In the present work, we studied the structure-activity relationship (SAR) of tautomycetin (TMC) and its derivatives. Further, we demonstrated the correlation between the immunosuppressive fuction, anticancer activity and protein phosphatase type 1 (PP1) inhibition of TMC and its derivatives. We have prepared some TMC derivatives via combinatorial biosynthesis, isolation from fermentation broth or chemical degradation of TMC. We found that the immunosuppressive activity was correlated with anticancer activity for TMC and its analog compounds, indicating that TMC may home at the same targets for its immunosuppressive and anticancer activities. Interestingly, TMC-F1, TMC-D1 and TMC-D2 all retained significant, albeit reduced PP1 inhibitory activity compared to TMC. However, only TMC-D2 showed immunosuppressive and anticancer activities in studies carried out in cell lines. Moreover, TMC-Chain did not show any significant inhibitory activity towards PP1 but showed strong growth inhibitory effect. This observation implicates that the maleic anhydride moiety of TMC is critical for its phosphatase inhibitory activity whereas the C1-C18 moiety of TMC is essential for the inhibition of tumor cell proliferation. Furthermore, we measured in vivo phosphatase activities of PP1 in MCF-7 cell extracts treated with TMC and its related compounds, and the results indicate that the cytotoxicity of TMC doesn't correlate with its in vivo PP1 inhibition activity. Taken together, our study suggests that the immunosuppressive and anticancer activities of TMC are not due to the inhibition of PP1. Our results provide a novel insight for the elucidation of the underlying molecular mechanisms of TMC's important biological functions.
Cell Line ; Cell Proliferation ; Fermentation ; Furans ; Lipids ; Maleic Anhydrides ; MCF-7 Cells ; Structure-Activity Relationship

PURPOSE: We evaluated the result of operative treatment of the hallux valgus in male patients. MATERAILS AND METHODS: Total 11 cases (10 patients) of the hallux valgus deformity that treated with operation were evaluated. Following Mann's radiological classification system, there was 1 cases of mild, 8 cases of moderate, and 2 cases of severe. Preoperative, postoperative, postoperative 3 months and postoperative 6 months follow up standing radiographs were used as radiologic evaluation. And we evaluated radiological outcomes by hallux valgus angle (HVA), first-second intermetatarsal angle (IMA), distal metatarsal articular angle (DMAA), proximal phalangeal articular angle (PPAA) and clinical outcomes by hallux-metatarsophalangeal scale of American Orthopaedic Foot and Ankle Society (AOFAS) score. RESULT: Radiologically, the mean preoperative HVA 37degrees and IMA 13.7degrees were improved postoperatively as HVA 11.9degrees and IMA 4.7degrees, and the mean preoperative DMMA 29.4degrees and PPAA 8.6degrees were improved postoperatively DMMA 13.9degrees and PPAA 7degrees. But, postoperative 6 months follow up HVA, IMA, DMMA and PPAA was increased at 14.2degrees, 6.3degrees, 16.1degrees and 8.3degrees. Average AOFAS score were improved from 61.2 points to 75.2 points. CONCULSION: In our study, operative treatment of hallux valgus in male patients with proximal metatarsal osteotomy and distal soft tissue procedure showed good results but it was necessary to pay attention to increase aspect of follow up radiologic measurements.
Animals ; Ankle ; Congenital Abnormalities ; Follow-Up Studies ; Foot ; Hallux ; Hallux Valgus ; Humans ; Male ; Maleic Anhydrides ; Metatarsal Bones ; Osteotomy ; Phthalic Anhydrides ; Polymers

The main objective of this study was to observe the adhesion, proliferation and differentiation of mouse osteblast-like MC3T3-E1 cells cultured on maleic anhydride-modified poly(D,L-lactic acid) (MPLA) and poly(D,L-lactic acid) (PDLLA) polymers, and to evaluate the cytocompatibility of MPLA polymer. The effects of MPLA and PDLLA polymers on the morphology, adhesion, proliferation, the content of total cellular protein, alkaline phosphatase (ALP) activity and the content of Ca of MC3T3-E1 cells were explored. These results indicated that MC3T3-E1 cells on MPLA polymer adhered and spread more fully. On MPLA polymer, the proliferation, total protein content, ALP activity, Ca content of the cells were significantly higher than those of the cells on PDLLA polymer (P < 0.01). It was concluded that MPLA polymer could promote the adhesion, spreading, proliferation and the synthesis of protein of osteoblasts, and also induced the differentiation and mineralization of osteoblasts, suggesting that MPLA polymer might have the better cytocompatibility than PDLLA.
Animals ; Biocompatible Materials ; chemistry ; pharmacology ; Cell Adhesion ; drug effects ; Cell Differentiation ; drug effects ; Cell Line ; Cell Proliferation ; drug effects ; Embryo, Mammalian ; Lactic Acid ; chemistry ; pharmacology ; Maleic Anhydrides ; chemistry ; pharmacology ; Mice ; Osteoblasts ; cytology ; Polyesters ; Polymers ; chemistry ; pharmacology