Search

Nonalcoholic fatty liver disease (NAFLD) is accompanied by a complex and multifactorial pathogenesis with sequential progressions from inflammation to fibrosis and then to cancer. This heterogeneity interferes with the development of precise diagnostic and prognostic strategies for NAFLD. The current approach for the diagnosis of simple steatosis, steatohepatitis, and cirrhosis mainly consists of ultrasonography, magnetic resonance imaging, elastography, and various serological analyses. However, individual dry and wet biomarkers have limitations demanding an integrative approach for the assessment of disease progression. Here, we review diagnostic strategies for simple steatosis, steatohepatitis and hepatic fibrosis, followed by potential biomarkers associated with fat accumulation and mitochondrial stress. For mitochondrial stress indicators, we focused on fibroblast growth factor 21 (FGF21), growth differentiation factor 15 (GDF15), angiopoietin-related growth factor and mitochondrial-derived peptides. Each biomarker may not strongly indicate the severity of steatosis or steatohepatitis. Instead, multidimensional analysis of different groups of biomarkers based on pathogenic mechanisms may provide decisive diagnostic/prognostic information to develop a therapeutic plan for patients with NAFLD. For this purpose, mitochondrial stress indicators, such as FGF21 or GDF15, could be an important component in the multiplexed and contextual interpretation of NAFLD. Further validation of the integrative evaluation of mitochondrial stress indicators combined with other biomarkers is needed in the diagnosis/prognosis of NAFLD.

Background There are no standard diagnostic criteria or interventions for internet gaming addiction (IGA) even though IGA is one of the most pervasive public health issues among youth worldwide. Internet gaming reasons or motivations have been studied as a potential predictor of IGA, but the results have been inconsistent and biological indicators of gaming reasons have rarely been studied. We sought to (1) identify categories of internet gaming reasons, (2) examine the relationship of gaming reasons to risk of IGA, and (3) describe biological indicators associated with reasons for gaming. Methods We used a multi-phase cross-sectional design including individual interviews; focus group discussion; and descriptive, comparative analysis. Fifteen Korean adolescent male internet gamers participated in individual interviews and eight participated in a focus group aimed at identifying reasons for internet gaming. Using the identified gaming reasons from these sources we surveyed 225 adolescent game users using a self-report questionnaire. Participants provided blood samples for assessment of norepinephrine (NE) and serum cortisol. Results We identified four major categories of internet gaming reasons: entertainment, getting along with friends, stress relief, and habitual gaming. The habitual group showed significantly greater risk of IGA than the other groups (p p = .035), possibly indicating an alteration in autonomic function. Conclusion Health care providers are encouraged to screen adolescents for excessive internet gaming and to intervene with those who report habitual gaming behaviors. When feasible, assessment of biological indicators, such as plasma NE, may help to identify youth at greatest risk of IGA.

The association between physical activity and telomere length (TL) has been continuously reported. However, the interplay of physical activity and TL among women with breast cancer has not been elucidated. Thus, the purpose of this systematic review was to synthesize the evidence for the association of physical activity with TL in women with breast cancer. Systematic searches were conducted to identify quantified studies using MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, and Clinical Trials.gov. Five studies were included in this systematic review. Three of the five studies reported that physical activity has a significant relationship in delaying TL shortening, but others observed no association between physical activity and TL in breast cancer survivors. Although the heterogeneous studies acted as limitations in drawing clear conclusions, physical activity strategies show encouraging impacts in delaying TL shortening. To understand the effects of physical activity on TL shortening in breast cancer survivors, further studies are needed considering the tissue site, treatments for breast cancer, DNA extraction methods, and tools for measuring physical activity.

To investigate the association of orthostatic hypotension (OH) with health-related quality of life (HRQoL) in older people living in the community. A cross-sectional design was used. A total of 217 participants aged 65 and older were classified as having OH if their systolic or diastolic blood pressure showed a drop of ≥ 20 mmHg systolic blood pressure or ≥ 10 mmHg diastolic blood pressure, respectively, within 3 min of standing. Participants provided demographic and medical information and responded to questionnaires about their HRQoL (EuroQoL-5D-3L), as well as depression, anxiety, cognitive function, and recent physical activities. The number of participants with OH was 117, and those without OH numbered 100. The mean HRQoL levels were 0.56 (SD 0.29) in the OH group and 0.74 (SD 0.25) in the non-OH group (p

With the continuous technological advancements being made in the medical field every day, the ability to improve drug delivery uptake in cardiac research is a prominent topic of discussion. Nanoparticles provide the opportunity to improve the efficiency of drug therapy while minimizing chemotherapy side effects through controllably releasing the encapsulated drug at the target site. Mono-disperse Fe3O4 nanoparticles/polystyrene composite nanospheres with a large volume fraction of trapped magnetite and fluorophores were used in an in vivo experiment. In this study, magnetic nanoparticles were successfully delivered into the heart by utilizing magnetic targeting. Magnetic targeting allowed the mono-disperse Fe3O4 nanospheres to be dramatically localized in the heart myocardium. This increased the quantity of delivery to the cardiac myocytes in comparison to magnetic nanospheres without magnetic targeting.

Insulin resistance is associated with increased risk for and recurrence of breast cancer. Recently, Wnt1-inducible signaling pathway protein-1 (WISP-1) was reported to impair glucose metabolism and insulin sensitivity. In various cancer tissues, Wnt signaling is upregulated and induces further oncogenic and metastatic activity. However, the effects of exercise on serum levels of WISP-1 and its upstream β-catenin have not been studied in cancer patients. We investigated the effects of exercise training on Wnt signaling and insulin sensitivity in breast cancer survivors (BCS). This single-center trial randomized 46 BCS into either 12-week exercise or control groups (1:1), and included an additional 12 age-matched healthy women. Kinanthropometric parameters, serum Wnt signaling markers, and gluco-lipid profiles were evaluated before and after the intervention. Serum β-catenin and WISP-1 concentrations were significantly higher in BCS than in healthy subjects. There was a positive correlation between β-catenin and WISP-1 levels. Exercise training in BCS significantly reduced body fat and waist circumference and enhanced aerobic and muscular fitness. Exercise decreased β-catenin and WISP-1 levels and improved gluco-lipid profiles. There was a notable correlation between changes in HOMA-IR indexes and serum WISP-1, but not with β-catenin during the exercise intervention. In conclusion, a 12-week community-based exercise intervention resulted in significant reductions in serum β-catenin and WISP-1 levels, accompanied by favorable improvements in body composition, physical fitness, and biochemical parameters in BCS. We also highlight that this is the first report concerning effects of exercise on circulating β-catenin and WISP-1 levels and correlations between WISP-1 and insulin sensitivity, which could be important for determining prognoses for BCS.

With‐no‐lysine 1 (WNK1) kinase is a substrate of the insulin receptor/Akt pathway. Impaired insulin signaling in skeletal muscle disturbs glucose transporter 4 (GLUT4) translocation associated with the onset of type 2 diabetes (T2D). WNK1 is highly expressed in skeletal muscle. However, it is currently unknown how insulin signaling targeting WNK1 regulates GLUT4 trafficking in skeletal muscle, and whether this regulation is perturbed in T2D. Hereby, we show that insulin phosphorylates WNK1 at its activating site via a phosphatidylinositol 3‐kinase‐dependent mechanism. WNK1 promotes the cell surface abundance of GLUT4 via regulating TBC1D4. Of note, we observed insulin resistance and decreased WNK1 phosphorylation in T2D db/db mice as compared to the control mice. These results provide a new perspective on WNK1 function in the pathogenesis of hyperglycemia in T2D.

Nonalcoholic fatty liver disease is the most common chronic liver disease and can present with advanced fibrosis or nonalcoholic steatohepatitis. The purpose of this study was to investigate the effect of a 7-day intense physical activity intervention on liver fat content in children with obesity. Fifty-seven obese children (mean body mass index: 26.5 ± 3.2 kg/m2; mean age: 12.0 ± 0.8 years) participated in a 7-day physical activity program. All participants were housed together, and their food intake and energy expenditure were strictly controlled. Anthropometric measurements, abdominal computerized tomography scans, and blood analyses were conducted at baseline and post-intervention. Participants lost weight by 2.53 ± 0.85 kg on average (61.0 ± 9.8 vs. 58.5 ± 9.5 kg, p < 0.05), fat mass (16.7 ± 5.1 vs. 15.7 ± 4.9 kg, p < 0.05), and serum insulin (13.7 ± 6.7 vs. 3.5 ± 2.0 μU/mL, p < 0.05). However, liver fat content was increased, presented as liver-to-spleen ratio (LSR) where lower LSR represents higher liver fat content. The intervention increased aspartate transaminase level (29.42 ± 6.78 IU/L vs. 33.50 ± 9.60 IU/L, p < 0.001). The change in liver fat content was not associated with the change in fasting insulin and liver enzymes. Short-term intense physical activity increased liver fat content independent of change in fasting insulin level and liver enzymes. This is the first human study to report increased liver fat content after physical activity-induced rapid weight loss.

Superparamagnetic nanoparticles with a high initial magnetic susceptibility χo are of great interest in a wide variety of chemical, biomedical, electronic, and subsurface energy applications. In order to achieve the theoretically predicted increase in χo with the cube of the magnetic diameter, new synthetic techniques are needed to control the crystal structure, particularly for magnetite nanoparticles larger than 10 nm. Aqueous magnetite dispersions (Fe3O4) with a χo of 3.3 (dimensionless SI units) at 1.9 vol %, over 3- to 5-fold greater than those reported previously, were produced in a one-pot synthesis at 210 °C and ambient pressure via thermal decomposition of Fe(II) acetate in triethylene glycol (TEG). The rapid nucleation and focused growth with an unusually high precursor-to-solvent molar ratio of 1:12 led to primary particles with a volume average diameter of 16 nm and low polydispersity according to TEM. The morphology was a mixture of stoichiometric and substoichiometric magnetite according to ...

Background Exercise has been identified as a beneficial intervention to enhance quality of life in breast cancer survivors. In addition, there has been a noteworthy increase in studies emphasizing the benefits of exercise in cancer. We sought to summarize the empirical literature concerning the effects of exercise on physical fitness and biomarker levels in breast cancer survivors according to the type of exercise. Methods We searched PubMed and PubMed Central for studies on the association of exercise with the levels of various biomarkers and physical fitness in breast cancer survivors. We investigated the effects of different types of exercise (aerobic, resistance, or combined) on breast cancer survivors, with changes in physical fitness and biomarker levels as the primary outcomes. Results In total, 118 research papers published from 2012 to July 2016 were retrieved from PubMed and PubMed Central. Of these, 24 papers met our inclusion criteria. All types of exercise were found to improve physical fitness in breast cancer survivors. However, the results with regard to biomarkers were controversial. Conclusion The findings of this review suggest that combined exercise is associated with better outcomes than aerobic or resistance exercise alone in breast cancer survivors.

Aim Myokines are peptides released by the skeletal muscle, and have gained popularity as potential biomarkers for sarcopenia. Irisin is a recently identified myokine, but its role in pathological sarcopenia remains unclear. We investigated the validity and accuracy of circulating irisin levels as a potential biomarker for sarcopenia. Methods We evaluated the anthropometrics, body composition, sarcopenia-related parameters and serum irisin levels of 715 community-dwelling Koreans. Sarcopenia was determined on the basis of the clinical diagnostic criteria of muscle atrophy and weakness, which were proposed by the Asian Working Group for Sarcopenia. Results Circulating irisin levels were correlated with appendicular lean mass/height2 (rmen = 0.275; rwomen = 0.321) and handgrip strength (rmen = 0.219; rwomen = 0.312) in both sexes (all P < 0.01). Furthermore, the mean circulating irisin levels were lower in the sarcopenia group than in the normal group (all P < 0.05). In the logistic regression models, the association between serum irisin concentration and incident sarcopenia persisted even after adjusting for potential confounders, such as sex, age and fat indices (odds ratio 0.20, 95% CI 0.07–0.60; P for trend

This study introduces a personalized automated exercise guidance system for the efficient reduction of obesity. The proposed system was composed of wearable biometric devices and exercise-machine control systems connected with the integrated database server. It was designed for providing customized exercise prescription (intensity, repetition, frequency, etc.) according to ACSM guidelines for obesity based on real-time biosignals feedback and an individual’s exercise capacity. Nineteen subjects participated in evaluating the proposed system, and we found that the risk factors (body composition, hemodynamics, blood enzymes, and exercise variables) related to obesity were statistically significantly improved. Other exercise prescriptions for chronic diseases and symptoms will be able to adapt to the proposed system so that we believe it would be substantially helpful to improve geriatric diseases and symptoms by using technology-driven exercise.

Irisin is a myokine secreted mainly from skeletal muscle that is known for having beneficial metabolic effects via enhancement of energy expenditure and insulin sensitivity. Studies show that irisin also acts as an autocrine/paracrine to promote myogenesis and muscle growth. However, the protective role of irisin against muscular wasting remains unclear. We confirmed that irisin secretion was upregulated by electrical pulse stimulation an in vitro exercise mimetic model. Next, we tested if irisin exerted an anti-atrophic effect on cultured C2C12 myotubes treated with dexamethasone (DEX), a representative inducer of muscular atrophy. Treatment of cultured myotubes with DEX reduced myotube size and increased proteasome activity, which were attenuated by irisin. Also, irisin effectively prevented dephosphorylation of forkhead box O (FoxO) 3α and upregulation of muscle-specific ubiquitin ligases in DEX-treated myotubes. The protective effect of irisin on DEX-mediated myotube atrophy was partially regulated by insulin-like growth factor-1-dependent signaling. These results suggested that irisin may prevent glucocorticoid-induced muscle atrophy by inhibiting FoxO-mediated ubiquitin-proteasome overactivity. Electronic supplementary material The online version of this article (10.1007/s00424-020-02367-4) contains supplementary material, which is available to authorized users.

Internet gaming addiction (IGA) has been associated with many negative health outcomes, especially for youth; however, few studies have examined the physiological parameters and personality features related to this addiction. This study aimed to identify differences in autonomic functions and distressed (type D) personality traits among Korean adolescent males with and without IGA. In a cross-sectional study, 68 adolescent males were recruited in a Korean city using convenience and snowball sampling methods. For each subject, heart rate variability (HRV) parameters were measured as autonomic functions and questionnaires were used to identify IGA and type D personality traits. Data were analyzed using descriptive analyses, t tests, χ2 tests, and Pearson's correlation. Most HRV parameters significantly differed between the IGA and non-IGA groups (all p

Background The number of people with Internet gaming addiction (IGA) is increasing around the world. IGA is known to be associated with personal characteristics, psychosocial factors, and physiological factors. However, few studies have examined the genetic factors related to IGA. This study aimed to investigate the association between IGA and stress-related genetic variants. Methods This cross-sectional study was conducted with 230 male high school students in a South Korean city. We selected five stress-related candidate genes: DAT1, DRD4, NET8, CHRNA4, and CRHR1. The DAT1 and DRD4 genes were genotyped by polymerase chain reaction, and the NET8, CHRNA4, and CRHR1 genes were genotyped by pyrosequencing analysis. We performed a Chi-square test to examine the relationship of these five candidate genes to IGA. Results Having the AA genotype and the A allele of the CRHR1 gene (rs28364027) was associated with higher odds of belonging to the IGA participant group (p = .016 and p = .021, respectively) than to the non-IGA group. By contrast, the DAT1, DRD4, NET8, and CHRNA4 gene polymorphisms showed no significant difference between the IGA group and control group. Conclusions These results indicate that polymorphism of the CRHR1 gene may play an important role in IGA susceptibility in the Korean adolescent male population. These findings provide a justification and foundation for further investigation of genetic factors related to IGA.

Angiopoietin-like 6 (ANGPTL6) is a hepatokine that antagonizes obesity and insulin resistance by increasing energy expenditure. Despite its beneficial effects on metabolism, human studies have shown a paradoxical increase in ANGPTL6 level in the serum of patients with metabolic diseases, which has been interpreted as a compensatory upregulation. However, the regulatory mechanism of ANGPTL6 remains unclear. Since upregulation of ANGPTL6 is induced on metabolic stress, we investigated the hepatic expression of ANGPTL6 by leptin, a representative adipokine of obesity. Mice on a high-fat diet showed increased serum leptin levels and hepatic Angptl6 expression, which were attenuated by exercise training. A single leptin injection also induced hepatic ANGPTL6 expression and increased serum ANGPTL6 levels. In an in vitro model using primary hepatocytes, leptin treatment significantly upregulated ANGPTL6 expression at the mRNA and protein levels, as well as the amount of secreted ANGPTL6 protein in conditioned media. Similarly, exercise training on human participants also showed diminished serum levels of leptin and ANGPTL6. Altogether, these results strongly indicated that hepatic ANGPTL6 expression was determined by leptin.

Aim The present cross-sectional study was carried out among community-dwelling Koreans to determine the validity of various muscle mass indices and to propose more clinically relevant diagnostic criteria. Methods This study measured the anthropometrics, body composition and physical capability of 415 older Koreans. Skeletal muscle indices were calculated by dividing appendicular lean mass by height or weight. Apart from this, we adjusted appendicular lean mass for body mass index, body surface area or waist-to-height ratio, which we then named the qualitative muscle mass index. Skeletal muscle function deficit was defined as a combination of weakness and slowness. Results Qualitative muscle indices were closely associated with physical capabilities. Receiver operating characteristic and logistic analyses showed that qualitative muscle indices had significantly greater discriminatory powers regarding low muscle function than did the height-adjusted index in both men and women, and even showed higher discriminatory potentials than the weight-adjusted index in men (all P

Background Insulin-like growth factor (IGF-1) is associated with chronic diseases such as diabetes, cardiovascular disease, and hypertension, as well as muscle dysfunction. Previous studies of exercise interventions yield controversial results regarding plasma IGF-1, IGFBP3, and IGF-1/IGFBP3 ratio. In this study, we examined whether 100 km walking exercise affects serum levels of IGF-1 and IGFBP3 and IGF-1/IGFBP3 ratio. We also investigated several metabolic-related blood parameters before and after walking. Methods Participants were 14 healthy middle aged men (41.0 ± 6.78 years of age). We assessed body composition and measured metabolic-related blood indicators, such as such as lipid profiles, glucose, renal and hepatic metabolic bio-markers before and after a 100 km walking race. Blood samples from all participants were taken before and immediately after the walkathon. We also analyzed serum levels of IGF-1 and IGFBP3, and calculated the IGF-1/IGFBP3 ratio. Results After participants completed a 100 km walking race, some of their metabolic profiles were markedly changed. Serum levels of IGF-1 and IGFBP3 were significantly decreased, and therefore the IGF-1/IGFBP3 ratio also decreased before and after 100 km of walking. Conclusion Our results indicate that intense walking exercise affects serum levels of IGF-1 and IGFBP3 as well as metabolic bio-markers including high density cholesterol, glucose and triglycerides.

Background The role of pentraxin-3 (PTX3) in the development of insulin resistance is still not clear. We aimed to test 1) whether circulating PTX3 levels are associated with insulin resistance and 2) whether changes in PTX3 levels after the physical activity are associated with changes in insulin resistance. Methods Fifty-seven overweight or obese children (39 boys, 18 girls; age: 12.04 ± 0.82 y, BMI: 26.5 ± 1.2 kg/m 2 ) participated in the study. All participants were housed together and their amount of physical activity (1823.5 ± 1.34 kcal/day) and food intake (1882 ± 68.8 kcal/day) were tightly controlled. Results Circulating PTX3 levels at baseline were negatively associated with fasting insulin ( r = − .336, p = 0.012) and homeostasis model assessment of insulin resistance (HOMA-IR) ( r = − .334, p = 0.014) even after adjustment for BMI and Tanner stage. The degree of change in PTX3 levels notably associated with changes in fasting insulin ( r = − .280, p = 0.035) and HOMA-IR ( r = − .281, p = .034) in response to the physical activity intervention. Subgroup analysis further indicates that HOMA-IR was improved more in subjects whose PTX3 levels were increased compared with subjects who PTX3 levels were decreased (HOMA-IR delta: − 2.33 ± 1.3 vs − 1.46 ± 0.70, p = 0.004). Conclusion PTX3 is negatively associated with insulin resistance and associated with changes in insulin resistance induced by physical activity in overweight and obese children.

Spectrally selective coatings (SSCs) are a critical component that enables high-temperature and high-efficiency operation of concentrating solar power (CSP) systems. In this Letter, we describe a novel design for a high-performance SSC based on multi-scaled nanostructures. Optimal design of the new structure for high optical performance of the SSC is predicted by the effective medium theory. To demonstrate the feasibility of the design, we fabricate the SSCs using fractal nanostructures with characteristic sizes ranging from ~10 nm to ~10 μm. Optical measurements on these structures show unprecedentedly high performance with ~90–95% solar absorptivity and

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and a serious health burden worldwide which increases risk of cirrhosis, type 2 diabetes mellitus (T2DM), and cardiovascular complications. Current epidemics of obesity, unhealthy dietary patterns, and sedentary lifestyles, all contribute to the high prevalence of NAFLD. Dietary patterns and nutrients are important contributors to the development, progression, and treatment of NAFLD. A healthy diet is beneficial for all NAFLD patients beyond weight reduction. Generally, hypercaloric diets, especially rich in trans/saturated fat and cholesterol, high consumption of red and processed meat, and fructose-sweetened beverages seem to increase the risk of progression toward nonalcoholic steatohepatitis (NASH), whereas reducing caloric intake and high-glycemic index (GI) foods, increasing consumption of monounsaturated fatty acids, omega-3 fatty acids, fibers, and specific protein sources such as fish and poultry have preventive and therapeutic effects. Therefore, nutrition serves as a major route of prevention and treatment of NAFLD, and patients with NAFLD should have an individualized diet recommendation. In this review, the evidence linking macronutrients to NAFLD are discussed.

Major pelvic ganglia (MPG) are relay centers for autonomic reflexes such as micturition and penile erection. MPG innervate the urogenital system, including bladder. γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system, and may also play an important role in some peripheral autonomic ganglia, including MPG. However, the electrophysiological properties and function of GABAA receptor in MPG neurons innervating bladder remain unknown. This study examined the electrophysiological properties and functional roles of GABAA receptors in bladder-innervating neurons identified by retrograde Dil tracing. Neurons innervating bladder showed previously established parasympathetic properties, including small membrane capacitance, lack of T-type Ca(2+) channel expression, and tyrosine-hydroxylase immunoreactivity. GABAA receptors were functionally expressed in bladder innervating neurons, but GABAC receptors were not. GABA elicited strong depolarization followed by increase of intracellular Ca(2+) in neurons innervating bladder, supporting the hypothesis GABA may play an important role in bladder function. These results provide useful information about the autonomic function of bladder in physiological and pathological conditions.

Injury to podocytes leads to the onset of chronic renal diseases characterized by proteinuria. Elevated transforming growth factor (TGF)-β in kidney tissue is associated with podocyte damage that ultimately results in apoptosis and detachment. We investigated the proapoptotic mechanism of TGF-β in immortalized mouse podocytes. Exogenous TGF-β1-induced podocyte apoptosis through caspase-3 activation, which was related to elevated ROS levels generated by selective upregulation of NADPH oxidase 4 (Nox4). In mouse podocytes, Nox4 was predominantly localized to mitochondria, and Nox4 upregulation by TGF-β1 markedly depolarized mitochondrial membrane potential. TGF-β1-induced ROS production and caspase activation were mitigated by an antioxidant, the Nox inhibitor diphenyleneiodonium, or small interfering RNA for Nox4. A TGF-β receptor I blocker, SB-431542, completely reversed the changes triggered by TGF-β1. Knockdown of either Smad2 or Smad3 prevented the increase of Nox4 expression, ROS generation, loss of mitochondrial membrane potential, and caspase-3 activation by TGF-β1. These results suggest that TGF-β1-induced mitochondrial Nox4 upregulation via the TGF-β receptor-Smad2/3 pathway is responsible for ROS production, mitochondrial dysfunction, and apoptosis, which may at least in part contribute to the development and progression of proteinuric glomerular diseases such as diabetic nephropathy.

Background Despite being an anti-obesity hepatokine, the levels of serum angiopoietin-like 6 (ANGPTL6) are elevated in various metabolic diseases. Thus, ANGPTL6 expression may reflect metabolic burden and may have compensatory roles. This study investigated the association between serum ANGPTL6 levels and new-onset metabolic syndrome. Methods In total, 221 participants without metabolic syndrome were randomly selected from a rural cohort in Korea. Baseline serum ANGPTL6 levels were measured using an enzyme-linked immunosorbent assay. Anthropometric and biochemical markers were analyzed before and after follow-up examinations. Results During an average follow-up period of 2.75 (interquartile range, 0.76) years, 82 participants (37.1%) presented new-onset metabolic syndrome and had higher ANGPTL6 levels before onset than those without metabolic syndrome (48.03±18.84 ng/mL vs. 64.75±43.35 ng/mL, P=0.001). In the multivariable adjusted models, the odds ratio for the development of metabolic syndrome in the highest quartile of ANGPTL6 levels was 3.61 (95% confidence interval, 1.27 to 10.26). The use of ANGPTL6 levels in addition to the conventional components improved the prediction of new-onset metabolic syndrome (area under the receiver operating characteristic curve: 0.775 vs. 0.807, P=0.036). Conclusion Increased serum ANGPTL6 levels precede the development of metabolic syndrome and its components, including low high density lipoprotein, high triglyceride, and high glucose levels, which have an independent predictive value for metabolic syndrome.

Highly ordered TiO2 nanotube arrays with large diameter of 680-750 nm have been prepared by high voltage anodization in an electrolyte containing ethylene glycol at room temperature. To effectively suppress dielectric breakdown due to high voltage, pre-anodized TiO2 film was formed prior to the main anodizing process. Vertically aligned, large sized TiO2 nanotubes with double-wall structure have been demonstrated by SEM in detail under various anodizing voltages up to 225 V. The interface between the inner and outer walls in the double-wall configuration is porous. Surface topography of the large diameter TiO2 nanotube array is substantially improved and effective control of the growth of large diameter TiO2 nanotube array is achieved. Interestingly, the hemispherical barrier layer located at the bottom of TiO2 nanotubes formed in this work has crinkles analogous to the morphology of the brain cortex. These structures are potentially useful for orthopedic implants, storage of biological agents for controlled release, and solar cell applications.

Hollow-sphere-structured magnetic nanocapsules containing intentionally trapped iron oxide nanoparticles and anticancer drugs have been prepared to provide a powerful magnetic vector under moderate gradient magnetic fields. It is shown that these nanocapsules can penetrate into the interior of tumors and allow a controlled on-off switchable release of the anticancer drug cargo via remote 100 KHz RF field. This smart drug delivery system is nanoscale compact, with the drug molecules and magnetic nanoparticles contained within the hollow capsules having ~ 80 ~ 150nm diameter. In vitro results using a mouse model indicate that such a nanocapsule-mediated, on-demand drug release is effective in reducing tumor cell growth.

Podocyte, the gatekeeper of the glomerular filtration barrier, is a primary target for growth factor and Ca

Background Wingless and integration site growth factor (Wnt) signaling is a tumorigenesis-related signaling pathway. Dickkpof-1 (DKK1) and secreted frizzled-related protein-1 (SFRP1) are endogenous negative regulators of Wnt/β-catenin signaling. Accumulating evidence indicates that higher serum levels of DKK1 are correlated with poor prognosis of various types of cancer. Here, we investigated whether exercise training causes changes in the serum levels of DKK1 and SFRP1 in patients with breast cancer. Methods Twenty-four breast cancer survivors, after chemo- or radiotherapy, participated in this single-blind randomized, controlled pilot study. Subjects were randomized to either an exercise program or a control group for 12 weeks and completed pre- and post-training tests for health-related fitness and body composition as well as blood biomarkers. The serum levels of DKK1 and SFRP1 were measured using enzyme-linked immunosorbent assay as the primary outcome. Results Exercise training for 12 weeks remarkably increased muscle strength, endurance, and flexibility and decreased body fat percentage, waist circumference, and visceral fat area (all p < 0.05). Exercise training lowered serum insulin levels and leptin/adiponectin ratios (all p < 0.05). The levels of DKK1 and SFRP1 were also significantly decreased by exercise training in breast cancer survivors (all p < 0.01). Conclusions Our results indicate that DKK1 and SFRP1 may be potentially useful biomarkers for evaluating the beneficial effects of long-term exercise on physical fitness and metabolism as well as the prognosis of patients with cancer. Trial registration ClinicalTrials.gov NCT02895178

Myokines are peptides released by the skeletal muscle, and have gained popularity as potential biomarkers for sarcopenia. Irisin is a recently identified myokine, but its role in pathological sarcopenia remains unclear. We investigated the validity and accuracy of circulating irisin levels as a potential biomarker for sarcopenia.We evaluated the anthropometrics, body composition, sarcopenia-related parameters and serum irisin levels of 715 community-dwelling Koreans. Sarcopenia was determined on the basis of the clinical diagnostic criteria of muscle atrophy and weakness, which were proposed by the Asian Working Group for Sarcopenia.Circulating irisin levels were correlated with appendicular lean mass/heightA low level of circulating irisin is a sensitive marker for muscle weakness and atrophy. Irisin is a potential biomarker for muscle dysfunction that could help predict the onset of sarcopenia and provide new avenues for monitoring age-related muscle changes. Geriatr Gerontol Int 2017; 17: 2266-2273.

Klotho is a type-1 membrane protein predominantly produced in the kidney, the extracellular domain of which is secreted into the systemic circulation. Membranous and secreted Klotho protect organs, including the kidney, but whether and how Klotho directly protects the glomerular filter is unknown. Here, we report that secreted Klotho suppressed transient receptor potential channel 6 (TRPC6)-mediated Ca2+ influx in cultured mouse podocytes by inhibiting phosphoinositide 3-kinase-dependent exocytosis of the channel. Furthermore, soluble Klotho reduced ATP-stimulated actin cytoskeletal remodeling and transepithelial albumin leakage in these cells. Overexpression of TRPC6 by gene delivery in mice induced albuminuria, and exogenous administration of Klotho ameliorated the albuminuria. Notably, immunofluorescence and in situ hybridization revealed Klotho expression in podocytes of mouse and human kidney. Heterozygous Klotho-deficient CKD mice had aggravated albuminuria compared with that in wild-type CKD mice with a similar degree of hypertension and reduced clearance function. Finally, disrupting the integrity of glomerular filter by saline infusion-mediated extracellular fluid volume expansion increased urinary Klotho excretion. These results reveal a potential novel function of Klotho in protecting the glomerular filter, and may offer a new therapeutic strategy for treatment of proteinuria.

The purpose of this study was to compare the resting-state plasma catecholamine and anxiety levels of Korean male adolescents with Internet game addiction (IGA) and those without IGA. This cross-sectional comparative study was conducted with 230 male high school students in a South Korean city. Convenience and snowball sampling methods were employed, and data were collected using (1) participant blood samples analyzed for dopamine (DA), epinephrine (Epi), and norepinephrine (NE) and (2) two questionnaires to assess IGA and anxiety levels. Using SPSS 15.0, data were analyzed by descriptive analysis, χ2-tests, t-tests, and Pearson's correlation tests. The plasma Epi (t = 1.962, p

Elevated plasma levels of inorganic phosphate (Pi) are harmful, causing, among other complications, vascular calcification and defective insulin secretion. The underlying molecular mechanisms of these complications remain poorly understood. We demonstrated the role of Pi transport across the plasmalemma on Pi toxicity in INS-1E rat clonal β cells and rat pancreatic islet cells. Type III sodium-phosphate cotransporters (NaPis) are the predominant Pi transporters expressed in insulin-secreting cells. Transcript and protein levels of sodium-dependent phosphate transporter 1 and 2 (PiT-1 and -2), isotypes of type III NaPi, were up-regulated by high-Pi incubation. In patch-clamp experiments, extracellular Pi elicited a Na+-dependent, inwardly rectifying current, which was markedly reduced under acidic extracellular conditions. Cellular uptake of Pi elicited cytosolic alkalinization; intriguingly, this pH change facilitated Pi transport into the mitochondrial matrix. Increased mitochondrial Pi uptake accelerated superoxide generation, mitochondrial permeability transition (mPT), and endoplasmic reticulum stress-mediated translational attenuation, leading to reduced insulin content and impaired glucose-stimulated insulin secretion. Silencing of PiT-1/2 prevented Pi-induced superoxide generation and mPT, and restored insulin secretion. We propose that Pi transport across the plasma membrane and consequent cytosolic alkalinization could be a therapeutic target for protection from Pi toxicity in insulin-secreting cells, as well as in other cell types.-Nguyen, T. T., Quan, X., Xu, S., Das, R., Cha, S.-K., Kong, I. D., Shong, M., Wollheim, C. B., Park, K.-S. Intracellular alkalinization by phosphate uptake via type III sodium-phosphate cotransporter participates in high-phosphate-induced mitochondrial oxidative stress and defective insulin secretion.