Bioproduction of low-pigment xanthan gum by a cell-wall deficient mutant of Xanthomonas campestris.

This work aims to enhance the bioproduction of xanthan gum by screening a hyper-yield producer from the wild-type Xanthomonas campestris during a long-term continuous subculture. We reported a cell-wall deficient mutant, which performed a shift of cell morphology from rod-shaped to round-shaped. Both the yield of xanthan gum and the conversion rate of feedstock were assessed using sucrose as a carbon source with the supplement of yeast extract powder, l-glutamic acid, and other raw materials. After 96 h aerobic fermentation, the yield of xanthan gum of the mutant reached up to 32 g/L, which was 3.4 times of that of the wild-type strain. The conversion rate of feedstock in the mutant was up to 92.1%, which was 3 times of that of the wild-type (31.2%). Furthermore, pigments generated were determined and compared. As a result, the fermentation broth of the wild-type performed an OD560nm of 0.296, which was 5.8 times of that (OD560nm = 0.051) of the mutant. Microscopy analysis showed that the percentage of free-living cells in broth affected the color of the final product. Moreover, the robustness of the fermentation performance of the cell-wall deficient mutant at a pilot scale showed potential for industrial application.

Oroxylin A prevents inflammation-related tumor through down-regulation of inflammatory gene expression by inhibiting NF-κB signaling.

Increasing evidence suggests that inflammatory microenvironment plays a critical role at different stages of tumor development. However, the molecular mechanisms of the interaction between inflammation and proliferation of cancer cells remain poorly defined. Here we reported the inhibitory effects of oroxylin A on the inflammation-stimulated proliferation of tumor cells and delineated the mechanism of its action. The results indicated that treatment with oroxylin A inhibited NF-κB p65 nuclear translocation and phosphorylation of IκBα and IKKα/ß in both human colon tumor HCT116 cells and human monocytes THP-1 cells. In addition, in THP-1 cells, oroxylin A significantly suppressed lipopolysaccharide (LPS)-induced secretion of prototypical proinflammatory cytokine IL-6 but not IL-1ß, and it was confirmed at the transcription level. Moreover, oroxylin A inhibited the proliferation of HCT116 cells stimulated by LPS-induced THP-1 cells in co-culture microenvironment. In summary, oroxylin A modulated NF-κB signaling pathway involved in inflammation-induced cancer initiation and progression and therefore could be a potential cancer chemoprevention agent for inflammation-related cancer.

Enhanced 5-fluorouracil cytotoxicity in high COX-2 expressing hepatocellular carcinoma cells by wogonin via the PI3K/Akt pathway.

Combination therapies may increase the antitumor effects and reduce the adverse effects for the treatment of hepatocellular carcinoma. In this study, we determined the effects of 5-fluorouracil alone or in combination with wogonin in vitro and in vivo, and we investigated the possible mechanisms. The combination of these 2 drugs led to a decrease in survival and a significant synergistic inhibitory effect on high COX-2 expression in SMMC-7721 hepatocellular carcinoma (HCC) cells. Furthermore, the results show that this combination inhibits COX-2 expression and increases sensitivity to chemotherapeutic agents partly through regulating the PI3K/Akt signaling pathway. Moreover, the combination treatment caused a significant growth inhibition of human tumor xenografts in vivo. In conclusion, wogonin may increase the cytotoxicity of some antineoplastic agents and it can be used in combination with these agents as a novel therapeutic regimen for HCC treatment.

Oroxylin A reverses CAM-DR of HepG2 cells by suppressing Integrinß1 and its related pathway.

Oroxylin A, a naturally occurring monoflavonoid extracted from Scutellariae radix, shows effective anticancer activities and low toxicities both in vivo and in vitro in previous studies. In this study, we investigated whether the CAM-DR model of HepG2 cells showed resistance to cytotoxic agents compared with normally cultured HepG2 cells. Furthermore, after the treatment of Paclitaxel, less inhibitory effects and decreased apoptosis rate were detected in the model. Data also revealed increased expression of Integrinß1 might be responsible for the resistance ability. Moreover, Integrinß1-siRNA-transfected CAM-DR HepG2 cells exhibited more inhibitory effects and higher levels of apoptosis than the non-transfected CAM-DR cells. The data corroborated that Integrinß1 played a significant role in CAM-DR. After the treatment of weakly-toxic concentrations of Oroxylin A, the apoptosis induced by Paclitaxel in the CAM-DR model increased dramatically. Western blot assay revealed Oroxylin A markedly down-regulated the expression of Integrinß1 and the activity of related pathway. As a conclusion, Oroxylin A can reverse the resistance of CAM-DR via inhibition of Integrinß1 and its related pathway. Oroxylin A may be a potential candidate of a CAM-DR reversal agent.

The collective influence of 1, 25-dihydroxyvitamin D3 with physiological fluid shear stress on osteoblasts.

1, 25-dihydroxyvitamin D3 (1, 25 (OH)2 D3) and mechanical stimuli in physiological environment contributes greatly to osteoporosis pathogenesis. Wide investigations have been conducted on how 1, 25-dihydroxyvitamin D3 and mechanical stimuli separately impact osteoblasts. This study reports the collective influences of 1, 25-dihydroxyvitamin D3 and flow shear stress (FSS) on biological functions of osteoblasts. 1, 25 (OH)2 D3 were prepared in various kinds of concentrations (0, 1, 10, 100 nmmol/L), while physiological fluid shear stress (12 dynes/cm2) was produced by using a parallel-plate fluid flow system. 1, 25 (OH)2 D3 affects the responses of ROBs to FSS, including the inhibition of NO release and cell proliferation as well as the promotion of PGE2 release and cell differentiation. These findings provide a possible mechanism by which 1, 25(OH)2 D3 influences osteoblasts' responses to FSS, thus most probably providing guidance for the selection of 1, 25(OH)2 D3 concentration and mechanical loading in order to produce functional bone tissues in vitro.