CKD-712, (S)-1-(α-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, Inhibits the NF-κB Activation and Augments Akt Activation during TLR4 Signaling

Since CKD-712 has been developed as an anti-inflammatory agent, we examined the effect of CKD-712 during TLR4 signaling. Using HEK293 cells expressing TLR4, CKD-712 was pre-treated 1 hr before LPS stimulation. Activation of NF-κB was assessed by promoter assay. The activation of ERK, JNK, p38, IRF3 and Akt was measured by western blotting. CKD-712 inhibited the NF-κB signaling triggered by LPS. The activation of ERK, JNK, p38 or IRF3 was not inhibited by CKD-712. On the contrary the activation of these molecules was augmented slightly. The activation of Akt with stimulation of LPS was also enhanced with CKD-712 pre-treatment at lower concentration, but was inhibited at higher concentration. We suggest that during TLR4 signaling CKD-712 inhibits NF-κB activation. However, CKD-712 augmented the activation of Akt as well as Map kinases. Therefore, we suggest that CKD-712 might have a role as an immunomodulator

Validation Study of Tripartite Model of Anxiety and Depression in Children and Adolescents: Clinical Sample in Korea

Although the currently available literature has provided some empirical support for a tripartite model of child and adolescent anxiety and depression, one of the limitations of these studies was that they have been conducted in America, primarily with Caucasians. In order to make this model more applicable to diverse ethnic and cultural groups, this study used a tripartite model for child and adolescent anxiety and depression in Korea, using confirmatory factor analysis with logically selected items from the Revised Children's Manifest Anxiety Scale (RCMAS), as well as the Children's Depression Inventory (CDI). The results indicated that the model fit of a three-factor model was superior to one- and two-factor models. In addition, the findings of discriminant analysis demonstrated that the correct classification rate with three factors of the tripartite model was superior to the classification rate achievable using CDI and RCMAS. In a departure from Clark and Watson's hypothesis, however, the correlations of three factors were significantly higher than had been expected. The results are discussed on the basis of cultural background

Differences of Clinical Characteristics and Phenotypes between Prepubertal- and Adolescent-Onset Bipolar Disorders

The aim of this study is to describe the clinical characteristics of prepubertal- and adolescent-onset bipolar disorder (BD) and to identify any clinical differences between patients with prepubertal- and adolescent-onset BD. We analyzed the clinical records of 53 inpatients with BD. These patients were divided into prepubertal-onset and adolescent-onset groups. We also divided the subjects into narrow, intermediate, and broad phenotypes according to the definitions proposed by Leibenluft and colleagues. Of the total sample, 16 patients (30.2%) were in the prepubertal-onset group and 37 (69.8%) were in the adolescent-onset group. Patients with prepubertal-onset BD were more likely to display an insidious clinical presentation, atypical features, and comorbid psychopathology. And the majority of the subjects, especially in the prepubertal-onset group, were classified under the intermediate and broad phenotypes. These results suggest that the clinical presentation of BD with prepubertal-onset is different from that of adolescent-onset BD. It is inferred that a significant number of patients with prepubertal- and adolescent-onset BD do not meet DSM-IV criteria for mania or hypomania from the results of this study

Psychiatric Comorbidity in Korean Children and Adolescents with Attention-Deficit Hyperactivity Disorder: Psychopathology According to Subtype

It is well-known that more than 50% of attention-deficit hyperactivity disorder (ADHD) cases also have comorbid psychiatric disorders. We evaluated the comorbid psychopathology of Korean children and adolescents with ADHD using a standardized diagnostic instrument. The Korean Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL-K) was administered and completed in 105 patients who had been referred to the outpatient and inpatient clinics at the Samsung Medical Center from March 2004 to May 2005. All of the cases were diagnosed as ADHD according to DSM-IV criteria. We analyzed their clinical characteristics and psychiatric comorbidities, and assessed the correlation of any comorbidity with gender, age and ADHD subtype. Among our 105 participants, 70 (66.7%) subjects were diagnosed with combined-type ADHD, 22 (21.0%) were the predominantly inattentive type, only 1 (1.0%) was determined to have the predominantly hyperactive-impulsive type of ADHD, and 12 (11.4%) were classified as not otherwise specified (NOS) ADHD. Eighty (76.2%) subjects had at least one comorbid disorder such as oppositional defiant disorder (n = 53, 50.5%), anxiety disorders (n = 35, 33.3%) and affective disorders (n = 15, 14.3%). Our patients ranged in age from five to 16 years. Among the factors including gender, age, and ADHD subtype, ADHD subtype was the only one significant to comorbidity in our study. The results of this study suggest that psychiatric comorbidity in Korean children with ADHD is similar to the results of previous studies in western countries. Out of all the ADHD subtypes, the combined-type group had a significantly higher ratio of comorbid disorders and psychopathologies

Methylsulfonylmethane Suppresses Breast Cancer Growth by Down-Regulating STAT3 and STAT5b Pathways

Breast cancer is the most aggressive form of all cancers, with high incidence and mortality rates. The purpose of the present study was to investigate the molecular mechanism by which methylsulfonylmethane (MSM) inhibits breast cancer growth in mice xenografts. MSM is an organic sulfur-containing natural compound without any toxicity. In this study, we demonstrated that MSM substantially decreased the viability of human breast cancer cells in a dose-dependent manner. MSM also suppressed the phosphorylation of STAT3, STAT5b, expression of IGF-1R, HIF-1α, VEGF, BrK, and p-IGF-1R and inhibited triple-negative receptor expression in receptor-positive cell lines. Moreover, MSM decreased the DNA-binding activities of STAT5b and STAT3, to the target gene promoters in MDA-MB 231 or co-transfected COS-7 cells. We confirmed that MSM significantly decreased the relative luciferase activities indicating crosstalk between STAT5b/IGF-1R, STAT5b/HSP90α, and STAT3/VEGF. To confirm these findings in vivo, xenografts were established in Balb/c athymic nude mice with MDA-MB 231 cells and MSM was administered for 30 days. Concurring to our in vitro analysis, these xenografts showed decreased expression of STAT3, STAT5b, IGF-1R and VEGF. Through in vitro and in vivo analysis, we confirmed that MSM can effectively regulate multiple targets including STAT3/VEGF and STAT5b/IGF-1R. These are the major molecules involved in tumor development, progression, and metastasis. Thus, we strongly recommend the use of MSM as a trial drug for treating all types of breast cancers including triple-negative cancers

Drop formation of Carbopol dispersions displaying yield stress, shear thinning and elastic properties in a flow-focusing microfluidic channel

The drop formation dynamics of a shear thinning, elastic, yield stress (τ o) fluid (Carbopol 980 (poly(acrylic acid)) dispersions) in silicone oil has been investigated in a flow-focusing microfluidic channel. The rheological character of each solution investigated varied from Netwonian-like through to highly non-Newtonian and was varied by changing the degree of neutralization along the poly (acrylic acid) backbone. We have observed that the drop size of these non-Newtonian fluids (regardless of the degree of neutralisation) showed bimodal behaviour. At first we observed increases in drop size with increasing viscosity ratio (viscosity ratio=viscosity of dispersed phase (DP) / viscosity of continuous phase (CP)) at low flowrates of the continuous phases, and thereafter, decreasing drop sizes as the flow rate of the CP increases past a critical value. Only at the onset of pinching and during the high extensional deformation during pinch-off of a drop are any differences in the non-Newtonian characteristics of these fluids, that is extents of shear thinning, elasticity and yield stress (τ o), apparent. Changes in these break-off dynamics resulted in the observed differences in the number and size distribution of secondary drops during pinch-off for both fluid classes, Newtonian-like and non-Newtonian fluids. In the case of the Newtonian-like drops, a secondary drop was generated by the onset of necking and breakup at both ends of the filament, akin to end-pinching behavior. This pinch-off behavior was observed to be unaffected by changes in viscosity ratio, over the range explored. Meanwhile, in the case of the non-Newtonian solutions, discrete differences in behaviour were observed, believed to be attributable to each of the non-Newtonian properties of shear thinning, elasticity and yield stress. The presence of a yield stress (τ o), when coupled with slow flow rates or low viscosities of the CP, reduced the drop size compared to the Newtonian-like Carbopol dispersions of much lower viscosity. The presence of shear thinning resulted in a rapid necking event post onset, a decrease in primary droplet size and, in some cases, an increase in the rate of drop production. The presence of elasticity during the extensional flow imposed by the necking event allowed for the extended maintenance of the filament, as observed previously for dilute solutions of linear polymers during drop break-up

Role of clays in fouling-resistant clay-embedded polyelectrolyte multilayer membranes for wastewater effluent treatment

<p>This study aimed to investigate the effects of cation exchange capacity (CEC) and location of clay nanoplatelets on the structure and performance of clay-embedded polyelectrolyte multilayer (c-PEM) membranes for wastewater effluent treatment. Two kinds of clay nanoplatelets, montmorillonite and kaolin, were deposited on the ultrafiltration membrane by employing layer-by-layer (LbL) assembly with poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA). Negatively charged clay platelets or PAA interacted with positively charged PAH to form a bilayer in the c-PEM membrane. The filtration effect of clay platelets was successively distinguished from PEM by reducing the number of (PAH/PAA) bilayers from four to one, while keeping the clay layer at the outermost layer of assembly. When the clay platelets were deposited only as the outermost layer of the LbL multilayers, the c-PEM membrane with one clay layer and one bilayer assembly showed significant flux barrier and fouling resistance. Clay platelets as the outermost layer physically increased the flow path length and decreased the number of pores, as well as effectively blocked the organic contaminants in the wastewater. Meanwhile, when the clay layer was embedded in the middle of the PEM, the synergistic effect of clay platelets and PEM for wastewater treatment was difficult to obtain because the presence of clay platelets defected the buildup of fully interdigitated c-PEM and the adsorption of clay platelets was decreased. For the clays having low CEC, a higher number of LbL multilayers were required to deposit the clay platelets and to improve the performance of membrane. The high CEC clays (montmorillonite) turned out to be better than the low CEC clays (kaolin) in the structure and performance of the c-PEM membrane for wastewater effluent treatment.</p

Spherical and cylindrical microencapsulation of living cells using microfluidic devices

Microencapsulation of cells within microfluidic devices enables explicit control of the membrane thickness or cell density, resulting in improved viability of the transplanted cells within an aggressive immune system. In this study, living cells (3T3 and L929 fibroblast cells) are encapsulated within a semi-permeable membrane (calcium crosslinked alginate gel) in two different device designs, a flow focusing and a core-annular flow focusing geometry. These two device designs produce a bead and a long microfibre, respectively. For the alginate bead, an alginate aqueous solution incorporating cells flows through a flow focusing channel and an alginate droplet is formed from the balance of interfacial forces and viscous drag forces resulting from the continuous (oil) phase flowing past the alginate solution. It immediately reacts with an adjacent CaCl drop that is extruded into the main flow channel by another flow focusing channel downstream of the site of alginate drop creation. Depending on the flow conditions, monodisperse microbeads of sizes ranging from 50-200 μm can be produced. In the case of the microfibre, the alginate solution with cells is extruded into a continuous phase of CaCl solution. The diameter of alginate fibres produced via this technique can be tightly controlled by changing both flow rates. Cell viability in both forms of alginate encapsulant was confirmed by a LIVE/DEAD cell assay for periods of up to 24 hours post encapsulation

Dispersion of unfractionated CO2-derived protein-rich microalgae (Chlorella sp. HS2) for ecofriendly polymer composite fabrication

© 2022 Elsevier LtdThis study investigates unfractionated protein-rich microalgae (Chlorella sp. HS2) (HS2) as a new CO2-derived biomass filler resource with which to develop an ecofriendly microalgae-based polymer composite. Unfractionated HS2 is mixed with poly(ethylene-vinyl acetate) (EVA) over wide range of concentrations ranging from 10 to 70 wt%. The dispersion of HS2 is analyzed based on morphological, rheological and mechanical measurements. Protein-rich HS2 has hydrophilic-hydrophobic surface due to the existence of chemical functional groups (C[dbnd]O, N-H) caused by high protein content (51% protein), predicting compatibility with EVA with polar functional (C[dbnd]O). Due to this compatibility, with 10–30 wt% of HS2, the composite shows a homogeneous micrometer-scale dispersion of HS2 in the EVA matrix (avg. diameter (Davg) ~ 7 µm). The composite maintains the dispersion of the HS2 without significant coalescence or network formation up to 50 wt% of HS2 (Davg ~ 10 µm). Correspondingly, the storage modulus (G′ at 0.1 rad/s) of the composite increases linearly until the HS2 content reaches 40 wt%, after which it increases exponentially with an increase in the HS2 content. An EVA composite with 10–20 wt% HS2 shows increased ductility (from 1700% to 2000% elongation at break with 10 wt% HS2) without a decrease in the tensile strength due to the homogeneous dispersion. Even with higher concentration of HS2, the composite maintains its ductile behavior and retains its synergistic effect with EVA (~ 500% elongation at break with 70 wt% HS2). The compatibility of HS2 with EVA and their hydrophilic surface delay agglomeration or percolation formation of HS2 cells in a polymer. This study suggests that protein-rich HS2 is a promising biomass filler that disperses in a polymer to the micrometer scale without additional chemical treatment.N