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ObjectiveTo investigate the effects and mechanism of quercetin on experimental autoimmune uveitis （EAU） by regulating the Wnt/β-catenin signaling pathway. MethodThe regulatory relationship between quercetin and EAU was preliminarily determined by network pharmacology. The model was identified by enzyme-linked immunosorbent assay（ELISA） and clinical grading score. The important inflammatory factors， including interleukin（IL）-6 and tumor necrosis factor（TNF）-α in the signaling pathway were detected by ELISA. The binding of important targets in the pathway was verified by molecular docking. The protein and mRNA expression levels of related targets in the signaling pathway were detected by Western blot and Real-time polymerase chain reaction（Real-time PCR）， respectively. ResultAs evaluated by ELISA and the clinical grading score， the model was properly induced. The results of ELISA showed that the levels of IL-6 and TNF-α were the highest in the model group and the dimethyl sulfoxide （DMSO） group， and decreased after medium- and high-dose drug interventions， but the changing tend was the same. Molecular docking showed that the binding energies of quercetin to β-catenin and LRP6 were ideal. Western blot revealed that the expression of β-catenin and LRP6 was the highest in the model group， and decreased with drug intervention at different doses， but the changing trend was the same. Besides， there was no significant difference between the low-dose group and the high-dose group. Real-time PCR results showed that the expression of β-catenin，MYC，AXIN2， and TCF was the highest in the model group，the lowest in the high-dose group， and decreased in the low-dose group. There was no significant difference between the high-dose group and the low-dose group. ConclusionQuercetin can reduce the inflammatory expression of EAU and relieve the pain of patients by regulating the Wnt/β-catenin signaling pathway.
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Objective@#The mitotic count of gastrointestinal stromal tumors (GIST) is closely associated with the risk of planting and metastasis. The purpose of this study was to develop a predictive model for the mitotic index of local primary GIST, based on deep learning algorithm. @*Materials and Methods@#Abdominal contrast-enhanced CT images of 148 pathologically confirmed GIST cases were retrospectively collected for the development of a deep learning classification algorithm. The areas of GIST masses on the CT images were retrospectively labelled by an experienced radiologist. The postoperative pathological mitotic count was considered as the gold standard (high mitotic count, > 5/50 high-power fields [HPFs]; low mitotic count, ≤ 5/50 HPFs). A binary classification model was trained on the basis of the VGG16 convolutional neural network, using the CT images with the training set (n = 108), validation set (n = 20), and the test set (n = 20). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated at both, the image level and the patient level. The receiver operating characteristic curves were generated on the basis of the model prediction results and the area under curves (AUCs) were calculated. The risk categories of the tumors were predicted according to the Armed Forces Institute of Pathology criteria. @*Results@#At the image level, the classification prediction results of the mitotic counts in the test cohort were as follows:sensitivity 85.7% (95% confidence interval [CI]: 0.834–0.877), specificity 67.5% (95% CI: 0.636–0.712), PPV 82.1% (95% CI: 0.797–0.843), NPV 73.0% (95% CI: 0.691–0.766), and AUC 0.771 (95% CI: 0.750–0.791). At the patient level, the classification prediction results in the test cohort were as follows: sensitivity 90.0% (95% CI: 0.541–0.995), specificity 70.0% (95% CI: 0.354–0.919), PPV 75.0% (95% CI: 0.428–0.933), NPV 87.5% (95% CI: 0.467–0.993), and AUC 0.800 (95% CI: 0.563–0.943). @*Conclusion@#We developed and preliminarily verified the GIST mitotic count binary prediction model, based on the VGG convolutional neural network. The model displayed a good predictive performance.
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Objective@#To investigate the correlation between Toll like receptor 4 (TLR4) expression and apoptosis in periventricular leukomalacia (PVL) rat model induced by hypoxia-ischemia.@*Methods@#One hundred and forty three-day-old sprague-dawley (SD) rats, which were divided into experimental group (ischemia-hypo-xia group) and control group (sham operation group) randomly, were used to establish a hypoxic model by ligating the right common carotid artery and inhaling gas mixtures with 60 mL/L oxygen and 940 mL/L nitrogen.The rats were killed 6 h, 12 h, 24 h, 3 d, 7 d after model reproducing and the brain tissues were used for the following experiments.The pathological changes and apoptosis of brain tissues were detected by way of hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (Tunel) assay respectively, and TLR4 expression was detected by adopting immunohistochemistry and reverse-transcription polymerase chain reaction(RT-PCR). The data were analyzed by using the SPSS 19.0 software.@*Results@#TLR4 expression in the modeling rat brain commenced to increase in 6 hours (0.541±0.069, 0.166±0.058)and reached the peak in 3 days(1.932±0.161, 0.300±0.039), and then began to decline in 7 days (1.242±0.109, 0.220±0.025) post hypoxia-ischemia.Compared with the control group, there were statistical significances at 6 h, 12 h, 24 h, 3 d and 7 d (all P<0.05). The apoptosis of brain ti-ssue cells in the modeling rat brain started to increase at 6 hours(21.33±3.50) and reached the peak in 3 days (35.97±4.20), and then began to decline in 7 days (31.02±4.22) post hypoxia-ischemia.Compared with the control group, there were statistical significance at 6 h, 12 h, 24 h, 3 d and 7 d (all P<0.05). The TLR4 expression was positively correlated with cell apoptosis (r=0.774, 0.575, all P<0.05).@*Conclusions@#In the rat model of PVL induced by hypoxia-ischemia, TLR4 is likely to injure the neural cell through apoptosis.
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<p><b>OBJECTIVE</b>To evaluate the therapeutic effect of transplantation of mesencephalic neural stem cells (mNSCs) genetically modified by glial cell line-derived neurotrophic factor (GDNF) gene in a rat model of Parkinson disease.</p><p><b>METHODS</b>mNSCs isolated from the lateral component of the midbrain of fetal rats at gestational age of 14 or 15 days were cultured for 5 days before genetic modification with GFP or GDNF gene. Rat models of Parkinson disease established by stereotactic injection of 6-hydroxy dopamine in the ventral area of the midbrain and the medial forebrain bundle were randomized into 3 groups to receive PBS injection, GFP gene-modified mNSCs transplantation, or GDNF gene-modified mNSCs transplantation into the right stratum. The behavioral changes of the rats were evaluated by observing rotations induced by intraperitoneal injection of apomorphine after the transplantation, and the survival, migration and differentiation of the transplanted cells were identified by immunohistochemistry.</p><p><b>RESULTS</b>Transplantation with GDNF gene-modified mNSCs significantly improved the behavioral abnormalities of the rat models as compared with PBS injection and GFP gene-modified mNSCs transplantation. At 56 days after the transplantation, a greater number of the transplanted cells survived in the rat brain and more differentiated dopaminergic neurons were detected in GDNF gene-modified mNSCs transplantation group than in GFP gene-modified mNSCs transplantation group.</p><p><b>CONCLUSION</b>GDNF gene-modified mNSCs transplantation can significantly improve dyskinesia in rat models of Parkinson disease, but the molecular mechanism needs further clarification.</p>
Subject(s)
Animals , Rats , Disease Models, Animal , Glial Cell Line-Derived Neurotrophic Factor , Genetics , Therapeutic Uses , Mesencephalon , Cell Biology , Neural Stem Cells , Transplantation , Parkinson Disease , Therapeutics , Stem Cell TransplantationABSTRACT
BACKGROUND: At present, bone defects usually repaired by autologous bone, allogenic bone, synthetic bone substitutes and other methods, which received poor clinical results. Preliminary studies have shown that adipose-derived mesenchymal stem cells (ADSCs) possess strong proliferation ability and differentiation potential, and can be induced differentiate into bone. OBJECTIVE: To analyze the application of ADSCs in bone tissue engineering, and to identify whether ADSCs can be used as seed cells in bone tissue engineering. METHODS: The databases of PubMed (1999-01/2008-12) and Tongfang (2003-01/2008-12) was retrieved using key words of "adipose tissue-derived mesenchymal stem cells, adipose mesenchymal stem cells, adipose stem cell; osteogenic induction, osteogenic inducement, bone induction, osteoblastic induced; chondroblast induction, cartilage induction; bone tissue engineering, tissue engineering bone, tissue engineering of bone". RESULTS AND CONCLUSION: A total of 361 literatures were collected, including 246 in Chinese and 115 in English. Totally 29 literatures were accordant with the study criteria. ADSCs is a truly multi-directional differentiation potential cells, which possess strong amplification and self-renewal potential, and can be directional differentiated into osteoblasts, cartilage cells, bone cells and muscle cells. It can be used as seed cells in bone tissue engineering when matching appropriate stents.