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1.
Small ; 19(34): e2300290, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37127866

ABSTRACT

This study suggests a Ru/ZnO bilayer grown using area-selective atomic layer deposition (AS-ALD) as a multifunctional layer for advanced Cu metallization. As a diffusion barrier and glue layer, ZnO is selectively grown on SiO2 , excluding Cu, where Ru, as a liner and seed layer, is grown on both surfaces. Dodecanethiol (DDT) is used as an inhibitor for the AS-ALD of ZnO using diethylzinc and H2 O at 120 °C. H2 plasma treatment removes the DDT adsorbed on Cu, forming inhibitor-free surfaces. The ALD-Ru film is then successfully deposited at 220 °C using tricarbonyl(trimethylenemethane)ruthenium and O2 . The Cu/bilayer/Si structural and electrical properties are investigated to determine the diffusion barrier performance of the bilayer film. Copper silicide is not formed without the conductivity degradation of the Cu/bilayer/Si structure, even after annealing at 700 °C. The effect of ZnO on the Ru/SiO2 structure interfacial adhesion energy is investigated using a double-cantilever-beam test and is found to increase with ZnO between Ru and SiO2 . Consequently, the Ru/ZnO bilayer can be a multifunctional layer for advanced Cu interconnects. Additionally, the formation of a bottomless barrier by eliminating ZnO on the via bottom, or Cu, is expected to decrease the via resistance for the ever-shrinking Cu lines.

2.
Biomater Res ; 27(1): 16, 2023 Feb 18.
Article in English | MEDLINE | ID: mdl-36803875

ABSTRACT

BACKGROUND: Although vasospastic angina (VSA) is known to be caused by coronary artery spasm, no study has fully elucidated the exact underlying mechanism. Moreover, in order to confirm VSA, patients should undergo invasive coronary angiography with spasm provocation test. Herein, we investigated the pathophysiology of VSA using peripheral blood-derived induced pluripotent stem cells (iPSCs) and developed an ex vivo diagnostic method for VSA. METHODS AND RESULTS: With 10 mL of peripheral blood from patients with VSA, we generated iPSCs and differentiated these iPSCs into target cells. As compared with vascular smooth muscle cells (VSMCs) differentiated from iPSCs of normal subjects with negative provocation test, VSA patient-specific iPSCs-derived VSMCs showed very strong contraction in response to stimulants. Moreover, VSA patient-specific VSMCs exhibited a significant increase in stimulation-induced intracellular calcium efflux (Changes in the relative fluorescence unit [ΔF/F]; Control group vs. VSA group, 2.89 ± 0.34 vs. 10.32 ± 0.51, p < 0.01), and exclusively induced a secondary or tertiary peak of calcium efflux, suggesting that those findings could be diagnostic cut-off values for VSA. The observed hyperreactivity of VSA patient-specific VSMCs were caused by the upregulation of sarco/endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) due to its enhanced small ubiquitin-related modifier (SUMO)ylation. This increased activity of SERCA2a was reversed by treatment with ginkgolic acid, an inhibitor of SUMOylated E1 molecules (pi/µg protein; VSA group vs. VSA + ginkgolic acid, 52.36 ± 0.71 vs. 31.93 ± 1.13, p < 0.01). CONCLUSIONS: Our findings showed that abnormal calcium handling in sarco/endoplasmic reticulum could be induced by the enhanced SERCA2a activity in patients with VSA, leading to spasm. Such novel mechanisms of coronary artery spasm could be useful for drug development and diagnosis of VSA.

3.
ACS Appl Mater Interfaces ; 14(50): 56310-56320, 2022 Dec 21.
Article in English | MEDLINE | ID: mdl-36461928

ABSTRACT

Controlling the contact properties of a copper (Cu) electrode is an important process for improving the performance of an amorphous indium-gallium-zinc oxide (a-IGZO) thin-film transistor (TFT) for high-speed applications, owing to the low resistance-capacitance product constant of Cu. One of the many challenges in Cu application to a-IGZO is inhibiting high diffusivity, which causes degradation in the performance of a-IGZO TFT by forming electron trap states. A self-assembled monolayer (SAM) can perfectly act as a Cu diffusion barrier (DB) and passivation layer that prevents moisture and oxygen, which can deteriorate the TFT on-off performance. However, traditional SAM materials have high contact resistance and low mechanical-adhesion properties. In this study, we demonstrate that tailoring the SAM using the chemical coupling method can enhance the electrical and mechanical properties of a-IGZO TFTs. The doping effects from the dipole moment of the tailored SAMs enhance the electrical properties of a-IGZO TFTs, resulting in a field-effect mobility of 13.87 cm2/V·s, an on-off ratio above 107, and a low contact resistance of 612 Ω. Because of the high electrical performance of tailored SAMs, they function as a Cu DB and a passivation layer. Moreover, a selectively tailored functional group can improve the adhesion properties between Cu and a-IGZO. These multifunctionally tailored SAMs can be a promising candidate for a very thin Cu DB in future electronic technology.

4.
Biomed Pharmacother ; 141: 111838, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34182414

ABSTRACT

Obesity is known as metabolic syndrome and it affects many tissues including adipose tissue, liver, and central nervous system (CVS). Gambi-jung (GBJ) is a modified prescription of Taeumjowi-tang (TJT), which has been used to treat obesity in Korea. GBJ is composed of 90% Ephedra sinica Stapf (ES). Therefore, the present study was designed to assess the antiobesity effects of GBJ and to compare the effects of GBJ and ES on obesity. GBJ administration remarkably reduced the body weight, Body mass index (BMI), and body fat percentage compared to the ES administration in human subjects. GBJ-treated mice had lower white adipose tissue (WAT) amounts than ES-treated mice. GBJ and ES administration enhanced adenosine monophosphate-activated protein kinase (AMPK) expression in 3T3-L1 adipocytes, epididymal WAT and liver of HFD-induced obese mice. Moreover, GBJ and ES reduced food intake by suppressing the mRNA levels of orexigenic peptides, agouti-related protein (AgRP) and neuropeptide-Y (NPY), as well as AMPK in the brain of HFD-induced obese mice. Furthermore, GBJ-treated mice had dramatically lower expression of macrophage marker F4/80 in epididymal WAT than those of ES-treated mice. Based on these results, we suggest the use of GBJ as a natural drug to control weight gain.


Subject(s)
Anti-Obesity Agents/therapeutic use , Obesity/drug therapy , Plant Extracts/therapeutic use , 3T3-L1 Cells , Adipose Tissue, White/drug effects , Adult , Aged , Animals , Appetite Depressants/chemistry , Appetite Depressants/pharmacology , Body Composition/drug effects , Body Mass Index , Eating/drug effects , Ephedra sinica/chemistry , Ephedrine/chemistry , Ephedrine/pharmacology , Female , Humans , MAP Kinase Signaling System , Male , Mice , Mice, Inbred C57BL , Middle Aged , Weight Loss/drug effects
5.
J Acad Nutr Diet ; 121(8): 1551-1564.e3, 2021 08.
Article in English | MEDLINE | ID: mdl-34144920

ABSTRACT

BACKGROUND: Portion control is a useful component of weight reduction interventions and meal replacement (MR) plans represent a promising strategy for portion control. Research performed with pooled data on the effect of MR plans according to various characteristics of MR interventions remains scarce. OBJECTIVE: Our aim was to assess the effects of MR-based diets compared with food-based diets on weight loss, according to calorie-restriction types and energy intake proportions from MR. METHODS: Electronic databases (Cochrane Central Register of Controlled Trials, PubMed, Embase, and Research Information Sharing Service) were searched for randomized controlled trials on weight loss results of MR-based calorie-restricted diets compared with food-based calorie-restricted diets from January 2000 to May 2020. Standardized mean differences (Hedges' g) from all study outcomes were calculated using a random-effects model. Heterogeneity was quantified by Q test and I2. Publication bias was assessed using a funnel plot and a trim and fill method. Both interventions (MR and control) were separated into very-low-energy diets and low-energy diets (LEDs). A meta-analysis of variance was conducted by dividing patient-related factors and treatment-related factors into subgroups. In multivariable meta-regressions, background variables were selected first, after which main independent variables were included. RESULTS: Twenty-two studies involving 24 interventions and 1,982 patients who were overweight or obese were included. The effect size in which MR-based LED was compared with food-based LED for weight loss was small, favoring MR (Hedges' g = 0.261; 95% CI 0.156 to 0.365; I2 = 21.9; 95% CI 0.0 to 53.6). Diets including ≥60% of total daily energy intake from MR had a medium effect size favoring MR with regard to weight loss among the groups (Hedges' g = 0.545; 95% CI 0.260 to 0.830; I2 = 42.7; 95% CI 0.0 to 80.8). CONCLUSIONS: The effect of MR-based LED on weight loss was superior to the effect of food-based LED, and receiving ≥60% of total daily energy intake from MR had the greatest effect on weight loss.


Subject(s)
Caloric Restriction , Energy Intake , Meals , Randomized Controlled Trials as Topic , Weight Loss , Adult , Female , Humans , Male , Middle Aged , Obesity/diet therapy , Overweight/diet therapy , Portion Size , Publication Bias/statistics & numerical data
6.
J Nanosci Nanotechnol ; 20(1): 206-212, 2020 Jan 01.
Article in English | MEDLINE | ID: mdl-31383157

ABSTRACT

The effects of environmental conditions on the interfacial adhesion between screen-printed Ag film and polyimide substrate interface are quantitatively evaluated using the 90° peel test. The adhesion of printed patterns is varied by annealing time and atmosphere conditions. The peel strengths of air, high vacuum, and N2 atmosphere samples increase after post-annealing for 24 h, which are closely related to the curing effect of binder in Ag paste. The peel strengths of air, high vacuum, and N2 atmosphere samples decrease after post-annealing for 48 and 100 h. Peel strengths of samples after 48 h post-annealing in air are lower than in high vacuum and N2, indicating the effects of post-annealing atmospheric conditions on interfacial adhesion strength. The decreased adhesion strength during post-annealing seems to be closely related to Ag2O formation at screen-printed Ag/polyimide. Therefore, the optimum annealing conditions of Ag binder must be carefully applied to obtain maximum interfacial adhesion. Furthermore, it is important to control Ag2O formation during environmental reliability testing.

7.
J Nanosci Nanotechnol ; 20(1): 278-284, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31383167

ABSTRACT

The effects of annealing, electromigration, and thermomigration on volume shrinkage and voiding mechanisms of Cu/Ni/Sn-2.5Ag microbumps are systematically investigated by using in-situ scanning electron microscopy under current stressing of 1.5×105 A/cm² at 150 °C. The resistance increases rapidly in the initial stage due to formation of intermetallic compounds (IMC)s followed by a gradual increase in resistance. Growth of Ni3Sn4 IMCs is controlled by a diffusion-dominant mechanism, and voids and volume shrinkage are closely related to IMC phase transformation of (Au, Ni)Sn4 to Ni3Sn4 in microbumps.

8.
J Nanosci Nanotechnol ; 20(1): 470-477, 2020 Jan 01.
Article in English | MEDLINE | ID: mdl-31383195

ABSTRACT

To develop highly reliable flexible electronics, mechanical reliability during mechanical deformation such as repeated bending is an important issue. Bending test methodologies to estimate long-term reliability during repeated mechanical deformation are attracting substantial interest from related researchers and industry insiders. In this study, four representative bending test methodologies for testing flexible electronics are introduced: free arc bending test, variable radius bending test, sliding plate test, and variable angle test. Correct name and characteristics of each method are also explained. Furthermore, electrical reliability of Cu film on polymer substrate samples was investigated in each bending test method through in situ monitoring of electrical resistance. With different bending test methodologies, different electrical resistance changes were observed. Fatigue damages occurred at different areas. Obtained electrical reliability and failure modes were analyzed by observing crack morphologies.

9.
Biomaterials ; 232: 119674, 2020 02.
Article in English | MEDLINE | ID: mdl-31865194

ABSTRACT

Many studies have shown the existence of cardiac stem cells in the myocardium and epicardial progenitor cells in the epicardium. However, the characteristics of stem cells in the endocardium has not been fully elucidated. In this study, we investigated the origin of newly identified cells in the blood and their therapeutic potential. The new population of cells, identified from human peripheral blood, was quite different from previously reported stem cells. These newly identified cells, which we named Circulating Multipotent Stem (CiMS) cells, were multipotent, and therefore differentiated into multiple lineages in vitro and in vivo. In order to determine the origin of these cells, we collected peripheral blood from a group of patients who underwent bone marrow, liver, heart, or kidney transplantation. We identified the endocardium as the origin of these cells because the Short Tandem Repeat profile of CiMS cells from the recipient had changed from the recipient's profile to the donor's profile after heart transplantation. CiMS cells significantly increased after stimuli to the endocardium, such as catheter ablation for arrhythmia or acute myocardial infarction. CiMS cells circulate in human peripheral blood and are easily obtainable, suggesting that these cells could be a promising tool for cell therapy.


Subject(s)
Endocardium , Multipotent Stem Cells , Myocardial Infarction , Cell Differentiation , Humans , Leukocyte Common Antigens , Myocardial Infarction/therapy , Myocardium , NFATC Transcription Factors , Platelet Endothelial Cell Adhesion Molecule-1
10.
PLoS One ; 13(10): e0205634, 2018.
Article in English | MEDLINE | ID: mdl-30308070

ABSTRACT

Symptomatic hyperventilation (SH) is a pathological condition that manifests with breathlessness, dyspnea, light-headedness, anxiety, and paresthesia. However, little is known about the prevalence of SH and its association with health-related quality of life (HRQoL) in a young population. The Nijmegen questionnaire (NQ), which measures severity of SH, had not previously been cross-culturally translated into Korean. In this study, the NQ was cross-culturally translated into Korean (KNQ), using translation and back-translation methods. To examine the reliability and validity levels of the KNQ, as well as its association with HRQoL, 237 college students (21.38 ± 2.45 years) were asked to complete the KNQ, the Korean version of the general health questionnaire (K-GHQ-30) and the short form-36 (K-SF-36). The KNQ showed satisfactory reliability (Cronbach's α = 0.878). In the construct validity test, four factors (neuropsychological, respiratory, neurogastrointestinal, and neuromuscular) were extracted (% of total variance = 59.8). Using a KNQ cut-off score of 23 points, the prevalence of SH was 22.8%. Physical and mental HRQoL levels estimated by the K-GHQ-30 score and the 8 subscale scores of the K-SF-36 were lower in the SH group than in those of the non-SH group. It is concluded that the cross-culturally translated KNQ is reliable and valid, and management of SH may prevent a reduction in physical and mental HRQoL in a young population.


Subject(s)
Hyperventilation , Quality of Life , Adult , Cross-Cultural Comparison , Cross-Sectional Studies , Female , Humans , Hyperventilation/diagnosis , Hyperventilation/epidemiology , Hyperventilation/psychology , Male , Middle Aged , Prevalence , Reproducibility of Results , Severity of Illness Index , Surveys and Questionnaires , Translating , Young Adult
11.
Article in English | MEDLINE | ID: mdl-29977315

ABSTRACT

Tongue diagnosis is a technique used to determine cold-heat pathologic patterns (CHPPs). Herein, we reviewed electronic medical records of tongue temperature measured using infrared thermography (IRT), tongue color (luminance, green/red, and blue/yellow balance), cold-heat pattern questionnaires (CHPQ), and body temperature for 134 women with gynecological problems (age, 38.97 ± 11.49 years). The temperatures of seven tongue regions (root, center, tip, and both sides of the center and root) were determined, and the effects of age, regional differences, and their correlations with color parameters were examined. Factor analysis was conducted separately with the 10 cold pattern (CP) and 10 heat pattern (HP) items. Tongue temperature showed an age effect (ß; -0.198 to -0.210) and regional differences (both sides of the root > center and root > tip). Tongue temperature was positively correlated with luminance (r: 0.236-0.246), indicating that a higher temperature was associated with a brighter color. The factor analysis extracted two factors (cold sensitivity-pain and discharge-complexion factors) from the CP items and three factors (heat sensation-pain, discharge-breath, and cold preference-thirst factors) from the HP items. Tongue temperature was negatively correlated with the discharge-complexion factor of CP and the discharge-breath factor of HP (r: -0.171 to -0.203), indicating that a lower tongue temperature may be a consequence of emission of excessive heat in HP and a lower blood perfusion in CP. Body temperature did not correlate with the CHPQ factor scores. In conclusion, tongue temperatures measured using IRT may be a partial indicator of CHPPs.

12.
Article in English | MEDLINE | ID: mdl-28265292

ABSTRACT

Background. De qi comprises varied senses depending on the individual. No single method can yet fully measure the multiple dimensions of de qi adequately. Objective. We examined the advantages of implementing multiple questionnaires for de qi measurement. Methods. Fourteen participants completed a preacupuncture questionnaire regarding their perception toward acupuncture treatment. After acupuncture stimulation at the HT7 point, de qi sensations were measured by MASS and ASQ. In groups with different levels of expectation, we compared the subtotal scores of each phase in the ASQ, as well as the VAS de qi intensity and MASS index using Kruskal-Wallis test. For the structural comparison of questionnaires, we first performed Spearman's rank correlation test between the scores of individual descriptors in MASS and ASQ. The subtotal scores of each phase in ASQ was compared with VAS de qi intensity and MASS index. Results. The subtotal score of the manipulation phase in ASQ strongly correlated with the VAS score of de qi intensity (Spearman's ρ = 0.654, p = 0.011) and MASS index (Spearman's ρ = 0.488, p = 0.076). MASS and ASQ showed strong correlations in certain analogous descriptors. Unpleasant perceptions toward acupuncture treatment did not significantly correlate with overall de qi intensity. Conclusions. De qi sensations in acupuncture treatment have multidimensional aspects. Intensity of stimulation, ASQ, and MASS index assess somewhat restricted aspects of de qi. Those questionnaires have exclusive differences of sets in spite of their strong intersections. Use of multiple questionnaires may enable a more comprehensive understanding of de qi properties and the elicitation of relevant construction in de qi features of acupuncture.

13.
BMC Complement Altern Med ; 17(1): 101, 2017 Feb 08.
Article in English | MEDLINE | ID: mdl-28178964

ABSTRACT

BACKGROUND: Acupuncture treatments that regulate the heart are used to treat various clinical disorders and conditions. Although many studies have been conducted to measure quantitatively the effects of acupuncture, thus far, models that describe these effects have not been established. The purpose of this study was to derive a transfer function model of acupuncture stimulation within the electrocardiograms based on the periods before, during, and after acupuncture. METHODS: Fourteen healthy subjects were included in this clinical trial. Five-minute electrocardiograms were captured before, during, and after acupuncture at HT7. For each period, signal-averaged electrocardiograms were created from all of the subjects' 5-min electrocardiograms for that period. Individual transfer functions, which has the highest average goodness of fit, were derived for each period pair. By averaging individual transfer functions, generalized transfer functions were derived. RESULTS: The transfer function with the highest average goodness of fit was a fraction with 4th order numerator and 5th order denominator. Fourteen individual transfer functions were derived separately for each pair of periods: before and during acupuncture, during and after acupuncture, and before and after acupuncture. Three generalized transfer functions were derived by averaging individual transfer functions for each period pair. CONCLUSION: The three generalized transfer functions that were derived may reflect the electrocardiogram changes caused by acupuncture. However, this clinical trial included only 14 subjects. Further studies with control groups and more subjects are needed. This clinical trial has been registered on the Clinical Research Information Service, Republic of Korea (No. KCT0001944). The first enrolment of subject started at 2 June 2015 and this trial was retrospectively registered at 14 June 2016.


Subject(s)
Acupuncture Therapy , Electrocardiography , Medicine, Korean Traditional , Adult , Feasibility Studies , Female , Humans , Male , Middle Aged , Models, Theoretical , Young Adult
14.
Article in English | MEDLINE | ID: mdl-28003851

ABSTRACT

Background. In Korea, a few studies regarding traditional Korean medicine (TKM) education have been conducted. The aim of this study is to evaluate students' perceptions regarding TKM education in Korea and compare them with those of other countries using a quantitative scale, Dundee Ready Educational Environment Measure (DREEM). Materials and Methods. We conducted a survey using DREEM in a TKM college. Totally, 325 students responded to this survey and we performed the descriptive statistics of scores in all items, subscales, and total. Additionally, subgroup comparisons according to gender, school year, and academic achievement were analyzed. Results. Mean overall DREEM score was 94.65 out of 200, which is relatively low compared to previous studies. Particularly, perceptions regarding subscales of learning, atmosphere, and self-perceptions were interpreted as problematic. There was no statistically significant difference between genders in spite of some differences among groups based on school year or academic achievement. Conclusions. We could examine students' perceptions regarding TKM education at a TKM college using DREEM for which validity and reliability were verified. TKM education was perceived relatively poor, but these quantitative indicators suggested which parts of education need improvement. We expect DREEM to be used widely in TKM or traditional medical education field.

15.
Sci Rep ; 6: 36979, 2016 11 11.
Article in English | MEDLINE | ID: mdl-27833146

ABSTRACT

In spite of its great success in reducing restenosis, drug-eluting stent (DES) has unfavorable aspects such as stent thrombosis and delayed re-endothelialization. We examined the effects of PKG activation by Exisulind on neointimal formation, platelet aggregation, and re-endothelialization. Exisulind significantly reduced VSMCs viability, cell cycle progression, migration, and neointimal hyperplasia after vascular injury in rat carotid arteries. Interestingly, in contrast to the effect on VSMC viability, Exisulind did not reduce the viability of endothelial cells. Increased PKG activity by Exisulind inhibited PDGF-stimulated phenotype change of VSMCs from a contractile to a synthetic form. Conversely, the use of PKG inhibitor or gene transfer of dominant-negative PKG reversed the effects of Exisulind, resulting in the increased viability of VSMCs and neointimal formation. In addition, Exisulind facilitated the differentiation of peripheral blood mononuclear cells to endothelial lineage via PKG pathway, while inhibiting to VSMCs lineage, which was correlated with the enhanced re-endothelialization in vivo. Finally, Exisulind reduced platelet aggregation, which was mediated via PKG activation. This study demonstrated that Exisulind inhibits neointimal formation and platelet aggregation while increasing re-endothelialization via PKG pathway. These findings suggest that Exisulind could be a promising candidate drug of DES for the prevention of restenosis without other complications.


Subject(s)
Cyclic GMP-Dependent Protein Kinases/metabolism , Endothelial Cells/cytology , Hyperplasia/drug therapy , Neointima/drug therapy , Sulindac/analogs & derivatives , Animals , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Humans , Hyperplasia/metabolism , Male , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/cytology , Myocytes, Smooth Muscle/metabolism , Neointima/metabolism , Platelet-Derived Growth Factor/pharmacology , Rats , Sulindac/pharmacology , Transcriptional Activation
16.
Circulation ; 134(3): 233-47, 2016 Jul 19.
Article in English | MEDLINE | ID: mdl-27407072

ABSTRACT

BACKGROUND: Several mechanisms have been proposed to account for diabetes-induced microvasculopathy (DMV). Although Notch signaling was reported to be affected by glucose metabolism in endothelial cells during developmental angiogenesis, it has not been investigated in vascular remodeling of adult capillaries in relation to diabetes mellitus. METHODS: We induced diabetes mellitus in 8-week-old adult mice by intravenously administering streptozotocin. After 6 weeks, we harvested organs, including retina, heart, and skeletal muscle, and evaluated the capillaries with immunofluorescence and confocal microscopy. We modulated endothelial Notch signaling using chemical inhibitors in wild-type mice or transgenic mice, inducing conditional knockout of Jagged1 or Mib1. RESULTS: DMV was characterized by capillary remodeling, regression, and decreased density. Notch ligand Jagged1, but not δ-like ligand 4, was markedly increased in endothelial cells of diabetic mice. Using endothelium-specific Jagged1 knockdown mice, we found that blocking Jagged1 prevented DMV even under diabetic conditions. Furthermore, in the inducible endothelium-specific Jagged1 knockdown mice, blocking Jagged1 even at 4 weeks after the establishment of DMV could reverse it, leading to normalization of retinal vasculature. A search for downstream signals revealed that diabetes mellitus decreased the nuclear localization of Notch1 intracellular domain and reduced the expression of VE-cadherin and N-cadherin in endothelial cells. Chemical Notch inhibition phenocopied DMV in normal mice. CONCLUSIONS: Our findings indicate that diabetes mellitus induces Jagged1 overexpression and suppresses Notch signaling in endothelial cells, leading to DMV in adult mice. We conclude that dysregulated intercellular Notch signaling may be a novel mechanism of DMV.


Subject(s)
Diabetes Mellitus, Experimental/pathology , Diabetic Retinopathy/metabolism , Endothelial Cells/metabolism , Jagged-1 Protein/physiology , Retinal Vessels/pathology , Animals , Apoptosis , Capillaries/pathology , Cells, Cultured , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/metabolism , Diabetic Retinopathy/prevention & control , Dibenzazepines/pharmacology , Endothelial Cells/pathology , Gene Expression Regulation , Humans , Jagged-1 Protein/biosynthesis , Jagged-1 Protein/deficiency , Male , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/pathology , Receptor, TIE-2/genetics , Receptors, Notch/physiology , Signal Transduction , Ubiquitin-Protein Ligases/deficiency
17.
J Tradit Chin Med ; 36(2): 165-72, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27400470

ABSTRACT

OBJECTIVE: To examine whether color parameters of tongue inspection (TI) using a digital camera was reliable and valid, and to examine which color parameters serve as predictors of symptom patterns in terms of East Asian medicine (EAM). METHODS: Two hundred female subjects' tongue substances were photographed by a mega-pixel digital camera. Together with the photographs, the subjects were asked to complete Yin deficiency, Phlegm pattern, and Cold-Heat pattern questionnaires. Using three sets of digital imaging software, each digital image was exposure- and white balance-corrected, and finally L* (luminance), a* (red-green balance), and b* (yellow-blue balance) values of the tongues were calculated. To examine intra- and inter-rater reliabilities and criterion validity of the color analysis method, three raters were asked to calculate color parameters for 20 digital image samples. Finally, four hierarchical regression models were formed. RESULTS: Color parameters showed good or excellent reliability (0.627-0.887 for intra-class correlation coefficients) and significant criterion validity (0.523-0.718 for Spearman's correlation). In the hierarchical regression models, age was a significant predictor of Yin deficiency (ß = 0.192), and b* value of the tip of the tongue was a determinant predictor of Yin deficiency, Phlegm, and Heat patterns (ß = - 0.212, - 0.172, and - 0.163). Luminance (L*) was predictive of Yin deficiency (ß = -0.172) and Cold (ß = 0.173) pattern. CONCLUSION: Our results suggest that color analysis of the tongue using the L*a*b* system is reliable and valid, and that color parameters partially serve as symptom pattern predictors in EAM practice.


Subject(s)
Diagnosis, Differential , Medicine, East Asian Traditional/methods , Tongue/chemistry , Yin Deficiency/diagnosis , Adolescent , Adult , Aged , Color , Female , Humans , Middle Aged , Surveys and Questionnaires , Young Adult
18.
J Mol Cell Cardiol ; 97: 266-77, 2016 08.
Article in English | MEDLINE | ID: mdl-27266389

ABSTRACT

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR)-δ is a nuclear receptor regulating cell metabolism. The role of PPAR-δ in late endothelial progenitor cells (EPCs) has not been fully elucidated. We aim to understand the effects of PPAR-δ activation on late EPC and to reveal the underlying mechanism. METHODS AND RESULTS: Treatment with a highly selective PPAR-δ agonist (GW501516) induced proliferation of late EPCs and enhanced their vasculogenic potential. Search for the target molecule of PPAR-δ activation revealed endothelial differentiation gene (Edg)-2. Chromatin immunoprecipitation and promoter assays demonstrated that Edg-2 gene was specifically induced by PPAR-δ through direct transcriptional activation. Lysophosphatidic acid (LPA), an Edg ligand, mimicked the pro-vasculogenic effects of GW501516 in late EPCs whereas Edg antagonist (Ki16425) blocked these effects. Edg-2 is a membrane receptor for LPA which is a major growth factor from activated platelets. Thus, the interaction between platelets and late EPCs via the LPA-Edg-2 axis was assessed. Platelet supernatant boosted the pro-vasculogenic effects of GW501516, which was reversed by antagonist to PPAR-δ (GSK0660) or Edg (Ki16425). Both of in vivo Matrigel plug model and mouse skin punch-wound model demonstrated that the combination of platelets and PPAR-δ-activated late EPCs synergistically enhanced vascular regeneration. CONCLUSIONS: There exists a synergistic interaction between human platelets and late EPCs leading to vascular regeneration. This interaction consists of LPA from platelets and its receptor Edg-2 on the surface of EPCs and can be potentiated by PPAR-δ activation in EPCs. A PPAR-δ agonist is a good candidate to achieve vasculogenesis for ischemic vascular disease.


Subject(s)
Blood Platelets/metabolism , Endothelial Progenitor Cells/metabolism , Lysophospholipids/metabolism , PPAR delta/metabolism , Receptors, Lysophosphatidic Acid/metabolism , Base Sequence , Binding Sites , Cell Communication , Consensus Sequence , Gene Expression Regulation , Humans , Lysophospholipids/pharmacology , Neovascularization, Physiologic , Protein Binding , Receptors, Lysophosphatidic Acid/chemistry , Receptors, Lysophosphatidic Acid/genetics , Transcriptional Activation , Wound Healing
19.
Article in English | MEDLINE | ID: mdl-27051447

ABSTRACT

Background. Phlegm pattern questionnaire (PPQ) was developed to evaluate and diagnose phlegm pattern in Korean Medicine and Traditional Chinese Medicine, but it was based on a dataset from patients who visited the hospital to consult with a clinician regarding their health without any strict exclusion or inclusion. In this study, we reinvestigated the construct validity of PPQ with a new dataset and confirmed the feasibility of applying it to a healthy population. Methods. 286 healthy subjects were finally included and their responses to PPQ were acquired. Confirmatory factor analysis (CFA) was conducted and the model fit was discussed. We extracted a new factor structure by exploratory factor analysis (EFA) and compared the two factor structures. Results. In CFA results, the model fit indices are acceptable (RMSEA = 0.074) or slightly less than the good fit values (CFI = 0.839, TLI = 0.860). Many average variances extracted were smaller than the correlation coefficients of the factors, which shows the somewhat insufficient discriminant validity. Conclusions. Through the results from CFA and EFA, this study shows clinically acceptable model fits and suggests the feasibility of applying PPQ to a healthy population with relatively good construct validity and internal consistency.

20.
BMC Oral Health ; 15(1): 129, 2015 Oct 21.
Article in English | MEDLINE | ID: mdl-26490372

ABSTRACT

BACKGROUND: The aim of this study was to investigate the physical properties and biological effects of an experimentally developed injectable premixed calcium-silicate root canal sealer (Endoseal) in comparison with mineral trioxide aggregate (MTA) and a resin-based sealer (AHplus). METHODS: The pH, solubility, dimensional change, flow, and radiopacity of the materials were evaluated. Biocompatibility was evaluated on the basis of cell morphology and a viability test using MC3T3-E1 cells. For evaluate inflammatory reaction, the tested sealers were implanted into dorsal subcutaneous connective tissue of Sprague Dawley rats. After 7 days, the implants with the surrounding tissue were retrieved, and histological evaluation was performed. RESULTS: Endoseal showed high alkalinity similar to that of MTA. The solubility of the tested materials was similar. The dimensional change and flow of Endoseal was significantly higher than that of other materials (P < 0.05). The radiopacity of Endoseal was lower than that of AHplus (P < 0.05). The biocompatibility was similar to those of MTA. Inflammatory reaction of Endoseal was similar with that of MTA, but lower than that of AHplus (P < 0.05). CONCLUSIONS: The present study indicates that Endoseal has favorable physical properties and biocompatibility. Therefore, we suggest that Endoseal has the potential to be used as a predictable root canal sealer.


Subject(s)
Calcium , Dental Pulp Cavity , Root Canal Filling Materials , Silicates , Aluminum Compounds , Animals , Calcium Compounds , Drug Combinations , Materials Testing , Oxides , Rats , Rats, Sprague-Dawley , Solubility , Zinc Oxide-Eugenol Cement
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