Mechanism of Tripterygium wilfordii in Treatment of Triple Negative Breast Cancer Based on Network Pharmacology and Experimental Validation / 中国实验方剂学杂志

ObjectiveTo explore the active ingredients， therapeutic targets， and relative signaling pathways of Tripterygium wilfordii in the treatment of triple negative breast cancer （TNBC） based on network pharmacology， and to verify the mechanism through in vitro cell model. MethodThe active ingredients of T. wilfordii were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. The targets of TNBC were obtained from DisGeNET and GeneCards. Venny was used to identify the potential therapeutic targets of T. wilfordii against TNBC. Protein-protein interaction （PPI） network was constructed with String database. Gene ontology （GO） annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment were carried out with DAVID to predict the mechanisms of potential targets. The molecular docking between triptolide and key targets were performed with AutoDock Vina. The effect of triptolide （0， 5， 10， 20， 30， 40， 50， 60， 80 nmol·L-1） on the proliferation of MDA-MB-231 cells was determined through methyl thiazolyl tetrazolium （MTT） assay. The effect of triptolide （0， 12.5， 25， 50 nmol·L-1） on the apoptosis of MDA-MB-231 cells was detected with Hoechst 33342 staining. Western blot was performed to detect the effect of triptolide （0， 25， 50 nmol·L-1） on the expression levels of key targets. ResultT. wilfordii had 23 active ingredients related to 55 potential targets of TNBC. GO and KEGG enrichment revealed that the potential targets were associated with 103 biological processes， 15 cellular components， and 35 molecular functions， and were involved in 140 signaling pathways including atherosclerosis and apoptosis. The results of molecular docking demonstrated that triptolide could bind with the targets including threonine kinase 1 （Akt1）， vascular endothelial growth factor A （VEGFA）， cellular tumor antigen p53 （p53）， transcription factor AP-1 （JUN）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， mitogen-activated protein kinase 8 （MAPK8）， prostaglandin G/H synthase 2 （PTGS2）， and Caspase-3. According to the results of MTT assay， triptolide （20， 30， 40， 50， 60， 80 nmol·L-1） inhibited the proliferation of MDA-MB-231 cells compared with blank control （P<0.05， P<0.01）. Hoechst 33342 staining showed that triptolide （12， 25， 50 nmol·L-1） induced the apoptosis of MDA-MB-231 cells compared with black control （P<0.05， P<0.01）. Western blot showcased that 50 nmol·L-1 triptolide down-regulated the relative expression levels of p-Akt， TNF-α， and VEGFA， while 25 and 50 nmol·L-1 triptolide up-regulated the relative expression level of p53 in a dose-dependent manner compared with the blank control （P<0.05， P<0.01）. ConclusionT. wilfordii has multiple ingredients， targets， and pathways in the treatment of TNBC. It may regulate p53， VEGFA， TNF-α and other key targets to induce cell apoptosis and suppress angiogenesis and inflammatory response， which provides a scientific basis for the further investigation and clinical application of T. wilfordii.

[A 2-year follow-up results of knee arthroscopic synovectomy plus disease modifying antirheumatic drugs for the treatment of rheumatoid arthritis].

OBJECTIVE: To evaluate the clinical efficacy of knee arthroscopic synovectomy plus disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA) patients. METHODS: A total of 97 RA patients were treated with knee arthroscopic synovectomy plus DMARD after arthroscopy. The control group received only DMARD. The patients were assessed at pre-treatment and 1, 6, 12, 24 month post-treatment. Tender joint count, swollen joint count, morning stiffness, resting pain, patient global assessment, physician global assessment, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF) and disease activity score (DAS) 28 were observed. RESULTS: Tender joint count, swollen joint count, morning stiffness, resting pain, patient global assessment, physician global assessment and DAS 28 score improved significantly at 1, 6 month post-treatment in the combined treatment group versus the control group. At 2 years post-treatment, there was still significant difference in DAS28 between two groups. CONCLUSION: The combined treatment of knee arthroscopic synovectomy and disease modifying antirheumatic drugs can control the disease activity of RA during an early period. And a long-term efficacy may be maintained.

[Significance of arthroscopy in the diagnosis of unilateral knee arthritis].

OBJECTIVE: To investigate the role of arthroscopy in the diagnosis of unilateral knee arthritis of unknown causes. METHODS: During December 2005 to February 2008,74 patients of unilateral knee arthritis of unknown origins were treated with arthroscopy. And magnetic resonance imaging (MRI) scans were performed for all of them before knee arthroscopy. The diagnosis was made by the synovial appearance in gross examination in arthroscopy combined with synovial pathology, synovial fluid analysis and clinical manifestations. RESULTS: Among these patients, 71 cases were definitely diagnosed and 3 cases had unknown causes. Thirty-nine cases (52.9%) were of rheumatoid arthritis (RA), 7 (9.5%) of seronegative spondyloarthropathy (SPA), 7 patients (9.5%) of septic arthritis, 6 patients (8.1%) of RA coexisting gout arthritis, 5 patients (6.5%) of gout arthritis, 5 patients (6.5%) of tuberculosis of knee joint, 1 patient (1.3%) of pigmented villonodular synovitis and 1 patient (1.3%) of multicentric reticulohistiocytosis. CONCLUSION: Arthroscopy provides valuable diagnostic information in unilateral knee arthritis of unknown causes. RA is the major cause of unilateral knee arthritis of unknown causes. Synovial appearance in gross examination in arthroscopy, synovial pathology and crystals are helpful to make a diagnosis.