Global Transcriptional Analyses of the Wnt-Induced Development of Neural Stem Cells from Human Pluripotent Stem Cells.

The differentiation of human pluripotent stem cells (hPSCs) to neural stem cells (NSCs) is the key initial event in neurogenesis and is thought to be dependent on the family of Wnt growth factors, their receptors and signaling proteins. The delineation of the transcriptional pathways that mediate Wnt-induced hPSCs to NSCs differentiation is vital for understanding the global genomic mechanisms of the development of NSCs and, potentially, the creation of new protocols in regenerative medicine. To understand the genomic mechanism of Wnt signaling during NSCs development, we treated hPSCs with Wnt activator (CHIR-99021) and leukemia inhibitory factor (LIF) in a chemically defined medium (N2B27) to induce NSCs, referred to as CLNSCs. The CLNSCs were subcultured for more than 40 passages in vitro; were positive for AP staining; expressed neural progenitor markers such as NESTIN, PAX6, SOX2, and SOX1; and were able to differentiate into three neural lineage cells: neurons, astrocytes, and oligodendrocytes in vitro. Our transcriptome analyses revealed that the Wnt and Hedgehog signaling pathways regulate hPSCs cell fate decisions for neural lineages and maintain the self-renewal of CLNSCs. One interesting network could be the deregulation of the Wnt/ß-catenin signaling pathway in CLNSCs via the downregulation of c-MYC, which may promote exit from pluripotency and neural differentiation. The Wnt-induced spinal markers HOXA1-4, HOXA7, HOXB1-4, and HOXC4 were increased, however, the brain markers FOXG1 and OTX2, were absent in the CLNSCs, indicating that CLNSCs have partial spinal cord properties. Finally, a CLNSC simple culture condition, when applied to hPSCs, supports the generation of NSCs, and provides a new and efficient cell model with which to untangle the mechanisms during neurogenesis.

Perspectives of patients with non-insulin-treated type 2 diabetes on self-monitoring of blood glucose: A qualitative study.

AIMS AND OBJECTIVES: To explore experiences of self-monitoring of blood glucose among patients with non-insulin-treated type 2 diabetes. BACKGROUND: Self-monitoring of blood glucose is essential to diabetes care and facilitates glycaemic control. Patients' perspectives of self-monitoring of blood glucose have seldom been discussed in the literature, and engagement in self-monitoring of blood glucose is consistently low. DESIGN: The descriptive phenomenological method was used. METHODS: Purposive sampling was conducted to recruit participants from the endocrinology departments of medical institutions in Taiwan based on the following criteria: (i) having a medical diagnosis of type 2 diabetes, (ii) not being treated with insulin, (iii) having engaged in self-monitoring of blood glucose at least once within the preceding 6 months, (iv) being at least 20 years old and (v) not having any major mental or cognitive disorders. Data were collected in outpatient consultation rooms, the participants' homes and other settings where the participants felt secure and comfortable. In-depth interviews were conducted to collect data from 16 patients with diabetes. RESULTS: The participants perceived that lifestyle affected blood glucose levels and did not know how to handle high or low blood glucose levels. Their willingness to continue self-monitoring of blood glucose depended on whether healthcare professionals checked or discussed their blood glucose levels with them. CONCLUSIONS: The patients' knowledge regarding blood glucose variation and healthcare professionals' attitudes affected the patients' self-monitoring of blood glucose behaviours. The empirical findings illustrated self-monitoring of blood glucose experiences and recommended that healthcare professionals' closely attend to patients' requirements and responses to diabetes and incorporate the self-monitoring of blood glucose into therapy plans. RELEVANCE TO CLINICAL PRACTICE: Healthcare professionals should reinforce patients' knowledge on appropriate responses to high and low blood glucose levels, intervene appropriately, discuss self-monitoring of blood glucose results with patients and track these results.

Altered apoptosis/autophagy and epigenetic modifications cause the impaired postimplantation octaploid embryonic development in mice.

Polyploids are pervasive in plants and have large impacts on crop breeding, but natural polyploids are rare in animals. Mouse diploid embryos can be induced to become tetraploid by blastomere fusion at the 2-cell stage and tetraploid embryos can develop to the blastocyst stage in vitro. However, there is little information regarding mouse octaploid embryonic development and precise mechanisms contributing to octaploid embryonic developmental limitations are unknown. To investigate the genetic and epigenetic mechanisms underlying octaploid embryonic development, we generated mouse octaploid embryos and evaluated the in vitro/in vivo developmental potential. Here we show that octaploid embryos can develop to the blastocyst stage in vitro, but all fetus impaired immediately after implantation. Our results indicate that cell lineage specification of octaploid embryo was disorganized. Furthermore, these octaploid embryos showed increased apoptosis as well as alterations in epigenetic modifications when compared with diploid embryos. Thus, our cumulative data provide cues for why mouse octaploid embryonic development is limited and its failed postimplantation development.

[Aberrant methylation of APC and Bikunin CpG islands in sporadic breast carcinomas].

OBJECTIVE: To investigate relationship between methylation status of the APC and Bikunin CpG islands and clinicopathological characteristics of breast carcinomas. METHODS: The methylation status of APC and Bikunin CpG islands in 152 sporadic breast carcinoma samples were analyzed by methylation specific PCR. RESULTS: 40.8% of breast carcinomas examined showed methylated signals for the APC. The methylation frequency of APC was significantly correlated to the tumor size (chi(2) = 4.041; P = 0.044), but not to patients' age, pathologic type of tumor, clinical stage, histological grade, lymph node metastasis and the status of estrogen or progestogen receptor. In addition, 24.6% of carcinoma samples examined revealed strong methylated signals for Bikunin. No significant correlation was found between the aberrant methylation of Bikunin and the clinicopathological characteristics of sporadic breast carcinomas. CONCLUSION: The aberrant methylations of APC and Bikunin are frequent events during breast carcinogenesis. APC methylation might play a role in the progression of breast cancer.