Blocking of YY1 reduce neutrophil infiltration by inhibiting IL-8 production via the PI3K-Akt-mTOR signaling pathway in rheumatoid arthritis.

Our previous study revealed that Yin Yang 1(YY1) played an important part in promoting interleukin (IL)-6 production in rheumatoid arthritis (RA). However, whether YY1 has any role in regulation of IL-8 in RA remains unclear. YY1 and IL-8 expression in RA patients were analyzed by real-time polymerase chain reaction (PCR). Ingenuity pathway analysis (IPA) was used to analyze the signaling pathway involved in YY1-induced IL-8 production. The expression of YY1 and proteins involved in the pathway were detected by Western blot and enzyme-linked immunosorbent assay (ELISA). Migration of neutrophils was performed by chemotaxis assay. In this study, we found that high expression of IL-8 was positively associated with YY1 expression in RA. Blocking YY1 expression by YY1-short hairpin (sh)RNA lentivirus reduced IL-8 production. Mechanistically, we showed YY1 activated IL-8 production via the phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. Further, using a co-culture system consisting of peripheral blood mononuclear cells (PBMC) and neutrophils, we found that migration of neutrophils would be inhibited by YY1 RNA interference. Finally, using the collagen-induced arthritis animal model, we showed that treatment with the YY1-shRNA lentivirus led to reduction of IL-8 levels and attenuation of inflammation and neutrophil infiltration in vivo. Our results reveal a role of YY1 involved in neutrophil infiltration in RA via the PI3K/Akt/mTOR/IL-8 signaling pathway. YY1 may be a new therapeutic target for treatment of RA.

ERCC1, defective mismatch repair status as predictive biomarkers of survival for stage III colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy.

BACKGROUND: Excision repair cross-complementation group 1 (ERCC1) expression status has been identified as a candidate marker for predicting efficacy of oxaliplatin (OX) treatment for metastatic colorectal cancer (CRC) in several trials. Also, an association between expression of mismatch repair (MMR) genes and favourable postoperative survival in stage II CRC receiving 5-FU chemotherapy has been identified. It is unknown if the expression of ERCC1 protein and MMR status are associated with survival of stage III colon cancer receiving OX-based chemotherapy. METHODS: Immunohistochemistry (IHC) analysis of the expression of MMR and ERCC1 was performed on tumour tissue of 255 patients with stage III colon cancer. In all, 95 patients received fluoropyrimidine-based chemotherapy and 160 patients received OX-based chemotherapy. A predictive model for 5-year disease-free survival (DFS) and overall survival (OS) was constructed using Kaplan-Meier analysis, logistic and Cox regression. RESULTS: Patients who were treated with OX-based therapy with positive ERCC1 tumours had lower 5-year DFS (54%) and OS (60%) than those with negative ERCC1 tumours (72% and 78%, respectively; DFS HR: 1.98, 95% confidence interval (CI): 1.19-3.31, P=0.009; OS HR: 2.44, 95% CI: 1.37-4.34, P=0.02). Excision repair cross-complementation group 1 status did not impact DFS or OS in fluorouracil group (DFS HR: 1.16, 95% CI: 0.63-2.14, P=0.62; OS HR: 1.16, 95% CI: 0.63-2.14, P=0.63), whereas MMR status had no impact on DFS or OS in either group. CONCLUSION: Excision repair cross-complementation group 1 status is highly predictive of which patients will benefit from the addition of OX to 5-FU for stage III colon cancer. Mismatch repair status had no predictive value in this setting.

Effects of hepatocyte growth-promoting factor and panax notoginseng saponins on intrasplenic hepatocellular autotransplantation.

AIM: To increase the weight of liver tissue mass present in spleen and to shorten the regeneration period of transplanted hepatocytes by stimulating DNA synthesis and protection against ischemic-reperfusion injury. METHODS: Hepatocyte growth-promoting factor (PHGF) and panax notoginseng saponins (PNGS) were used after intrasplenic hepatocellular autologous transplantation (IHAT) with 70 % partial hepatectomy. Histological examinations were carried out under both light and electron microscopy and content of ALT in hepatized spleen homogenate was investigated 2 weeks after transplantation. Furthermore, 99mTc diethyl-iminodiacetic acid (99mTc-HIDA) splenic scintiphotography was carried out and proliferation index of transplanted hepatocytes was detected by flow cytometry at the 12th week after operation. RESULTS: (1) Hepatocellular degeneration was slightly less in group B [intrasplenic hepatocyte autologous transplantation (IHAT) + PNGS 25 mg/kg, im, qd] vs the control group (group C, IHAT without drugs) at the 2nd week after transplantation, and the ALT content of group B (928 U/g +/- 268 U/g) was higher than that of group C (639 U/g +/- 138 U/g, P < 0.01). (2) At the 12th week, hepatocellular regeneration in group A (IHAT + PHGF 5 mg/kg, im, qd) was obviously better than that in group C, and the ALT content (2325 U/g +/- 401 U/g ), the radioactivity accumulation of 99mTc-HIDA (58 Bq +/- 18 Bq), and proliferation index (3.8 % +/- 0.4 %) of group A were all higher than those of control (P < 0.05). CONCLUSION: PHGF has effects in increasing the weight of liver tissue grown in spleen and shortening the regeneration period of the transplanted hepatocytes, while PNGS has certain effects on protecting the hepatocytes against ischemic reperfusion injury in the early stage of transplantation.

[Chemical constituents of Artemisia dalailamae Kraschen].

Five compounds were isolated from Artemisia dalailamae. They were identified as taraxeryl acetate, isofraxidin, scopoletin, scopolin and kumatakenin.