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@#The potential antiviral and anti-inflammatory mechanism of Anti-601 Mixture, a traditional Chinese medicine compound preparation, was studied by network pharmacology and molecular docking. The chemical constituents and targets of astragali radix, phellodendri chinensis cortex, rhei radix et rhizome, isatidis radix and lonicerae japonicae flos in Anti-601 Mixture were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The genes corresponding to the target were searched through the UniProt database, and the drug-compound-target (gene) network was constructed by Cytoscape 3.7.2. Then the functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted through Webgestalt to predict the mechanism. The network of drug-compound-target (gene) contained 5 drugs, 100 compounds and 207 targets. Functional enrichment analysis resulted in 717 GO items (P≤0.05), among which 240 were biological process (BP) items, 240 were cell composition (CC) items, and 237 were molecular function (MF) items. The 209 signaling pathways were obtained by enrichment screening of KEGG pathway (P≤0.05). Molecular docking showed that the active ingredients of Anti-601 Mixture, such as Stigmasterol, quercetin, luteolin, acacetin, β-sitosterol, kaempferol,had strong affinity with PTGS2 target. Active compounds in Anti-601 Mixture may regulate multiple signaling pathways including advanced glycation end products and its receptor (AGE-RAGE), IL-17, tumor necrosis factor (TNF) through target of prostaglandin-endoperoxidase synthase 2(PTGS2), thus playing an antiviral and anti-inflammatory role.
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Objective To investigate the effect of human hepatocellular carcinoma HepG2 cell-derived Exosome on the differentiation of mesenchymal stem cells(MSC)into cancer-associated myofibroblasts(CAF)and the impacts of CAF on liver cancer cell proliferation,migration,and invasion. Methods The protein expression of HepG2 cell-derived Exosome was detected by Western blotting. MSCs were separated from human adipose tissue and cultured with HepG2 cell-derived Exosome(100 ng/nl)to initiate differentiation. The expressions of mesenchymal markers and several interleukins were also detected by Western blotting. HepG2 cells were co-cultured with the conditioned media(CM),in which HepG2 Exosome induced the differentiation of MSC into CAF. The expressions of epithelial and mesenchymal markers were detected by real-time polymerase chain reaction(PCR)and Western blotting. Cell proliferation was assessed using MTS assay. Transwell chambers were used in the in vitro migration and invasion assay. Results HepG2 cell-derived particles expressed CD63,70 kilodalton heat shock proteins,and 90 kilodalton heat shock proteins. With the treatment of HepG2 cell-derived Exosome,the expressions of mesenchymal marker α-smooth muscle actin,fibroblast activation protein α,interleukin(IL)-6,IL-8,and IL-1β were up-regulated,while vascular endothelial growth factor had no significant change. The conditioned media which HepG2 Exosome induced MSC differentiation CAF(CAF-CM)could significantly promote HepG2 cells proliferation(1.075±0.104),compared to BSA control(0.874±0.066,P=0.023)and MSC-CM(0.649±0.034,P=0.0005). CAF-CM could significantly enhance cell migration [(42.5±9.1) cells vs.(18.5±3.1) cells,P=0.001] and invasion [(29.0±3.5) cells vs.(13.1±3.7) cells,P=0.009] compared to its control group. Moreover the conditioned medium which HepG2 Exosome induced MSC to differentiate into CAF could also promote the expressions of mesenchyme-related genes Smad interacting protein 1(P=0.040),β-catenin(P=0.038),fibronectin(P=0.029),and Vimentin(P=0.013)and inhibit the expression of epithelial related genes zonula ocdudens-1(P=0.010).Conclusions Exosome extracted from HepG2 cells can induce human adipose-derived MSC to differentiate into cancer-associated myofibroblasts. CAF-like cells can promote the migration of the liver cancer cell line HepG2.
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Objective To investigate the therapeutic effect of exosomes extracted from human adipose-derived mesenchymal stem cells(hAMSCs) on traumatic brain injury (TBI) and its possible mechanism.Methods Mesenchymal stem cells(MSCs) were isolated from healthy human adipose tissue and the exosomes were extracted by ultrafiltration.Rats were divided into four groups: sham group, PBS control group, MSCs treatment group and exosomes treatment group.24 h After TBI, the treatment group was locally injected along the lesion area, 30 μL of PBS, 2×105 MSC, 25 μg protein of exosomes respectively, the total volume was 30 μL.We performed the Modified Neurological Severity Score(mNSS) and the forelimb Foot-Fault Test in all rats before injury and at 1, 3, 7, 10, 13, 16, 21 and 30 days after TBI.The rats were sacrificed at 3 and 7 days after TBI respectively,total RNA was extracted from rat brain tissue.The expression of TNF-α and IL-1β were detected by quantitative PCR.The rats were also killed at 30 days after TBI for testing the neuronal apoptosis in lesion area by tunel-neun double imm-unofluorescence.Results Exosomes treatment significantly promotes the recovery of neurological deficits caused by TBI,and the therapeutic effect is similar to MSCs, its possible mechanism may be the inhibition of the acute inflammation and the reducing of the neurons apoptosis after TBI.Conclusions Exosomes extracted from human adipose-derived mesenchymal stem cellshas promoted neurological functionrecovery after traumatic brain injury, which will provide a new and safer TBI treatment for clinical practice.
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@#To investigate the effects of curcumin on mitochondrial dysfunction induced by high glucose(40 mmol/L glucose, 24 h)in L6 cells, curcumin(10, 20, 40 μmol/L)was administered for 24 h after high glucose culture. The effects of curcumin on the mitochondrial dysfunction were evaluated by mitochondrial membrane potential, reactive oxygen species(ROS), ATP content and mtDNA copy number. The mRNA and protein expression of uncoupling protein 2(UCP2), PPARγ coactivator 1α(PGC-1α)and sirtuin-1(Sirt3)were also determined. As improvement of high glucose damage, curcumin significantly raised mitochondrial membrane potential and ATP content, and decreased ROS level. Curcumin significantly ameliorated the down regulation of UCP2 yet with little effect on mtDNA copy number and PGC-1α and Sirt3 expression. In conclusion, curcumin could significantly ameliorate mitochondrial dysfunction in L6 cells induced by high glucose, which involved the mechanism of multiple antioxidants.
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<p><b>OBJECTIVE</b>To explore an ideal method for comprehensive correcting of the unilateral cleft lip nasal defomity.</p><p><b>METHODS</b>The operation includes replacement of the displaced tissue, excision of the deviated septum, and correction of the deviated septum and the deformity of the lower nose. The excised nasal septum was grafted on the alar base, the nasal columella and the nasal tip.</p><p><b>RESULTS</b>32 patients were treated with this method from 1994 to 1999. Postoperative fellow-up for 1-3 years demonstrated satisfactory results.</p><p><b>CONCLUSION</b>Through excision and grafting of the nasal septum, the deviated septum and the deformity of the lower nose are effectively corrected. Complete undermining and replacement of the displaced structure are the basis of correcting the cleft lip nasal deformity.</p>