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Chen M.-C.,Graduate Institute of Medical science | Lee C.-F.,Institute of Preventive Medicine | Huang W.-H.,National Defense Medical Center | Chou T.-C.,National Defense Medical Center
Biochemical Pharmacology | Year: 2013

The hypoxic environment in tumors is an important factor causing tumor angiogenesis by activating the key transcription factor, hypoxia-inducible factors-1α (HIF-1α). Magnolol isolated from Magnolia officinalis has been reported to exhibit an anticancer activity via elevation of apoptosis. However, whether magnolol inhibits tumor angiogenesis remains unknown. In the present study, we demonstrated that magnolol significantly inhibited angiogenesis in vitro and in vivo evidenced by the attenuation of hypoxia and vascular endothelial growth factor (VEGF)-induced tube formation of human umbilical vascular endothelial cells, vasculature generation in chicken chorioallantoic membrane and Matrigel plug. In hypoxic human bladder cancer cells (T24), treatment with magnolol inhibited hypoxia-stimulated H 2O2 formation, HIF-1α induction including mRNA, protein expression, and transcriptional activity as well as VEGF secretion. Additionally, the enhanced degradation of HIF-1α protein via enhancing prolyl hydroxylase activity and the decreased newly-synthesized HIF-1α protein in hypoxic T24 cells may involve the reduction of HIF-1α protein accumulation by magnolol. Interestingly, magnolol also acts as a VEGFR2 antagonist, and subsequently attenuates the down-stream AKT/mTOR/p70S6K/4E-BP-1 kinase activation both in hypoxic T24 cells and tumor tissues. As expected, administration of magnolol greatly attenuated tumor growth, angiogenesis and the protein expression of HIF-1α, VEGF, CD31, a marker of endothelial cells, and carbonic anhydrase IX, an endogenous marker for hypoxia, in the T24 xenograft mouse model. Collectively, these findings strongly indicate that the anti-agngiogenic activity of magnolol is, at least in part, mediated by suppressing HIF-1α/VEGF-dependent pathways, and suggest that magnolol may be a potential drug for human bladder cancer therapy. © 2013 Elsevier Inc. Source


Aarestrup J.,Institute of Preventive Medicine
International Journal of Obesity | Year: 2016

Background:Heavy children have an increased risk of being overweight young adults. Whether this risk remains in late adulthood is not well-understood. We investigated body mass index (BMI; kg m-2) tracking from childhood to late adulthood.Methods:From the Copenhagen School Health Records Register, 72 959 men and 25 252 women born between 1930 and 1989 with BMI values at 7 and/or 13 years and as adults were included. Using a meta-regression approach, age- and sex-specific partial correlation analyses and logistic regressions were performed.Results:Correlations between BMI at 7 years and young adult ages (18–19 years) were r=0.55 for men and r=0.55 for women. At late ages (60–69 years) these were r=0.28 for men and r=0.26 for women. The correlations did not differ by birth years. Compared with normal-weight 7-year-olds, overweight children had a higher odds of overweight at 18–19 years; odds ratio (OR)=14.02 (95% confidence interval (CI): 12.14–16.19) for men and 10.46 (95% CI: 4.82–22.70) for women. At ages 60–69 years ORs were 5.46 (95% CI: 0.95–31.36) for men and 1.61 (95% CI: 0.83–3.15) for women. Correlations and ORs were stronger at age 13 years than age 7 years as expected, but the overall patterns were similar.Conclusions:BMI tracking was weaker at late adult ages than at young adult ages. Although BMI tracks across the life course, childhood BMI is relatively poor at identifying later adult overweight or obesity at ages when chronic diseases generally emerge.International Journal of Obesity advance online publication, 28 June 2016; doi:10.1038/ijo.2016.88. © 2016 Macmillan Publishers Limited, part of Springer Nature Source


Vamosi M.,University of Southern Denmark | Heitmann B.L.,Institute of Preventive Medicine | Kyvik K.O.,University of Southern Denmark
Obesity Reviews | Year: 2010

The prevalence of obesity is on a global-wide increase, but still the aetiology of adult obesity is poorly understood. It has been shown that overweight children suffer from adverse psychological events, but less is known about the potential effects of adverse psychological factors among normal weight children for later development of obesity. The purpose of this study was to systematically review current literature on associations between psychological factors in childhood and development of obesity in adulthood. A systematic search was conducted in three electronic databases MEDLINE (silverplatter 1977-2008), PsycINFO (1972-2008) and PsycINFO Weekly (week 1 January 2007-week 3 July 2008) to identify studies of interest. Six prospective and two retrospective studies were identified. Psychosocial factors related to adult obesity were lack of childhood care, abuse and childhood anxiety disorders. In addition, depression in adolescence tended to be related to adult obesity but among young girls only. Learning difficulties and scholastic proficiencies below average were also risk factors. The current literature suggests that specific psychosocial factors in childhood may act as determinants for developing obesity in adulthood. © 2009 International Association for the Study of Obesity. Source


Kau J.H.,Institute of Preventive Medicine
PloS one | Year: 2010

Lethal toxin (LT), the major virulence factor produced by Bacillus anthracis, has been shown to suppress the immune system, which is beneficial to the establishment of B. anthracis infections. It has been suggested that the suppression of MEK/MAPK signaling pathways of leukocytes contributes to LT-mediated immunosuppressive effects. However, the involvement of MAPK independent pathways has not been clearly elucidated; nor has the crucial role played by LT in the early stages of infection. Determining whether LT exerts any pathological effects before being enriched to an MEK inhibitory level is an important next step in the furtherance of this field. Using a cell culture model, we determined that low doses of LT inhibited phagocytosis of macrophages, without influencing MAPK pathways. Consistent low doses of LT significantly suppressed bacterial clearance and enhanced the mortality of mice with bacteremia, without suppressing the MEK1 of splenic and peripheral blood mononuclear cells. These results suggest that LT suppresses the phagocytes in a dose range lower than that required to suppress MEK1 in the early stages of infection. Source


Chang H.,National Chiayi University | Yeh M.-K.,Institute of Preventive Medicine
International Journal of Nanomedicine | Year: 2012

Research on liposome formulations has progressed from that on conventional vesicles to new generation liposomes, such as cationic liposomes, temperature sensitive liposomes, and virosomes, by modulating the formulation techniques and lipid composition. Many research papers focus on the correlation of blood circulation time and drug accumulation in target tissues with physicochemical properties of liposomal formulations, including particle size, membrane lamellarity, surface charge, permeability, encapsulation volume, shelf time, and release rate. This review is mainly to compare the therapeutic effect of current clinically approved liposome-based drugs with free drugs, and to also determine the clinical effect via liposomal variations in lipid composition. Furthermore, the major preclinical and clinical data related to the principal liposomal formulations are also summarized. © 2012 Chang and Yeh. Source

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