Dysregulation of the Wnt pathway causes various diseases including cancer, Parkinson’s disease, Alzheimer’s disease, schizophrenia, osteoporosis, obesity and chronic kidney diseases. The modulation of dysregulated Wnt pathway is absolutely necessary. In the present study, we evaluated the anti-inflammatory effect and the mechanism of action of Wnt-C59, a Wnt signaling inhibitor, in lipopolysaccharide (LPS)-stimulated epithelial cells and macrophage cells. Wnt-C59 showed a dose-dependent anti-inflammatory effect by suppressing the expression of proinflammatory cytokines including IL6, CCL2, IL1A, IL1B, and TNF in LPS-stimulated cells. The dysregulation of the Wnt/β-catenin pathway in LPS stimulated cells was suppressed by WntC59 treatment. The level of β-catenin, the executor protein of Wnt/β-catenin pathway, was elevated by LPS and suppressed by Wnt-C59. Overexpression of β-catenin rescued the suppressive effect of Wnt-C59 on proinflammatory cytokine expression and nuclear factor-kappa B (NF-κB) activity. We found that the interaction between β-catenin and NF-κB, measured by co-immunoprecipitation assay, was elevated by LPS and suppressed by Wnt-C59 treatment. Both NF-κB activity for its target DNA binding and the reporter activity of NF-κB-responsive promoter showed identical patterns with the interaction between β-catenin and NF-κB. Altogether, our findings suggest that the anti-inflammatory effect of Wnt-C59 is mediated by the reduction of the cellular level of β-catenin and the interaction between β-catenin and NF-κB, which results in the suppressions of the NF-κB activity and proinflammatory cytokine expression.

Dysregulation of the Wnt pathway causes various diseases including cancer, Parkinson’s disease, Alzheimer’s disease, schizophrenia, osteoporosis, obesity and chronic kidney diseases. The modulation of dysregulated Wnt pathway is absolutely necessary. In the present study, we evaluated the anti-inflammatory effect and the mechanism of action of Wnt-C59, a Wnt signaling inhibitor, in lipopolysaccharide (LPS)-stimulated epithelial cells and macrophage cells. Wnt-C59 showed a dose-dependent anti-inflammatory effect by suppressing the expression of proinflammatory cytokines including IL6, CCL2, IL1A, IL1B, and TNF in LPS-stimulated cells. The dysregulation of the Wnt/β-catenin pathway in LPS stimulated cells was suppressed by WntC59 treatment. The level of β-catenin, the executor protein of Wnt/β-catenin pathway, was elevated by LPS and suppressed by Wnt-C59. Overexpression of β-catenin rescued the suppressive effect of Wnt-C59 on proinflammatory cytokine expression and nuclear factor-kappa B (NF-κB) activity. We found that the interaction between β-catenin and NF-κB, measured by co-immunoprecipitation assay, was elevated by LPS and suppressed by Wnt-C59 treatment. Both NF-κB activity for its target DNA binding and the reporter activity of NF-κB-responsive promoter showed identical patterns with the interaction between β-catenin and NF-κB. Altogether, our findings suggest that the anti-inflammatory effect of Wnt-C59 is mediated by the reduction of the cellular level of β-catenin and the interaction between β-catenin and NF-κB, which results in the suppressions of the NF-κB activity and proinflammatory cytokine expression.

OBJECTIVES: Clinical utility of the Short Form of the Samsung Dementia Questionnaire (S-SDQ) as a screening instrument for Mild Cognitive Impairment (MCI). METHODS: Three groups (n=27, Subjective Memory Impairment (SMI); n=41 MCI; n=79, Early Alzheimer's Disease(AD)) recruited from memory clinic were administered a battery of neuropsychological tests including S-SDQ and Korean version-Mini Mental State Examination (K-MMSE). RESULTS: S-SDQ, unlike the K-MMSE, had no association with the age and education of the subjects. Scores of S-SDQ was found to correlate (r=-.496) with scores of K-MMSE. Result of Receiver Operating Characteristic (ROC) analysis revealed that S-SDQ discriminated between the SMI and the MCI groups. CONCLUSION: S-SDQ may be a solution to the problem of contamination by education and age which affect traditional cognitive screening instruments like K-MMSE, and it may be a useful tool for screening MCI.
Dementia* ; Education ; Mass Screening ; Memory ; Mild Cognitive Impairment* ; Neuropsychological Tests ; Surveys and Questionnaires* ; ROC Curve

Methods: We developed a questionnaire related to VFSS protocols and test diet. It was sent to the expert physicians who directly implementing VFSS in 35 training hospitals, which were sent out and collected by e-mail from December 7, 2017 to February 19, 2018. Among them, 12 out of 28 hospitals selected randomly and we conducted field survey including observing the process of the VFSS. Results: The most common protocol was to provide a test sample with 7 stages (28.1%). In the order of provided test samples, ‘the small amount of liquid’ was the most provided in the 1st stage (53.1%). Among the used samples of thin liquid level, the mixing ratio of the liquid samples and barium was not uniform among each institution. ‘Yogurt (semi-solid type)’ was the most commonly used sample for ‘nectar thick’ and ‘honey thick’ diet. Various samples were used on ‘pudding thick’ diet. Conclusion These results indicate that, in the 32 Korean general hospitals, each hospital uses samples depending on experience or according to its own standards rather than unified standard among the institutions. Thus, the protocols for each hospital are not standardized, which make them difficult to the accurate sharing of information about the test results. Therefore, it will be necessary to make a consensus for the protocol and establish nationwide standard of VFSS through future research

OBJECTIVE: To investigate the correlation between mechanography and clinical parameters in older people at 3 and 6 months after hip fracture surgery.METHODS: A longitudinal follow-up study was conducted in university hospitals with 38 patients at 3 months and 29 patients at 6 months after hip fracture surgery. Subjects 65 years and older completed measurements on the Berg Balance Scale (BBS), Functional Ambulation Category (FAC), walking ability by Koval, Korean version of the fatigue, resistance, ambulation, illnesses, and loss of weight (K-FRAIL) scale, and hand grip strength. The Romberg test with center of foot pressure (COP), chair rise test (CRT), and maximal power (W/kg) were conducted using the Leonardo Mechanograph.RESULTS: COP area and pathway length were correlated with BBS at 3 and 6 months. Change in BBS was correlated with change in COP area, but not with change in COP length. COP area and pathway length were correlated with K-FRAIL at 3 months after hip fracture surgery. The same COP variables showed correlations with FAC and walking ability by Koval at 6 months after surgery. Maximal power during CRT had correlation with chair rise time but not with other clinical parameters.CONCLUSION: The study revealed correlations between mechanography and clinical parameters in older people at 3 and 6 months after hip fracture surgery. Both the clinical assessment and objective test with mechanography may be required for the quantitative and sensitive measurement of postural balance and lower limb muscle power.
Dependent Ambulation ; Fatigue ; Follow-Up Studies ; Foot ; Hand ; Hand Strength ; Hip Fractures ; Hip ; Hospitals, University ; Humans ; Lower Extremity ; Muscle Strength ; Postural Balance ; Walking

PURPOSE: Plasma adiponectin concentrations are inversely related with metabolic syndrome (MetS), and MetS is associated with increased risk for heart failure (HF). However, the relationship between adiponectin and MetS in HF remains undetermined. Therefore, we tested whether MetS was associated with the degree of plasma adiponectin concentrations in HF patients. MATERIALS AND METHODS: One hundred twenty eight ambulatory HF patients with left ventricular ejection fraction of <50% (80 males, 61.8+/-11.9 years old) were enrolled for this cross-sectional study. Echocardiographic measurements were performed, and plasma concentrations of adiponectin, lipoproteins, apolipoproteins (apoB, apoA1) and high sensitive C-reactive protein (hsCRP) were measured. RESULTS: Adiponectin concentrations in HF patients with MetS (n=43) were significantly lower than those without MetS (n=85) (9.7+/-7.0 vs. 15.8+/-10.9 microg/mL, p=0.001). Higher concentrations of apoB (p=0.017), apoB/A1 ratio (p<0.001), blood urea nitrogen (p=0.034), creatinine (p=0.003), and fasting insulin (p=0.004) were observed in HF patients with MetS compared with those without MetS. In HF patients with MetS, adiponectin concentrations were negatively correlated with hsCRP (r=-0.388, p=0.015) and positively correlated with the ratio of early mitral inflow velocity to early diastolic mitral annular velocity, E/E' (r=0.399, p=0.015). There was a significant trend towards decreased adiponectin concentrations with an increasing number of components of MetS (p for trend=0.012). CONCLUSION: Our study demonstrated that adiponectin concentrations decreased in HF patients with MetS, and that relationship between adiponectin, inflammation and abnormal diastolic function, possibly leading to the progression of HF.
Adiponectin/*blood ; Aged ; Diabetes Mellitus, Type 2/epidemiology/metabolism ; Female ; Heart Failure/*epidemiology/*metabolism/ultrasonography ; Humans ; Male ; Metabolic Syndrome X/*epidemiology/*metabolism ; Middle Aged ; Risk Factors ; Ventricular Function, Left/physiology

A novel robotic mirror therapy system was recently developed to provide proprioceptive stimulus to the hemiplegic arm during a mirror therapy. Validation of the robotic mirror therapy system was performed to confirm its synchronicity prior to the clinical study. The mean error angle range between the intact arm and the robot was 1.97 to 4.59 degrees. A 56-year-old male who had right middle cerebral artery infarction 11 months ago received the robotic mirror therapy for ten 30-minute sessions during 2 weeks. Clinical evaluation and functional magnetic resonance imaging (fMRI) studies were performed before and after the intervention. At the follow-up evaluation, the thumb finding test score improved from 2 to 1 for eye level and from 3 to 1 for overhead level. The Albert's test score on the left side improved from 6 to 11. Improvements were sustained at 2-month follow-up. The fMRI during the passive motion revealed a considerable increase in brain activity at the lower part of the right superior parietal lobule, suggesting the possibility of proprioception enhancement. The robotic mirror therapy system may serve as a useful treatment method for patients with supratentorial stroke to facilitate recovery of proprioceptive deficit and hemineglect.
Arm ; Brain ; Clinical Study ; Exoskeleton Device ; Follow-Up Studies ; Hemiplegia ; Humans ; Infarction, Middle Cerebral Artery ; Magnetic Resonance Imaging ; Male ; Methods ; Middle Aged ; Neurological Rehabilitation ; Parietal Lobe ; Pilot Projects* ; Proprioception* ; Stroke ; Thumb ; Upper Extremity*

PURPOSE: Elderly patients (pts) (EPs; > or = 65 years old) with newly diagnosed-acute decompensated heart failure (ND-ADHF) have not yet been studied. The aim of the present study was to investigate clinical characteristics, including echocardiographic findings and prognosis, for EPs with ND-ADHF and to compare those with non-elderly pts (NEPs). MATERIALS AND METHODS: We retrospectively investigated 256 pts (144 males, 63.0 +/- 14.8 years old) who were admitted to our hospital between January 2005 and March 2009 with ND-ADHF. Clinical characteristics and echocardiographic parameters were analyzed in EPs (n = 135, 58 males) and NEPs (n = 121, 86 males). RESULTS: In intergroup comparison, female gender, diabetes mellitus, previous stroke and hypertension were more common in EPs. Body mass index (22.3 +/- 4.5 vs. 24.0 +/- 4.4 kg/m2), estimated glomerular filtration rate (54.8 +/- 24.3 vs. 69.2 +/- 30.7 mL/min/m2), C-reactive protein (28.5 +/- 46.9 vs. 7.6 +/- 11.6 mg/dL), hemoglobin (12.3 +/- 2.1 vs. 13.6 +/- 2.3 g/dL) and N-terminal pro-brain natriuretic peptide level (10,538.2 +/- 10,942.3 vs. 6,771.0 +/- 8,964.7 pg/mL) were significantly different (p < 0.05 for all). Early mitral inflow velocity to early diastolic mitral annular velocity (E/E') was significantly higher in EPs than in NEPs (21.2 +/- 9.4 vs. 18.0 +/- 8.9, p < 0.05). During follow-up (44.7 +/- 14.5 months), there were no significant differences in in-hospital mortality, re-hospitalization and cardiovascular mortality between EPs and NEPs (p = NS for all). CONCLUSION: EPs with ND-ADHF have different clinical characteristics and higher LV filling pressure when compared with NEPs. However, the clinical outcomes for NEPs with ND-ADHF are not necessarily more favorable than those for EPs.
Aged ; Echocardiography/*methods ; Female ; Heart Failure/*diagnosis/*epidemiology ; Humans ; Male ; Middle Aged ; Retrospective Studies

BACKGROUND AND OBJECTIVES: Apoptosis has been known to be an important mechanism of doxorubicin-induced cardiotoxicity. Survivin, which belongs to the inhibitor of apoptosis protein family, is associated with apoptosis and alteration of the cardiac myocyte molecular pathways. Therefore, we investigated the anti-apoptotic effect and cellular mechanisms of survivin using a protein delivery system in a doxorubicin-induced cardiac myocyte injury model. MATERIALS AND METHODS: We constructed a recombinant survivin which was fused to the protein transduction domain derived from HIV-TAT protein. In cultured H9c2 cardiac myocytes, TAT-survivin (1 microM) was added for 1 hour prior to doxorubicin (1 microM) treatment for 24 hours. Cell viability and apoptosis were evaluated by 2-(4,5-dimethyltriazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, caspase-3 activity, and terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay. We measured the expression levels of several apoptosis-related signal proteins. RESULTS: The survivin level was significantly reduced in a dose dependent manner up to 1 microM of doxorubicin in concentration. Purified recombinant TAT-survivin protein was efficiently delivered to H9c2 cardiac myocytes, and its transduction showed an anti-apoptotic effect, demonstrated by reduced caspase-3 activity and the apoptotic index, concomitantly with increased cell viability against doxorubicin injury. The phosphorylation of p38 mitogen-activated protein (MAP) kinase and the release of Smac from mitochondria were suppressed and the expression levels of Bcl-2 and cAMP response element-binding protein (CREB), the transcription factor of Bcl-2, were recovered following TAT-survivin transduction, indicating that survivin had an anti-apoptotic effect against doxorubicin injury. CONCLUSION: Our results suggest that survivin has a potentially cytoprotective effect against doxorubicin-induced cardiac myocyte apoptosis through mechanisms that involve a decrease in the phosphorylation of p38 MAP kinase, mitochondrial Smac release, and increased expression of Bcl-2 and CREB.
Apoptosis ; Caspase 3 ; Cell Death ; Cell Survival ; Cyclic AMP Response Element-Binding Protein ; Doxorubicin ; Humans ; Inhibitor of Apoptosis Proteins ; Mitochondria ; Myocytes, Cardiac ; p38 Mitogen-Activated Protein Kinases ; Phosphorylation ; Phosphotransferases ; Transcription Factors

OBJECTIVE: This study examined the efficacy and safety of memantine-an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist-in the treatment of moderate-to-severe dementia. METHODS: Forty-four patients with moderate-to-severe dementia received 20 mg of memantine daily for 24 weeks. The primary efficacy variable was measured by the Korean version of Severe Impairment Battery(K-SIB), and the secondary efficacy variables were measured using the Seoul-Activites of Daily Living(S-ADL) and Neuropsychiatric Inventory-Questionnaire(NPI-Q). Neuropsychological assessments were administrated at baseline, 12 weeks, and 24 weeks. Safety parameters were monitored. RESULTS: Of 44 patients recruited, 30 completed the study and 14 dropped out. Memantine-treated patients showed a therapeutic benefit in all efficacy variables ; the K-SIB, S-ADL, and NPI-Q total scores were not significantly different from baseline either at the endpoint(in the analysis of intention-to-treat, with the last observation carried forward, ITT-LOCF) or at week 24(in the analysis of observed cases, OC). The response rates, when "response" was defined as improved or unchanged in the K-SIB or the S-ADL scores, were 43.3 and 50%, respectively(in the analysis of OC). The responders showed significant improvement in the cognitive subdomain of memory function, praxis, visuospatial ability, and orienting to name. Memantine was shown to be tolerable and safe. CONCLUSIONS: Memantine treatment reduced or delayed clinical deterioration in cognition, function, and behavior in patients with moderate-to-severe dementia.
Cognition ; Dementia* ; Humans ; Memantine* ; Memory ; N-Methylaspartate