CD206 modulates the role of M2 macrophages in the origin of metastatic tumors.

Tumor metastasis is a key factor affecting the life of patients with malignant tumors. For the past hundred years, scientists have focused on how to kill cancer cells and inhibit their metastasis in vivo, but few breakthroughs have been made. Here we hypothesized a novel mode for cancer metastasis. We show that the phagocytosis of apoptotic tumor cells by macrophages leads to their polarization into the M2 phenotype, and that the expression of stem cell related as well as drug resistance related genes was induced. Therefore, it appears that M2 macrophages have "defected" and have been transformed into the initial "metastatic cancer cells", and thus are the source, at least in part, of the distal tissue tumor metastasis. This assumption is supported by the presence of fused cells with characteristics of both macrophage and tumor cell observed in the peripheral blood and ascites of patients with ovarian cancer. By eliminating the expression of CD206 in M2 macrophages using siRNA, we show that the growth and metastasis of tumors was suppressed using both in vitro cell line and with experimental in vivo mouse models. In summary, we show that M2 macrophages in the blood circulation underwent a "change of loyalty" to become "cancer cells" that transformed into distal tissue metastasis, which could be suppressed by the knockdown of CD206 expression.

[Experimental study on the pharmacology of 999 ganmaoling, a compound recipe of Chinese and Western materia medica].

OBJECTIVE: To study the pharmacologic characteristics in synergism and complementation of 999 Ganmaoling (GML), a compound recipe composed of Chinese and Western materia medica (CMM & WMM), as well as its theoretical basis of matching of Chinese and Western materia medica. METHODS: The torsion response induced by glacial acetic acid in mice, toe swelling induced by carrageenanin rats, delayed hypersensitive response in mice and fever induced by endotoxin in rats and rabbits were used to comparatively study the actions of CMM & WMM in GML. The effect of CMM in antagonizing liver damage caused by WD (acetaminophen) in mice was also studied. RT-PCR method was used to analyze the expression of related cytokines. RESULTS: GML showed a significant antipyretic and analgesic effect, it could inhibit the carrageenan induced inflammation, antagonize the endotoxin induced fever, and promote the amount for expression of cytokines in rats' splenic tissue with pneumococci infection to some extent. The CMM in GML showed certain protective effect on acetaminophen induced liver damage. CONCLUSION: GML has a potent antipyretic, analgesic and anti-inflammatory effects, CMM & WMM in GML showed markedly synergism and complementation, and CMM in it has liver protective effect.

[Comparison of seed oil physicochemical characteristics among three cultivars of Jatropha curcas L].

Taking the cultivars Nanyou 1, 2, and 3 of barbadosnut (Jatropha curcas L. ) with different genotypes that can grow and seed normally at the inshore land in Hainan as test materials, the characters of their seeds and the physicochemical characteristics of their seed oils were analyzed and compared. No significant differences were observed in the seed length, width, thickness, and surface area among the cultivars, but Nanyou 2 had greater 1000 seed mass and lower unsound kernel percentage than Nanyou 1 and Nanyou 3, suggesting that the seed satiation of Nanyou 2 was good and the fecundity was excellent. The kernel oil content of Nanyou 3 was significantly higher than that of Nanyou 1 and Nanyou 2, and there was no significant difference between Nanyou 1 and Nanyou 2. The seed oil peroxide value, refractive index, and saponification value of the three cultivars had no significant differences, but the acid value for Nanyou 2 was much lower than that for Nanyou 1 and Nanyou 3. The seed oil iodine value of the three cultivars was all below 100, and was significantly lower for Nanyou 2 than for Nanyou 1 and Nanyou 3. The fatty acids in the three cultivars seed oils were mainly oleic acid, palmitic acid, linoleic acid, stearic acid, and margaric acid, and dominated by unsaturated fatty acids. The contents of saturated fatty acids in Nanyou 2 seed oil were relatively higher than those in Nanyou 1 and Nanyou 3 seed oils, indicating that comparing with Nanyou 1, cultivars Nanyou 2 and Nanyou 3 had relatively good potential for application.

Establishment of liver specific glucokinase gene knockout mice: a new animal model for screening anti-diabetic drugs.

AIM: To characterize the liver-specific role of glucokinase in maintaining glucose homeostasis and to create an animal model for diabetes. METHODS: We performed hepatocyte-specific gene knockout of glucokinase in mice using Cre-loxP gene targeting strategy. First, two directly repeated loxP sequences were inserted to flank the exon 9 and exon 10 of glucokinase in genomic DNA. To achieve this, linearized targeting vector was electroporated into ES cells. Then G418- and Gancyclovir-double-resistant clones were picked and screened by PCR analysis and the positives identified by PCR were confirmed by Southern blot. A targeted clone was selected for microinjection into C57BL/6J blastocysts and implanted into pseudopregnant FVB recipient. Chimeric mice and their offspring were analyzed by Southern blot. Then by intercrossing the Alb-Cre transgenic mice with mice containing a conditional gk allele, we obtained mice with liver-specific glucokinase gene knockout. RESULTS: Among 161 double resistant clones 4 were positive to PCR and Southern blot and only one was used for further experiments. Eventually we generated the liver specific glucokinase knockout mice. These mice showed increased glucose level with age and at the age of 6 weeks fasting blood glucose level was significantly higher than control and they also displayed impaired glucose tolerance. CONCLUSION: Our studies indicate that hepatic glucokinase plays an important role in glucose homeostasis and its deficiencies contribute to the development of diabetes. The liver glucokinase knockout mouse is an ideal animal model for MODY2, and it also can be applied for screening anti-diabetic drugs.