyroptosis to varying degrees， and the high-dose group had the closest cell morphology and structure to the blank group. Under the optical microscope， RAW264.7 cells were spherical in the blank group and irregular with protrusions in the model group. Compared with the model group， the intervention groups showed improved cell morphology， and the cell morphology in the group with the dose of 20% was the closest to that in the blank group. The mRNA and protein levels of NLRP3， Caspase-1， and GSDMD in the model group were higher than those in the blank group （P<0.05）. Compared with the model group， each intervention group showed down-regulated expression of the above indicators （P<0.05）. Compared with the blank group， the model group presented elevated levels of IL-18 and IL-1β （P<0.05）， which were lowered in the intervention （10%， 20%） groups （P<0.01）. ConclusionModified Weijingtang inhibits the pyroptosis of macrophages by down-regulating the Caspase-1/GSDMD pathway and reducing the release of proinflammatory cytokines.
摘要
Nonalcoholic fatty liver disease (NAFLD) has been renamed as metabolic-associated fatty liver disease, and systemic metabolic dysfunction has become one of the concerns of this disease. NAFLD is a metabolic disease based on dyslipidemia in the liver, which is closely associated with adipose tissue. Hepatokines and adipokines secreted by the liver and adipose tissue play an important role in regulating liver lipid metabolism. This article summarizes the hepatokines and adipokines that can promote or inhibit lipid metabolism, focusing on the mechanism of lipid metabolism mediated by hepatokines and adipokines in NAFLD, so as to provides ideas and a theoretical basis for clinical prevention and treatment.
摘要
Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease in which a large amount of fat accumulates in hepatocytes due to lipid metabolism disorders. Conventional anti-inflammatory and transaminase-lowering treatment regimens often have an unsatisfactory therapeutic effect, and restoring the normal biosynthesis and metabolism of lipids is the key to the treatment of NAFLD. Studies have shown that brown adipose tissue can improve metabolic diseases by enhancing insulin sensitivity and regulating lipid metabolism, and the treatment of NAFLD by promoting white fat browning has attracted wide attention in the medical field. This article reviews the mechanism of white fat browning in improving NAFLD and summarizes the hepatokines that can promote white fat browning, so as to provide new ideas for the clinical treatment of NAFLD.
摘要
Ferroptosis is a type of iron-dependent cell death driven by lipid peroxidation, and its mechanism is associated with iron homeostasis imbalance, lipid peroxidation, and slC7A11-GSH-GPX4 antioxidant system. Ferroptosis plays a key role in the development and progression of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), and inhibition of ferroptosis can almost completely inhibit the development of NASH. This article reviews the research advances in the mechanism of ferroptosis and its role in NAFLD/NASH and proposes the research strategies and technical means for ferroptosis, so as to provide a reference for research on the mechanism of NAFLD/NASH.
摘要
Objective To investigate the effect of Huatan Qushi Huoxue prescription on lipopolysaccharide (LPS)-induced pyroptosis of RAW264.7 cells and its mechanism. Methods An in vitro cell model of LPS-induced activated RAW264.7 was established and divided into blank group, model group, high-, middle-, and low-dose Huatan Qushi Huoxue prescription groups, and control group. The corresponding drug-containing serum intervention was performed for 24 hours. A scanning electron microscope was used to observe cell morphology, and immunofluorescence assay was used to perform quantitative localization of GSDMD-N. Results The cells in the blank group were round and regular in shape with smooth surface, and those in the control group were swollen, with folds on the surface and gaps in the capsule, which were consistent with the morphology of cell pyroptosis. The cells in the control group had bubbles on the surface with obvious pseudopodia and pores in cell membrane, and those in the high-dose group were not swollen and had a rough surface with pseudopodia, with no obvious pores in cell membrane. The cells in the low- and middle-dose groups were swollen and had a rough surface of cell membrane with pores and pseudopodia. Immunofluorescence assay showed that compared with the blank group, the model group had a significant increase in the positive staining intensity of GSDMD-N, and compared with the model group, the control group and the Traditional Chinese medicine group had a reduction in the positive staining intensity of GSDMD-N. Conclusion Huatan Qushi Huoxue prescription can improve the pyroptosis of macrophages and reduce the expression of GSDMD-N.
摘要
ObjectiveTo investigate the association of gene mutations in the pre-C, C, and basic core promoter (BCP) regions of hepatitis B virus (HBV) with traditional Chinese medicine (TCM) syndrome types in patients with chronic hepatitis B (CHB). MethodsA retrospective analysis was performed for the clinical data of CHB patients who were diagnosed and treated at the outpatient service and ward of Spleen, Stomach, and Hepatobiliary Department, The First Affiliated Hospital of Henan University of Chinese Medicine, from November 2014 to June 2018. Related clinical data were collected and recorded, including general information, HBV serological markers, HBV gene mutations, and information obtained by four TCM diagnostic methods. Syndrome differentiation and typing were performed for each patient with reference to the criteria for TCM syndrome differentiation of viral hepatitis, and the association of gene mutation in the pre-C, C, and BCP regions of HBV with TCM syndrome types was analyzed. The chi-square test was used for comparison of categorical data between groups, and the Kruskal-Wallis H test was used for comparison of continuous data between multiple or two groups. ResultsA total of 235 patients with CHB were enrolled, among whom 101 had internal retention of damp-heat, 88 had stagnation of liver Qi and spleen deficiency, 17 had blood stasis obstructing the collaterals, 19 had liver-kidney Yin deficiency, and 10 had spleen-kidney Yang deficiency. There were significant differences in sex, age, and course of disease between the patients with different TCM syndrome types (χ2=17.389, H=173.280, H=86.520, all P＜0.01), and there was a significant difference in age between the CHB patients with gene mutations in the pre-C, C and BCP regions of HBV (H=30.150, P＜0.001). There was a significant difference in the distribution of TCM syndrome types between the CHB patients with gene mutations in the pre-C, C and BCP regions of HBV (χ2=58.117, P＜0.001), and internal retention of damp-heat and stagnation of liver Qi and spleen deficiency were major TCM syndrome types accounting for 80.43%. The patients with internal retention of damp-heat tended to have A1762T and G1764A mutations, and those with stagnation of liver Qi and spleen deficiency tended to have G1896A, A1762T, and G1764A mutations; G1764A mutation was often observed in the patients with blood stasis obstructing the collaterals or liver-kidney Yin deficiency, and I97L mutation was often observed in the patients with spleen-kidney Yang deficiency. ConclusionGene mutations in the pre-C, C, and BCP regions of HBV are associated with TCM syndrome types in CHB patients, and internal retention of damp-heat and stagnation of liver Qi and spleen deficiency are the most common TCM syndrome types. I97L mutation is often observed in patients with spleen-kidney Yang deficiency.
摘要
Objective@#To investigate the effect of omeprazole on plasma concentration, efficacy and adverse reactions of capecitabine in patients with colon cancer.@*Methods@#Seventy-two patients with colon cancer treated with capecitabine were analysed retrospective. The patients treated with capecitabine combined with omeprazole were identified as experimental group and the capecitabine treatment alone as control group.The differences of blood concentration and the side effects of capecitabine between these two groups were compared.@*Results@#The plasma concentration of 5-Fluorouracilum in experimental group was (126.25±50.59) μg/ml, without significant difference of (123.09±56.70) μg/ml in control group (P=0.121). The incidence of Ⅲ to Ⅳ degree bone marrow suppression, nausea, vomiting, diarrhea and hand-foot syndrome in experimental group were 13.8%, 0%, 0% and 19.4%, respectively. In control group, the incidence of Ⅲ to Ⅳ degree bone marrow suppression, nausea, vomiting, diarrhea and the hand-foot syndrome were 11.1%, 0%, 0% and 19.4%, respectively, without significant difference of experimental group (P>0.05). The incidence of acid reflux and heartburn in the control group was 72.2%, significantly higher than 44.4% of the experimental group (P<0.05). The objective response rate (ORR) and progression-free survival time (PFS) in these two groups were 30.6% and 33.3%, and 8.0 month and 8.5 month, respectively, without significant difference (P>0.05).@*Conclusion@#The intravenous omeprazole attenuates reflux and heartburn of colon cancer patients treated with capecitabine, without affecting its plasma concentration and side effects and has no impact on the PFS of these patients.