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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.

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.

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.

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.

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.

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.

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.

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

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.

Delivery of therapeutic or diagnostic agents across an intact blood–brain barrier (BBB) remains a major challenge. Here we demonstrate in a mouse model that magnetic nanoparticles (MNPs) can cross the normal BBB when subjected to an external magnetic field. Following a systemic administration, an applied external magnetic field mediates the ability of MNPs to permeate the BBB and accumulate in a perivascular zone of the brain parenchyma. Direct tracking and localization inside endothelial cells and in the perivascular extracellular matrix in vivo was established using fluorescent MNPs. These MNPs were inert and associated with low toxicity, using a non-invasive reporter for astrogliosis, biochemical and histological studies. Atomic force microscopy demonstrated that MNPs were internalized by endothelial cells, suggesting that trans-cellular trafficking may be a mechanism for the MNP crossing of the BBB observed. The silica-coated magnetic nanocapsules (SiMNCs) allow on-demand drug release via remote radio frequency (RF) magnetic field. Together, these results establish an effective strategy for regulating the biodistribution of MNPs in the brain through the application of an external magnetic field.

Assuming that photons absorbed by a vessel do not have acute variations, DC component reflect the basal blood volume (or diameter) before blood pulsation. Vascular stiffness and reflection is influenced by changes in basal blood volume (or diameter). This paper describes analysis of the characteristic variations of vascular stiffness, according to relative variations in DC components of the PPG signal (25-75%). For quantitative analysis, we have used parameters that were proposed previously, reflection and stiffness index, and the second derivative of PPG waveform, b/a and d/a. Significantly, the vascular stiffness and reflections were increased according to increase in DC component of the PPG signal for more than about 3% of baseline values. The systolic blood pressure were increased from to mmHg, about 2.76% (r

Nanocapsules containing intentionally trapped magnetic nanoparticles and defined anticancer drugs have been prepared to provide a powerful magnetic vector under moderate gradient magnetic fields. These nanocapsules can penetrate into the interior of tumors and allow a controlled on-off switchable release of the drug cargo via remote RF field. This smart drug delivery system is compact as all the components can be self-contained in 80-150 nm capsules. In vitro as well as in vivo results indicate that these nanocapsules can be enriched near the mouse breast tumor and are effective in reducing tumor cell growth.

This paper describes the development of a new class of N-linked imidazoles as potential pH-sensitive, cleavable linkers for use in cancer drug delivery systems. Kinetic analysis of eight derivatives of N-ethoxybenzylimidazoles (NEBIs) showed that their rates of hydrolysis are accelerated in mild aqueous acidic solutions compared to in solutions at normal, physiological pH. Incorporation of electron donating or electron withdrawing substituents on the phenyl ring of the NEBI resulted in the ability to tune the rates of hydrolysis under mild acidic conditions with half-lives ranging from minutes to months. A derivative of NEBI carrying doxorubicin, a widely used anticancer agent, also showed an increased rate of hydrolysis under mild acid compared to that at normal physiological pH. The doxorubicin analogue resulting from hydrolysis from the NEBI exhibited good cytotoxic activity when exposed to human ovarian cancer cells. These results demonstrate a potentially useful, general strategy for conjugating a wide range of drugs to imidazole-containing delivery vessels via NEBI functionalities for controlled release of therapeutics for drug delivery applications.

Aqueous dispersions of iron oxide nanoparticles with a high initial magnetic susceptibility (χi) are of interest as contrast agents in electromagnetic tomography. Nanoclusters composed of iron oxide primary particles were formed by co-precipitation of Fe(II) and Fe(III) chlorides at alkaline conditions and high temperature of 95 °C. Two-step addition of citrate was used to produce large primary particles and then stabilize the nanoclusters. The size of the primary particles was tuned from 5 nm to 15 nm by varying the citrate/iron precursor ratio during the normal phase hydrolysis reaction, while the second iteration of citrate stabilized the nanoclusters with hydrodynamic diameters of 30–75 nm. The crystallinity of the iron oxide nanoparticles was promoted by annealing at 95 °C and systematically studied with Superconducting Quantum Interference Device (SQUID), Vibrating Sample Magnetometer (VSM), Transmission Electron Microscopy (TEM) and X-ray Diffraction (XRD). The dependence of χi was examined over a range of low volume fractions (0.005

Background Socioeconomic status is closely associated with an individual’s health status. However, there are few studies examining the role of exercise-training as part of a community-based social welfare program in socially vulnerable groups. Given this, our aim was to measure whether long-term exercise training as a social welfare program affects the prevalence of depressive symptoms, metabolic syndrome and peripheral blood vessel condition among participants with low household income. Methods Twenty-nine adults and twenty-two older adults were recruited into this study with non-radomized, pre/post-test design. The subjects underwent a combined training consisting of aerobic and muscle strengthening exercises for 6 months or more. Depressive symptoms were evaluated using the Beck Depression Inventory and the Korean version of Geriatric Depression Scale. Metabolic syndrome was defined according to the International Diabetes Federation criteria. Blood vessel condition was assessed using non-invasive accelerated photoplethysmograph. Results Mean skeletal muscle mass increased after exercise-training, but body mass index and percent body fat were unchanged. Overall age-specific physical fitness and performance increased markedly among both adult and elderly subjects, respectively. The proportion of depressive symptoms was significantly reduced by 33% after exercise-training among all participants. The prevalence of individuals having metabolic syndrome was significantly reduced by 19.6% and the number of individual components of metabolic syndrome decreased after the exercise intervention. Among components of metabolic syndrome, waist circumference, HDL cholesterol and systolic blood pressure significantly improved. In addition, the proportions of moderate and severe arteriosclerotic progression significantly decreased. Conclusion Long-term exercise-training as a social welfare program is beneficial for health promotion and effective in simultaneously improving psychological and physiological health status in a low income population. This suggests that the development and expansion of an exercise intervention as a health-promoting welfare program are needed to address the inequality of exercise participation among socially vulnerable groups.

Sarcopenia is the gradual decreases of skeletal muscle mass and functions during aging. In general, muscle mass index as a predictor of sarcopenia should be well reflected by those of functions. Ho...

WNK (with-no-lysine [K]) kinases (WNK1-4) are serine/threonine protein kinases with an atypical placement of the catalytic lysine and tissue-specific expression. WNK1, ubiquitously expressed including skeletal muscle, is known as a downstream effector of insulin signaling and WNKs have been implicated in protein trafficking highly correlated with insulin resistance or diabetes. However, expression pattern and functional role of WNKs in skeletal muscle and linkage between WNKs and insulin signaling effectors such as PKB/Akt and glucose transports in skeletal muscle with type II diabetes are ill-defined. In the present study, WNK1 and WNK2, not WNK4 are expressed in C2C12. The expression levels of WNK1 and WNK2 significantly decreased in db/db mice, a type II diabetic model, compared to that of wild type mice. Phosphorylated Akt in skeletal muscle decreased in db/db mice supporting insulin resistance in skeletal muscle. Insulin stimulates Akt followed by WNK1 phosphorylation. Insulin stimulation of WNK1 is ...

1 We studied the modulation of pacemaker activities by bradykinin in cultured interstitial cells of Cajal (ICC) from murine small intestine with the whole-cell patch-clamp technique. Externally applied bradykinin produced membrane depolarization in the current-clamp mode and increased tonic inward pacemaker currents in the voltage-clamp mode. 2 Pretreatment with bradykinin B1 antagonist did not block the bradykinin-induced effects on pacemaker currents. However, pretreatment with bradykinin B2 antagonist selectively blocked the bradykinin-induced effects. Also, only externally applied selective bradykinin B2 receptor agonist produced tonic inward pacemaker currents and ICC revealed a colocalization of the bradykinin B2 receptor and c-kit immunoreactivities, but bradykinin B1 receptors did not localize in ICC. 3 External Na+-free solution abolished the generation of pacemaker currents and inhibited the bradykinin-induced tonic inward current. However, a Cl− channel blocker (DIDS) did not block the bradykinin-induced tonic inward current. 4 The pretreatment with Ca2+-free solution and thapsigargin, a Ca2+-ATPase inhibitor in endoplasmic reticulum, abolished the generation of pacemaker currents and suppressed the bradykinin-induced action. 5 Chelerythrine and calphostin C, protein kinase C inhibitors or naproxen, an inhibitor of cyclooxygenase, did not block the bradykinin-induced effects on pacemaker currents. 6 These results suggest that bradykinin modulates the pacemaker activities through bradykinin B2 receptor activation in ICC by external Ca2+ influx and internal Ca2+ release via protein kinase C- or cyclooxygenase-independent mechanism. Therefore, the ICC are targets for bradykinin and their interaction can affect intestinal motility. British Journal of Pharmacology (2006) 148, 918–926. doi:10.1038/sj.bjp.0706806