A Novel Derivative of (-)mycousnine Produced by the Endophytic Fungus Mycosphaerella nawae, Exhibits High and Selective Immunosuppressive Activity on T Cells.

An endophytic fungus, Mycosphaerella nawae ZJLQ129, was isolated from the leaves of the traditional Chinese medicine Smilax china. From the fermentation broth and mycelium, a dibenzofurane compound (-)mycousnine (1) was isolated. Chemical modification of it to the amide derivative (-)mycousnine enamine (2), which is new to science, was found to have high and selective immunosuppressive activity: similar to cyclosporin A, (-)mycousnine enamine (2) selectively inhibited T cell proliferation, suppressed the expression of the surface activation antigens CD25 and CD69 and the formation and expression of the cytokines interleukin-2 as well as interferon γ in activated T cells, but did not show any effect on the proliferation of B cells and cancer cells (PANC-1 and A549) and the activation of macrophages. Furthermore, the cytotoxicity of (-)mycousnine enamine was lower than that of cyclosporin A, and its therapeutic index (TC50/EC50) was 4,463.5, which is five-fold higher than that of cyclosporin A. We conclude that (-)mycousnine enamine (2), the semi-synthestic product prepared from the native product (-)mycousnine (1) of the endophyte M. nawae is a novel effective immunosuppressant showing low toxicity and high selectivity.

Extraskeletal Ewing sarcomas in late adolescence and adults: a study of 37 patients.

BACKGROUND: Extraskeletal Ewing sarcoma (EES)/primitive neuroectodermal tumours (PNET) are rare soft tissue sarcomas. Prognostic factors and optimal therapy are still unconfirmed. MATERIALS AND METHODS: We performed a retrospective analysis on patients to explore the clinic characteristics and prognostic factors of this rare disease. A total of 37 patients older than 15 years referred to our institute from Jan., 2002 to Jan., 2012 were reviewed. The characteristics, treatment and outcome were collected and analyzed. RESULTS: The median age was 28 years (range 15-65); the median size of primary tumours was 8.2 cm (range 2-19). Sixteen patients (43%) had metastatic disease at the initial presentation. Wide surgical margins were achieved in 14 cases (38%). Anthracycline or platinum-based chemotherapy was performed on 29 patients (74%). Radiotherapy was delivered in 13 (35%). At a median follow-up visit of 24 months (range 2-81), the media event-free survival (EFS) and overall survival (OS) were 15.8 and 30.2 months, respectively. The 3-year EFS and OS rates were 24% and 43%, respectively. Metastases at presentation and wide surgical margins were significantly associated with OS and EFS. Tumour size was significantly associated with OS but not EFS. There were no significant differences between anthracycline and platinum based chemotherapy regarding EFS and OS. CONCLUSIONS: EES/PNET is a malignant tumour with high recurrence and frequent distant metastasis. Multimodality therapy featuring wide surgical margins, aggressive chemotherapy and adjuvant local radiotherapy is necessary for this rare disease. Platinum-based chemotherapy can be used as an adjuvant therapy.

[Effects of kaixinsan on behavior and expression of p-CREB in hippocampus of chronic stress rats].

OBJECTIVE: To study the effects of kaixinsan on behavior and expression of p-CREB in hippocampus of the chronic stress rats. METHOD: The male Wistar rats which gained the similar scores by Open-field test were selected, then the depression model rat was produced by separation and chronic unpredictable mild stress. Open-field test was performed to detect the behavior of rats and immunohistochemistry was used to observe the changes of p-CREB expression in hippocampus. RESULT: On the 22nd day, the body weight and sacchar-intake of the depression model rats were all lower than those of the normal rats and the body weight and sacchar-intake of the rats treated by drugs were higher compared with model rats (P < 0.01). The depressive behavior in kaixinsan 4 g x kg(-1) group was significantly improved compared with the model group, the crossing scores and rearing scores were all increased (P < 0.01) and the expression of p-CREB in CA1, CA3 and DG in hippocampus was higher than that in the model group (P < 0.05 and P < 0.01). CONCLUSION: Kaixinsan might improve depressive behavior by increasing expression of p-CREB in CA1, CA3 and DG in hippocampus of the chronic stress rats.

[Effect of erigeron injection on platelet level of CD62p and serum content of TNF-alpha and IL-6 in patients with acute cerebral infarction].

OBJECTIVE: To investigate the clinical effect of Erigeron injection (El) on positive expression rate of CD62p in platelet and content of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in serum of patients with acute cerebral infarction (ACI). METHODS: Sixty-eight patients with ACI were randomly divided into the treated group (n = 35) and the control group (n = 33). Conventional treatment were given to both groups, and EI 40 ml/d were given additionally to the treated group, the treatment course for both groups was 15 days. The positive expression of platelet CD62p and the serum TNF-alpha and IL-6 in patients before and after treatment were determined with flow cytometric (FCM) and electrochemical-luminescence (ECL) techniques respectively. RESULTS: The total curative effect in the treated group were significantly higher than that in the control group (P < 0.05). Levels of platelet CD62p and serum TNF-alpha and IL-6 in ACI patients before and after treatment were significant higher than those in the healthy group (P < 0.05), all the three parameters were significantly decreased after treatment, and the lowering in the treated group was more significant than that in the control group (P < 0.05). CONCLUSION: The effect of El on ACI patients may relate to its action in down-regulating the expression of platelet CD62p, alleviating the immune response and inflammatory injury of central nervous system induced by cytokines.