Notoginsenoside R1 attenuates breast cancer progression by targeting CCND2 and YBX3 / 中华医学杂志(英文版)

BACKGROUND@#Breast cancer (BC) is a common malignancy with highly female incidence. So far the function of notoginsenoside R1 (NGR1), the extract from Panax notoginseng, has not been clearly elucidated in BC.@*METHODS@#Optimal culture concentration and time of NGR1 were investigated by cell counting kit-8 assay. Cell proliferation ability was measured by colony formation assays. Transwell assay was used to detect the effect of NGR1 on cell migration and invasion. The apoptosis rate of cells between each group was measured by TUNEL assay.@*RESULTS@#NGR1 treatment has an inhibitory effect on proliferation, migration, invasion, and angiogenesis and a stimulating effect on cell cycle arrest and apoptosis of Michigan Cancer Foundation-7 (MCF-7) cells. The 50% growth inhibitory concentration for MCF-7 cells at 24 h was 148.9 mmol/L. The proportions of MCF-7 cells arrested in the G0/G1 phase were 36.94±6.78%, 45.06±5.60%, and 59.46±5.60% in the control group, 75, and 150 mmol/L groups, respectively. Furthermore, we revealed that NGR1 treatment attenuates BC progression by targeted downregulating CCND2 and YBX3 genes. Additionally, YBX3 activates phosphatidylinositol 3-phosphate kinase (PI3K)/protein kinase B (Akt) signaling pathway by activating kirsten rat sarcoma viral oncogene, which is an activator of the PI3K/Akt signaling pathway.@*CONCLUSION@#These results suggest that NGR1 can act as an efficacious drug candidate that targets the YBX3/PI3K/Akt axis in patients with BC.

Bacterial immune interaction in experimental colitis.

OBJECTIVES: This study aimed to analyze the effects of 5-aminosalicylic acid (5-ASA) on intestinal microbiota and immune regulation in inflammatory bowel disease (IBD) and to investigate the correlation between intestinal microbiota and immune factors. METHODS: Colitis in mice was induced by oxazolone. The community composition of luminal and mucosal microbiota was analyzed by a terminal restriction fragment length polymorphism. The expression of occludin, toll-like receptor (TLR)-2, TLR-4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 proteins were measured by immunohistochemistry and Western blot. Linear correlation between intestinal microbial community and the severity of the colitis or intestinal microbial community and expressions of immune factors were determined. RESULTS: Protective bacteria decreased while aggressive bacteria increased in the colitis group. The richness and diversity of both luminal and mucosal microbiota decreased in the colitis group the decrease was enhanced in the 5-ASA-treated group. The diversity of mucosal microbiota significantly correlated with the extent of the colitis. Expressions of occludin, TLR-2, TLR-4, tumor necrosis factor-α and NF-κB p65 were significantly correlated with the diversity of mucosal microbiota. CONCLUSIONS: Mucosal microbiota are important in the pathogenesis of IBD. 5-ASA increases protective bacteria but decreases aggressive bacteria, thus inducing the new intestinal microbial homeostasis.

[A retrospective analysis of azathioprine in the treatment of 24 patients with refractory ulcerative colitis].

OBJECTIVE: To evaluate the efficacy and safety of azathioprine (AZA) in the treatment of refractory ulcerative colitis (UC). METHODS: Retrospective analysis of the clinical improvement, endoscopic improvement and mucosal healing rate, inflammation marker improvement after AZA administration and its safety in 24 refractory UC patients were performed, who were recruited between January 2007 and December 2011 in West China Hospital, Sichuan University, China. RESULTS: Twenty-four patients were enrolled, with a median age of 36 years old and a median course of 4 years. Among them, 14 cases were moderate UC and 10 cases were severe UC. The patients were treated with AZA in a dose of (1.23 ± 0.34) mg×kg(-1)×d(-1) from 7 weeks to 42 months. Efficacy was judged by Mayo disease activity index. At 3 months, 6 months and 1 year after treatment, the effective rates were 73.9% (17/23), 81.8% (18/22) and 14/16 respectively, and the remission rates were 17.4% (4/23), 54.5% (12/22) and 12/16 respectively. Both ESR and C reactive protein level after treatment for 6 months and 1 year were significantly lower than those before treatment [(9.3 ± 8.9) mm/1h, (10.9 ± 7.3) mm/1h vs (22.3 ± 10.7) mm/1h; 2.5(1.0-22.3) mg/L, 2.3(1.0-28.0) mg/L vs 18.4(3.6-137.0) mg/L; all P < 0.05]. Corticosteroid withdrawal rates at 3 months and 1 year after AZA treatment were 16/18 and 15/16, respectively. At 6 months and 1 year after AZA treatment, the endoscopic improvement rates were 85.7% (18/21) and 13/15 respectively; the endoscopic remission rates were 61.9% (13/21) and 11/15 respectively; and the mucosal healing rates were 61.9% (13/21) and 11/15 respectively. Adverse effects were occurred in 8 patients. Leukopenia was the most common adverse effect, followed by liver function injury, alopecia and epigastric discomfort. CONCLUSIONS: AZA is effective in the treatment of refractory UC patients with a low dose of (1.23 ± 0.34) mg×kg(-1)×d(-1), especially in the steroid withdrawing, maintaining remission and mucosal healing without severe adverse effects.

Inflammatory bowel disease in the 21(st) century in China: turning challenges into opportunities.

Inflammatory bowel disease (IBD) has been an international hot spot for research for a long period of time. In China, the prevalence of IBD is rapidly increasing in recent years, mimicking the same fast growing footsteps of the developed world. Chinese literature of the 20(th) century shows that the total number of IBD cases increased by approximately 2.5-fold over the previous decade, in particular a 15.7-fold in patients with Crohn's disease (CD). Articles on basic research have increased 4.3-fold, with a particular 9.9-fold increase on immunological mechanisms. The predominantly Traditional Chinese Medicine (TCM) related clinical trials implied tendency to use a combination of Western Medicine and TCM in the management of Chinese IBD patients. IBD research and collaborations overseas have been markedly promoted since the Chinese Organization for the Study of Inflammatory Bowel Disease (COIBD) was founded at the beginning of the 21(st) century. From the second decade of the century onwards, we need to focus on the research hot spots to catch up with the rapid advances worldwide. Big challenges and present achievements provide us with great opportunities for further developments of the study on IBD. The development of some novel target pathogenic factors of the disease will provide us with more effective roll for modern management and optimistic treatment of IBD during this century.