1.Exploring the mechanism of action of curcumin in the treatment of silicosis based on network pharmacology and molecular docking
Zhijia WU ; Jiayun WU ; Yuanting LIANG ; Meimei ZHONG ; Wei WEI ; Yiru QIN ; Na ZHAO
China Occupational Medicine 2023;50(4):361-369
Objective To explore the mechanism of action of curcumin in the treatment of silicosis by network pharmacology combined with molecular docking technology. Methods The targets prediction network of curcumin in treating silicosis was established based on the collection of targets of curcumin and silicosis in multiple databases, cross-targets were submitted to the STRING database, and their connectivity was analyzed by Cytoscape software. Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the top 20 genes. The molecular docking was performed on the key targets to study the mechanism of action of curcumin in treating silicosis. Results A total of 311 targets related to curcumin, 270 targets related to silicosis, and 74 cross-targets were obtained from the databases. GO function analysis revealed 2 665 related pathways, and KEGG pathway enrichment analysis revealed 188 related pathways. Molecular docking results showed that curcumin had good binding ability with the targets of mitogen-activated protein kinase 3 (MAPK3), interleukin (IL) 6, serine/threonine kinase 1 (AKT1), vascular endothelial growth factor A (VEGFA), signal transducer and activator of transcription 3, albumin, Jun proto-oncogene, tumor necrosis factor (TNF), IL1B, tumor protein p53, C-C motif chemokine ligand 2 and fibronectin 1. Conclusion The therapeutical effects of curcumin on silicosis were implemented through multi-targets and multi-pathways. Curcumin may play a role in the treatment of silicosis by binding to the core targets MAPK3, IL6, AKT1, VEGFA and TNF and regulating the MAPK, IL6, TNF, phosphatidylinositol 3-kinase/protein kinase B and VEGF signaling pathways.
2.Mangiferin inhibits proliferation,migration and inflammatory factor expression of fibroblast-like synoviocytes in rheumatoid arthritis
Mengfan HU ; Qiuhui YAN ; Mengran DENG ; Meimei LIANG ; Liang LIANG ; Sisi YI ; Jiagang DENG ; Chenxia YUN
Chinese Journal of Tissue Engineering Research 2024;28(11):1690-1695
BACKGROUND:Mangiferin is a biphenylpyridone compound extracted from mango leaves,bark and roots.Previous studies have shown that mangiferin can exert anti-systemic inflammatory effects through the activation of transcription factors such as NF-κB and JAK/STAT. OBJECTIVE:To investigate the effects and mechanisms of mangiferin on proliferation,migration and inflammatory factor release of rheumatoid arthritis fibroblast-like synovial cells(RA-FLS). METHODS:RA-FLS were divided into blank group,R848(TLR7/8 agonists)stimulated group,mangiferin low-,medium-,high-dose groups(2,4 and 8 μg/mL)and positive control group(Cu-CPT8,TLR8 pathway inhibitor).The cytotoxic effect of different mass concentrations of mangiferin was detected using cell counting kit-8 method and the final cellular dosing mass concentration was screened.The proliferation ability of RA-FLS was detected by cell clone formation assay,the migration ability of RA-FLS was detected by scratch assay and Transwell migration assay,and the expression of interleukin 1β,interleukin 6 and tumor necrosis factor α mRNA in RA-FLS was detected by qRT-PCR. RESULTS AND CONCLUSION:Compared with the blank group,the viability of RA-FLS was inhibited after treatment with mangiferin at 2-10 μg/mL,but there was no significant difference among groups(P>0.05),indicating that the toxic effect on RA-FLS was minimal.Compared with the R848-stimulated group,mangiferin decreased the number of cell clones,the scratch healing rate and the number of migrating cells in all dosing groups(P<0.01);and the expression of interleukin 1β,interleukin 6 and tumor necrosis factor α mRNA was also reduced in the mangostin medium-and high-dose groups(P<0.01).Compared with the R848-stimulated group,the number of cell clones,the scratch healing rate and the number of migrating cells as well as the expression levels of interleukin 6 and tumor necrosis factor α mRNA were significantly reduced in the positive control group(P<0.05,P<0.01).But there was no significant difference in the expression level of interleukin 1β.To conclude,mangiferin may exert its anti-rheumatoid arthritis effects through the TLR7/8 signaling pathway by inhibiting RA-FLS proliferation,migration,and inflammatory factor release.
3.Association between apolipoprotein E polymorphism and myocardial infarction in patients with type 2 diabetes mellitus
Liang MA ; Yuan YUAN ; Yongwei JIANG ; Xiaomu KONG ; Wenquan NIU ; Xiao CONG ; Yi LIU ; Meimei ZHAO ; Peng GAO ; Shukun YAO ; Yongtong CAO
Chinese Journal of Laboratory Medicine 2021;44(10):926-930
Objective:To investigate the relationship between the E2 and E4 alleles of apolipoprotein E (apoE) gene and myocardial infarction (MI) in type 2 diabetes Mellitus (T2DM) patients, and to explore the relationship between apoE polymorphism and blood lipid metabolism.Methods:This case control study was conducted from August 2016 to March 2020 in China-Japan Friendship Hospital, 3 459 inpatients with T2DM were included including 3 044 patients without MI (T2DM group) and 415 patients with MI (T2DM+MI group). Real time fluorescent quantitative PCR was used to detect apoE polymorphism. Automatic biochemical analyzer was used to detect lipid levels. Logistic regression analyses were performed to determine the association of apoE with risk of MI in patients with T2DM.Results:(1) The frequency of E4 allele in T2DM+MI group (12.29%, 102/830) was significantly higher than in T2DM group (9.13%,556/6 088), while the frequency of E2 allele in T2DM+MI group (7.35%,61/830) was significantly lower than that in T2DM group (8.21%,500/6 088), P=0.012. Logistic regression analyses showed that E4 allele carrier (E3/E4+E4/E4) faced a higher risk for MI in T2DM patients ( OR=1.48, 95% CI 1.14-1.92, P=0.003), while E2 allele carrier(E2/E3+E2/E2)did not face a higher risk of MI in T2DM patients ( OR=0.88, P=0.642). (2) The levels of apoE polymorphism and blood lipid: The levels of TC, LDL-C and apoB increased in the order of E4 allele, wild type and E2 allele ( P<0.05). The levels of HDL-C, apoA1 and apoE decreased in the order of E4 allele, Wild type and E2 allele ( P<0.05). Conclusion:The E4 allele is a risk factor for MI in T2DM patients, and apoE polymorphism can affect blood lipid level in this patent cohort.
4.Application of case-based learning combined with online teaching in standardized residency training of rheumatology and immunology
Rongyue JING ; Lei XU ; Changsong XU ; Meimei XU ; Liang GUO ; Yueyue CHEN ; Yamei ZHU ; Bo XU
Chinese Journal of Medical Education Research 2023;22(11):1705-1708
Objective:To investigate the effectiveness of case-based learning (CBL) combined with online teaching in standardized residency training of rheumatology and immunology.Methods:A total of 78 individuals who participated in standardized residency training in Department of Rheumatology and Immunology in our hospital from June 2019 to August 2020 were included and divided into observation group and control group. The individuals in the control group received traditional teaching, and those in the observation group received CBL combined with online teaching. The physicians receiving standardized residency training were evaluated by theoretical examination, clinical operation skill assessment, and instructor rating, and the degree of satisfaction with teaching, degree of satisfaction with teaching methods, and classroom learning atmosphere were also evaluated.Results:The observation group had a theoretical examination score of (94.10±2.01) and a clinical operation skill assessment score of (90.44±1.57), which were significantly higher than those of the control group ( P<0.05), and the observation group had a significantly better instructor rating (89.36±1.33) than the control group ( P<0.05). Compared with the control group, the observation group had significantly higher degree of satisfaction with teaching (3.79±0.41), degree of satisfaction with teaching methods (3.92±0.27), and evaluation of classroom learning atmosphere (3.90±0.31) ( P<0.05). Conclusion:CBL combined with online teaching can help to improve learning efficiency, stimulate the enthusiasm for learning, expand clinical thinking, promote the growth of teaching and learning, and form a virtuous cycle among trainees receiving standardized residency training, which holds promise for further exploration.
5.Pharmacologically targeting molecular motor promotes mitochondrial fission for anti-cancer.
Yi QIAN ; Meimei ZHAO ; Qinghua HAN ; Jingkang WANG ; Lixi LIAO ; Heng YANG ; Dan LIU ; Pengfei TU ; Hong LIANG ; Kewu ZENG
Acta Pharmaceutica Sinica B 2021;11(7):1853-1866
Mitochondrial shape rapidly changes by dynamic balance of fusion and fission to adjust to constantly changing energy demands of cancer cells. Mitochondrial dynamics balance is exactly regulated by molecular motor consisted of myosin and actin cytoskeleton proteins. Thus, targeting myosin-actin molecular motor is considered as a promising strategy for anti-cancer. In this study, we performed a proof-of-concept study with a natural-derived small-molecule J13 to test the feasibility of anti-cancer therapeutics