Mitochondrial protease ClpP supplementation ameliorates diet-induced NASH in mice.

BACKGROUND & AIMS: Mitochondrial dysfunction is considered a pathogenic linker in the development of non-alcoholic steatohepatitis (NASH). Inappropriate mitochondrial protein-quality control, possibly induced by insufficiency of the mitochondrial matrix caseinolytic protease P (ClpP), can potentially cause mitochondrial dysfunction. Herein, we aimed to investigate hepatic ClpP levels in a diet-induced model of NASH and determine whether supplementation of ClpP can ameliorate diet-induced NASH. METHODS: NASH was induced by a high-fat/high-fructose (HF/HFr) diet in C57BL/6J mice. Stress/inflammatory signals were induced in mouse primary hepatocytes (MPHs) by treatment with palmitate/oleate (PA/OA). ClpP levels in hepatocytes were reduced using the RNAi-mediated gene knockdown technique but increased through the viral transduction of ClpP. ClpP activation was induced by administering a chemical activator of ClpP. RESULTS: Hepatic ClpP protein levels in C57BL/6J mice fed a HF/HFr diet were lower than the levels in those fed a normal chow diet. PA/OA treatment also decreased the ClpP protein levels in MPHs. Overexpression or activation of ClpP reversed PA/OA-induced mitochondrial dysfunction and stress/inflammatory signal activation in MPHs, whereas ClpP knockdown induced mitochondrial dysfunction and stress/inflammatory signals in these cells. On the other hand, ClpP overexpression or activation improved HF/HFr-induced NASH characteristics such as hepatic steatosis, inflammation, fibrosis, and injury in the C57BL/6J mice, whereas ClpP knockdown further augmented steatohepatitis in mice fed a HF/HFr diet. CONCLUSIONS: Reduced ClpP expression and subsequent mitochondrial dysfunction are key to the development of diet-induced NASH. ClpP supplementation through viral transduction or chemical activation represents a potential therapeutic strategy to prevent diet-induced NASH. LAY SUMMARY: Western diets, containing high fat and high fructose, often induce non-alcoholic steatohepatitis (NASH). Mitochondrial dysfunction is considered pathogenically linked to diet-induced NASH. We observed that the mitochondrial protease ClpP decreased in the livers of mice fed a western diet and supplementation of ClpP ameliorated western diet-induced NASH.

Acupuncture combined with multidisciplinary care for recovery after traumatic multiple rib fractures: a prospective feasibility cohort study.

INTRODUCTION: Acute pain significantly delays early physiological recovery and results in chronic functional disability in patients with traumatic multiple rib fractures (MRFs). This prospective cohort study aimed to investigate the feasibility of acupuncture combined with multidisciplinary care during recovery in patients with traumatic MRFs. METHODS: Twenty patients with traumatic MRFs who were admitted to a regional trauma centre in South Korea were enrolled. A combination of acupuncture and multidisciplinary inpatient ward management was provided at the trauma ward. Patients were permitted to continue acupuncture treatments at outpatient clinics for 3 months after the traumatic events. Clinical outcomes, including pain, acute physiological recovery, quality of life, patient satisfaction with the care provided, respiratory function and use of opioids, were evaluated up to 6 months after trauma. RESULTS: Seventeen (85%) participants completed the 6-month follow-up. One patient withdrew consent during admission due to discomfort after three sessions of acupuncture. The proportion of patients with above-moderate level of pain decreased from 95% at baseline to 41% at 6 months. Quality of life appeared to deteriorate consistently throughout the study period. Around 80% of respondents expressed satisfaction with the acupuncture treatments and stated that they found acupuncture to be acceptable. Over 94% of respondents reported slight or considerable improvement. CONCLUSION: The provision of acupuncture combined with multidisciplinary care for recovery in patients with traumatic MRFs was feasible in a regional trauma centre in South Korea. Randomised trials are needed to investigate the role of acupuncture combined with multidisciplinary care in the future. TRIAL REGISTRATION NUMBER: KCT0002911 (Clinical Research Information Service).

The Yin-Yang personality from biopsychological perspective using revised Sasang Personality Questionnaire.

BACKGROUND: The biopsychological, pathological and physical characteristics of Yin-Yang (Eum-Yang in Korean) have been suggested using Sasang Personality Questionnaire (SPQ), however, the revision of SPQ is required for escalating its clinical use and multidimensional study on Yin-Yang. METHODS: 274 university students were recruited to complete the SPQ, candidate items of revised SPQ (rSPQ) along with the Temperament and Character Inventory (TCI). After selecting rSPQ items using Item Analysis and Explorative Factor Analysis, its psychometric property was examined using Confirmatory Factor Analysis, Pearson's correlation and t-test. The biopsychological features of Yin and Yang personality groups based on rSPQ total score were illustrated with the TCI using ANOVA and Profile Analysis. RESULTS: The behavior, cognition and emotion subscales of 15-item rSPQ had robust psychometric construct and showed distinctive psychological characteristics of Yin-Yang. The rSPQ-total score was correlated positively with SPQ-total (r = 0.644, p < 0.01) and TCI Novelty-Seeking (r = 0.398, p < 0.01), and negatively with TCI Harm-Avoidance (r = -0.364, p < 0.01). And, the Yin personality group (34.45 ±â€¯10.36 and 46.82 ±â€¯12.27) has significantly different scores in Novelty-Seeking and Harm-Avoidance compared to Yang personality group (43.2 ±â€¯9.1 and 36.53 ±â€¯10.78). Yin and Yang personality groups showed distinctive TCI subscale profiles as shown in previous studies. CONCLUSION: The current study showed the organized subscale structure and clinical validity of rSPQ for Yin-Yang personality, and it would provide foundation for East-West cross-cultural psychology and integrative medicine.

Suppressive effects of S100A8 and S100A9 on neutrophil apoptosis by cytokine release of human bronchial epithelial cells in asthma.

S100A8 and S100A9 are important proteins in the pathogenesis of allergy. Asthma is an allergic lung disease, characterized by bronchial inflammation due to leukocytes, bronchoconstriction, and allergen-specific IgE. In this study, we examined the role of S100A8 and S100A9 in the interaction of cytokine release from bronchial epithelial cells, with constitutive apoptosis of neutrophils. S100A8 and S100A9 induce increased secretion of neutrophil survival cytokines such as MCP-1, IL-6 and IL-8. This secretion is suppressed by TLR4 inhibitor), LY294002, AKT inhibitor, PD98059, SB202190, SP600125, and BAY-11-7085. S100A8 and S100A9 also induce the phosphorylation of AKT, ERK, p38 MAPK and JNK, and activation of NF-κB, which were blocked after exposure to TLR4i, LY294002, AKTi, PD98059, SB202190 or SP600125. Furthermore, supernatants collected from bronchial epithelial cells after S100A8 and S100A9 stimulation suppressed the apoptosis of normal and asthmatic neutrophils. These inhibitory mechanisms are involved in suppression of caspase 9 and caspase 3 activation, and BAX expression. The degradation of MCL-1 and BCL-2 was also blocked by S100A8 and S100A9 stimulation. Essentially, neutrophil apoptosis was blocked by co-culture of normal and asthmatic neutrophils with BEAS-2B cells in the presence of S100A8 and S100A9. These findings will enable elucidation of asthma pathogenesis.

Validity of Yin-Yang temperament in Sasang Personality Questionnaire.

BACKGROUND: The Yin-Yang is a pivotal concept of traditional East-Asian medicine, however the stability of Yin-Yang temperament in Sasang Personality Questionnaire (SPQ) over time has not been extensively studied. The purpose of this study was to examine the test-retest validity of SPQ with a large number of participants. METHODS: SPQ test was conducted two times with three months interval in 247 Korean university students. The structural validity of first SPQ data was examined with Factor analysis and Cronbach's alpha, and the correlation between first and second measure of SPQ was attested with Pearson's correlation. Yang, Uncertain and Yin temperament groups were determined with SPQ total scores, and agreement of temperament group clustering between first and second measures were analyzed with Cohen's Kappa. RESULTS: Three subscales of SPQ explained 55.25% of total variances, and internal consistency of SPQ total score was 0.772. The correlation coefficient between first and second measures of SPQ were 0.851 and 0.888 in male and female, respectively, and the agreement of first and second Yin-Yang temperament group clustering as Cohen's Kappa was 0.536 for male and 0.637 for female. CONCLUSION: The repeatability of SPQ measuring Yin-Yang temperament at three months of interval was found to be satisfactory. The SPQ would be a reliable clinical measure for the biopsychological studies of traditional East-Asian medicine.

Regulation of the pacemaker activities in cultured interstitial cells of Cajal by Citrus unshiu peel extracts.

The Citrus unshiu peel has been widely used for the treatment of gastrointestinal (GI) disorders in Eastern traditional medicine. The present study aimed to investigate the effects of Citrus unshiu peel extract (CPE) on the pacemaker activity of the GI tract in cultured interstitial cells of Cajal (ICCs) derived from the mouse small intestine. The whole­cell patch­clamp configuration was used to record pacemaker potentials. In current clamp mode, exposure to CPE caused membrane pacemaker depolarization in a concentration­dependent manner. In the presence of the muscarinic M2 receptor antagonist, methoctramine, CPE induced membrane pacemaker depolarization, whereas treatment with the muscarinic M3 receptor antagonist, 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide, inhibited CPE­induced responses. When the pipette solution contained guanosine 5'-(ß-thio) diphosphate trilithium salt (1 mM), CPE marginally induced membrane pacemaker depolarization. In addition, CPE­induced membrane pacemaker depolarization was inhibited following exposure to the active phospholipase C (PLC) inhibitor U­73122, but not the inactive PLC inhibitor U­73343. In the presence of a p42/p44 mitogen­activated protein kinase (MAPK) inhibitor (PD98059), a p38 MAPK inhibitor (SB203580) or a c­jun NH2­terminal kinase (JNK) II inhibitor, CPE failed to induce membrane pacemaker depolarization. These results suggest that CPE may affect GI motility through modulating ICC pacemaker activity by activating the muscarinic M3 receptor and inducing the G­protein dependent PLC and MAPK signaling pathways.

Biopsychological structure of Yin-Yang using Cloninger's Temperament model and Carver and White's BIS/BAS scale.

Introduction. The purpose of this study was to examine the psychological structure of Yin-Yang based on the Sasang Personality Questionnaire (SPQ) in relation to Carver and White's Behavior Inhibition/Behavior Activation System (BIS/BAS) Scale and Cloninger's temperament model of the West. Methods. A total of 188 university students were classified as high (30%), middle (40%), and low (30%) groups based on their SPQ score and their differences in Cloninger's temperaments and BIS/BAS subscales were analyzed using analysis of covariance after controlling the sex. Correlation among SPQ, Cloninger's four temperaments and BIS/BAS subscales was also examined. Results. Significant differences in BAS (F = 11.703, p < .001), Novelty-Seeking (F = 4.945, p < .01), and Harm-Avoidance (F = 10.912, p < .001) were observed between high and low SPQ score groups after controlling for sex. The SPQ showed significant correlation with BAS (r = 0.303), Novelty-Seeking (r = 0.225), and Harm-Avoidance (r = - 0.273). However, BIS showed no significant differences between SPQ groups, and did not show correlation with the SPQ. Discussion. The current study demonstrated that Yin-Yang has similarities with and disparities from the Western tradition and may be examined with objective instruments. We showed that the emotionality of the East which is defined as mobility of emotion, not emotional instability as traditionally defined in Western theories, is pivotal for understanding the nature of emotion in the East. Suggestions are made for cross-cultural psychobiological study of the East and West.

Validation of the Sasang Personality Questionnaire in high school students.

BACKGROUND: The Sasang Personality Questionnaire (SPQ) is an objective measure of Yin-Yang temperament of Sasang typology with proven clinical and structural validity; however, it has not been validated in people younger than 20 years. The purpose of this study was to examine the biopsychological structure of the SPQ in high school students. METHODS: A total of 670 Korean high school students (365 boys and 305 girls) completed the SPQ, Junior version of Temperament and Character Inventory (JTCI), and weight and height measures. The correlation between the SPQ and JTCI subscales was investigated, and the differences of these subscales, body mass index, and Pondera Index between the high (30%), middle (40%), and low (30%) SPQ total score groups were examined with analysis of variance. The profile analysis was also performed to compare JTCI subscale profiles of the three SPQ total score groups. RESULTS: The SPQ total score significantly correlated positively with JTCI novelty seeking (r = 0.548 and r = 0.540) and negatively with JTCI harm avoidance (r = -0.393 and r = -0.395) in boys and girls, respectively. The JTCI novelty-seeking score is significantly higher in the high SPQ total score group (24.12 ± 5.27 and 24.15 ± 5.17 for boys and girls, respectively) than in the low SPQ total score group (16.49 ± 5.08 and 17.24 ± 4.83, respectively), and the JTCI harm-avoidance score is significantly higher in the low SPQ total score group (25.34 ± 6.08 and 26.64 ± 5.77 for boys and girls, respectively) than in the high SPQ total score group (19.27 ± 6.62 and 19.23 ± 6.00, respectively). The JTCI subscale profiles for the three SPQ total score groups were significantly different for boys (degrees of freedom = 3.416, F = 292.16, p < 0.001) and girls (degrees of freedom = 3.4, F = 230.51, p < 0.001). There were no significant correlations or differences in body mass index and Pondera Index among the SPQ total score groups. CONCLUSION: The results showed that the biopsychological structure of the SPQ in adolescents is robust, similar to that in the adult population. The SPQ might be useful for the application of Sasang typology in pediatrics.

Production of Ginsenoside F2 by Using Lactococcus lactis with Enhanced Expression of ß-Glucosidase Gene from Paenibacillus mucilaginosus.

This study aimed to produce a pharmacologically active minor ginsenoside F2 from the major ginsenosides Rb1 and Rd by using a recombinant Lactococcus lactis strain expressing a heterologous ß-glucosidase gene. The nucleotide sequence of the gene (BglPm) was derived from Paenibacillus mucilaginosus and synthesized after codon optimization, and the two genes (unoptimized and optimized) were expressed in L. lactis NZ9000. Codon optimization resulted in reduction of unfavorable codons by 50% and a considerable increase in the expression levels (total activities) of ß-glucosidases (0.002 unit/mL, unoptimized; 0.022 unit/mL, optimized). The molecular weight of the enzyme was 52 kDa, and the purified forms of the enzymes could successfully convert Rb1 and Rd into F2. The permeabilized L. lactis expressing BglPm resulted in a high conversion yield (74%) of F2 from the ginseng extract. Utilization of this microbial cell to produce F2 may provide an alternative method to increase the health benefits of Panax ginseng.

Study on the Difference of BIS/BAS Scale between Sasang Types.

Introduction. The purpose of this study was to examine the differences in temperament between So-Yang (SY) and So-Eum (SE) Sasang types using Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scale to elucidate the biopsychological mechanism underlying the Sasang typology, a traditional Korean personalized medicine. Methods. 248 university students were categorized into three Sasang types, and series of t-tests were conducted, separately for male and female participants, to examine the difference of Behavioral Inhibition System (BIS), Behavioral Activation System (BAS), BAS-Drive (BAS-D), BAS-Fun Seeking (BAS-FS), and BAS-Reward Responsiveness (BAS-RR) scores between SY and SE Sasang types. Results. There were significant differences between Sasang types in the BIS/BAS subscales with consideration of gender. In male participants, BAS-total score of SY type (39.75 ± 4.56) was significantly (t = 2.462, p = 0.016) higher than that of SE type (36.68 ± 4.97). On the other hand, in female participants, BIS score of SY type (20.10 ± 4.01) was significantly (t = -2.097, p = 0.039) lower than that of SE type (21.83 ± 3.91). Discussion. The current study suggested relationship between Sasang typology and Behavior Inhibition and Activation Systems and showed significant differences in BIS/BAS scale between SY and SE Sasang types. Further studies on biological base of Sasang typology are needed.

Personality construct of Sasang Personality Questionnaire in an adolescent sample.

BACKGROUND: Sasang typology is a widely used personalized traditional medicine in clinical diagnosis and treatment in Korea. The aim of this study was to examine the personality construct of the Sasang Personality Questionnaire (SPQ) to replicate the previous findings in the adolescent sample. METHODS: A total of 543 high school students completed the SPQ and the Korean version of the Junior Temperament and Character Inventory (JTCI). The relationships between the subscales of JTCI and SPQ were examined using Pearson's correlation. The profile analysis and analysis of variance were used to investigate the difference among high, middle, and low SPQ total score groups. RESULTS: The SPQ and its subscales were significantly correlated with the JTCI subscales. SPQ total score was positively correlated with Novelty Seeking (r = 0.424) and negatively correlated with Harm Avoidance (r = -0.291). The high, middle, and low SPQ total score groups showed significantly different JTCI profile (flatness with Greenhouse-Geisser correction, df = 3.424, F = 443.812, p < 0.001; parallelism with Greenhouse-Geisser correction, df = 6.848, F = 18.610, p < 0.001). CONCLUSION: The validity of the SPQ construct was confirmed with adolescents. Further investigation on its personality construct would extend the clinical application of SPQ to young age groups including children.

A novel non-agonist peroxisome proliferator-activated receptor γ (PPARγ) ligand UHC1 blocks PPARγ phosphorylation by cyclin-dependent kinase 5 (CDK5) and improves insulin sensitivity.

Thiazolidinedione class of anti-diabetic drugs which are known as peroxisome proliferator-activated receptor γ (PPARγ) ligands have been used to treat metabolic disorders, but thiazolidinediones can also cause several severe side effects, including congestive heart failure, fluid retention, and weight gain. In this study, we describe a novel synthetic PPARγ ligand UNIST HYUNDAI Compound 1 (UHC1) that binds tightly to PPARγ without the classical agonism and which blocks cyclin-dependent kinase 5 (CDK5)-mediated PPARγ phosphorylation. We modified the non-agonist PPARγ ligand SR1664 chemically to improve its solubility and then developed a novel PPARγ ligand, UHC1. According to our docking simulation, UHC1 occupied the ligand-binding site of PPARγ with a higher docking score than SR1664. In addition, UHC1 more potently blocked CDK5-mediated PPARγ phosphorylation at Ser-273. Surprisingly, UHC1 treatment effectively ameliorated the inflammatory response both in vitro and in high-fat diet-fed mice. Furthermore, UHC1 treatment dramatically improved insulin sensitivity in high-fat diet-fed mice without causing fluid retention and weight gain. Taken together, compared with SR1664, UHC1 exhibited greater beneficial effects on glucose and lipid metabolism by blocking CDK5-mediated PPARγ phosphorylation, and these data indicate that UHC1 could be a novel therapeutic agent for use in type 2 diabetes and related metabolic disorders.

Biopsychological traits of Sasang typology based on Sasang personality questionnaire and body mass index.

BACKGROUND: The purpose of present study was to examine biological and psychological characteristics of people according to the Sasang typology, which is popular in Korea. We evaluated the Sasang Personality Questionnaire (SPQ) as a measure of temperament, and Body Mass Index (BMI) as a measure of the somatic properties of each Sasang type. METHODS: Subjects were 2506 (877 males, 1629 females) outpatients between the ages of 20 through 70 who requested traditional medical assessment and treatment in Korea. The structural validity of the SPQ was examined and its correlation with BMI was analyzed. The SPQ and BMI measures of each Sasang type across age and gender were presented and their differences were analyzed with Analysis of Variance. RESULTS: Confirmatory factor analysis and path analysis identified an acceptable three-factor structure of the SPQ measuring differences in individual's behavior, emotion, and cognition. SPQ scores (29.71 ± 1.00, 28.29 ± 0.19 and 26.14 ± 0.22) and BMI scores (22.92 ± 0.09, 25.56 ± 0.10 and 21.44 ± 0.10) were significantly (p < 0.001) different among So-Yang, Tae-Eum and So-Eum Sasang types, respectively. CONCLUSIONS: The results showed that the SPQ and BMI is a reliable measure for quantifying the biopsychological characteristics of each types, and useful for guiding personalized and type-specific treatment with medical herbs and acupuncture.

Short-term change of handgrip strength after trigger point injection in women with muscular pain in the upper extremities.

OBJECTIVE: To determine overall handgrip strength (HGS), we assessed the short-term change of HGS after trigger point injection (TPI) in women with muscular pain in the upper extremities by comparison with established pain scales. METHODS: The study enrolled 50 female patients (FMS with MPS group: 29 patients with combined fibromyalgia [FMS] and myofascial pain syndrome [MPS]; MPS group: 21 patients with MPS) who presented with muscular pain in the upper extremities at Konyang University Hospital. In addition, a total of 9 healthy women (control group) were prospectively enrolled in the study. We surveyed the three groups using the following established pain scales: the Fibromyalgia Impact Questionnaire (FIQ), the 36-Item Short Form Health Survey (SF-36), and the Short Form McGill Pain Questionnaire (MPQ). HGS was measured in both hands of study participants using a handgrip dynamometer. We performed TPI (0.5% lidocaine, total 10 mL, injected at the pain site of upper extremities). After 20 minutes, we remeasured the patient's HGS and MPQ score. RESULTS: ANOVA analysis was conducted among groups. Based on Tukey multiple comparison test, the majority of FIQ and SF-36 subscales, total FIQ and SF-36 scores, MPQ and HGS were significantly different between FMS with MPS and the other groups. There was no statistically significant difference between MPS and control groups. Higher HGS was positively associated with enhanced physical function, negatively associated with total FIQ and MPQ scores, and positively associated with the total SF-36 score calculated using Spearman correlation. Post-TPI MPQ decreased and HGS increased. In patient groups, a negative correlation was found between MPQ and HGS. CONCLUSION: The HGS test might potentially be a complementary tool in assessing the short-term treatment effects of women with muscular pain in the upper extremities.

Protective effect of nicotinamide on high glucose/palmitate-induced glucolipotoxicity to INS-1 beta cells is attributed to its inhibitory activity to sirtuins.

This study was initiated to determine whether the protective effect of nicotinamide (NAM) on high glucose/palmitate (HG/PA)-induced INS-1 beta cell death was due to its role as an anti-oxidant, nicotinamide dinucleotide (NAD+) precursor, or inhibitor of NAD+-consuming enzymes such as poly (ADP-ribose) polymerase (PARP) or sirtuins. All anti-oxidants tested were not protective against HG/PA-induced INS-1 cell death. Direct supplementation of NAD+ or indirect supplementation through NAD+ salvage or de novo pathway did not protect the death. Knockdown of the NAD+ salvage pathway enzymes such as nicotinamide phosphoribosyl transferase (NAMPT) or nicotinamide mononucleotide adenyltransferase (NMNAT) did not augment death. On the other hand, pharmacological inhibition or knockdown of PARP did not affect death. However, sirtinol as an inhibitor of NAD-dependant deacetylase or knockdown of SIRT3 or SIRT4 significantly reduced the HG/PA-induced death. These data suggest that protective effect of NAM on beta cell glucolipotoxicity is attributed to its inhibitory activity on sirtuins.

Development and validation of a personality assessment instrument for traditional korean medicine: sasang personality questionnaire.

Objective. Sasang typology is a traditional Korean medicine based on the biopsychosocial perspectives of Neo-Confucianism and utilizes medical herbs and acupuncture for type-specific treatment. This study was designed to develop and validate the Sasang Personality Questionnaire (SPQ) for future use in the assessment of personality based on Sasang typology. Design and Methods. We selected questionnaire items using internal consistency analysis and examined construct validity with explorative factor analysis using 245 healthy participants. Test-retest reliability as well as convergent validity were examined. Results. The 14-item SPQ showed acceptable internal consistency (Cronbach's alpha = .817) and test-retest reliability (r = .837). Three extracted subscales, SPQ-behavior, SPQ-emotionality, and SPQ-cognition, were found, explaining 55.77% of the total variance. The SPQ significantly correlated with Temperament and Character Inventory novelty seeking (r = .462), harm avoidance (r = -.390), and NEO Personality Inventory extraversion (r = .629). The SPQ score of the So-Eum (24.43 ± 4.93), Tae-Eum (27.33 ± 5.88), and So-Yang (30.90 ± 5.23) types were significantly different from each other (P < .01). Conclusion. Current results demonstrated the reliability and validity of the SPQ and its subscales that can be utilized as an objective instrument for conducting personalized medicine research incorporating the biopsychosocial perspective.

Temperament profiles of Sasang typology in a child clinical sample.

BACKGROUND: Sasang typology is a personalized traditional medicine widely used in clinical diagnosis and treatment in Korea. The aim of this study was to examine the biopsychological personality profiles of traditional Korean Sasang typology in a clinical sample of Korean children. METHODS: A total of 150 children were classified as one of three traditional Korean Sasang types (19 So-Yang, 118 Tae-Eum, and 13 So-Eum) by two clinical experts in Sasang typology. The childrens' mothers completed the Korean version of the Junior Temperament and Character Inventory (JTCI). The four temperament dimensions of JTCI were compared between the different Sasang types using analysis of variance (ANOVA) and profile analysis. RESULTS: There were no significant differences in age, gender, and parents' education levels across the Sasang types. The JTCI temperament profile for each of the child Sasang types was significantly different (profile analysis, df = 5.315, F = 2.508, p = 0.027). There were significant differences in novelty-seeking (F = 3.850, p = 0.023) and novelty-seeking subscales, but not with other temperament dimensions. CONCLUSION: These results demonstrated distinct temperament traits associated with traditional Korean Sasang types in children using an objective biopsychological personality inventory. With further investigation into the biopsychological profiles of the children, the longitudinal stability of the Sasang typology can be examined.

Analgesic and anti-inflammatory effects of ethyl acetate fraction of Polygonum cuspidatum in experimental animals.

Polygonum cuspidatum (PC) has been used for the treatment of arthritis and urinary diseases in traditional medicine. Despite recent evidence that PC has anti-oxidant, anti-tumoral, and anti-inflammatory effects, analgesic and anti-inflammatory effects of PC have not been elucidated yet in vivo. Thus, in the present study, analgesic and anti-inflammatory effects of ethyl acetate extract of PC (EAPC) were investigated in vivo for the first time. Hot plate test and tail-flick test revealed that EAPC at 200 mg/kg exerts analgesic effect (p < 0.05). In contrast, EAPC did not show significant analgesic effect in acetic acid-induced writhing test. Serotonin-induced paw edema model and Freund's complete adjuvant (FCA)-induced adjuvant arthritis model were used to examine anti-inflammatory effect of EAPC in vivo. In serotonin-induced paw edema model, EAPC suppressed swelling inflammatory response within 12 min after serotonin injection, at both 100- and 200-mg/kg dose (p < 0.05). Consistently, in FCA-induced adjuvant arthritis model, FCA at 200 mg/kg significantly suppressed FCA-induced joint swelling within 3 days (p < 0.05), whereas FCA at 100 mg/kg showed the similar result within 5 days (p < 0.05). Furthermore, EAPC effectively inhibited positive responses of c-reactive protein and rheumatoid factor compared to untreated control. Taken together, our findings suggest that EAPC can be a potent candidate for rheumatoid arthritis treatment.

Alstonia scholaris R. Br. Significantly Inhibits Retinoid-Induced Skin Irritation In Vitro and In Vivo.

Topical retinoids inhibit matrix metalloproteinases and accelerate collagen synthesis, thereby triggering antiaging effects in the skin. However, topical retinoids can cause severe skin reactions, including scaling, erythema, papules, and inflammation. The present study demonstrates that the ethanolic bark extract of Alstonia scholaris R. Br. can significantly inhibit all-trans retinoic acid-induced inflammation in human HaCat keratinocyte cells. Furthermore, two representative retinoid-induced proinflammatory cytokines, monocyte chemoattractant protein-1 and interleukin-8, were significantly suppressed by A. scholaris extract (by 82.1% and 26.3% at 100 ppm, and dose-dependently across the tested concentrations) in vitro. In a cumulative irritation patch test, A. scholaris extract decreased retinol-induced skin irritation, while strengthening the ability of retinoids to inhibit matrix metalloproteinase-1 expression, which is strongly associated with aging effects. These results suggest that A. scholaris is a promising compound that may increase the antiaging function of retinoids while reducing their ability to cause skin irritation.

Supplement of TCA cycle intermediates protects against high glucose/palmitate-induced INS-1 beta cell death.

The aim of this study is to investigate the effect of mitochondrial metabolism on high glucose/palmitate (HG/PA)-induced INS-1 beta cell death. Long-term treatment of INS-1 cells with HG/PA impaired energy-producing metabolism accompanying with depletion of TCA cycle intermediates. Whereas an inhibitor of carnitine palmitoyl transferase 1 augmented HG/PA-induced INS-1 cell death, stimulators of fatty acid oxidation protected the cells against the HG/PA-induced death. Furthermore, whereas mitochondrial pyruvate carboxylase inhibitor phenylacetic acid augmented HG/PA-induced INS-1 cell death, supplementation of TCA cycle metabolites including leucine/glutamine, methyl succinate/α-ketoisocaproic acid, dimethyl malate, and valeric acid or treatment with a glutamate dehydrogenase activator, aminobicyclo-heptane-2-carboxylic acid (BCH), significantly protected the cells against the HG/PA-induced death. In particular, the mitochondrial tricarboxylate carrier inhibitor, benzene tricarboxylate (BTA), also showed a strong protective effect on the HG/PA-induced INS-1 cell death. Knockdown of glutamate dehydrogenase or tricarboxylate carrier augmented or reduced the HG/PA-induced INS-1 cell death, respectively. Both BCH and BTA restored HG/PA-induced reduction of energy metabolism as well as depletion of TCA intermediates. These data suggest that depletion of the TCA cycle intermediate pool and impaired energy-producing metabolism may play a role in HG/PA-induced cytotoxicity to beta cells and thus, HG/PA-induced beta cell glucolipotoxicity can be protected by nutritional or pharmacological maneuver enhancing anaplerosis or reducing cataplerosis.