Non-alcoholic steatohepatitis (NASH) has become a serious public health problem associated with metabolic syndrome. The mechanisms by which NASH induces hepatocellular carcinoma (HCC) remain unknown. There are no approved drugs for treating NASH or preventing NASH-induced HCC. We used a genetic mouse model in which HCC was induced via high-fat diet feeding. This mouse model strongly resembles human NASH-induced HCC. The natural product honokiol (HNK) was tested for its preventative effects against NASH progression to HCC. Then, to clarify the mechanisms underlying HCC development, human HCC cells were treated with HNK. Human clinical specimens were also analyzed to explore this study's clinical relevance. We found that epidermal growth factor receptor (EGFR) signaling was hyperactivated in the livers of mice with NASH and human HCC specimens. Inhibition of EGFR signaling by HNK drastically attenuated HCC development in the mouse model. Mechanistically, HNK accelerated the nuclear translocation of glucocorticoid receptor (GR) and promoted mitogen-inducible gene 6 (MIG6)/ERBB receptor feedback inhibitor 1 (ERRFI1) expression, leading to EGFR degradation and thereby resulting in robust tumor suppression. In human samples, EGFR-positive HCC tissues and their corresponding non-tumor tissues exhibited decreased <i>ERRFI1</i> mRNA expression. Additionally, GR-positive non-tumor liver tissues displayed lower EGFR expression. Livers from patients with advanced NASH exhibited decreased <i>ERRFI1</i> expression. EGFR degradation or inactivation represents a novel approach for NASH-HCC treatment and prevention, and the GR-MIG6 axis is a newly defined target that can be activated by HNK and related compounds.
(1987). A Commentary On Children and Fitness: A Public Health Perspective. Research Quarterly for Exercise and Sport: Vol. 58, No. 4, pp. 326-330.
This paper looks at pedestrian travel in Atlanta by US youths aged 5–18 years. Relationships between five urban form variables and walking in specific demographic subgroups are assessed using stratified logistic models and controlling for participant demographics. All five urban form and recreation measures were related to walking among whites, but only land use mix and access to recreation spaces were significantly related to walking in non-whites. There were more significant urban form physical activity associations in high-income than in low-income households. More urban form variables were related to walking in households with 3 or more cars than in households with no cars. Living in mixed use-areas and having access to recreational space were related to youth walking for transport in 11 of 13 population subgroups studied.
We examined associations of micro-scale environment attributes (e.g., sidewalks, street crossings) with three physical activity (PA) measures among Hispanic/Latino adults (n = 1776) living in San Diego County, CA. Systematic observation was used to quantify micro-scale environment attributes near each participant’s home. Total PA was assessed with accelerometers, and PA for transportation and recreation were assessed by validated self-report. Although several statistically significant interactions between individual and neighborhood characteristics were identified, there was little evidence micro-scale attributes were related to PA. An important limitation was restricted environmental variability for this sample which lived in a small area of a single county.
The design of communities and transportation systems is strongly related to nonmotorized transportation (NMT) behavior; however, the effect of environmental policy variables on total physical activity is not clear. Because large proportions of people in the United States live in the sprawling and exclusively residential environments associated with low levels of walking for transport, land use and transportation policies may already be having a substantial, although generally undocumented, impact on public health. Professionals from numerous fields are concerned that we have built our communities so that it is difficult, and in many cases dangerous, to walk or bike, and have thus engineered physical activity out of our daily lives. There is a public health imperative to evaluate environmental and policy variables and their associations with NMT, recreational physical activity, and total physical activity. The results of such studies can inform efforts to alter the environments in which people live their daily lives so as to promote population shifts in physical activity and improve transportation systems. Conducting and applying research on environmental correlates of NMT and physical activity will require collaboration among researchers from a wide range of professions.
Purpose: To investigate the relationships among exercise aids available at home, physical activity, and perceived neighborhood safety. Methods: Physical activity was assessed using the 7-d recall interview for adolescents (n = 878) and the International Physical Activity Questionnaire for parents (n = 853). Parents reported exercise aids such as fitness equipment, running shoes, and dogs in their household using a 16-item checklist and perceptions of neighborhood safety using the Neighborhood Environment Walkability Scale. Physical activity scores were dichotomized to represent meeting weekly guidelines for children (300 min) and adults (150 min). Logistic regression analyses investigated the interaction between exercise equipment and neighborhood safety in relation to the two physical activity outcomes, controlling for participant demographics. Results: The number of home-use (OR = 1.27) and outdoor-use (OR = 1.24) exercise aids was significantly related to physical activity in adolescent girls but not boys. An interaction effect indicated that the relationship between home-use exercise equipment and physical activity levels was specific for girls in neighborhoods perceived as less-safe (OR = 4.40), rather than those perceived as safe (OR = 1.07, P < 0.01). In the parent sample, home-use (OR = 1.24) and outdoor use (OR = 1.16) exercise aids were significantly related to physical activity levels. An interaction between outdoor exercise aids and safety indicated that the effect was specific to parents who lived in neighborhoods perceived as safe (OR = 2.43) compared to those perceived as less-safe (OR = 0.91, P < 0.01). Conclusion: Girls living in neighborhoods their parents perceive to be less-safe may benefit from having exercise equipment they can use in the home. Parents living in neighborhoods perceived to be safe may benefit from having exercise aids that they can use outside.