[Epithelial-mesenchymal transition induces cancer stem cell generation in human thyroid cancer cells in vitro].

OBJECTIVE: Epithelial-mesenchymal transition (EMT) has been implicated in the initiation and conversion of early stage tumors into invasive malignancies and is associated with the "stemness" of cancer cells. The present study was designed to identify whether EMT induces cancer stem cell generation and tumor progression in human thyroid cancer cells in vitro. METHODS: FTC133 cells, as EMT-negative cells, were used for EMT induction by hypoxia-inducible factor-1α (HIF-1α) transfection. And EMT features were then examined by Western blot, immunofluorescent staining, invasion and proliferation assays. Moreover, stem-like side population (SP) cells were sorted with flow cytometry from FTC133 cells before and after EMT. The proportion of SP was compared and stemness, self-renewal and tumorigenicity in vitro were identified in SP cells. RESULTS: Overexpression of HIF-1α induced FTC133 cells to undergo EMT. And it down-regulated epithelial marker E-cadherin, up-regulated mesenchymal marker vimentin and caused nucleus translocation of ß-catenin and highly invasive and metastatic properties. Most importantly, the induction of EMT promoted proportion of stem-like side population cells (0.70% vs 0.03%, P < 0.05) with higher sphere formation and clone forming capability in contrast to non-side population cells. CONCLUSIONS: EMT can induce cancer stem cell generation and tumor progression in thyroid cancers. Further understanding the role of EMT and cancer stem cells in cancer progression may reveal new preventive and therapeutic targets for thyroid cancers.

Effect of two intensive insulin therapy regimens on perioperative glycemic control in bone fracture patients with type 2 diabetes mellitus.

BACKGROUND: Currently, there are no uniform standards and methods for perioperative glycemic control in bone fracture patients with Type 2 diabetes mellitus (T2DM). We retrospectively analyzed the efficacy and safety of two intensive insulin therapy regimens administered to bone fracture patients with T2DM in the perioperative period, to explore the best method of achieving perioperative glycemic control. METHODS: A number of 159 bone fracture patients with T2DM were divided into two groups. One group (n = 81) received multiple subcutaneous insulin injections (MSII group) and the other (n = 78) received continuous subcutaneous insulin infusion (CSII group). Blood glucose (BG) levels, time to achieve glycemic target, insulin dosage, and the incidence of hypoglycemia and complications were compared between groups. RESULTS: Both regimens reduced BG to desired levels before surgery. The time to reach glycemic target in CSII group (2.5 days) was significantly shorter than that in the MSII group (7.3 days; P < 0.001). Mean insulin dosage in the CSII group (0.66 IU×kg(-1)×d(-1)) was significantly lower than that in the MSII group (0.74 IU×kg(-1)×d(-1); P = 0.005), as were the incidences of hypoglycemia (15.4% vs 32.1%) and infection (6.4% vs. 23.5%). Multiple regression analysis showed that the time to reach glycemia target was associated with the insulin therapy regimen and dosage. The insulin dosage on reaching glycemia target was positively associated with body mass index (BMI), diabetes mellitus course, glycated hemoglobin A1c (HbA1c), and ß-hydroxybutyric acid, and was negatively associated with age. CONCLUSION: The efficacy and safety of CSII was superior to that achieved with MSII, suggesting that CSII should be considered as initial therapy to control perioperative BG in bone fracture patients with T2DM.

Epithelial-mesenchymal transition triggers cancer stem cell generation in human thyroid cancer cells.

Increasing evidence has shown that cancer stem cells or tumor initiating cells are the 'root cause' of malignant cancers. However, the exact origin of cancer stem cells still remains obscure in thyroid research. EMT has been implicated in the initiation and conversion of early-stage tumors into invasive malignancies and is associated with the stemness of cancer cells. Based on these facts, a new hypothesis was suggested that EMT induces cancer stem cell generation and tumor progression in human thyroid cancer cells in vitro. In the present study, FTC133 cells identified as EMT-negative cells were used for EMT induction by HIF­1α transfection. Overexpression of HIF-1α induced FTC133 cells to undergo EMT, downregulated the epithelial markers E-cadherin, upregulated the mesenchymal marker vimentin, and associated with highly invasive and metastatic properties. Most importantly, the induction of EMT promoted the stem-like side population cell proportion in the FTC133 cells. These results indicate that EMT induction promotes CSC traits and cell proportions in the thyroid cancer cells, which implies that EMT could induce cancer stem cell generation and tumor progression in thyroid cancers. Further understanding of the role of EMT and cancer stem cells in cancer progression may reveal new targets for the prevention or therapy of thyroid cancers.

[Waterborne iron migration by groundwater irrigation pumping in a typical irrigation district of Sanjiang Plain].

The iron concentration in groundwater, iron's seasonal migration from groundwater to sun-basked pools, paddy fields and drainage canals, and its distribution in the sediments/soils were observed in the Jiansanjiang Branch Bureau, Heilongjiang Agricultural Cultivation Bureau. The results suggested that the total iron mass concentration of the studied area was (1.73 +/- 0.41) mg x L(-1), ranging from 0.01 to 11.4 mg x L(-1), with the variation coefficient of 1.29%. The annual iron input mass from groundwater to paddy fields and other surface water bodies was 4 976.40 t in 2010, according to the rice planting area and rating irrigation volume. Dissolved Fe2+, Fe3+ and iron, as well as the total iron (dissolved and particle) had seasonal variation, with greater values presented in June and July. These waterborne irons in paddy field waters were greater than those in sun-basked pools and drainage canals. Obvious enrichment effect was observed in sun-basked pools and paddy fields, with their total iron mass concentrations were 6.17 and 21.65 times greater than that in groundwater. Either the total iron or iron oxides in sun-baked pool sediments were greater than that in paddy field soils, field canal and main canal sediments. The differences of the total iron and iron oxides in paddy field soils, field canal and main canal sediments were not significantly different. Considerable irons were precipitated within sun-basked pools and paddy fields during the transfer from groundwater to surface water, with a part of irons exporting into canals through drainage and then precipitated there. Not only the change of total iron mass, but the transformation of iron chemical speciation was observed during the transfer, which was affected by paddy irrigation management directly. The long-term irrigation pumping could cause the substantial enrichment of iron in paddy soils and canal sediments, resulting in the increase of potential pollution risk.

Contribution of the Akt2 gene to type 2 diabetes in the Chinese Han population.

BACKGROUND: The Akt2 protein kinase is thought to be a key mediator of the insulin signal transduction process. Akt2 is suggested to play a role in glucose metabolism and the development or maintenance of proper adipose tissue and islet mass. In order to determine whether the Akt2 gene plays a role in the pathogenesis of type 2 diabetes characterized by insulin resistance, and to further identify if variations in this gene have a relationship with type 2 diabetes, we sequenced the entire coding region and splice junctions of Akt2 and made a further case-control study to explore the association between single-nucleotide polymorphisms (SNPs) in this gene and type 2 diabetes in the Chinese Han population. METHODS: We selected 23 probands with a type 2 diabetic pedigree whose family members' average onset age was within 25 to 45 years old. The body mass index of all the participants was lower than 28 kg/m(2) and all of them were insulin-resistant (the fasting insulin level > 100 pmol/L or 16 µIU/ml). The entire coding region and splice junctions of Akt2 were directly sequenced in these 23 probands. SNPs with a frequency of minor allele over 20 percent were selected to be further studied in a case-control study. We chose 743 non-diabetic subjects as the control group and 742 type 2 diabetic patients as the case group. All these subjects were genotyped. A Snapshot Technology Platform (Applied Biosystems) was used for genotyping. RESULTS: The Akt2 genes from all 23 subjects were successfully sequenced. We did not identify any mutation in the type 2 diabetic pedigree. Two SNPs were identified, 13010323T > C and 13007939G > T. 13010323T > C was in intron 9, which was the location of rs2304188 reported in Genbank. Its minor allele frequency was 13.04%. 13007939G > T was in the 3'-untranslated region (UTR) of exon 14, which was the location of rs2304186 reported in Genbank. Its minor allele frequency was 34.78%. The allele frequency of rs2304188 and rs2304186 were consistent with the frequency reported in Genbank. In the case-control study with 742 patients and 743 controls, there was no significant difference between the two groups for the allele frequency of rs2304186 (odd ratio: 0.96, 95% confidence interval: 0.82 - 1.12, P = 0.597). CONCLUSIONS: The Akt2 gene is not a major cause of diabetes in a non-obese Chinese Han population characterized by insulin resistance. There is no significant relationship between rs2304186 and type 2 diabetes in the Chinese Han population.

[Effects of Chinese herbal medicine Bushen Gubiao Recipe on toll-like receptor 4 and CD4(+)CD25(+)foxp3(+) regulatory T cells in mice with recurrent respiratory tract infections].

OBJECTIVE: To evaluate the effects of Bushen Gubiao Recipe (BGR), a compound traditional Chinese herbal medicine, on toll-like receptor 4 (TLR4) signaling pathway and CD4(+)CD25(+)foxp3(+)regulatory T cells (CD4(+)CD25(+)foxp3(+)Tregs) in mice with recurrent respiratory tract infections (RRTIs). METHODS: A mouse model of kidney-yang deficiency which simulated physical characteristics of RRTIs was established by intraperitoneal injection of hydrocortisone for 14 d. The model mice were divided into 4 groups, model group, high-dose BGR group, low-dose BGR group, and nucleic acid and casein oral solution group. They were administered respectively with distilled water, high-dose BGR (50 g/kg body weight), low-dose BGR (25 g/kg body weight) and nucleic acid and casein oral solution. Besides, a normal control group was set up and gastrogavage with distilled water. The effect of intervention was evaluated 4 weeks later by estimating the changes in behaviors of mice. Expressions of TLR4 and nuclear factor-kappa B (NF-κB) p65 in lung tissue were detected by immunohistochemical SABC method, the expression of TLR4 mRNA in lung tissue was detected by fluorescence quantitative-polymerase chain reaction (FQ-PCR), and the level of blood CD4(+)CD25(+)foxp3(+) Tregs was determined by flow cytometry. RESULTS: A kidney-yang deficiency mouse model with RRTIs was successfully established by intraperitoneal injection of hydrocortisone. BGR could improve the abnormal behavioral condition of the mice and enhance the expressions of TLR4 and NF-κB p65 in the lung tissue. Expression of TLR4 mRNA in high-dose BGR group was higher than that in model group (P<0.05), while the difference was not statistically significant between high-dose BGR group and low-dose BGR group (P>0.05). Levels of CD4(+)CD25(+)foxp3(+)Tregs in high-dose BGR group and nucleic acid and casein oral solution group were lower than that in model group (P<0.05), while the difference was not statistically significant between high-dose BGR group and low-dose BGR group (P>0.05). CONCLUSION: BGR can improve the behavior of the kidney-yang deficiency mice, and improve the innate immune function by up-regulating TLR/NF-κB signaling pathway. BGR can adjust the immune imbalance of T-helper cell (Th) 1/Th2 through reducing the activity of CD4(+)CD25(+)foxp3(+)Tregs and enhancing the immune response of Th1 type.