Beob-Yi Lee

Honokiol causes the p21WAF1-mediated G(1)-phase arrest of the cell cycle through inducing p38 mitogen activated protein kinase in vascular smooth muscle cells

Honokiol, an active component in extracts of Magnolia officinalis, has been proposed to play a role in anti‐inflammatory, antioxidant activity, anti‐angiogenic and anti‐tumor activity. Although honokiol has a variety of pharmacological effects on certain cell types, its effects on vascular smooth muscle cells (VSMC) are unclear. This issue was investigated in the present study, honokiol was found to inhibit cell viability and DNA synthesis in cultured VSMC. These inhibitory effects were associated with G1 cell cycle arrest. Treatment with honokiol blocks the cell cycle in the G1 phase, down‐regulates the expression of cyclins and CDKs and up‐regulates the expression of p21WAF1, a CDK inhibitor. While honokiol did not up‐regulate p27, it caused an increase in the promoter activity of the p21WAF1 gene. Immunoblot and deletion analysis of the p21WAF1 promoter showed that honokiol induced the expression of p21WAF1 and that this expression was independent of the p53 pathway. Furthermore, the honokiol‐mediated signaling pathway involved in VSMC growth inhibition was examined. Among the relevant pathways, honokiol induced a marked activation of p38 MAP kinase and JNK. The expression of dominant negative p38 MAP kinase and SB203580, a p38 MAP kinase specific inhibitor, blocked the expression of honokiol‐dependent p38 MAP kinase and p21WAF1. Consistently, blockade of p38 MAPK kinase function reversed honokiol‐induced VSMC proliferation and cell cycle proteins. These data demonstrate that the p38 MAP kinase pathway participates in p21WAF1 induction, subsequently leading to a decrease in the levels of cyclin D1/CDK4 and cyclin E/CDK2 complexes and honokiol‐dependent VSMC growth inhibition. In conclusion, these findings concerning the molecular mechanisms of honokiol in VSMC provides a theoretical basis for clinical approaches to the use therapeutic agents in treating atherosclerosis.

Effects of age, gender, and weight on the cerebellar volume of Korean people

The average cerebellar volume of Korean men (135.19 cm3) is larger than that of Korean women (123.06 cm3), and that of subjects in their twenties (134.28 cm3) is larger than that of subjects in their forties (121.83 cm3). Atrophy of the cerebellum is more markedly observed in men than in women. There is a relation between body weight and cerebellar volume for men, but not for women.

Effects of gender, age, and body parameters on the ventricular volume of Korean people

The purpose of this study was to measure the average ventricular volume of normal Koreans (aged in their 20s or 40s) and to analyze the effects of gender, age, and body parameters, such as height and weight on ventricle size. Magnetic resonance brain images were recorded for 118 people in their 20s (58 men, 60 women) and 100 in their 40s (41 men, 59 women). Using automatic and manual segmentation techniques, the volumes of the lateral and the third and fourth ventricles were calculated. To investigate the different and interactive effects of gender and age on ventricular volume, two-way analysis of variance (ANOVA) with gender and age as independent variables was carried out. Multiple regression analysis was used to investigate the effect of body parameters, such as height and weight according to gender on changes in ventricular volume. The average ventricular volume for people in their 20s was 16.2 cm3, and that for people in their 40s was 24.9 cm3. The average ventricular volume for men and women was 22.9 and 18.1 cm3, respectively. The average ventricular volume for men was greater than that for women, and that for people in their 40s was greater than that in their 20s. Enlargement of the ventricles on aging was more markedly observed in men than in women. There was a positive relationship between the body height and ventricular volume for men but not for women. There was no relationship between weight and ventricular volume for either men or women.

Relationship between nutrition factors and osteopenia: Effects of experimental diets on immature bone quality

To investigate the influence of experimental diets on morphological and mechanical characteristics of immature bone, this study thoroughly examined the nutrition-bone connection. A non-destructive evaluation method involving high-resolution in-vivo micro-computed tomography and finite element (FE) analysis was used to investigate the relationship between obesity and osteopenia-two disorders of body composition. Correlation of nutritional deficiency with bone characteristics was also investigated. Some recent studies have shown that both obesity and osteopenia share several common genetic and environmental factors. However, there have been few studies correlating these pathologies in-vivo from a structural and biomechanical point of view. In the present study, detailed changes in morphological and mechanical characteristics of trabecular bone architecture were detected and tracked by longitudinal studies of morphometric parameters and simulated compression testing. Rats were randomized into three groups: overeaten diet (OD) for formation of obesity, normal diet (ND), and restricted diet (RD) in which rats received 65% of the normal diet. In the OD and ND groups, all structural parameters changed significantly (p<0.05). The degree of alteration in the structural parameters of the ND group was similar to that of the RD group (p<0.05). In simulated compression tests using FE models, the effective modulus of the OD group significantly decreased, depending on measuring time (p<0.05), whereas that of the ND and RD groups significantly increased (p>0.05). The key finding of the present study is that fat mass is morphologically and mechanically inversely correlated with bone mass when the mechanical loading effects of greater body weight on bone mass are applied.

A study on the effects of 40% oxygen on addition task performance in three levels of difficulty and physiological signals.

This study investigated the effect of 40% oxygen administration on addition task performance in three levels of difficulty and physiological signals, such as blood oxygen saturation and heart rate. The accuracy rates of the addition tasks were enhanced with 40% oxygen administration compared to 21% oxygen. As the difficulty level increased, the difference in the accuracy rate between 40% and 21% oxygen administration increased. When 40% concentration oxygen was supplied, blood oxygen saturation was increased and heart rate was decreased compared to that with 21% oxygen administration. A positive correlation was found between task performance and oxygen saturation level during the Task3 phase. This result suggests that 40% oxygen administration would lead to increases in addition task performance.

Sanguinarine-induced G1-phase arrest of the cell cycle results from increased p27KIP1 expression mediated via activation of the Ras/ERK signaling pathway in vascular smooth muscle cells

The present study identified a novel mechanism for the effects of sanguinarine in vascular smooth muscle cells (VSMC). Sanguinarine treatment of VSMC resulted in significant growth inhibition as a result of G1-phase cell-cycle arrest mediated by induction of p27KIP1 expression, and resulted in a down-regulation of the expression of cyclins and CDKs in VSMC. Moreover, sanguinarine-induced inhibition of cell growth appeared to be linked to activation of Ras/ERK through p27KIP1-mediated G1-phase cell-cycle arrest. Overall, the unexpected effects of sanguinarine treatment in VSMC provide a theoretical basis for clinical use of therapeutic agents in the treatment of atherosclerosis.

Cerebral activation and lateralization due to the cognition of a various driving speed difference: An fMRI study

This study investigated the changes of cerebral activation and lateralization due to the cognition of three driving speeds in comparison to a reference driving speed using functional magnetic resonance imaging fMRI. A driving video as a visual stimulation source was recorded with four different driving speeds in a real driving situation. The experiment consisted of three blocks and each block included a one-minute control phase and a one-minute stimulation phase. The activation area and the lateralization index were analyzed by subtracting high speed data from low speed data. Such areas as occipital, parietal and frontal lobes, which is related to visual cognition, high order visual and spatial attention (or vigilance), were activated due to the cognition of various driving speed differences. As the driving speed difference increased, the activation area increased in the areas related to spatial attention (or vigilance), such as the frontal lobe, however, changes of neuronal activation in the occipital and parietal lobes were inconsistent. As the driving speed difference increased, the absolute value of cerebral lateralization decreased. These results may provide some basic data for elucidating the brain-function mechanism related to the cognition of a various driving speed difference based on a realistic visual stimulation.

Differences in psychophysiological responses due to simulator sickness sensitivity

The present study tried to investigate the simulator sickness objectively by observing the change of the simulator sickness for the different level of sickness groups (sick and non-sick group). The subjective evaluations using Simulator Sickness Questionnaire (SSQ) and physiological responses were measured every five minutes when they were driving as 60km/h in the driving graphic simulator. Response level of the subjective evaluation for all subjects on the simulator sickness was linearly increased with time for every item, and the response level of sick group was bigger than that of non-sick group. When the analysis on central nervous system was done separately on the sick and the non-sick group, there was significant difference in the parameter ϑ/total at Fz and Cz. Although the analysis on autonomic nervous system for all subjects showed the increased activation of sympathetic nervous system, there was no significant difference between the sick and non-sick group.

Difference between smokers and non-smokers in the corpus callosum volume.

The purpose of this study was to analyze the effects of smoking on corpus callosum volume. In addition, the relationships between smoking duration, smoking frequency, and corpus callosum volume were analyzed. Magnetic resonance brain images were acquired for 58 normal Korean men (30 smokers (age 32.82±14.12 years) and 28 non-smokers (age 35.49±13.11 years)). The corpus callosum volume was measured using Brain Voyager 2000S/W and was normalized by intracranical volume, which was calculated using cerebral sizes. The corpus callosum volume for smokers was significantly smaller than that for non-smokers. Also, there was a negative correlation between corpus callosum volume and smoking duration. The change of white matter volume (e.g., corpus callosum) might be a primary factor for characterizing the effects of smoking.

Comparative analyses of influenza virus receptor distribution in the human and mouse brains

Accumulating evidence suggests a potential link between influenza A virus infection and the occurrence of influenza-associated neurological disorders. As influenza infection is mediated by specific receptors on the host cell surface, it is important to understand the distribution patterns of influenza receptors in target organs. We carried out comprehensive experiments to localize influenza receptors in the brains of two different mouse strains and the human brain for comparison using lectin histochemistry. We further compared the brain regions in which influenza receptors were expressed and the regions in which experimental influenza infection was observed. Our results show that the expression patterns for influenza receptors in mouse and human brains are different. In the mouse brain, human influenza virus receptors (HuIV-R) were expressed in part of brainstem and cerebellar white matter while avian influenza virus receptors (AIV-R) were expressed in the cerebellar Purkinje neurons. In contrast, in the human brain, many neurons and glia in widespread regions, including the cerebral cortex, hippocampus, brainstem, and cerebellum, express both AIV-R and HuIV-R. Importantly, vascular endothelial cells, choroid plexus epithelial cells and ependymal cells in both mouse and human brains express high levels of HuIV-R and AIV-R. The regional reciprocity was not observed when comparing regions with influenza receptor expression and the regions of influenza infection within the mouse brain. Our results demonstrate a differential influenza receptor expression pattern in mouse and human brains, and a disparity between influenza receptor distribution and regions with actual influenza infection.