104 research outputs found

    Nuclear Factor Erythroid-Derived 2-Like 2-Induced Reductive Stress Favors Self-Renewal of Breast Cancer Stem-Like Cells via the FoxO3a-Bmi-1 Axis

    Get PDF
    Aims: A subpopulation of cancer cells, termed cancer stem cells (CSCs), has stemness properties, such as self-renewal and differentiation, which drive cancer recurrence and tumor resistance. CSCs possess enhanced protection capabilities to maintain reduced intracellular levels of reactive oxygen species (ROS) compared with nonstem-like cancer cells. This study investigated whether reductive stress could regulate self-renewal activity in breast CSCs. Results: We found that manifestation of stemness in breast cancer stem-like cells was associated with an elevated production of reduced glutathione (GSH) maintained by upregulation of glutamate cysteine ligase catalytic subunit (GCLC) and consequently, lowered ROS levels. This was accompanied by upregulation of phospho-AMP-activated protein kinase, FoxO3a, and Bmi-1. Notably, expression of nuclear factor erythroid-derived 2-like 2 (Nrf2) protein was substantially increased in cells undergoing sphere formation. We noticed that expression of Bmi-1 was inhibited after introduction of Nrf2 short interfering RNA into MCF-7 mammosphere cells. Silencing of Nrf2 expression suppressed the xenograft growth of subcutaneously or orthotopically injected human breast cancer cells. Innovation: Association between Nrf2 and self-renewal signaling in CSCs has been reported, but the underlying molecular mechanism remains largely unresolved. This study demonstrates the Nrf2-mediated signaling pathway in maintenance of reductive stress in breast CSCs. Conclusion: Nrf2 overactivation in breast CSCs upregulates GCLC expression and consequently enhances GSH biosynthesis with concurrent reduction in intracellular ROS accumulation, thereby provoking the reductive stress. The consequent upregulation of nuclear FoxO3a and its binding to the promoter of the gene encoding Bmi-1 account for the self-renewal activity of breast cancer stem-like cells and their growth in a xenograft mouse model.

    Estimation of Stellate Ganglion Block Injection Point Using the Cricoid Cartilage as Landmark Through X-ray Review

    Get PDF
    BACKGROUND: Stellate ganglion block is usually performed at the transverse process of C6, because the vertebral artery is located anterior to the transverse process of C7. The purpose of this study is to estimate the location of the transverse process of C6 using the cricoid cartilage in the performance of stellate ganglion block. METHODS: We reviewed cervical lateral neutral-flexion-extension views of 48 patients who visited our pain clinic between January and June of 2010. We drew a horizontal line at the surface of the cricoid cartilage in the neutral and extension views of cervical lateral x-rays. We then measured the change in the shortest distance from this horizontal line to the lowest point of the transverse process of C6 between the neutral and extension views. RESULTS: There was a statistically significant difference in the shortest distance from the horizontal line at the surface of the cricoid cartilage to the lowest point of transverse process of C6 between neutral position and neck extension position in both males and females, and between males and females in both neutral position and neck extension position. The cricoid cartilage level was 4.8 mm lower in males and 14.4 mm higher in females than the lowest point of transverse process of C6 in neck extension position. CONCLUSIONS: Practitioners should recognize that the cricoid cartilage has cephalad movement in neck extension. In this way, the cricoid cartilage can be still useful as a landmark for stellate ganglion block.ope

    Transient receptor potential channel TRPV4 mediates TGF-β1-induced differentiation of human ventricular fibroblasts

    Get PDF
    Background: Cardiac fibroblasts (CFs) are principal extracellular matrix-producing cells. In response to injury, CFs transdifferentiate into myofibroblasts. Intracellular calcium (Ca2+) signaling, involved in fibroblast proliferation and differentiation, is activated in fibroblasts through transient receptor potential (TRP) channels, but the function of these channels has not been investigated in human ventricular CFs. Under evaluation in this study, was the role of TRP channels in the differentiation of human ventricular CFs induced by transforming the growth factor beta (TGF-β), a pro-fibrotic cytokine. Methods: Human ventricular CFs were used in this study. The differentiation of CFs into myofibroblast was induced with TGF-β and was identified by the expression of smooth muscle actin. Results: Results indicate that Ca2+ signaling was an essential component of ventricular CF dif­ferentiation. CFs treated with TGF-β demonstrated increased expression of a TRP channel, TRPV4, both at the mRNA and protein levels, which corresponded with CF-myofibroblast trans-differentiation, as evidenced by the upregulation of α-smooth muscle actin, a myofibroblast marker, and plasminogen activator inhibitor-1, which are fibrogenesis markers. An agonist of TRPV4 induced the conversion of CFs into myofibroblasts, whereas it’s antagonist as well a Ca2+ chelating agent reduced it, indicating that the Ca2+ influx throughTRPV4 is required for CF trans-differentiation. Overall, these results dem­onstrate that TRPV4-mediated Ca2+ influx participates in regulating the differentiation of human ventricular CFs into myofibroblasts through the MAPK/ERK pathway. Conclusions: Overall, these results demonstrate that TRPV4-mediated Ca2+ influx participates in regulating the differentiation of human ventricular CFs into myofibroblasts through the MAPK/ERK pathway

    Comparisons of obesity assessments in over-weight elementary students using anthropometry, BIA, CT and DEXA

    Get PDF
    Obesity was characterized in Korean elementary students using different obesity assessment tests on 103 overweight elementary students from three schools of Jeonbuk Province. The body mass index (BMI) and obesity index (OI) were compared, and the data using DEXA and CT were compared with the data using BIA and a tape measure. The results of this study are as follows: first, 27 students who were classified as obese by OI were classified as overweight by BMI, and 3 students who were classified as standard weight by BMI were classified as overweight by OI. Secondly, by DEXA and BIA measurements, there was 1.51% difference in body fat percentage (boys 1.66%, girls 1.17%) and the difference in body fat mass between boys and girls was 0.77 kg (boys 0.85 kg, girls 0.59 kg), but those differences in body fat percentage and mass were not statistically significant. Thirdly, the average total abdominal fat (TAF) measured by CT scans of obese children was more significantly related with subcutaneous fat (r = 0.983, P < 0.01) than visceral fat (r = 0.640, P < 0.01). Also, TAF were highest significant with waist circumference by a tape measure (r = 0.744, P < 0.01). In summary, as there are some differences of assessment results between two obesity test methods (BMI, OI), we need more definite standards to determine the degree of obesity. The BIA seems to be the most simple and effective way to measure body fat mass, whereas waist/hip ratio (WHR) using a tape measurer is considered to be the most effective method for assessing abdominal fat in elementary students

    Changes in lipid and carnitine concentrations following repeated fasting-refeeding in mice

    Get PDF
    The purpose of this study was to evaluate the effects of repeated fasting and refeeding on lipid metabolism. Thirty male ICR mice, aged 6 weeks, were fed an AIN-93 control diet during the experimental period. The mice were divided into 5 groups: Non fasting group (ad libitum-fed, NF), fasting for 3 days (F), fasting for 3 days and then refeeding for 4 days repeated once (FRF1), fasting for 3 days and then refeeding for 4 days repeated twice (FRF2), and fasting for 3 days and then refeeding for 4 days repeated three times (FRF3). Rates of body weight gain, epididymal fat weight, and serum TG were significantly decreased in the F, FRF1, FRF2, and FRF3 groups, compared to the NF group. LDL-cholesterol was significantly higher in the FRF3 group than the NF and F groups, but HDL-cholesterol and HDL/TC were significantly lower in the FRF3 group than in the NF and F groups. Serum total carnitine was significantly lower in the FRF1, FRF2, FRF3 groups than the NF and F groups. However, rates of serum and hepatic acyl-carnitine concentration were significantly lower in FRF1, FRF2, and FRF3 than in NF and F. Repeated fasting-refeeding resulted in visible reductions of body weight and fat mass, but it caused ill-effects with lipid and carnitine metabolism in the body

    Etiology of Invasive Bacterial Infections in Immunocompetent Children in Korea (1996-2005): A Retrospective Multicenter Study

    Get PDF
    The purpose of this study was to identify the major etiological agents responsible for invasive bacterial infections in immunocompetent Korean children. We retrospectively surveyed invasive bacterial infections in immunocompetent children caused by eight major pediatric bacteria, namely Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pyogenes, Listeria monocytogenes, and Salmonella species that were diagnosed at 18 university hospitals from 1996 to 2005. A total of 768 cases were identified. S. agalactiae (48.1%) and S. aureus (37.2%) were the most common pathogens in infants younger than 3 months. S. agalactiae was a common cause of meningitis (73.0%), bacteremia without localization (34.0%), and arthritis (50%) in this age group. S. pneumoniae (45.3%) and H. influenzae (20.4%) were common in children aged 3 months to 5 yr. S. pneumoniae was a common cause of meningitis (41.6%), bacteremia without localization (40.0%), and bacteremic pneumonia (74.1%) in this age group. S. aureus (50.6%), Salmonella species (16.9%), and S. pneumoniae (16.3%) were common in older children. A significant decline in H. influenzae infections over the last 10 yr was noted. S. agalactiae, S. pneumoniae, and S. aureus are important pathogens responsible for invasive bacterial infections in Korean children
    corecore