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Objective This study standardizes the Parental Stress Scale (PSS) for Republic of Korean parents of children with attention-deficit/hyperactivity disorder (ADHD) and verifies its reliability and validity.Methods Data from 160 parents of children with ADHD who completed the following self-reported questionnaires were analyzed: the Korean ADHD Rating Scales, the Patient Health Questionnaire-9, the State–Trait Anxiety Inventory, the PSS, and the Global Assessment of Recent Stress Scale. All scale items were measured for reliability and validity, and the appropriate factors for measuring stress in Korean parents with ADHD children were extracted.Results Exploratory and confirmatory factor analyses derived two sub-factors and 11 items. Goodness of fit was confirmed, and the scale was deemed suitable for explaining stress in parents of children with ADHD.Conclusion In this study, the validity and reliability of the K-PSS-ADHD were investigated. We expect that the K-PSS-ADHD will be used as a basis for future studies on stress in parents of children with ADHD.

Mitochondrial membrane potential directly powers many critical functions of mitochondria, including ATP production, mitochondrial protein import, and metabolite transport. Its loss is a cardinal feature of aging and mitochondrial diseases, and cells closely monitor membrane potential as an indicator of mitochondrial health. Given its central importance, it is logical that cells would modulate mitochondrial membrane potential in response to demand and environmental cues, but there has been little exploration of this question. We report that loss of the Sit4 protein phosphatase in yeast increases mitochondrial membrane potential, both through inducing the electron transport chain and the phosphate starvation response. Indeed, a similarly elevated mitochondrial membrane potential is also elicited simply by phosphate starvation or by abrogation of the Pho85-dependent phosphate sensing pathway. This enhanced membrane potential is primarily driven by an unexpected activity of the ADP/ATP carrier. We also demonstrate that this connection between phosphate limitation and enhancement of the mitochondrial membrane potential is also observed in primary and immortalized mammalian cells as well as inDrosophila. These data suggest that mitochondrial membrane potential is subject to environmental stimuli and intracellular signaling regulation and raise the possibility for therapeutic enhancement of mitochondrial functions even with defective mitochondria.

Veterinary biocides used in animal husbandry have the potential to cause human health concerns. Biocidal products for veterinary use, which contain pesticides approved in Korea, comprise 49 active ingredients within 234 products. Within 17 of these products there are 3 ingredients which are highly hazardous pesticides: coumaphos, dichlorvos and methomyl. In this study, the content of the active ingredients of 160 products sold domestically was investigated. Samples were collected for 119 biocidal products for veterinary use. These were analysed by high‐performance liquid chromatography (HPLC) and gas chromatography (GC). Seventeen products were noncompliant (insufficient or excess quantity of active ingredients). The ingredients that were below the stated concentrations were amitraz, chlorpyrifos‐methyl, cypermethrin, cyromazine, dichlorvos, fipronil, muscamone and trichlorfon. The ingredients that exceeded the stated concentrations were abamectin, fluvalinate and pyriproxyfen. The noncompliance rate in biocidal products for veterinary use was 9.19%. The results of this study show that three highly hazardous pesticides (coumaphos, dichlorvos and methomyl) and 10 active ingredients (abamectin, amitraz, chlorpyrifos‐methyl, cypermethrin, cyromazine, fipronil, fluvalinate, muscamone, pyriproxyfen and trichlorfon) deviated from the stated concentrations. Thus, management plans should be established to ensure compliant veterinary drugs by post‐distribution quality control, such as planning for regular inspection., Three highly hazardous pesticides (coumaphos, dichlorvos and methomyl) and 10 active ingredients (abamectin, amitraz, chlorpyrifos‐methyl, cypermethrin, cyromazine, fipronil, fluvalinate, muscamone, pyriproxyfen and trichlorfon) deviated from the stated concentrations. Thus, management plans should be established to distribute compliant veterinary drugs by post‐distribution quality control, such as planning inspection.

Objectives Although aggressive behavior in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) has previously shown correlations with hyperactivity/impulsivity, few studies have examined its association with inattention or the effect of working memory on aggressive behavior. This study aimed to assess the relationship between inattention and aggressive behavior and the effect of working memory on the relationship between inattention and aggressive behavior in children and adolescents with ADHD. Methods Thirty-one children and 26 adolescents with ADHD were retrospectively investigated. The subjects completed the Korean Wechsler Intelligence Scale for Children-Fourth Edition (KWISC-IV), the Korean Child Behavior Checklist (K-CBCL), and the Korean Children's Depression Inventory (CDI). Results Inattention was positively correlated with aggressive behavior in children and adolescents with ADHD and working memory showed an insignificant correlation. However, working memory had a significant moderating effect on aggressive behavior by interacting with inattention. The moderating effect of working memory manifested when the working memory index score on the K-WISC-IV was 73.5 points or higher, and it had a significant effect on aggressive behavior. Conclusion This study shows that the severity of inattention and hyperactivity/impulsivity should be addressed to provide appropriate treatment to children and adolescents with ADHD who exhibit aggressive behavior.

The excessive intake of a high-fat diet (HFD) leads to obesity, including metabolic syndromes, disturbs gut microbiota composition, causes colitis, and increases the plasma concentration of lipopolysaccharide (LPS). In the present study, we examined the role of gut microbiota in the occurrence of HFD-induced psychiatric disorders in mice. C57BL/6 J male mice fed a HFD for 9 weeks were led to obesity; their memory impairment was assessed by the Y-maze and novel object recognition test, and anxiety-like behaviors by the elevated plus maze. The intake of a HFD suppressed brain-derived neurotrophic factor (BDNF) expression in the hippocampus and increased blood TNF-α and LPS levels. HFD treatment more potently increased NF-κB activation and Iba1+ (microglial) cell populations in the hippocampus. Furthermore, HFD feeding increased TNF-α expression, myeloperoxidase activity, and CD11b+/CD11c+ cell (macrophages and dendritic cells) populations in the colon and altered gut microbiota composition including increases in the Proteobacteria population, and increases in fecal LPS levels. The stool lysates of HFD-treated mice suppressed BDNF expression and CREB phosphorylation in SH-SY5Y cells and increased NF-κB activation in BV-2 microglial cells compared to those of low-fat diet-treated mice while these effects were attenuated by treatment with anti-LPS antibody. These findings suggest that excessive intake of HFD can simultaneously cause obesity and psychiatric disorders by suppressing hippocampal BDNF expression with the disturbance of gut microbiota composition, particularly the increase in Proteobacteria population and LPS production.

Olfactory receptors are ectopically expressed in extra-nasal tissues. The gut is constantly exposed to high levels of odorants where ectopic olfactory receptors may play critical roles. Activation of ectopic olfactory receptor 544 (Olfr544) by azelaic acid (AzA), an Olfr544 ligand, reduces adiposity in mice fed a high-fat diet (HFD) by regulating fuel preference to fats. Herein, we investigated the novel function of Olfr544 in the gut. In GLUTag cells, AzA induces the cAMP-PKA-CREB signaling axis and increases the secretion of GLP-1, an enteroendocrine hormone with anti-obesity effects. In mice fed a HFD and orally administered AzA, GLP-1 plasma levels were elevated in mice. The induction of GLP-1 secretion was negated in cells with Olfr544 gene knockdown and in Olfr544-deficient mice. Gut microbiome analysis revealed that AzA increased the levels of Bacteroides acidifaciens and microbiota associated with antioxidant pathways. In fecal metabolomics analysis, the levels of succinate and trehalose, metabolites correlated with a lean phenotype, were elevated by AzA. The function of Olfr544 in gut inflammation, a key feature in obesity, was further investigated. In RNA sequencing analysis, AzA suppressed LPS-induced activation of inflammatory pathways and reduced TNF-α and IL-6 expression, thereby improving intestinal permeability. The effects of AzA on the gut metabolome, microbiome, and colon inflammation were abrogated in Olfr544-KO mice. These results collectively demonstrated that activation of Olfr544 by AzA in the gut exerts multiple effects by regulating GLP-1 secretion, gut microbiome and metabolites, and colonic inflammation in anti-obesogenic phenotypes and, thus, may be applied for obesity therapeutics.

We demonstrate the mechanism by which C3G, a major dietary anthocyanin, regulates energy metabolism and insulin sensitivity. Oral administration of C3G reduced hepatic and plasma triglyceride levels, adiposity, and improved glucose tolerance in mice fed high-fat diet. Hepatic metabolomic analysis revealed that C3G shifted metabolite profiles towards fatty acid oxidation and ketogenesis. C3G increased glucose uptake in HepG2 cells and C2C12 myotubes and induced the rate of hepatic fatty acid oxidation. C3G directly interacted with and activated PPARs, with the highest affinity for PPARα. The ability of C3G to reduce plasma and hepatic triglycerides, glucose tolerance, and adiposity and to induce oxygen consumption and energy expenditure was abrogated in PPARα-deficient mice, suggesting that PPARα is the major target for C3G. These findings demonstrate that the dietary anthocyanin C3G activates PPARs, a master regulators of energy metabolism. C3G is an agonistic ligand of PPARs and stimulates fuel preference to fat., Jia, Wu, Kim et al. show that cyanidin-3-O-glucoside (C3G), a major dietary anthocyanin, functions as a ligand for PPARalpha to regulate energy metabolism and insulin sensitivity in mouse models of obesity and diabetes. This study suggests that C3G slows down the metabolism of glucose, making it a promising therapeutic agent.

Cells harbor two systems for fatty acid synthesis, one in the cytoplasm (catalyzed by fatty acid synthase, FASN) and one in the mitochondria (mtFAS). In contrast to FASN, mtFAS is poorly characterized, especially in higher eukaryotes, with the major product(s), metabolic roles, and cellular function(s) being essentially unknown. Here we show that hypomorphic mtFAS mutant mouse skeletal myoblast cell lines display a severe loss of electron transport chain (ETC) complexes and exhibit compensatory metabolic activities including reductive carboxylation. This effect on ETC complexes appears to be independent of protein lipoylation, the best characterized function of mtFAS, as mutants lacking lipoylation have an intact ETC. Finally, mtFAS impairment blocks the differentiation of skeletal myoblasts in vitro. Together, these data suggest that ETC activity in mammals is profoundly controlled by mtFAS function, thereby connecting anabolic fatty acid synthesis with the oxidation of carbon fuels., eLife digest In human, plant and other eukaryotic cells, fats are an important source of energy and also play many other roles including waterproofing, thermal insulation and energy storage. Eukaryotic cells have two systems that make the building blocks of fats (known as fatty acids) and one of these systems, called the mtFAS pathway, operates in small compartments known as mitochondria. This pathway only has one known product, a small fat molecule called lipoic acid, which mitochondria attach to several enzymes to allow them to work properly. The main role of mitochondria is to break down fats and other molecules to release chemical energy that powers many processes in cells. They achieve this using large groups of proteins known as ETC complexes. To build these complexes, families of proteins known as ETC assembly factors carefully coordinate the assembly of many proteins and small molecules into specific structures. However, it remains unclear precisely how this process works. Here, Nowinski et al. used a gene editing technique to mutate the genes encoding three enzymes in the mtFAS pathway in mammalian cells. The experiments found that the mutant cells had fewer ETC complexes and seemed to be less able to break down fats and other molecules than ‘normal’ cells. Furthermore, a family of ETC assembly factors were less stable in the mutant cells. These findings suggest that the mtFAS pathway controls how mitochondria assemble ETC complexes. Further experiments indicated that lipoic acid is not involved in the assembly of ETC complexes and that the mtFAS pathway produces another, as yet unidentified, product that regulates this process, instead. MEPAN syndrome is a rare neurological disorder that leads to progressive loss of control of movement, slurred speech and impaired vision in children. Patients with this syndrome have genetic mutations affecting components of the mtFAS pathway, therefore, a better understanding of how the pathway works may help researchers develop new treatments in the future. More broadly, these findings will have important ramifications for many other situations in which the activity of ETC complexes in mitochondria is modified.

Cells harbor two systems for fatty acid synthesis, one in the cytoplasm (catalyzed by fatty acid synthase, FASN) and one in the mitochondria (mtFAS). In contrast to FASN, mtFAS is poorly characterized, especially in higher eukaryotes, with the major product(s), metabolic roles, and cellular function(s) being essentially unknown. Here we show that hypomorphic mtFAS mutants display a severe loss of electron transport chain (ETC) complexes and exhibit compensatory metabolic activities including reductive carboxylation. This effect on ETC complexes appears to be independent of protein lipoylation, the best characterized function of mtFAS, as mutants lacking lipoylation have an intact ETC. Finally, mtFAS impairment blocks the differentiation of skeletal myoblasts in vitro. Together, these data suggest that ETC activity in mammals is profoundly controlled by mtFAS function, thereby connecting anabolic fatty acid synthesis with the oxidation of carbon fuels.

Activation of brown adipose tissue (BAT) has been proposed as a promising target against obesity due to its increased capacity for thermogenesis. In this study, we explored the effect of [Formula: see text]-Lapachone ([Formula: see text]L), a compound obtained from the bark of the lapacho tree, against obesity. In vivo administration of [Formula: see text]L into either high fat diet (HFD)-induced obese C57BL6 mice and genetically obese Lepr[Formula: see text] mice prevented body weight gain, which was associated with tissue weight loss of white adipose tissue (WAT). In addition, [Formula: see text]L elevated thermogenic proteins including uncoupling protein 1 (UCP1) and mitochondrial count in BAT and human adipose tissue-derived mesenchymal stem cells (hAMSCs). [Formula: see text]L also induced AMP-activated protein kinase (AMPK) phosphorylation, subsequent upregulation of acetyl-CoA carboxylase (ACC) and UCP1, and these effects were diminished by AMPK inhibitor compound C, suggesting that AMPK underlies the effects of [Formula: see text]L. Mitogen-activated protein kinase pathways participated in the thermogenesis of [Formula: see text]L, specifically p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2) were activated by [Formula: see text]L treatment in hAMSCs. Additionally, inhibitors of p38/JNK/ERK1/2 abrogated the activity of [Formula: see text]L. Taken together, [Formula: see text]L exerts anti-obese effects by inducing thermogenesis mediated by AMPK signaling pathway, suggesting that [Formula: see text]L may have a potential therapeutic implication of obesity. Taken together, [Formula: see text]L exerts anti-obese effects by not only inducing thermogenesis on brown adipocytes but also inducing the browning of white adipocytes. The anti-obese effect of [Formula: see text]L is mediated by AMPK signaling pathway, suggesting that [Formula: see text]L may have potential therapeutic implication of obesity.

Energy expenditure is a target gaining recent interest for obesity treatment. The antiobesity effect of vanillic acid (VA), a well-known flavoring agent, was investigated in vivo and in vitro. High-fat diet (HFD)-induced obese mice and genetically obese db/db mice showed significantly decreased body weights after VA administration. Two major adipogenic markers, peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), were reduced while the key factor of energy metabolism, AMPKα, was increased in the white adipose tissue and liver tissue of VA-treated mice. Furthermore, VA inhibited lipid accumulation and reduced hepatotoxic/inflammatory markers in liver tissues of mice and HepG2 hepatocytes. VA treatment also decreased differentiation of 3T3-L1 adipocytes by regulating adipogenic factors including PPARγ and C/EBPα. AMPKα small interfering RNA was used to examine whether AMPK was associated with the actions of VA. In AMPKα-nulled 3T3-L1 cells, the inhibitory action of VA on PPARγ and C/EBPα was attenuated. Furthermore, in brown adipose tissues of mice and primary cultured brown adipocytes, VA increased mitochondria- and thermogenesis-related factors such as uncoupling protein 1 and PPARγ-coactivator 1-α. Taken together, our results suggest that VA has potential as an AMPKα- and thermogenesis-activating antiobesity agent.-Jung, Y., Park, J., Kim, H.-L., Sim, J.-E., Youn, D.-H., Kang, J., Lim, S., Jeong, M.-Y., Yang, W. M., Lee, S.-G., Ahn, K. S., Um, J.-Y. Vanillic acid attenuates obesity via activation of the AMPK pathway and thermogenic factors in vivo and in vitro.

Benign prostatic hyperplasia (BPH) is a common disease in the male population, especially in elderly men. Vanillic acid (VA), a dihydroxybenzoic derivative used as a flavoring agent, is reported to have an anti-inflammatory effect. However, there are no reports of its effects on BPH to date. BPH was induced with a pre-4-week treatment of daily subcutaneous injections of testosterone propionate (TP), and the normal control group received injections of ethanol with corn oil instead. Six weeks of further injections were done with (a) ethanol with corn oil, (b) TP only, (c) TP + finasteride, and (d) TP + VA. Finasteride was used as a positive control group. VA had protective effects on the TP-induced BPH. In the VA treatment group, the prostate weight was reduced, and the histological changes including the epithelial thickness and lumen area were restored like in the normal control group. Furthermore, in the VA treatment group, two proliferation related factors, high molecular weight cytokeratin 34βE12 and α smooth muscle actin, were significantly down-regulated compared to the TP-induced BPH group. The expressions of dihydrotestosterone and 5α-reductase, the most crucial factors in BPH development, were suppressed by VA treatment. Expressions of the androgen receptor, estrogen receptor α and steroid receptor coactivator 1 were also significantly inhibited by VA compared to the TP-induced BPH group. In addition, we established an in vitro model for BPH by treating a normal human prostatic epithelial cell line RWPE-1 with TP. VA successfully inhibited proliferation and BPH-related factors in a concentration-dependent manner in this newly established model. These results suggest a new and potential pharmaceutical therapy of VA in the treatment of BPH.

Objective The mismatch negativity (MMN) event-related potential is an index of the pre-attentive stage of neural auditory information processing and an electrophysiological signal indicative of the integrity of auditory information processing with regard to the attention deficit symptom of attention deficit hyperactivity disorder (ADHD). We investigated the association between the MMN amplitude and latency in frontal brain regions and symptom severity in children with ADHD and subclinical ADHD symptoms. Methods This study included 29 children: 16 (10 boys; mean age, 13.06 ± 3.67 years) with ADHD (ADHD group) and 13 (eight boys; mean age, 13.40 ± 3.31 years) with sub-clinical ADHD symptoms (subclinical ADHD group). We performed the following assessments: Korean ADHD rating scale-IV (K-ARS-IV), children depression inventory, state/trait anxiety inventory for children, and MMN (measured at Fz, FCz, Cz, and CPz). Results There were no sex or mean age differences between the groups (χ2 = -0.01, p = 0.958; Z = -1.88, p = 0.060, respectively). The ADHD group had a significantly higher mean K-ARS-IV score (26.13 ± 9.56 vs. 17.15 ± 11.73, Z = -2.11, p = 0.035). Significant differences were found according to symptom severity in the MMN amplitude at FCz (Z = -2.11, p = 0.035) and MMN latency at Fz and FCz (Z = -2.48, p = 0.013; Z = -2.57, p = 0.010). The K-ARS-IV, K-ARS inattention subscale, and K-ARS hyperactivity-impulsivity subscale scores in the ADHD group correlated significantly with the MMN amplitude at Cz and CPz. Conclusion This study found differences in the MMN amplitude and latency according to the severity of ADHD symptoms and identified MMN as a potential adjunct to the diagnosis of ADHD.

// Dong-Hyun Youn 1, * , Jinbong Park 1, * , Hye-Lin Kim 2 , Yunu Jung 1 , JongWook Kang 1 , Mi-Young Jeong 2 , Gautam Sethi 3 , Kwang Seok Ahn 2 , Jae-Young Um 1, 2 1 Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Dongdaemun-Gu, Seoul, 02447, Republic of Korea 2 College of Korean Medicine, Basic Research Laboratory for Comorbidity Regulation, Kyung Hee University, Dongdaemun-Gu, Seoul, 02447, Republic of Korea 3 Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, Singapore * These authors have contributed equally to this work Correspondence to: Jae-Young Um, email: jyum@khu.ac.kr Keywords: benign prostatic hyperplasia-BPH, chrysophanic acid, prostate specific antigen, 5α-reductase, extracellular signal-regulated kinase Received: April 28, 2016 Accepted: October 31, 2016 Published: November 17, 2016 ABSTRACT Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases in male population, of which incidence increases gradually with age. In this study, we investigated the effect of chrysophanic acid (CA) on BPH. BPH was induced by a 4-week injection of testosterone propionate (TP). Four weeks of further injection with vehicle, TP, TP + CA, TP + finasteride was carried on. In the CA treatment group, the prostate weight was reduced and the TP-induced histological changes were restored as the normal control group. CA treatment suppressed the TP-elevated prostate specific antigen (PSA) expression. In addition, 5α-reductase, a crucial factor in BPH development, was suppressed to the normal level close to the control group by CA treatment. The elevated expressions of androgen receptor (AR), estrogen receptor α and steroid receptor coactivator 1 by TP administration were also inhibited in the CA group when compared to the TP-induced BPH group. Then we evaluated the changes in three major factors of the mitogen-activated protein kinase chain during prostatic hyperplasia; extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38). While ERK was elevated in the process of BPH, JNK and p38 was not changed. This up-regulated ERK was also reduced as normal by CA treatment. Further in vitro studies with RWPE-1 cells confirmed TP-induced proliferation and elevated AR, PSA and p-ERK were all reduced by CA treatment. Overall, these results suggest a potential pharmaceutical feature of CA in the treatment of BPH.

Cox23 is a known conserved assembly factor for cytochrome c oxidase, although its role in cytochrome c oxidase (CcO) biogenesis remains unresolved. To gain additional insights into its role, we isolated spontaneous suppressors of the respiratory growth defect in cox23∆ yeast cells. We recovered independent colonies that propagated on glycerol/lactate medium for cox23∆ cells at 37°C. We mapped these mutations to the mitochondrial genome and specifically to COX1 yielding an I101F substitution. The I101F Cox1 allele is a gain-of-function mutation enabling yeast to respire in the absence of Cox23. CcO subunit steady-state levels were restored with the I101F Cox1 suppressor mutation and oxygen consumption and CcO activity were likewise restored. Cells harboring the mitochondrial genome encoding I101F Cox1 were used to delete genes for other CcO assembly factors to test the specificity of the Cox1 mutation as a suppressor of cox23∆ cells. The Cox1 mutant allele fails to support respiratory growth in yeast lacking Cox17, Cox19, Coa1, Coa2, Cox14 or Shy1, demonstrating its specific suppressor activity for cox23∆ cells.

Although arctigenin (ARC) has been reported to have some pharmacological effects such as anti-inflammation, anti-cancer, and antioxidant, there have been no reports on the anti-obesity effect of ARC. The aim of this study is to investigate whether ARC has an anti-obesity effect and mediates the AMP-activated protein kinase (AMPK) pathway. We investigated the anti-adipogenic effect of ARC using 3T3-L1 pre-adipocytes and human adipose tissue-derived mesenchymal stem cells (hAMSCs). In high-fat diet (HFD)-induced obese mice, whether ARC can inhibit weight gain was investigated. We found that ARC reduced weight gain, fat pad weight, and triglycerides in HFD-induced obese mice. ARC also inhibited the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) in in vitro and in vivo. Furthermore, ARC induced the AMPK activation resulting in down-modulation of adipogenesis-related factors including PPARγ, C/EBPα, fatty acid synthase, adipocyte fatty acid-binding protein, and lipoprotein lipase. This study demonstrates that ARC can reduce key adipogenic factors by activating the AMPK in vitro and in vivo and suggests a therapeutic implication of ARC for obesity treatment. J. Cell. Biochem. 117: 2067-2077, 2016. © 2016 Wiley Periodicals, Inc.

Insulin and insulin-like peptides play a pivotal role in a wide variety of cellular and physiological events, including energy storage, proliferation, aging, and differentiation. Variants of insulin and insulin-like peptides may therefore be probes for studying the insulin signaling pathway and therapeutic candidates for treating metabolic diseases. Here, we report a method for genetically displaying single-chain insulin-like peptides on the surface of Saccharomyces cerevisiae strain DY1632. Using a previously reported single-chain insulin analogue, SCI-57, as a model, we demonstrate that nearly 70% of yeast binds to insulin receptor (IR), suggesting that SCI-57 is folded correctly and maintains its IR binding property. Furthermore, the interaction between displayed SCI-57 and IR can be weakened using increasing concentrations of native insulin as a soluble competitor, suggesting that the interaction is insulin-dependent. We further applied this methodology to three other single-chain insulin analogues with various lengths and confirmed their interactions with IR. In summary, we successfully displayed a number of insulin-like peptides on a yeast surface and demonstrated insulin-dependent interactions with IR. This method may, therefore, be used for construction of libraries of insulin-like peptides to select for chemical probes or therapeutic molecules.

Arctii Fructus is traditionally used in oriental pharmacies as an anti-inflammatory medicine. Although several studies have shown its anti-inflammatory effects, there have been no reports on its use in obesity related studies. In this study, the anti-obesity effect of Arctii Fructus was investigated in high-fat diet (HFD)-induced obese mice, and the effect was confirmed in white and primary cultured brown adipocytes. Arctii Fructus inhibited weight gain and reduced the mass of white adipose tissue in HFD-induced obese mice. Serum levels of triglyceride and LDL-cholesterol were reduced, and HDL-cholesterol was increased in the Arctii Fructus treated group. In 3T3-L1 cells, a water extract (WAF) and 70% EtOH extract (EtAF) of Arctii Fructus significantly inhibited adipogenesis and suppressed the expression of proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha. In particular, EtAF activated the phosphorylation of AMP-activated protein kinase. On the other hand, uncoupling protein 1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha, known as brown adipocytes specific genes, were increased in primary cultured brown adipocytes by WAF and EtAF. This study shows that Arctii Fructus prevents the development of obesity through the inhibition of white adipocyte differentiation and activation of brown adipocyte differentiation which suggests that Arctii Fructus could be an effective therapeutic for treating or preventing obesity.

Objectives: The objective of the present study was to assess the factors that influence the health of workers, especially nurses, and to propose methods for health management. Methods: A total of 246 nurses were surveyed to ascertain the health status score, Sasang constitution diagnosis, health-related life and job factors, psychosocial stress, and job stress. Depending on their health status score, the subjects were categorized into unhealthy, intermediate, or healthy groups, and each factor was compared with the stress score of the groups. Further, each Sasang constitution factor was also compared with the stress scores. Results: Analysis based on the health status scores indicated that the patients in the intermediate group were older and had longer tenure than those in the unhealthy or healthy groups. The healthy group had higher number of married individuals, and they were subjectively assessed as healthy. Patients in this group were more satisfied with their work than those in the unhealthy group. Analysis of the Sasang constitution showed that a lower percentage of individuals with a Soeumin constitution were married, and most considered themselves to be unhealthy during the subjective health assessment. Conclusions: The findings of this survey revealed that in order to maintain health, efforts should be made to improve the work environment, achieve health confidence, and practice health behavior while considering one’s own body, mental state, and constitution.

This study was designed to evaluate the effects of Platycodon grandiflorum A. DC. ethanolic extract (PG) on obesity in brown/white preadipocytes. The effect of PG on the differentiation and mitochondrial biogenesis of brown adipocytes is still not examined. An in vivo study showed that PG induced weight loss in mice with high-fat-diet-induced obesity. PG successfully suppressed the differentiation of 3T3-L1 cells by down-regulating cellular induction of the peroxisome proliferators activated receptor γ (PPARγ), CCAAT enhancer binding protein α (C/EBPα), lipin-1, and adiponectin but increasing expression of silent mating type information regulation 2 homologue 1 (SIRT1) and the phosphorylation of AMP-activated protein kinase α (AMPKα). The effect of PG on the adipogenic factors was compared with that of its bioactive compound platycodin D. In addition, PG increased expressions of mitochondria-related genes, including uncoupling protein 1 (UCP1), peroxisome proliferator activated receptor-coactivator 1 α (PGC1α), PR domain containing 16 (PRDM16), SIRT3, nuclear respiratory factor (NRF), and cytochrome C (CytC) in primary brown adipocytes. These results indicate that PG stimulates the differentiation of brown adipocytes through modulation of mitochondria-related genes and could offer clinical benefits as a supplement to treat obesity.

Cox23 is a known conserved assembly factor for cytochrome c oxidase, although its role in cytochrome c oxidase (CcO) biogenesis remains unresolved. To gain additional insights into its role, we isolated spontaneous suppressors of the respiratory growth defect in cox23∆ yeast cells. We recovered independent colonies that propagated on glycerol/lactate medium for cox23∆ cells at 37°C. We mapped these mutations to the mitochondrial genome and specifically to COX1 yielding an I101F substitution. The I101F Cox1 allele is a gain-of-function mutation enabling yeast to respire in the absence of Cox23. CcO subunit steady-state levels were restored with the I101F Cox1 suppressor mutation and oxygen consumption and CcO activity were likewise restored. Cells harboring the mitochondrial genome encoding I101F Cox1 were used to delete genes for other CcO assembly factors to test the specificity of the Cox1 mutation as a suppressor of cox23∆ cells. The Cox1 mutant allele fails to support respiratory growth in yeast lacking Cox17, Cox19, Coa1, Coa2, Cox14 or Shy1, demonstrating its specific suppressor activity for cox23∆ cells.

Mitochondria and lysosomes are functionally linked, and their interdependent decline is a hallmark of aging and disease. Despite the long-standing connection between these organelles, the function(s) of lysosomes required to sustain mitochondrial health remains unclear. Here, working in yeast, we show that the lysosome-like vacuole maintains mitochondrial respiration by spatially compartmentalizing amino acids. Defects in vacuole function result in a breakdown in intracellular amino acid homeostasis, which drives age-related mitochondrial decline. Among amino acids, we find that cysteine is most toxic for mitochondria and show that elevated non-vacuolar cysteine impairs mitochondrial respiration by limiting intracellular iron availability through an oxidant-based mechanism. Cysteine depletion or iron supplementation restores mitochondrial health in vacuole-impaired cells and prevents mitochondrial decline during aging. These results demonstrate that cysteine toxicity is a major driver of age-related mitochondrial deterioration and identify vacuolar amino acid compartmentation as a cellular strategy to minimize amino acid toxicity.

Hovenia dulcis Thunb. is well known as a treatment for liver disease. Several studies have demonstrated that extracts of Hovenia dulcis Thunb. or its purified compounds can serve as detoxifying agents for alcohol poisoning. However, its anti-obesity effect has not been reported thus far. In this study, the anti-obesity effect of water extracts from the fruits or stems of Hovenia dulcis Thunb. was examined in 3T3-L1 preadipocytes. The cellular lipid contents in 3T3-L1 adipocytes were assessed by Oil Red O staining. Fruits of Hovenia dulcis Thunb. (FHD) significantly inhibit lipid accumulation during adipogenesis in a dose-dependent manner, but not stems of Hovenia dulcis Thunb. FHD (100 μg ml(-1)) significantly down-regulates the expression of the peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein-α, adipocyte fatty acid-binding protein 2, adiponectin, and resistin, and the inhibition rates were 29.33%, 54.36%, 34.5%, 55.69%, and 60.39%, respectively. In addition, FHD (100 μg ml(-1)) also up-regulates the phosphorylation of AMP-activated protein kinase (AMPK)-α, liver kinase B1 as a major AMPK kinase, and the downstream substrate acetyl-CoA carboxylase, and the inhibition rates were 43.52%, 38.25%, and 20.39%, respectively. These results indicate that FHD has a significant anti-obesity effect through the modulation of the AMPK pathway, suggesting that FHD has a potential benefit in preventing obesity.

To investigate the anti-obesity effect of Rubi Fructus (RF) extract using brown adipose tissue (BAT) and primary brown preadipocytes in vivo and in vitro.Male C57BL/6 J mice (n=5 per group) were fed a high-fat diet (HFD) for 10 weeks with or without RF. Brown preadipocytes from the interscapular BAT of mice (age, post-natal days 1-3) were cultured with differentiation media (DM) including isobutylmethylxanthine, dexamethasone, T3, indomethacin and insulin with or without RF.In HFD-induced obese C57BL/6 J mice, long-term RF treatment significantly reduced weight gain as well as the weights of the white adipose tissue, liver and spleen. Serum levels of total cholesterol and low-density lipoprotein cholesterol were also reduced in the HFD group which received RF treatment. Furthermore, RF induced thermogenic-, adipogenic- and mitochondria-related gene expressions in BAT. In primary brown adipocytes, RF effectively stimulated the expressions of thermogenic- and mitochondria-related genes. In addition, to examine whether LIPIN1, a regulator of adipocyte differentiation, is regulated by RF, Lipin1 small interfering RNA (siRNA) and RF were pretreated in primary brown adipocytes. Pretreatment with Lipin1 siRNA and RF downregulated the DM-induced expression levels of thermogenic- and mitochondria-related genes. Moreover, RF markedly upregulated AMP-activated protein kinase. Our study shows that RF is capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes.This study demonstrates that RF prevents the development of obesity in mice fed with a HFD and that it is also capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes, which suggests that RF has potential as a therapeutic application for the treatment or prevention of obesity.

Saengmaeksan (SMS) is a Korean herbal prescription consisting of three different herbal drugs: Liriopis Tuber (tuber of Liriope platyphylla, Liliaceae), Ginseng Radix (root of Panax ginseng) and Schisandrae Fructus (fruit of Schisandra chinensis). SMS is commonly used in Korea to treat various diseases that involve the respiratory and cardiovascular systems. However, to date, the mechanism underlying the anti-inflammatory effects of SMS is not clearly understood. In this study, we attempt to determine the effects of SMS on lipopolysaccharide (LPS)-induced inflammatory responses in mouse peritoneal macrophages.Cell viability was measured by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and nitric oxide (NO) levels were measured by using Griess reagent. The tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels secreted by the cells were measured using a modified enzyme-linked immunosorbent assay. Expression of cyclooxygenase (COX)-2 and nuclear factor-kappa B (NF-κB), respectively was investigated using a western blot analysis. A caspase colorimetric assay kit was used to assay enzymatic caspase-1 activity.The findings of this study showed that SMS reduced TNF-α and IL-6 production induced by LPS. During the inflammatory process, COX-2 and NO levels were increased in mouse peritoneal macrophages, but SMS decreased the enhanced levels of COX-2 and the production of NO. In addition, SMS suppressed the activation of NF-κB and receptor interacting protein-2/caspase-1.Our results provide novel insights into the pharmacological actions of SMS, a molecule that can potentially be exploited in the treatment of inflammatory diseases.