13-Cis Retinoic Acid Induces Neuronal Differentiation in Daoy (Medulloblastoma) Cells Through Epigenetic Regulation of Topoisomerase IIß.

Medulloblastoma (MB) is a malignant tumor of the cerebellum that occurs in children and infants. Abnormal neuronal differentiation can lead to brain tumors, and topoisomerase IIß (Top IIß) plays an important role in neuronal differentiation. The aim of this study was to investigate the molecular mechanism of 13-cis retinoic acid (13-cis RA) promoting the expression of Top IIß and inducing neuronal differentiation in human MB Daoy cells. The results showed that 13-cis RA inhibited the cell proliferation and induced cell cycle arrest in G0/G1 phase. The cells differentiated into a neuronal phenotype, with high expression of the neuronal marker microtubule-associated protein 2 (MAP2) and abundant Top IIß, and obvious neurite growth. Chromatin immunoprecipitation (ChIP) assay showed that histone H3 lysine 27 tri-methylation (H3K27me3) modification in Top IIß promoter decreased after 13-cis RA-induced cell differentiation, while jumonji domain-containing protein 3 (JMJD3) binding in Top IIß promoter increased. These results suggest that H3K27me3 and JMJD3 can regulate the expression of Top IIß gene, which is related to inducing neural differentiation. Our results provide new insights into understanding the regulatory mechanisms of Top IIß during neuronal differentiation and imply the potential application of 13-cis RA in the clinical treatment of MB.

The protective effect of nitronyl nitroxide radical on peroxidation of A549 cell damaged by iron overload.

Particulate pollution in the air has strong links with increased morbidity of cardiopulmonary diseases. Iron is one of the major carcinogens in air pollution and can produce hydroxyl radical which induce oxidative stress, lead to cell damage and even to cancer. In this work, a novel nitronyl nitroxide radical NITPh(OMe)2 (2-(2,4-dimethoxyphenyl) -4,4,5,5- tetramethylimidazoline- 1- oxyl-3- oxide) was prepared and characterized by electron spin-resonance spectroscopy (ESR), X-ray crystal diffraction, Fourier transform infrared (IR), X-ray powder diffraction (XRD), elemental analysis, ultraviolet and visible spectra (UV-Vis), and the electronic transition processes was also calculated by time-dependent density functional theory (TDDFT) to analysis UV-Vis spectrum. In vitro cell model of oxidative damage was established by ferric ammonium citrate (FAC) overload, and NITPh(OMe)2 was studied as a free radical scavenger to protect peroxidation of A549 cells. Results showed that NITPh(OMe)2 could significantly alleviate the damage of A549 cells by iron overload in cell morphology, cell viability, cell proliferation and cell apoptosis. The apoptotic signaling pathway of A549 cells induced by FAC and the protection mechanism of NITPh(OMe)2 were all discussed through the expression of three relating proteins, Bcl-2, Bax and DDIT3. This work confirms that nitroxide radicals are effective antioxidants, and have potential application in clinical practice as therapeutic agents.

The regulation of iron metabolism in the mononuclear phagocyte system.

The daily iron absorption and loss are small and iron metabolism in human is characterized by a limited external exchange and by an efficient reutilization of iron from internal sources. The mononuclear phagocyte system (MPS) plays a key role in recycling iron from hemoglobin of senescent or damaged erythrocytes, which is important in maintaining iron homeostasis. Many iron-related proteins are expressed in the MPS, including heme oxygenase (HO) for heme degradation, the iron importer transferrin receptor 1 (TfR1) and divalent metal transport 1 (DMT1), the iron exporter ferroportin 1 (FPN1) and the iron regulatory hormone hepcidin. Insights into the regulatory mechanisms that control the regulation of iron metabolism proteins in the MPS will deepen our understanding about the molecular mechanism of iron homeostasis and iron-related diseases.

Fall risk factors assessment tool: enhancing effectiveness in falls screening.

A quasi-experimental study was conducted to explore the effectiveness of fall prevention among hospital patients based on the modified fall risk factors assessment tool. We investigated the frequency of falls among hospital patients at a medical center in Taiwan. The experimental group of falls victims was selected from patients (n = 39) hospitalized in 2002 after falls. The control group of patients falls was selected by means of a retrospective incident report review which identified patients (n = 43) hospitalized one year earlier. The results showed that there was no significant difference in the incidence of falls between the two groups. Nevertheless, there were significant differences in age, indications of falls, use of sedatives, walking ability and evaluated grade of fall risk factors. In addition, the average level of satisfaction under recently modified fall risk factors evaluation guideline was 2.68 points (upper limit = 4 points) based upon investigation derived from nursing staff ' s opinions. Moreover, nursing staff from GYN/OBS and orthopedics departments acknowledged the enhanced effectiveness of these new guidelines. The screening rate for high-risk orthopedic patients was increased from 20.7 % to 41.9 %. Furthermore, the screening rate among the experimental group (74.4 % ) was also higher than that among the control group (60.5 % ) ( p <.01). In line with our effective tool to screen high-risk patients, we also added the concept of continuous quality improvement in nursing care to implement a fall prevention program to reduce unnecessary injury. This strategy may assist nursing personnel in providing immediate and individualized care as well as health education for high-risk patients. It may also cause the incidence of patient falls in hospitals to continue to decline.