CX3CL1 promotes tumour cell by inducing tyrosine phosphorylation of cortactin in lung cancer

It has been reported that chemokine CX₃CL1 can regulate various tumours by binding to its unique receptor CX₃CR1. However, the effect of CX₃CL1-CX₃CR1 on the lung adenocarcinoma and lung squamous cell carcinoma is still unclear. Here, we showed that CX₃CL1 can further invasion and migration of lung adenocarcinoma A549 and lung squamous cell carcinoma H520. In addition, Western blot and immunofluorescence test indicated CX₃CL1 up-regulated the phosphorylation level of cortactin, which is a marker of cell pseudopodium. Meanwhile, the phosphorylation levels of c-Src and c-Abl, which are closely related to the regulation of cortactin phosphorylation, are elevated. Nevertheless, the src/abl inhibitor bosutinib and mutations of cortactin phosphorylation site could inhibit the promotion effect of CX₃CL1 on invasion and migration of A549 and H520. Moreover, these results of MTT, Hoechst staining and Western blot suggested that CX₃CL1 had no effect on the proliferation and apoptosis of A549 and H520 in vitro. The effects of CX₃CL1 were also verified by the subcutaneous tumour formation in nude mice, which showed that it could promote proliferation and invasion of A549 in vivo. In summary, our results indicated that CX₃CL1 furthered invasion and migration in lung cancer cells partly via activating cortactin, and CX₃CL1 may be a potential molecule in regulating the migration and invasion of lung cancer.     

Significance of seed culture methods on mycelial morphology and production of a novel anti-cancer anthraquinone by marine mangrove endophytic fungus Halorosellinia sp. (No. 1403)

The effects of seed culture methods on the mycelial morphology and production of a novel promising anti-cancer anthraquinone 1403C by marine mangrove saprophytic fungus Halorosellinia sp. (No. 1403) was investigated. Inoculums were prepared using different seed culture methods, i.e., mycelia obtained by grinding biomass that was harvested from baffled flask culture (M1); biomass harvested from baffled flask culture (M2); biomass obtained from unbaffled flask culture with glass beads (M3); biomass attained from unbaffled flask culture (Control). The corresponding fermentations using M1, M2 and M3 enhanced 1403C production by 243.5%, 194.8% and 70.2%, respectively, as compared to that using Control (0.33 ± 0.03 g/l). Interestingly, 1403C production increased with the increase of ratio of number of clumps to pellets. Maximum 1403C production from baffled flask cultures was 4.8-fold of that from unbaffled flask culture. Increasing shaking speed from 170 rpm to 260 rpm could highly improve 1403C production by 151.8%.     

多类型保护地生态承载力核算模型及应用

生态承载力核算是进行保护地科学保护和有效利用的重要基础。多类型保护地是多种类型的保护地分布集中、相邻相连、交叉重叠的地理空间。研究将多类型保护地功能空间与生态系统服务相对应,划分为生态空间、生产空间、生活空间和游憩空间,在此基础上将多类型保护地生态承载力定义为生态系统在这四类空间中维持其重要生态系统服务功能的能力,并将其划分为自然基础承载力、社会经济活动承载力以及游憩承载力,构建了适用于多类型保护地的生态承载力核算框架模型。以三江源国家公园黄河源园区为案例区,进行了生态承载力核算。研究能够为多类型保护地经济建设规模、结构与布局优化调控研究提供科学依据。     

A high-fat diet catalyzes progression to hyperglycemia in mice with selective impairment of insulin action in Glut4-expressing tissues

Insulin resistance impairs postprandial glucose uptake through glucose transporter type 4 (GLUT4) and is the primary defect preceding type 2 diabetes. We previously generated an insulin-resistant mouse model with human GLUT4 promoter-driven insulin receptor knockout (GIRKO) in the muscle, adipose, and neuronal subpopulations. However, the rate of diabetes in GIRKO mice remained low prior to 6 months of age on normal chow diet (NCD), suggesting that additional factors/mechanisms are responsible for adverse metabolic effects driving the ultimate progression of overt diabetes. In this study, we characterized the metabolic phenotypes of the adult GIRKO mice acutely switched to high-fat diet (HFD) feeding in order to identify additional metabolic challenges required for disease progression. Distinct from other diet-induced obesity (DIO) and genetic models (e.g., db/db mice), GIRKO mice remained leaner on HFD feeding, but developed other cardinal features of insulin resistance syndrome. GIRKO mice rapidly developed hyperglycemia despite compensatory increases in β-cell mass and hyperinsulinemia. Furthermore, GIRKO mice also had impaired oral glucose tolerance and a limited glucose-lowering benefit from exendin-4, suggesting that the blunted incretin effect contributed to hyperglycemia. Secondly, GIRKO mice manifested severe dyslipidemia while on HFD due to elevated hepatic lipid secretion, serum triglyceride concentration, and lipid droplet accumulation in hepatocytes. Thirdly, GIRKO mice on HFD had increased inflammatory cues in the gut, which were associated with the HFD-induced microbiome alterations and increased serum lipopolysaccharide (LPS). In conclusion, our studies identified important gene/diet interactions contributing to diabetes progression, which might be leveraged to develop more efficacious therapies.     

Effects of Probucol on Restenosis after Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

Background

Restenosis after percutaneous coronary intervention (PCI) is a remained clinical problem which limits long-term success of PCI. Although there was recognition that probucol in treating restenosis after percutaneous transluminal coronary angioplasty, the efficacy of probucol on restenosis after stent-implantation is controversial. So this meta-analysis was conducted to investigate the association between probucol and late restenosis.

Methods

Articles were assessed by four trained investigators, with divergences resolved by consensus. PubMed, EMBASE, ScienceDirect and the Cochrane Central Register of clinical trials were searched for pertinent studies. Inclusion criteria were random allocated to treatment and a comparison of probucol-treated patients and control patients (not treated with lipid-lowering drug) undergoing PCI.

Results

Fifteen studies with 859 subjects were analyzed. Major outcome, binary angiographic restenosis defined as >50% stenosis upon follow-up angiography, was significantly decreased with probucol treatment (RR = 0.59 [0.43, 0.80] among vessels, P = 0.0007; and RR = 0.52 [0.40, 0.68] among patients, P<0.00001). Probucol also increased the minimal luminal diameter (SMD = 0.45 [0.30, 0.61], P<0.00001) and decreased late loss upon follow-up after 6 months (SMD = -0.41 [-0.60, -0.22], P<0.0001). Moreover, there was a significantly lower incidence of major adverse cardiac events (MACE) in the probucol group than control group (RR = 0.69 [0.51, 0.93], P = 0.01).

Conclusion

Probucol is more than a lipid-lowering drug. It is also effective in reducing the risk of restenosis and incidence of MACE after PCI.     

Nutrition and bioprocess development for efficient biosynthesis of an antitumor compound from marine-derived fungus

An integrated nutrition and bioprocess strategy was developed for improving the biosynthesis of an antitumor compound, 1403C, by a marine-derived fungus, Halorosellinia sp. (no. 1403). First, statistical design strategies were synthetically applied to optimize the nutritional composition. The resulting 1403C production reached 2.07 g/l, which was 143.5 % higher than the original production. However, it only produced 0.44 g/l of 1403C in 5-l bioreactor fermentation. Thus, the operating parameters including culture pH, dissolved oxygen, agitation speed, impeller type and inoculum level were considered to improve the fermentation process, and an effective control strategy for 1403C production by Halorosellinia sp. submerged in a 5-l bioreactor was established. When inoculating 0.22 g/l dry biomass, controlling dissolved oxygen not lower than 30 % during the growth phase but ranging between 30 and 40 % during the stationary phase, using a double-layer six-flat-blade Rushton disc turbine agitated at 400 rpm, keeping short-term low pH and rapid-rising pH with glucose starvation, the highest 1403C production was finally obtained at 1.32 g/l, which was promoted by 200 % compared to before optimization. Fermentation scale-up was finally performed in a 500-l bioreactor, and 1403C production of 1.09 g/l was obtained.