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Background In our previous study, N end of the Circumsporozoite protein (CSP I-plus) modified recombinant human Endostatin (rEndostatin, endostar) (rES-CSP) was constructed, which had antiangiogenic capability and bound to hepatocellular carcinoma in vivo and in vitro. In this study, the inhibition of rES-CSP on hepatocellular carcinoma metastasis was verified in vivo and in vitro, and its possible mechanism was explored. Methods Firstly, the impact of rES-CSP on the migration, adhesion of hepatoma cell HCCLM3 was identified by wound healing, transwell, and on metastasis of orthotopic xenograft model was identified in nude mouse. Then the expression of metastasis-associated molecules (MMP2, E-cadherin, integrinβ1) and angiogenesis-related factors (VEGFA) in vitro and in vivo were detected by real-time PCR, western blotting, immunohistochemistry. Results Finally, we found that rES-CSP could inhibit the migration and invasion of HCCLM3, and decrease tumor metastasis and growth in nude mouse orthotopic xenograft models. The tumor inhibiting rates of rES-CSP and Endostar were 42.46 ± 5.39% and 11.1 ± 1.88%. The lung metastasis rates of the control, Endostar and rES-CSP were 71, 50, and 42.8%, respectively. Compared with Endostar, rES-CSP significantly down-regulated the expression of VEGFA and integrinβ1. Heparin, a competitive inhibitor of CSP I-plus, which can be bind to the highly-sulfated heparan sulfate proteoglycans (HSPGs) over-expressed in liver and hepatocellular carcinoma, alleviated the down-regulation of VEGFA and integrinβ1. Conclusions These indicate that rES-CSP may play a role in inhibiting tumor growth and metastasis by down-regulating the angiogenic factor VEGF and the metastasis-related molecules or by interfering with HSPGs-mediated tumor metastasis.

Microbial secondary metabolites are one of the main sources of bioactive natural products. It is estimated that around 75% of all antibiotics are derived from secondary metabolites produced by filamentous actinomycete. Gordonia sp. are members of the actinomycete family, their contribution to the environment improvement and environmental protection by their biological degradation ability, but there are few studies on the antimicrobial activity of their secondary metabolites. Our team isolated a Gordonia strain WA 4–31 with anti-Candida albicans activity from the intestinal tract of Periplaneta americana in the early stage. In this study, we firstly identified the strain WA 4–31 by the morphological characteristics and the phylogenetic analyses, and found that it homologous to a strain of Gordonia from the Indian desert by 100%. Then four compounds, Actinomycin D (1), Actinomycin X2 (2), Mojavensin A (3) and cyclic (leucine-leucne) dipeptide (4) were purified from the ethyl acetate extract of the fermented broth of the strain. The compounds 1–4 had activities against Candida albicans, Aspergillus niger, Aspergillus fumigatus and Trichophyton rubrum. They also had activities against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli.coli in different degree. Interestingly, we found that when Mojavensin A was mixed with compound 4 ratio of 1:1, the activity of the mixture on anti-Candida albicans was better than the single. Besides, compounds 1–3 had varying degrees of antiproliferative activity on CNE-2 cells and HepG-2 cells. These indicated that Gordonia rare actinomycete from the intestinal tract of Periplaneta americana possessed a potential as a source of active secondary metabolites.

Background: As we all know, bacterial and fungal infections have become one of the threats to human health. Microbial secondary metabolites are one of the main sources of bioactive natural products. It is estimated that around 60% of all foregone antibiotics are derived from secondary metabolites produced by filamentous actinomycete bacteria. Gordonia spp. are members of the actinomycete family, their contribution to the environment improvement and environmental protection by their biological degradation ability, but there are few studies on their antimicrobial activity of their secondary metabolites. Our team isolated a Gordonia strain WA 4-31 with anti-Candida albicans activity from the intestinal tract of Periplaneta americana in the early stage.Results: In this study, we firstly identified the strain WA 4-31 by the morphological characteristics and the phylogenetic analyses, and found that it homologous to a strain of Gordonia from the Indian desert (EU333873) by 100%. Then four compounds, Actinomycin D (1), Actinomycin X2 (2), Mojavensin A (3) and cyclic (leucine-leucne) dipeptide (4) were purified from the EtOH extract of the fermented broth of the strain. The compounds 1-4 had activities against Candida albicans, Aspergillus niger, Aspergillus fumigatus and Trichophyton rubrum. They also had activities against MRSA, S.aureus, K.peneumoniae and E.coli in different degree. The minimum inhibitory concentration of Actinomycin D and Actinomycin X2 on MASA was 0.25 μg/mL. Interestingly, we found that when Mojavensin A was mixed with compound 4 ratio of 1:1, the solution of the compounds was better than the single on anti-Candida albicans. Besides, compounds 1-3 had varying degrees of cytotoxicity on CNE-2 cells and HepG-2 cells.Conclusions: The present study firstly reported the antimicrobial compounds isolated from Gordonia. These indicated that rare actinomycetes from the intestinal tract of Periplaneta americana possessed a potential as a source of active secondary metabolites.

A new method is proposed in this work to detect and isolate faults in a system consisting of multivariate normal data. The proposed method reduces the variable dimension via a T2 decomposition and combines multivariate monitoring and diagnosis in a unified approach. An adaptive regression adjusted (ARA) chart is introduced to utilize the diagnosis result in order to improve the monitoring scheme. Once an out-of-control alarm is detected, the fault isolation can be done directly. Copyright � 2007 John Wiley & Sons, Ltd.

An important supply chain research problem is the bullwhip effect caused by information distortion and variation amplification along a supply chain, which can lead to tremendous inefficiencies, such as excessive inventory investment and lost revenues. Motivated by engineering process control methods, this paper proposes a class of order-up-to policies and develops a nearly optimal policy to reduce the bullwhip effect. The proposed policy can significantly reduce the order variance while keeping the expected cost nearly optimal. According to our numerical studies, the order variance of the nearly optimal policy can be reduced by more than 50% while the expected cost is only slightly greater than that of the optimal policy derived in Lee et al. [12].