Toxicokinetic analyses of naphthalene, fluorene, phenanthrene, and pyrene in humans after single oral administration.

Polycyclic aromatic hydrocarbons (PAHs) are generated by incomplete combustion of organic matter. They have health effects in multiple organs and can cause lung, skin, and bladder cancers in humans. Although data regarding their toxicity is available, information on the absorption, distribution, metabolism, and excretion of PAHs in humans is very limited. In the present study, deuterium-labeled naphthalene (Nap), fluorene (Flu), phenanthrene (Phe), and pyrene (Pyr) were orally administered as a single dose (0.02-0.04 mg/kg) to eight healthy adults. Both serum and urine samples were monitored for 72 h after the exposure. Parent compounds and PAH metabolites (monohydroxy-PAHs; OH-PAHs) were measured by headspace-solid phase microextraction coupled with gas chromatography-mass spectrometry and high-performance liquid chromatography-tandem mass spectrometry, respectively. Based on the time-concentration profiles in serum and urine, non-compartmental analysis was performed, and two-compartment models were constructed and validated for each PAH. Subsequently, all of the parent compounds were rapidly absorbed (Tmax: 0.25 to 1.50 h) after oral administration and excreted in urine with a biological half-life (T1/2) of 1.01 to 2.99 h. The fractional urinary excretion (Fue) of OH-PAHs ranged from 0.07 % to 11.3 %; their T1/2 values ranged from 3.4 to 11.0 h. The two-compartment models successfully described the toxicokinetic characteristics of each PAH and its metabolites. Fue and the two-compartment models could be useful tools for exposure simulation or dose-reconstruction of PAHs. The results of this study will provide useful information for interpreting biomonitoring data of PAHs.

A Study on the Influence of Social Leisure Activities on the Progression to the Stage of Frailty in Korean Seniors.

In this study, we performed a logistic regression analysis according to the frequency of participation in social leisure activities (education, clubs, social groups, volunteer activities, religious activities, and senior citizens' welfare center use) by men and women aged ≥ 65 years. We investigated the frequency of participation in social leisure activities and their association with the level of frailty (health vs. pre-frailty, health vs. frailty, pre-frailty vs. frailty). This study included 10,297 older adults (men: 4128, women: 6169) who participated in the 2017 National Survey of Older Koreans, and were divided into three groups (healthy, pre-frailty, and frailty). Five frailty index components were used to measure the frailty level. There was a positive relationship between the elderly's religious activities, four times a week, from the healthy stage to the frailty stage, from the healthy stage to the pre-frailty stage, and from the pre-frailty stage to the frailty. In addition, positive associations emerged in leisure activities and club activities, respectively, from the healthy stage to the frailty stage (once a week, respectively). Positive association also emerged from the healthy stage to the pre-frailty and from the pre-frailty stage to the frailty stage (once a month to once in a two-week period).

Relationships between Exercise Modality and Activity Restriction, Quality of Life, and Hematopoietic Profile in Korean Breast Cancer Survivors.

This study aimed to examine the relationships between activity restriction, quality of life (QoL), and hematopoietic profile in breast cancer survivors according to exercise modality. The subjects in this study were 187 female breast cancer survivors among a total of 32,631 participants in the Korea National Health and Nutrition Examination Survey, which was conducted from 2016 to 2018. The selected subjects participated in a questionnaire survey and blood analysis. A cross-analysis was conducted to determine the relationship between participation in various modality of exercise (e.g., aerobic exercise, resistance exercise, walking exercise). The phi coefficients or Cramer's V value for activity restriction and QoL were calculated; an independent t-test was conducted to evaluate the differences between hematopoietic profiles based on the modality of exercise. Statistically significant correlations were seen between obesity and aerobic exercise and walking frequency, as well as between diabetes and aerobic exercise and activity restriction. With respect to QoL, there was a statistically significant correlation between participation in aerobic exercise and exercise ability, participation in aerobic exercise and anxiety/depression, participation in resistance exercise and subjective health status, participation in resistance exercise and exercise ability, and participation in weekly walking exercise and self-care ability. Regarding hemodynamic changes, red blood cells increased significantly in breast cancer survivors who participated in weekly resistance exercise compared to in those who did not. In conclusion, exercise participation had a positive effect on activity restriction, QoL, and hematopoietic profile in breast cancer survivors; in particular, some modalities of aerobic exercise were more effective.

Effectiveness of SaBang-DolGi Walking Exercise Program on Physical and Mental Health of Menopausal Women.

OBJECTIVE: We investigated the effectiveness of a 12-week SaBang-DolGi walking exercise program on the physical and mental health of menopausal women and aimed to provide the basic data needed to develop health promotion programs for the active and healthy aging of menopausal women. MATERIALS AND METHODS: The participants comprised 40 women aged 50-65 years who were divided into two randomly selected groups in training sessions (exercising group, n = 21 and control group, n = 19). A physical (grip, muscle and endurance) test and mental health test (simple mental health test II) were conducted using questionnaires with the aim of examining subjects' physical and mental health before and after exercise. RESULTS: After the intervention, the participants experienced positive changes in the physical dimension, with significant enhancements particularly in mental well-being and menopause-related health and subdomains. Controlled and regular exercise for 12 weeks was significantly correlated with a positive change in vitality and mental health. CONCLUSIONS: We found that the SaBang-DolGi walking exercise program helps to promote the physical and mental health of menopausal women who are exposed to the various stresses and depressions that accompany physical deterioration; the program was found to encourage active and healthy aging.

Weight Control in Postmenopausal Korean Patients with Osteo-arthritis.

BACKGROUND: Weight control is crucial for osteoarthritis management. This study investigated weight control methods in postmenopausal Korean osteoarthritis patients and examined their correlation with subjective health status and figure recognition, obesity, quality of life (QoL), and hemodynamic variables. METHODS: One thousand six hundred and seventy-eight female postmenopausal osteoarthritis patients participated in the 2018 Korea National Health and Nutrition Examination Survey. A frequency analysis was conducted for weight control methods, and phi coefficients for crossover analyses or Cramer's V coefficient were calculated to identify the relationships between weight-control-related variables and subjective health status and QoL. Using independent t-tests, we examined the relationships of weight control methods with hemodynamic variables. RESULTS: Postmenopausal osteoarthritis patients' preferred weight control methods were exercise, meal volume reduction, functional diet consumption, and the skipping of meals. Osteoarthritis patients who performed exercise demonstrated improved subjective figure recognition and health status, body weight, and recent 2-week discomfort, QoL, and hemodynamic variables (systolic blood pressure and fasting glucose, hemoglobin A1C, total cholesterol, high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein [hs-CRP] levels). However, patients who attempted weight control by food volume reduction made relatively harder efforts to lose weight but were more likely to view themselves as obese, and demonstrated higher pain levels, anxiety/depression, and recent 2-week discomfort. Further, they exhibited lower triglyceride levels, as did patients who skipped meals. CONCLUSION: Overall, Korean postmenopausal osteoarthritis patients' preferred weight control methods were exercise and reduced food intake. Although reduced food intake was effective for weight control, exercise improved mental health and hemodynamics, particularly inflammation (hs-CRP) levels.

Neurogenic effect of exercise via the thioredoxin-1/ extracellular regulated kinase/ß-catenin signaling pathway mediated by ß2-adrenergic receptors in chronically stressed dentate gyrus.

PURPOSE: Chronic stress is a precipitating factor for depression, whereas exercise is beneficial for both the mood and cognitive process. The current study demonstrates the anti-depressive effects of regular exercise and the mechanisms linked to hippocampal neurogenesis. METHODS: Mice were subjected to 14 consecutive days of restraint, followed by 3 weeks of treadmill running, and were then subjected to behavioral tests that included the forced swimming and Y-maze tests. Protein levels were assessed using western blot analysis and newborn cells were detected using 5-bromo-2'-deoxyuridine (BrdU). RESULTS: Three weeks of treadmill running ameliorated the behavioral depression caused by 14 days of continuous restraint stress. The exercise regimen enhanced BrdU-labeled cells and class III ß-tubulin levels in the hippocampal dentate gyrus, as well as those of thioredoxin-1 (TRX-1) and synaptosomal ß2-adrenergic receptors (ß2-AR) under stress. In vitro experiments involving treatment with recombinant human TRX-1 (rhTRX-1) augmented the levels of phospho-extracellular signal-regulated kinases 1 and 2 (ERK1/2), nuclear ß-catenin, and proliferating cell nuclear antigens, which were previously inhibited by U0216 and FH535 (inhibitors of ERK1/2 and ß-catenin/T cell factor-mediated transcription, respectively). The hippocampal neurogenesis elicited by a 7-day exercise regimen was abolished by a selective inhibitor of ß2-AR, butoxamine. CONCLUSION: These results suggest that TRX-1-mediated hippocampal neurogenesis by ß2-AR function is a potential mechanism underlying the psychotropic effect of exercise.

The effects of peripherally-subacute treatment with irisin on hippocampal dendritogenesis and astrocyte-secreted factors.

PURPOSE: Fibronectin type III domain containing 5 (FNDC5)/irisin is an exercise-induced myokine, which contributes to cognitive functions. However, the relationship between the neuroprotective effects of FNDC5/irisin and hippocampal dendritic remodeling and astrocyte-secreted factors remains unclear. Therefore, we explored whether subchronic recombinant irisin treatment affected hippocampal morphology and some astrocyte-derived molecules. METHODS: Mice were intraperitoneally injected with irisin (0.5 µg/kg/day) for seven days, followed by their sacrifice two days later. Hippocampal morphometric parameters were analyzed and pgc-1a, fndc5, bdnf, and some astrocyte-derived factors mRNA levels were measured. RESULTS: Dendritic length, arborization, and spine density were enhanced by irisin regimen in hippocampal CA1 and CA3 areas. Hippocampal pgc-1a, fndc5, and bdnf mRNA levels were significantly increased by irisin treatment. Moreover, hevin mRNA levels were significantly enhanced, whereas tgf-b1 levels downregulated by irisin treatment. CONCLUSION: FNDC5/irisin has dendritogenic activity probably through hevin induction and TGF-ß1 suppression.

Maternal exercise during pregnancy affects mitochondrial enzymatic activity and biogenesis in offspring brain.

The present study addresses whether exercise during pregnancy in mouse alters mitochondrial function in the brains of the resultant offspring. We divided pregnant mice into four groups: a control group and groups of mice that exercised for 20 (E20m), 30 (E30m) and 40 min/d (E40m). The pregnant mice ran on a treadmill at 12 m/min, 5 d/week for a duration of 3 weeks. The protein expression of cytochrome c oxidase subunit Va (CVa) was downregulated in the offspring of the E20m group, unlike that in the control animals, whereas CVa expression was reserved in the E40m neonates. The F1-ATPase catalytic core (Core) protein expression levels were the highest in the E40m group neonates. Complex I, IV and ATPase activities were significantly lower in the E20m group than that in the control group neonates and were reserved in the E30m and E40m group neonates. The activities of citrate synthase and pyruvate dehydrogenase were consistent with those of complex I, IV and ATPase. Peroxisome proliferator-activated receptor-gamma coactivator 1-alpha, mitochondrial transcription factor A, nuclear respiratory factor-1 and mitochondrial DNA showed high levels of expression in the E40m neonates compared with the other groups. Malondialdehyde (MDA) levels in E40m neonates were higher than that in the controls but were lower than that in the E20m neonates. Finally, 40 min/d of maternal exercise improved mitochondrial function in the resultant pups and was concomitant with brain-derived trophic factor induction in the hippocampus, thereby functionally improving short-term memory.

The effect of exercise in cool, control and hot environments on cardioprotective HSP70 induction.

A number of environmental and metabolic stimuli rapidly induce the expression of several highly conserved proteins such as heat shock proteins (HSPs) or stress proteins. The purpose of this study was to investigate the effects of a single bout of submaximal exercise in varying ambient temperatures on cardiac and skeletal muscle. Adult male Sprague-Dawley rats were randomly placed in one of three ambient temperature groups; control (23 degrees C), hot (41 degrees C) and cool (11 degrees C). Each exercise bout consisted of treadmill running at 17 m/min and 0% grade. Tissue HSP70 levels for all groups were determined using analysis of variance in two factorial design (2 x 3). Baseline rectal temperature was similar for all three groups. In the control and hot temperature groups, final rectal temperatures differed from the baseline values (p<.05). The rectal temperature from the control/exercise group were 38.5+/-0.3 degrees C at rest and 39.8+/-0.3 degrees C at exhaustion, the hot/exercise group were 38.4+/-0.3 degrees C at rest and 41.2+/-0.9 degrees C at exhaustion and the cool/exercise group were 38.2+/-0.3 degrees C at rest and 38.5+/-0.2 degrees C at exhaustion. The running time was 102.0+/-39.5 min at the control/exercise group, 44.1+/-18.0 min at the hot/exercise group, and 55.4+/-11.9 min at the cool/exercise group. The level of soleus, cardiac and extensor digitorium longus (EDL) HSP70 in cool temperature does not change during a single bout of submaximal exercise. Whereas a single bout of submaximal exercise in hot and control ambient temperatures increases HSP70 accumulation in locomotor muscles, such as the soleus and cardiac, but not in the EDL tissue. This study shows that the changes of HSP70 level induced by a single bout of submaximal exercise at various ambient temperatures (control, hot and cool) depend on the rectal temperature.

Defective erythropoiesis in bone marrow is a mechanism of anemia in children with cancer.

Evaluation of the mechanism of anemia in cancer patients might help to select patients for the more efficient use of erythropoietin (EPO, a growth factor for erythroid precursor cells). For this, we investigated whether the production of EPO responds to anemia and the bone marrow responds to EPO appropriately, and whether chronic inflammation is inhibitory to erythropoiesis in anemic cancer children. Serum levels of EPO, soluble transferrin receptor (sTfR), tumor necrosis factor (TNF)-alpha, and erythrocyte sedimentation rate (ESR) in anemic cancer children were measured by enzyme-linked immunosorbent assay and then the correlation coefficients between those parameters and hemoglobin (Hb) were determined. Both in leukemia and in solid tumor patients, there were significant inverse correlations between Hb and EPO (leukemia: tau=-0.547, p<0.0001; solid tumor: tau=-0.591, p<0.0001), and between sTfR and EPO (leukemia: tau=-0.223, p<0.05; solid tumor: tau=-0.401, p<0.05). In contrast, sTfR showed a correlation with Hb in leukemia (tau=0.216, p<0.05) but not in solid tumor patients. sTfR was suppressed in 53% of anemic episodes of leukemia and 78% of those of solid tumor patients. Our results suggest that in cancer children, the EPO production is not defective and chronic inflammation is not inhibitory to erythropoiesis. Rather, the defective erythropoiesis itself is thought to be responsible for the anemia.