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1. Bioactive compounds from medicinal plants with anticancer and anti-inflammatory effects have become key resources in drug discovery fields for the treatment of various malignancies and immunological disorders. 2. Tripterygium wilfordii (TW) is a medicinal plant that exhibits profound immunosuppressive effects and has been used in herbal regimens for the treatment of immunological diseases for thousand years in China. 3. Procedures for the isolation and characterization of TW bioactive compounds have been well established. Over the past three decades, more than 46 diterpenoids, 20 new triterpenoids, 26 alkaloids and other small molecules have been identified from TW. 4. Triptolide, celastrol and tripchlorolide are among the bioactive compounds conferring the immunosuppressive and anticancer activities of TW. Accumulated evidence suggests that the TW bioactive compounds exert their pharmacological actions by modulating the transcriptional activity of nuclear factor-κB signalling molecule. 5. Triptolide derivatives with improved water solubility have emerged as promising drug candidates. Clinical trials are being conducted on the derivatives to provide encyclopaedic knowledge on triptolide pharmacokinetics in patients.

Background:The role of S100A14 in tumorigenesis and the underlying mechanisms have not been fully understood. Results: S100A14 affects cell invasiveness by regulating MMP2 transcription in a p53-dependent manner. Conclusion: S100A14 acts as either an inducer or an inhibitor of cell invasion depending on the p53 status of cells. Significance: These studies significantly increase our understanding of how S100A14 regulates cell invasiveness.

BackgroundThe one-stage procedure for treatment of older developmental dislocation of the hip (DDH) is used widely. However, the best age group for this operation is still unknown. The aims of our study were to evaluate middle-term outcomes of one-stage surgical treatment of a large number of patients with late-diagnosed DDH, and to explore the best age group for treatment.MethodsWe retrospectively reviewed 652 patients with a total of 864 hip joints with DDH, all aged >18 months. All the hip joints were treated with one-stage procedures including open reduction, pelvic osteotomy, and femoral shortening. The patients were divided into three groups according to age at surgery: Group I: 1.5–2.5 years; Group II: 2.5–8 years; and Group III: >8 years. The latest clinical and radiographic outcomes, complications and avascular necrosis (AVN) of the femoral head were evaluated and compared among the three groups.ResultsThe mean age at surgery was 5.8 years (range: 1.5–13.2 years). The average time of follow-up was 6.2 years (range: 3.2–8.9 years). A total of 79.4% of good or excellent outcomes were obtained for clinical functional evaluation according to the McKay classification. For radiographic outcomes, 732 hips (84.7%) were classified as good or excellent according to the Severin classification. A total of 27.4% of all hips had a poor outcome according to the Kalamchi and MacEwen classification for AVN. The poorest outcomes were observed for clinical, radiographic and AVN results in Group III (p < 0.001). Compared with Group I, the better results for clinical and AVN outcomes were found in Group II (p < 0.001). However, similar clinical outcomes were observed between Groups I and II (p > 0.05). A significantly higher incidence of redislocation and residual acetabular dysplasia was observed in Tonnis grade II and III hip dislocation (p < 0.001).ConclusionsOne-stage treatment of late-diagnosed DDH had a good outcome in young and middle group. Younger patients achieved better results than older patients. However, the best age group was 2.5–8 years. Tonnis grade II and III DDH is a risk factor for redislocation and residual acetabular dysplasia after the one-stage operation.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-401) contains supplementary material, which is available to authorized users.

Reelin (RELN), which is a glycoprotein secreted by Cajal-Retzius cells of the developing cerebral cortex, plays an important role in neuronal migration, but its role in cell migration and cancer metastasis is largely unclear. Here, we showed that cell motility was significantly increased in KYSE-510 cells by TGF-β1 treatment. Moreover, TGF-β1 decreased RELN mRNA expression and overexpression of Reelin at least partly reversed TGF-β1-induced cell migration in KYSE-30 cells. Furthermore, this negative regulation of Reelin expression by TGF-β1 was through Snail, one transcription factor which was induced by TGF-β1 in KYSE-510 cells. RELN promoter activity was reduced in parallel with the induction of Snail after TGF-β1 treatment and Snail suppressed both RELN promoter activity and expression through binding to E-box sequences in the RELN promoter region in ESCC cells. Knockdown of RELN induced cell migration in KYSE-510 cells, together with the increase of mesenchymal markers expression. Taken together, Reelin is an essential negative regulator in the TGF-β1-induced cell migration process, and is suppressed by TGF-β pathway at the transcriptional level through Snail regulation. Therefore, the correlation of Reelin and TGF-β pathway was critical in cancer metastasis, and Reelin could be one potential anti-metastasis target in future clinical practice.

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Liver fibrosis is the excessive accumulation of extracellular matrix proteins, resulting from maladaptive wound healing responses to chronic liver injury. γδT cells are important in chronic liver injury pathogenesis and subsequent liver fibrosis; however, their role and underlying mechanisms are not fully understood. The present study aims to assess whether γδT cells contribute to liver fibrosis regression. Using a carbon tetrachloride (CCl4)-induced murine model of liver fibrosis in wild-type (WT) and γδT cell deficient (TCRδ−/−) mice, we demonstrated that γδT cells protected against liver fibrosis and exhibited strong cytotoxicity against activated hepatic stellate cells (HSCs). Further study show that chronic liver inflammation promoted hepatic γδT cells to express NKp46, which contribute to the direct killing of activated HSCs by γδT cells. Moreover, we identified that an IFNγ-producing γδT cell subset (γδT1) cells exhibited stronger cytotoxicity against activated HSCs than the IL-17-producing subset (γδT17) cells upon chronic liver injury. In addition, γδT cells promoted the anti-fibrotic ability of conventional natural killer (cNK) cells and liver-resident NK (lrNK) cells by enhancing their cytotoxicity against activated HSCs. The cell crosstalk between γδT and NK cells was shown to depend partly on co-stimulatory receptor 4-1BB (CD137) engagement. In conclusion, our data confirmed the protective effects of γδT cells, especially the γδT1 subset, by directly killing activated HSCs and increasing NK cell-mediated cytotoxicity against activated HSCs in CCl4-induced liver fibrosis, which suggest valuable therapeutic targets to treat liver fibrosis.

Long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis and cancer progression. The c-Myc upregulated lncRNA MYU (VPS9D1 antisense RNA1, annotated as VPS9D1-AS1) has been reported in several common types of human cancers, which has revealed that lncRNA MYU could function as either an oncogene or a tumor-suppressor gene in different cancer types. However, the function of lncRNA MYU in prostate cancer remains unknown. In the present study, we demonstrated that lncRNA MYU is significantly upregulated in prostate cancer tissues. MYU knockdown impaired prostate cancer cell growth and migration as shown from cell viability, colony formation, Transwell and wound healing assays. In contrast, MYU overexpression displayed opposite effects. No correlation was noted between MYU and its cognate VPS9D1 expression level. Moreover, lncRNA MYU did not regulate the expression of VPS9D1 either at the mRNA or protein level as detected using qRT-PCR and western blotting assays. Furthermore, lncRNA MYU was able to be transported into the extracellular milieu by means of exosomes, and then promoted adjacent cell proliferation and migration. Mechanistically, lncRNA MYU upregulated c-Myc by competitively binding miR-184 and then induced the proliferation of prostate cancer. Thus, this study demonstrated that lncRNA MYU functions as an oncogene in prostate cancer at least in part through the miR-184/c-Myc axis, and may serve as a potential diagnostic biomarker and therapeutic target.