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Abstract The occurrence of osteoporosis gradually increases within the aging population. As the side effects of therapeutic agents currently used for osteoporosis are increasing, the development of preventive and therapeutic agents derived from natural products without any long-term side effects is important. Here, we investigated the effect of wheat seedling extract (WSE) on the RANKL-mediated differentiation, fusion, and function of osteoclasts. WSE inhibited the differentiation of RANKL-induced bone marrow macrophages and phosphorylation of AKT and ERK. Moreover, the protein and mRNA expression levels of c-Fos and NFATc1 as well as RANKL-induced transcription of TRAP and OSCAR were suppressed by WSE treatment. DC-STAMP and cathepsin K, which are essential for cell fusion and bone degradation, were also inhibited by WSE. Furthermore, eight components constituting WSE were confirmed to decrease the osteoclast TRAP activity. Taken together, WSE may have potential implications as a useful therapeutic or preventive agent for inhibition of bone loss.

Tumor cells in hypoxic conditions control cancer metabolism and angiogenesis by expressing HIF-1α. Tanshinone is a traditional Chinese medicine that has been shown to possess antitumor properties and exerts a therapeutic impact on angiogenesis. However, the precise molecular mechanism responsible for the antitumor activity of 3-Hydroxytanshinone (3-HT), a type of tanshinone, has not been fully understood. Therefore, our study aimed to investigate the mechanism by which 3-HT regulates the expression of HIF-1α. Our findings demonstrate that 3-HT inhibits HIF-1α activity and expression under hypoxic conditions. Additionally, 3-HT inhibits hypoxia-induced angiogenesis by suppressing the expression of VEGF. Moreover, 3-HT was found to directly bind to α-enolase, an enzyme associated with glycolysis, resulting in the suppression of its activity. This inhibition of α-enolase activity by 3-HT leads to the blockade of the glycolytic pathway and a decrease in glycolysis products, ultimately altering HIF1-α expression. Furthermore, 3-HT negatively regulates the expression of HIF-1α by altering the phosphorylation of AMP-activated protein kinase (AMPK). Our study’s findings elucidate the mechanism by which 3-HT regulates HIF-1α through the inhibition of the glycolytic enzyme α-enolase and the phosphorylation of AMPK. These results suggest that 3-HT holds promise as a potential therapeutic agent for hypoxia-related angiogenesis and tumorigenesis.

Investigating the impact of urinary mercury and cadmium on anthropometric parameters in Korean children is crucial amid growing concerns about heavy metal exposure and childhood growth. Using data from the Korean National Environmental Health Survey (2015–2017), we assessed age- and sex-specific associations of urinary mercury and cadmium with height and body mass index (BMI) z-scores in 1458 children aged 3–5 (n = 571) and 6–11 years (n = 887). Overall, 5.0% had stunted height (3–5 years: 6.9%, 6–11 years: 3.8%), whereas older children exhibited higher overweight/obesity prevalence (29.2%) than younger ones did (22.2%). In 3–5-year-old boys, urinary mercury correlated negatively with height z-scores (p < 0.001), whereas in girls, urinary cadmium correlated positively (p = 0.015). Boys aged 6–11 years showed positive associations between mercury/cadmium levels and BMI z-scores (p = 0.012). Logistic regression indicated associations between urinary mercury and stunted height likelihood (p = 0.001) and between urinary cadmium and reduced overweight likelihood (p = 0.039) in 3–5-year-old boys. In boys aged 6–11 years, urinary cadmium levels were positively associated with overweight likelihood (p = 0.003). This study underscores the link between elevated urinary mercury, cadmium levels, and growth disruptions in Korean children, emphasizing the need for public health strategies for reducing childhood heavy metal exposure.

Objectives: Existing literature provides limited information on the association between childhood obesity and polycyclic aromatic hydrocarbons (PAHs), which are potentially obesogenic. We examined the association between urinary concentrations of PAH metabolites and obesity in the Korean pediatric population. Methods: We analyzed the data of 2286 children/adolescents aged 3–17 years who participated in the Korean National Environmental Health Survey between 2015 and 2017. Urinary concentrations of 2-naphthol, 2-hydroxyfluorene, 1-hydroxyphenanthrene, and 1-hydroxypyrene were assayed using gas chromatography–mass spectrometry. Overweight/obesity was defined as a body mass index (BMI) for age ≥85th percentile. Multiple linear and logistic regression models were used to analyze the relationship of BMI z-score and overweight with urinary concentrations of PAH metabolites after adjusting for age, sex, household income, parental education level, physical activity, fast-food consumption, and environmental tobacco smoke exposure. Results: BMI z-score was positively associated with 2-naphthol concentrations in children aged 6–11 and 12–17 years and with 1-hydroxypyrene concentrations in children aged 6–11 years. In the overall population, a significant rise in odds ratios for overweight/obesity across 2-naphthol quartiles was noted. Specifically, the 3rd and 4th quartiles displayed odds ratios of 1.39 [1.03, 1.88] and 1.46 [1.08, 1.99] respectively, compared to the 1st quartile (P-for-trend = 0.006). Similar associations between 2-naphthol and overweight/obesity status were observed in the 6–11- and 12–17-year age groups. There was little evidence of an association between overweight/obesity and other PAH hydroxy derivatives. Conclusions: PAH exposure may be associated with increased childhood adiposity, a potential risk factor for adult obesity and adverse metabolic outcomes.

Purpose The coronavirus disease 2019 (COVID-19) pandemic has affected people's daily lives and increased their time spent at home. This study aims to investigate the changes in lifestyle factors and obesity among Korean adolescents before and during the COVID-19 outbreak. Methods We used the data of 109,282 adolescents aged 12–18 years, from the Korea Youth Risk Behavior Survey conducted in 2019 and 2020 before and during the COVID-19 pandemic, respectively. The changes in the prevalence of obesity and lifestyle factors (diet, exercise, sitting time, and sleep duration) were assessed. The adjusted odds ratios (ORs) (95% confidence intervals [CIs]) of predictors for obesity were calculated. Results The prevalence of overweight (10% to 10.5%) and obesity (11.5% to 12.7%) increased significantly, especially among males younger than 15 years, whereas significant differences were absent among females. The mean body mass index z-score increased from 0.28 to 0.39 in males but decreased from 0.08 to 0.04 in females. Fruit consumption, regular exercise, and average sleep duration decreased, whereas sitting time increased. After controlling for covariates, a short sleep duration (OR, 1.14) and an increased sitting time (OR, 1.14) were significantly associated with an elevated risk for overweight/obesity. Conclusions During the COVID-19 pandemic, the prevalence of obesity and overweight increased, particularly in males, as did unfavorable trends in related lifestyle factors. Sex- and age-specific strategies to improve lifestyle factors associated with obesity are needed, especially during the COVID-19 pandemic.

Background Phthalates and bisphenol A (BPA) are synthetic chemicals widely used in daily life. This study investigated urinary phthalate and BPA levels in Korean children and their associations with obesity. Methods A total of 2,351 children aged 3 to 17 years who participated in the Korean National Environmental Health Survey 2015 to 2017 were included. Urinary dilution was corrected using covariate-adjusted standardization (CAS). We examined the geometric mean (GM) concentrations of urinary phthalate metabolites, including di (2-ethylhexyl) phthalate (DEHP) metabolites (mono [2-ethyl-5-hydroxyhexyl] phthalate, mono [2-ethyl-5-oxohexyl] phthalate, and mono [2-ethyl-5-carboxypentyl] phthalate [MECPP]), mono-benzyl-phthalate (MBzP), mono (carboxyoctyl) phthalate (MCOP), mono (carboxy-isononyl) phthalate (MCNP), mono (3-carboxypropyl) phthalate, and mono-n-butyl-phthalate (MnBP), and BPA. We also analyzed the odds ratio (OR) for obesity according to the quartiles of each analyte. Results The urinary GM levels of DEHP metabolites and MnBP were notably higher among Korean children than among American, Canadian, and German children. The CAS-applied GM concentrations of most analytes, except for MBzP, MCOP, and MCNP, were higher in children aged 3 to 5 years than in those aged 6 to 17 years. The OR for obesity in the highest quartile of MECPP was significantly higher than in the lowest quartile after adjusting for covariates. However, the other phthalate metabolites and BPA were not significantly associated with obesity. Conclusion The concentrations of urinary DEHP metabolites and MnBP were higher in Korean children than in children in Western countries. Urinary MECPP exposure, but not other phthalates or BPA, showed a positive association with obesity in Korean children. Further studies are required to elucidate the causal relationships.

Background Over the last few decades, there has been growing evidence of earlier onset and progression of puberty worldwide. This population-based longitudinal cohort study aimed to analyze the change in the annual incidence rate of central precocious puberty (CPP) among Korean children over the most recent decade, using the national registry data. Method The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) and insurance claims for gonadotropin-releasing hormone agonist (GnRHa) treatment were used to identify CPP patients who were using the Korean Health Insurance Review & Assessment Service (HIRA) database between 2008 and 2020. Patients who began GnRHa therapy before the age of 9 and 10 for girls and boys, respectively, were included in the study. Results A total of 6,906 boys and 126,377 girls were diagnosed with CPP between 2008 and 2020. The annual incidence of CPP increased by 83.3 times in boys (from 1.2 to 100 per 100,000 persons) and by 15.9 times in girls (from 88.9 to 1414.7 per 100,000 persons). The age-specific annual incidence of CPP increased remarkably more in older children than in younger ones; the 2020 CPP incidence among 9-year-old boys and 8-year-old girls reached 705.2 and 7,967.3 per 100,000 persons, respectively. The annual prevalence of CPP in boys and girls increased from 2.7 to 206.5 (76.5 times) and from 141.8 to 3439.9 (24.3 times) per 100,000 persons, respectively. Conclusion Based on GnRHa treatment insurance claims, our study suggests that the annual incidence of CPP has substantially increased in Korea during the past 13 years. These findings highlight the importance of meticulous judgment by doctors in determining GnRHa treatment.

Vascular dementia (VaD) is characterized by a time-dependent memory deficit and essentially combined with evidence of neuroinflammation. Thus, polyphenol-rich natural plants, which possess anti-inflammatory properties, have received much scientific attention. This study investigated whether Perilla frutescens leaf extract (PFL) exerts therapeutic efficacy against VaD. Sprague Dawley rats were divided into five groups: SO, sham-operated and vehicle treatment; OP, operated and vehicle treatment; PFL-L, operated and low-dose (30 mg/kg) PFL treatment; PFL-M, operated and medium-dose (60 mg/kg) PFL treatment; and PFL-H, operated and high-dose (90 mg/kg) PFL treatment. Two-vessel occlusion and hypovolemia (2VO/H) were employed as a surgical model of VaD, and PFL was given orally perioperatively for 23 days. The rats underwent the Y-maze, Barnes maze, and passive avoidance tests and their brains were subjected to histologic studies. The OP group showed VaD-associated memory deficits, hippocampal neuronal death, and microglial activation; however, the PFL-treated groups showed significant attenuations in all of the above parameters. Using lipopolysaccharide (LPS)-stimulated BV-2 cells, a murine microglial cell line, we measured PFL-mediated changes on the production of nitric oxide (NO), TNF-α, and IL-6, and the activities of their upstream MAP kinases (MAPKs)/NFκB/inducible NO synthase (iNOS). The LPS-induced upregulations of NO, TNF-α, and IL-6 production and MAPKs/NFκB/iNOS activities were globally and significantly reversed by 12-h pretreatment of PFL. This suggests that PFL can counteract VaD-associated structural and functional deterioration through the attenuation of neuroinflammation.

Background There is a lack of recent research on the changes in risk factors for metabolic syndrome (MetS) in the Asian pediatric population. We aimed to determine the 12-year trends in the prevalence of MetS and relevant lifestyle factors such as smoking, exercise, and calorie intake among Korean adolescents. Methods We investigated trends in MetS and lifestyle factors among 6,308 adolescents aged 12 to 18 years from the Korea National Health and Nutrition Examination Survey, 2007 to 2018. Results The prevalence of MetS was stable from 2007 to 2018 (1.7% to 2.2%). There were significant increases in the prevalence of central obesity (from 8.1% to 11.2%, P=0.012) and hyperglycemia (from 5.3% to 10.4%, P

Purpose This study sought to identify changes in anthropometric values among Korean school students by comparing the most recent nationwide data with previous data. Methods Data from the Korea School Health Examination Survey 2018 were used. The study population consisted of 107,954 Korean school students ranging from the 1st grade in elementary school through the 3rd year of high school. The difference in height and weight values for each sex and school grade was analyzed by comparison with the Korea School Health Examination Survey 2010. Results The mean heights of the 3rd-year high school students were 173.8 cm and 160.9 cm for boys and girls, respectively. The mean height of the 3rd-year high school students showed no difference between 2010 and 2018 for either sex. However, the mean height of the age group from the 3rd grade in elementary school through the 1st year in high school was significantly taller in 2018 compared to 2010 for both sexes. The mean weights of the 3rd-year high school students were 71.3 kg and 57.5 kg for boys and girls, respectively. The mean weight of students in 2018 was significantly higher compared to students in 2010 for most school grades. Conclusions Although no significant change was found in near-final height between 2010 and 2018 among high school seniors, the mean height during the growth spurt was significantly higher in 2018 compared to 2010. Weight was significantly higher in almost all school grades in 2018 compared to 2010.

Abstract This study was aimed to evaluate the association between urinary bisphenol A (BPA) levels and risk of obesity in Korean adults. We analyzed data from the Korean National Environmental Health Survey (KoNEHS) Cycle 2 (2012–2014) and Cycle 3 (2015–2017). A total of 10,021 participants aged ≥ 19 years were included. Urine dilution was corrected by the covariate-adjusted standardization (CAS) method. We performed meta-analysis, logistic regression analysis by matching all covariates with a 1:1 propensity score, and a 4-knot restricted cubic spline plot model to calculate the odds ratios (ORs) for obesity according to natural log-transformed BPA levels. Mean urinary BPA concentration was 1.12 µg/L in KoNEHS Cycle 2 and 1.32 µg/L in Cycle 3. BPA levels were significantly higher among obese adults than among non-obese adults in both KoNEHS Cycles 2 and 3. In pooled data of KoNEHS Cycles 2 and 3, BPA showed significant positive associations with ORs for obesity in both sexes, which were more prominent in females (linear) than in males (non-linear). These associations were confirmed in spline analyses. CAS-applied BPA concentrations were positively associated with obesity in nationwide representative samples of Korean adults. Further studies are warranted to confirm and elucidate the underlying mechanism.

Childhood obesity is a global health concern. Air pollution is also a crucial health threat, especially in developing countries. Over the past decade, a number of epidemiologic and animal studies have suggested a possible role of pre- or postnatal exposure to air pollutants on childhood obesity. Although no clear mechanism has been elucidated, physical inactivity, oxidative stress, and epigenetic modifications have been suggested as possible mechanisms by which obesity develops due to air pollution. In this review, we summarize and review previous epidemiologic studies linking air pollution and childhood obesity and discuss the possible mechanisms underlying air pollution-induced obesity based on in vivo and in vitro evidence.

The recombinant human growth hormone (GH) has been used for the treatment of growth hormone deficiency (GHD) and diverse short stature state, and its physiological and therapeutic effects are well documented. However, since the effect of GH treatment on metabolic disorders has not been well characterized, we injected GH to Western diet-fed low-density lipoprotein receptor-deficient (Ldlr−/−) mice to understand the exact effect of GH on metabolic diseases including atherosclerosis, hepatic steatosis, and obesity. Exogenous GH treatment increased plasma IGF-1 concentration and decreased body weight without affecting serum lipid profiles. GH treatment changed neither atherosclerotic lesion size nor collagen and smooth muscle cells accumulation in the lesion. GH treatment reduced macrophage accumulation in adipose tissue. Importantly, GH treatment attenuated hepatic steatosis and inflammation. The hepatic expression IL-1β mRNA were decreased by GH treatment. The mRNA and protein levels of CD36 were markedly decreased in GH treated mice without significant changes in other molecules related to lipid metabolism. Therefore, the treatment of GH treatment could attenuate hepatic steatosis and inflammation with downregulation of CD36 expression in hyperlipidemic condition.

Abstract Adults with short stature have been previously reported to have increased risk of cardiovascular events and hyper-LDL-cholesterolemia. We aimed to assess the association between height and lipid profiles among Korean adolescents and adults. We analyzed data from the Korea National Health and Nutrition Examination Survey from 2007 to 2015, from 37,889 individuals (aged 12–59 years). In adolescents, total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) levels had profound associations with height in both boys and girls, while high density lipoprotein-cholesterol (HDL-C) levels had an inverse association with height only in boys. Height was inversely associated with TC, triglycerides (TG), and LDL-C concentrations in men and women and positively correlated with HDL-C concentration in women. In boys, the odds ratios (ORs) for hypercholesterolemia, hypertriglyceridemia, hyper-LDL-cholesterolemia were higher for shorter subjects (ORs = 2.38~7.01), while only the OR of hyper-LDL-cholesterolemia was significantly higher in girls with short stature (OR = 3.12). In adults, the ORs for hypercholesterolemia, hypo-HDL-cholesterolemia, and hyper-LDL-cholesterolemia were significantly higher in short subjects than in tall subjects after controlling for covariates (ORs = 1.50~2.61). Also, short men showed significantly higher ORs for hypertriglyceridemia (OR = 1.85) than tall men. Short stature was significantly associated with adverse lipid profiles in both adolescents and adults.

Purpose This study was conducted to investigate the distributions of the triglyceride (TG) to high-density lipoprotein-cholesterol (HDL-C) ratio and total cholesterol (TC) to HDL-C ratio, and to explore their usefulness as markers of metabolic syndrome (MetS) in Korean adolescents. Methods We obtained data for 2,721 adolescents (1,436 boys and 1,285 girls) aged 10–18 years who participated in the Korean National Health and Nutrition Examination Surveys from 2008 to 2010. International Diabetes Federation criteria were used to define MetS. Results There were no significant gender-related differences in TG/HDL-C or TC/HDL-C ratios. These lipid ratios showed significant associations with homeostatic model assessment for insulin resistance (HOMA-IR) and waist circumference. Areas under the receiver operating characteristic curve to identify MetS were 0.947 for TG/HDL-C and 0.924 for TC/HDL-C, which were higher than that of HOMA-IR (0.822). Optimal cutoff values (sensitivity, specificity) of TG/HDL-C and TC/HDL-C ratios for MetS prediction were 3.3 (85.7%, 89.9%), and 3.8 (92.9%, 82.8%), respectively. Odds ratio (OR; 95% confidence intervals [CIs]) for MetS in adolescents with TC/HDL-C ratio above the cutoff value was 14.8 (2.8–77.4), while that for TG/HDL-C ratio about the cutoff value was 30.6 (6.0–157.6). In adolescents who had both lipid ratios above the cutoff values, the OR (95% CI) for MetS was 36.2 (7.2–186.2). Conclusion TG/HDL-C and TC/HDL-C ratios are useful markers of metabolic syndrome with high predictive value in Korean adolescents.

PurposeObesity has been associated with higher total blood mercury levels, based on animal studies; however, studies that focus on children and adolescents are lacking. We aimed to assess the association between total blood mercury levels and the incidence of overweight and abdominal obesity in Korean adolescents.MethodsThe study population comprised 1,567 adolescents (793 boys and 774 girls; aged 10–19 years), who participated in the Korea National Health and Nutrition Examination Survey 2010–2013. We analyzed total blood mercury levels according to obesity status in all participants.ResultsThe geometric mean of total blood mercury levels was 1.93 µg/L. Participants with overweight (2.20 µg/L) and obesity (2.17 µg/L) had higher levels than those with normal weight (1.86 µg/L, P

Growth hormone (GH) is important for promotion of somatic growth and the regulation of substrate metabolism. Metabolic action of GH occurs in multiple tissues including the liver, muscle, fat and pancreas either directly or indirectly through insulin-like growth factor 1. The diabetogenic action of GH has been well-described in previous in vivo studies. In this paper, we review the metabolic effects of GH on peripheral tissues focusing on glucose metabolism and insulin resistance, and discuss results from human studies on the long-term effects of GH administration on insulin resistance and hyperglycemia.

PurposeThis study aimed to assess the reference values and factors influencing blood lead levels among Korean adolescents.MethodsThe study population consisted of 1,585 adolescents (801 males, 784 females; aged 10-19 years) who participated in the Korea National Health and Nutrition Examination Survey 2010-2013. We analyzed blood lead concentrations in relation to demographic/lifestyle characteristics for all participants. "Reference values" of blood lead levels were calculated as the upper limit of the 95% confidence interval of the 95th percentile.ResultsThe average "reference value" for blood lead concentrations among Korean adolescents was 2.25 µg/dL (2.49 µg/dL for males, 2.07 µg/dL for females), and the geometric mean of the blood lead concentrations was 1.34 µg/dL. Males had higher blood lead concentrations than females (male, 1.48 µg/dL; female, 1.19 µg/dL; P

PurposeOnly a few studies have explored nationwide trends in lipid profiles among Asian adolescents. We aimed to assess trends in lipid profiles and the associated lifestyle factors among Korean children.MethodsWe analyzed data for 2,094 adolescents who were aged 10–18 years and had participated in the Korea National Health and Nutrition Examination Surveys in 1998 and 2010.ResultsDuring 1998–2010, the prevalence of obesity significantly increased in boys, but no changes were observed in girls. Over this period, there was a small but significant decrease in the mean low-density lipoprotein (LDL)-cholesterol level in boys (1998, 87.5 mg/dL; 2010, 83.6 mg/dL; P=0.019) and mean triglyceride levels in girls (1998, 90.8 mg/dL; 2010, 85.8 mg/dL; P=0.020). There were no significant changes in the prevalence of dyslipidemia in boys, but a modest decrease was noted in girls (1998, 25.1%; 2010, 18.3%; P=0.052). During the study period, the prevalence of breakfast skipping decreased, whereas that of regular exercise increased in both groups. Daily total energy intake did not change between these years. In multivariable logistic regression analyses, breakfast skipping was associated with increased risk of hyper-LDL-cholesterolemia in boys (odds ratio [OR], 5.77) and hypertriglyceridemia (OR, 2.27) in girls. Regular exercise was associated with decreased risk of hypo-HDL-cholesterolemia (OR, 0.40) in boys.ConclusionAlthough the prevalence of obesity in boys increased, favorable or constant trends in lipid profiles were observed among Korean adolescents during 1998–2010. Decrease in breakfast skipping and increase in regular exercise may have contributed to these trends.

[This corrects the article DOI: 10.1371/journal.pone.0208081.].

OBJECTIVE:We assessed the associations of percentage fractions of urinary di(2-ethylhexyl) phthalate (DEHP) metabolites with obesity and insulin resistance in Korean girls. METHODS:In total, 137 girls, aged 6 to 13 years (65 overweight cases and 72 controls), were recruited. Anthropometric indices and the homeostatic model assessment of insulin resistance (HOMA-IR) index were determined. Four major urinary DEHP metabolites were analyzed in spot urine samples by gas chromatography-tandem mass spectrometry, including mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate. RESULTS:There were no significant differences in the urinary concentrations of the DEHP metabolites between the overweight and control groups. The percentage fraction of MEHHP (MEHHP%) among all DEHP metabolites was significantly higher in the overweight prepubertal girls than in the controls (P = 0.035). MEHHP% was positively associated with the body mass index percentile, waist circumference, body fat percentage, and HOMA-IR index in the prepubertal girls. After adjusting for covariates, the prepubertal girls in a higher MEHHP% quartile were found to have a higher odds ratio for central obesity than those in a lower quartile (odds ratios: 5.05 for quartile 3; 7.30 for quartile 4). The relative rate of MEHHP oxidation to MEOHP was negatively associated with the body mass index percentile and waist circumference in the prepubertal girls. However, no such association was observed in the pubertal girls. CONCLUSIONS:MEHHP% was positively associated with obesity and insulin resistance in prepubertal girls. Further studies are necessary to elucidate the causal links between altered phthalate metabolism and increased susceptibility to insulin resistance in children.

The number of patients with bone metabolic disorders including osteoporosis is increasing worldwide. These disorders often facilitate bone fractures, which seriously impact the patient’s quality of life and could lead to further health complications. Bone homeostasis is tightly regulated to balance bone resorption and formation. However, many anti-osteoporotic agents are broadly categorized as either bone forming or anti-resorptive, and their therapeutic use is often limited due to unwanted side effects. Therefore, safe and effective therapeutic agents are needed for osteoporosis. This study aims to clarify the bone protecting effects of oat bran water extract (OBWE) and its mode of action. OBWE inhibited RANKL (receptor activator of nuclear factor-κB ligand)-induced osteoclast differentiation by blocking c-Fos/NFATc1 through the alteration of I-κB. Furthermore, we found that OBWE enhanced BMP-2-stimulated osteoblast differentiation by the induction of Runx2 via Smad signaling molecules. In addition, the anti-osteoporotic activity of OBWE was also evaluated using an in vivo model. OBWE significantly restored ovariectomy-induced bone loss. These in vitro and in vivo results showed that OBWE has the potential to prevent and treat bone metabolic disorders including osteoporosis.

The slow and regular pacemaking activity of midbrain dopamine (DA) neurons requires proper spatial organization of the excitable elements between the soma and dendritic compartments, but the somatodendritic organization is not clear. Here, we show that the dynamic interaction between the soma and multiple proximal dendritic compartments (PDCs) generates the slow pacemaking activity in DA neurons. In multipolar DA neurons, spontaneous action potentials (sAPs) consistently originate from the axon-bearing dendrite. However, when the axon initial segment was disabled, sAPs emerge randomly from various primary PDCs, indicating that multiple PDCs drive pacemaking. Ca2+ measurements and local stimulation/perturbation experiments suggest that the soma serves as a stably-oscillating inertial compartment, while multiple PDCs exhibit stochastic fluctuations and high excitability. Despite the stochastic and excitable nature of PDCs, their activities are balanced by the large centrally-connected inertial soma, resulting in the slow synchronized pacemaking rhythm. Furthermore, our electrophysiological experiments indicate that the soma and PDCs, with distinct characteristics, play different roles in glutamate-induced burst-pause firing patterns. Excitable PDCs mediate excitatory burst responses to glutamate, while the large inertial soma determines inhibitory pause responses to glutamate. Therefore, we could conclude that this somatodendritic organization serves as a common foundation for both pacemaker activity and evoked firing patterns in midbrain DA neurons. [ABSTRACT FROM AUTHOR]