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To test the potential use of the fern Pyrrosia lingua as an anti-inflammatory functional material, we examined the effects of P. lingua ethanol extract (PLE) on RAW 264.7 macrophages treated with the pro-inflammatory molecule lipopolysaccharide (LPS). Notably, up to 100 μg/mL PLE did not result in any discernable inhibition of cellular metabolic activity or cytotoxicity in the macrophages. However, supplementing LPS-treated RAW 264.7 macrophages with PLE significantly suppressed various pro-inflammatory responses in a dose-dependent manner, including i) phosphorylation of nuclear factor-kappa B (NF-κB) subunit p65; ii) accumulation of inducible nitric oxide synthase and cyclooxygenase-2; iii) expression of pro-inflammatory mediators, including prostaglandin E synthase 2 and nitrite; and iv) expression of pro-inflammatory biomarker genes, including interleukin 1 beta, interleukin 6, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1. Taken together, our results indicate that PLE regulates NF-κB signaling and inhibits cytokine production. Therefore, the use of domestic biological resources like could be increased P. lingua as a novel functional material.

The purpose of this study is to investigate the surface activity of starch nanocrystals (SNC), material derived from starch, and confirm their usefulness as a surfactant. In order to evaluate the surface activity, the surface tension change of suspended SNC solution via the Wilhelmy plate method was measured and the values were compared with various synthetic surfactants. The effect of SNC as emulsifier was evaluated on emulsion formation and physical stability. The surface tension of the SNC-dispersed solution was decreased while its concentration was increased. When the 5.0% (w/v) of SNC was added, the surface tension was decreased from 70.3 to 49.5 mN/m. It was confirmed that the physical stability of the emulsion prepared by adding the SNC was improved compared to that of surface inactivity material (PEG 400). The phase separation was observed within 1 hour after preparation of the emulsion containing PEG 400, but the emulsion containing SNC was stable for 5 hours or more. To summarize this study, SNC, a natural-derived and non-toxic material, exhibits sufficient surface activity, thereby confirming the possibility of being applied to the food and pharmaceutical industry.

This study aimed to investigate the neuroprotective effects of 1-methoxylespeflorin G11 (MLG), a pterocarpan, against glutamate-induced neurotoxicity in neuronal HT22 hippocampal cells. The protective effects of MLG were evaluated using MTT assay and microscopic analysis. The extent of apoptosis was studied using flow cytometric analysis performed on the damaged cells probed with annexin V/propidium iodide. Moreover, mitochondrial reactive oxygen species (ROS) were assessed using flow cytometry through MitoSOXTM Red staining. To determine mitochondrial membrane potential, staining with tetramethylrhodamine and JC-1 was performed followed by flow cytometry. The results demonstrated that MLG attenuates glutamate-induced apoptosis in HT22 cells by inhibiting intracellular ROS generation and mitochondrial dysfunction. Additionally, MLG prevented glutamate-induced apoptotic pathway in HT22 cells through upregulation of Bcl-2 and downregulation of cleaved PARP-1, AIF, and phosphorylated MAPK cascades. In addition, MLG treatment induced HO-1 expression in HT22 cells. These results suggested that MLG exhibits neuroprotective effects against glutamate-induced neurotoxicity in neuronal HT22 cells by inhibiting oxidative stress and apoptosis.

Background and objectives Outbred mice are widely used in toxicology, pharmacology, and fundamental biomedical research. However, there have been no reports of in vitro culture systems for spermatogonial stem cells (SSCs) derived from these mice. Methods As a step towards constructing a non-cellular niche supporting the in vitro maintenance of outbred mouse SSC self-renewal, we systematically investigated the types of integrin heterodimers that are expressed transcriptionally, translationally, and functionally in SSCs derived from Imprinting Control Region (ICR) mice. Results Among the genes encoding 25 integrin subunits, integrin α1, α5, α6, α9, αV, and αE, and integrin β1 and β5 had significantly higher transcriptional levels than the other subunits. Furthermore, at the translational level, integrin α5, α6, α9, αV, and αE, and β1 were localized on the surface of SSCs, but integrin α1 and β5 not. Moreover, significantly stronger translational expression than integrin α9 and αE was observed in integrin α5, α6, αV, and β1. SSCs showed significantly increased adhesion to fibronectin, laminin, tenascin C and vitronectin, and functional blocking of integrin α5β1, α6β1, α9β1 or αVβ1 significantly inhibited adhesion to these molecules. Conclusions We confirmed that integrin α5β1, α6β1, α9β1 and αVβ1 actively function on the surface of undifferentiated SSCs derived from outbred ICR mice.

Previously, we reported that endometrial stromal (ES) and endometrial epithelial (EE) cells did not attach to tenascin C, indicating the absence of active integrin α9β1 on the surface of mouse ES and EE cells. However, that study used recombinant tenascin C without fibronectin (FN) type III repeats interacting with integrin heterodimers. Therefore, we re-evaluated the presence of integrin α9β1 actively functioning on the surface of mouse ES and EE cells using full-length native tenascin C with FN type III repeats. The functionality of integrin α9β1 was confirmed using attachment and antibody inhibition assays. Both mouse ES and EE cells showed significantly increased adhesion to native tenascin C, and functional blocking of integrin α9β1 significantly inhibited adhesion to native tenascin C. These results demonstrate that the integrin α9 and β1 subunits function as active heterodimers on the plasma membrane of mouse ES and EE cells, respectively.

The instability of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) under a humid condition is the major limitation in the practical development of a flexible thermistor. Here, we introduced a functionalized graphene oxide–polyvinylidene fluoride (FGO–PVDF) composite as an encapsulation layer to prove the reliability of PEDOT:PSS thermistors under high-humidity conditions. The FGO–PVDF-encapsulated thermistor exhibited good linearity, a resolution of 1272.57 Ω per °C, a temperature coefficient of resistance equal to −3.95 × 10−3 per °C, stable performance, and an acceptable response time (∼40 s per °C) calibrated in the temperature range between −10 °C and 30 °C, resembling the temperature of a cold chain system. For applications in a food cold chain system, this thermistor was integrated into a roll-to-roll (R2R) gravure-printed NFC antenna, a microcontroller-embedded Si-chip transponder, and a printed battery to work as a smart label to wirelessly monitor the time–temperature history (TTH) of a food package. A proof-of-concept study was demonstrated by attaching an NFC-enabled hybrid TTH logger, a smart label, in a chicken package.

Paclitaxel, a member of the taxane family, exhibits antitumour effects by targeting the microtubules in cancer cells. Recently, oral paclitaxel has been developed to overcome the side effects of intravenous paclitaxel administration in human patients. The objective of this study was to investigate the antitumour effects of oral paclitaxel in vitro and in vivo. Three weeks after inoculation, oral paclitaxel (25 and 50 mg/kg) or saline was administered every week for three consecutive weeks. To explore the underlying mechanism, tumour angiogenesis was examined by immunohistochemistry with an anti-CD31 antibody. Tumour cell apoptosis was detected by Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling assay, and cell cycle arrest was confirmed by western blot analysis. Oral paclitaxel treatment of canine melanoma cells exerted mediated antiproliferative effects and mediated cell cycle arrest in vitro. In animal experiments, after oral paclitaxel administration, the average tumour size decreased to approximately 30% of that in the control. Histologically, oral paclitaxel showed anti-angiogenic effects and induced the apoptosis in tumour tissues. Oral paclitaxel also downregulated the intratumoural expression of cyclin D1 and inhibited cell proliferation. The study findings support potential application of oral paclitaxel as a novel chemotherapeutic strategy to treat canine melanoma. This is the first study to investigate the potential of oral paclitaxel as a therapeutic drug against canine tumours.

Introduction Hair growth-promoting herbal extract mixtures (4HGF) exhibits significant anti-inflammatory activities relevant to promoting hair growth; however, its efficacy in patients with hair loss has been limited majorly due to its low penetration ability into hair follicles. Herein, we prepared hydrogels via dropwise addition of poly(γ-glutamic acid) (PGA) solution containing 4HGF into chitosan (CS) solution, resulting in quick formation of ~400 nm-sized hydrogel particles through electrostatic interaction-derived ionic gelation with over 50% encapsulation efficiency of 4HGF (PGA-4HGF). Methods The size and morphology of PGA-4HGF were characterized by TEM, SEM, and dynamic light scattering analyses. Encapsulation efficiency and loading capacity of 4HGF within PGA-4HGF, as well as in vitro release profiles were determined by simply measuring the characteristic absorbance of 4HGF. Penetrating efficiency of PGA-4HGF was evaluated by tracking the respective fluorescence through model porcine skin with confocal laser microscope system. By treating PGA-4HGF on telogenic mice and dermal papilla cells (DPCs), we evaluated the size of hair bulbs in mice, as well as morphological changes in DPCs. Results Negligible and sustained release of entrapped 4HGF from the hydrogel nanoparticles were observed under acidic and physiological pH conditions, respectively, which is quite advantageous to control their release and prolong their hair growth-promoting effect. The hydrogel nanoparticles were penetrable through the porcine skin after incubation with or without shaking. After treating telogenic mice and DPCs with PGA-4HGF, we detected enlargement of hair bulbs and remarkable shape changes, respectively, thereby showing its potential in induction of hair growth. Conclusion These results suggest that the hydrogel nanoparticle formulation developed in this study can be employed as a potential approach for the preservation of hair growth-promoting compounds, their delivery of into hair follicles, and enhancing hair growth.

Symphyocladia latiuscula (Harvey) Yamada is a red alga with a myriad of bromophenols accompanied by a diverse array of biological activities. The main purpose of the present study was to characterize the anti-Alzheimer's disease activity of bromophenols from S. latiuscula via inhibition of cholinesterases (AChE and BChE), β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and glycogen synthase kinase-3β (GSK-3β). The results of enzyme inhibition assays demonstrated 2,3,6-tribromo-4,5-dihydroxybenzyl alcohol (1), 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (2), and bis-(2,3,6-tribromo-4,5-dihydroxybenzyl) ether (3) as potent inhibitors of aforementioned enzymes. Among the tested bromophenols, 3 showed multifold higher inhibition of all of the tested enzymes. Enzyme kinetics revealed different modes of inhibition, and in silico molecular docking simulation demonstrated the importance of the 7-OH group and bromine number for H-bond and halogen-bond interactions, respectively. Similarly, 1-3 at 20 μM concentration showed more than 50% inhibition of self-induced Aβ25-35 aggregation. These results suggest that bromophenols from S. latiuscula, especially highly brominated (3), may represent a novel class of anti-Alzheimer's disease drugs.

Vitamin D hydroxylation-deficient rickets type 1A (VDDR1A, OMIM 264700) is a rare autosomal recessive inherited disorder. Pathogenic variants in the CYP27B1 gene lead to loss of 1α-hydroxylase activity. We report the case of a 22-month-old toddler who presented with growth retardation and delayed development. The patient exhibited the typical laboratory findings of VDDR1A, including hypocalcemia (calcium: 5.2 mg/dL), elevated serum level of alkaline phosphatase (2,600 U/L), elevated serum level of intact-parathyroid hormone (238 pg/mL), low 1,25(OH)2D3 level (11.2 pg/mL), and normal 25(OH)D3 level (40.7 ng/mL). His height and weight were 76.5 cm and 9.5 kg, respectively (both

Nonalcoholic fatty liver disease is a progressive disease involving the accumulation of lipid droplets in the liver. In this study, we investigated the anti-hepatosteatosis effects of fermented Cordyceps militaris extract (CME) in AML-12 hepatocytes. Although the levels of adenosine and cordycepin were reduced in the extracts of CM grown on germinated soybean (GSCE) and fermented CM grown on germinated soybean (GSC) by Pediococcus pentosaceus ON188 (ON188E), the expression of fatty acid oxidation (FAO) genes were upregulated only by GSC-ON188E treatment in a dose-dependent manner. In contrast, a lipogenic gene, stearoyl Coenzyme A desaturase 1, was downregulated by ON188E. Formation of intracellular lipid droplets by the addition of oleic acid was reduced by ON188E to levels observed in WY14643-treated cells. When cells were treated with ON188E, sphingosine kinase 2 mainly responsible for hepatic sphingosine 1-phosphate (S1P) synthesis was upregulated and S1P was elevated. Collectively, the fermented GSC extract activates FAO through elevation of S1P synthesis and has potential as a therapeutic for hepatosteatosis.

The synthesis and biological evaluation as potential urotensin-II receptor antagonists of a series of 5-arylfuran-2-carboxamide derivatives 1, bearing a 4-(3-chloro-4-(piperidin-4-yloxy)benzyl)piperazin-1-yl group, are described. The results of a systematic SAR investigation of furan-2-carboxamides with C-5 aryl groups possessing a variety of aryl ring substituents led to identification of the 3,4-difluorophenyl analog 1y as a highly potent UT antagonist with an IC50 value of 6 nM. In addition, this substance was found to display high metabolic stability, and low hERG inhibition and cytotoxicity, and to have an acceptable PK profile.

Germinated black bean (Rhynchosia nulubilis) (GRN) has several beneficial health effects, including immunostimulation. To enhance the immunostimulatory effect of GRN, it was fermented with lactic acid bacteria (LAB). A total of 57 strains of LAB that showed good growth on GRN were isolated from various fermented foods and vegetables. Among them, Lactobacillus pentosus SC65 was selected as a starter culture for GRN fermentation. Optimum solid–state fermentation conditions of GRN with L. pentosus SC65 (GRN–SC65) were: water content of 40% (v/w), fermentation time of 24 h, fermentation temperature of 30 °C, and inoculation volume of 5% (v/w). RAW264.7 cells treated with hot water extract of GRN–SC65 showed high nitric oxide production and phagocytic activity, indicating high immunostimulatory activity of GRN–SC65.

Dendropanax morbifera leaves (DML) have long been used as traditional medicine to treat diverse symptoms in Korea. Ethyl acetate-soluble extracts of DML (DMLE) rescued HT22 mouse hippocampal neuronal cells from glutamate (Glu)-induced oxidative cell death, however, the protective compounds and mechanisms remain unknown. Here, we aimed to identify the neuroprotective ingredients and mechanisms of DMLE in the Glu-HT22 cell model. Five antioxidant compounds were isolated from DMLE and characterized as chlorogenic acid, hyperoside, isoquercitrin, quercetin, and rutin by spectroscopic methods. Isoquercitrin and quercetin significantly inhibited Glu-induced oxidative cell death by restoring intracellular reactive oxygen species (ROS) levels and mitochondrial superoxide generation, Ca2+ dysregulation, mitochondrial dysfunction, and nuclear translocation of apoptosis-inducing factor. These two compounds significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the presence or absence of Glu treatment. Combinatorial treatment of the five compounds based on the equivalent concentrations in DMLE showed that significant protection was found only in the cells cotreated with isoquercitrin and quercetin, both of whom showed prominent synergism, as assessed by drug–drug interaction analysis. These findings suggest that isoquercitrin and quercetin are the active principles representing the protective effects of DMLE, and these effects were mediated by the Nrf2/HO-1 pathway.

Background Ultraviolet B (UVB) irradiation is viewed as the main factor of skin aging, associated with acceleration of elastin, collagen degradation and expression of matrix metalloproteinases (MMPs). Apples are one of the most commonly eaten fruits in the world, and isoquercitrin is the main active ingredient in new bred varieties "Green ball" apple. Therefore, we are studying the functionality of the active ingredient of apple, a natural raw material that does not have toxicity or sensitivity problems. Objectives The aim of this study, we scrutinized the effects of isoquercitrin on skin photoaging in UVB-exposed human fibroblasts (CCD-986Sk). Methods To investigate the inhibition effect on photoaging factor regulation, isolated isoquercitrin were treated with UVB, which induces photoaging-related factors in CCD-986Sk fibroblast cells. Pro-inflammatory factors were measured by ELISA, Western blotting and real-time PCR. Results Isoquercitrin exhibited antioxidant activity and UVB-induced generation of photoaging-related factor inhibition without showing any toxicity. Anti-photoaging effect for protein levels using Isoquercitin was competent, of both the combate MMP-1 and MMP-9. Also, effect of COL1A2 product significantly increase, from up regulating the TIMP-1 mediated pathway in CCD-986Sk cells via the inhibition of MMPs. Isoquercitrin also downregulated the mRNA gene expression of MMPs while upregulating type I procollagen, HAS2 by modulating TIMP-1 and TGF-β in UVB-irradiated CCD-986Sk cells. Conclusions Collectively, our results show that isoquercitrin might be useful as a functional food while being a good candidate in the development of cosmetic products and medicines for the remedy of UVB-induced skin photoaging.

Rhynchosia nulubilis (black soybean) has many applications in oriental medicine. It is traditionally used to treat disease related with high blood pressure, diabetes, inflammation, and osteoporosis. Furthermore, fermented soybean foods have traditionally been used for immunity enhancement in East Asia. However, the anti-inflammatory effects of germinated R. nulubilis (GR) against delayed-type hypersensitivity (DTH) are not fully understood.This study aimed to investigate the anti-inflammatory effects of germinated Rhynchosia nulubilis (GR) fermented with the lactic acid bacterium Lactobacillus pentosus SC65 (GR-SC65) isolated from pickled burdock.We investigated the effects of GR-SC65 (300 mg/kg/day) on ear thickness and immune cell infiltration in DNFB-induced DTH in mice. We used dexamethasone (3 mg/kg) as a reference drug. Changes in infiltration of CD4Two lactic acid bacterial strains (Lactobacillus pentosus SC65 and Pediococcus pentosaceus ON81A) were selected for fermenting GR due to their high 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity. The total polyphenol contents (TPCs) in GR-SC65 and GR-ON81A were higher than that in unfermented GR (∗∗∗P 0.001 vs. GR). Content of daidzein, glycitein, and genistein, the deglycosylated form of isoflavonoids, was higher in GR-SC65 than in unfermented GR. The ethanol extracts of GR-SC65 exerted a stronger anti-inflammatory activity than GR by inhibiting pro-inflammatory cytokines, such as tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in LPS-induced RAW264.7 macrophages. GR-SC65 reduced 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced ear swelling and hyperplasia as well as vascular permeability. Fewer infiltrated CD4These data suggest that GR-SC65 can be used as a health supplement or a prophylactic against delayed-type hypersensitive inflammatory disease.

In vivo, melanocytes occupy three-dimensional (3D) space. Nevertheless, most experiments involving melanocytes are performed in a two-dimensional microenvironment, resulting in difficulty obtaining accurate results. Therefore, it is necessary to construct an artificial in vivo-like 3D microenvironment. Here, as a step towards engineering a precisely defined acellular 3D microenvironment supporting the maintenance of human epidermal melanocytes (HEMs), we examined the types of integrin heterodimers that are expressed transcriptionally, translationally, and functionally in HEMs. Real-time PCR and fluorescent immunoassay analyses were used to elucidate the expression of integrin α and β subunit genes at the transcriptional and translational levels, respectively. The functionality of the presumed integrin heterodimers was confirmed using attachment and antibody-inhibition assays. Among the genes encoding 12 integrin subunits (α1, α2, α3, α4, α5, α6, α7, αV, β1, β3, β5, and β8) showing significantly higher transcription levels, proteins translated from the integrin α2, α4, α5, β1, β3, and β5 subunit genes were detected on the surface of HEMs. These HEMs showed significantly increased adhesion to collagen I, fibronectin, laminin, and vitronectin, and functional blockade of the integrin α2 subunits significantly inhibited adhesion to collagen I, fibronectin, and laminin. In addition, there was no significant inhibition of the adhesion to fibronectin or vitronectin in HEMs with functional blockade of the integrin α4, α5, or αV subunits. These results indicate that the active integrin α2β1 heterodimer and the inactive integrin α4, α5, αV, β3, and β5 subunits are all localized on the surface of HEMs.

Significance Parkinson’s disease and its associated dementia can be caused by elevated levels of α-synuclein protein. Despite many efforts, however, targeting α-synuclein at the protein level has been challenging. In this manuscript, we describe the design of a small molecule that selectively targets the messenger RNA that encodes α-synuclein protein and selectively inhibits its translation. Furthermore, the compound is cytoprotective. Collectively, our findings show that difficult-to-target proteins can indeed be regulated by small molecules by binding the encoding mRNA. This strategy is a potentially promising way to slow the progression of Parkinson’s disease and related neurological disorders., Many proteins are refractory to targeting because they lack small-molecule binding pockets. An alternative to drugging these proteins directly is to target the messenger (m)RNA that encodes them, thereby reducing protein levels. We describe such an approach for the difficult-to-target protein α-synuclein encoded by the SNCA gene. Multiplication of the SNCA gene locus causes dominantly inherited Parkinson’s disease (PD), and α-synuclein protein aggregates in Lewy bodies and Lewy neurites in sporadic PD. Thus, reducing the expression of α-synuclein protein is expected to have therapeutic value. Fortuitously, the SNCA mRNA has a structured iron-responsive element (IRE) in its 5′ untranslated region (5′ UTR) that controls its translation. Using sequence-based design, we discovered small molecules that target the IRE structure and inhibit SNCA translation in cells, the most potent of which is named Synucleozid. Both in vitro and cellular profiling studies showed Synucleozid directly targets the α-synuclein mRNA 5′ UTR at the designed site. Mechanistic studies revealed that Synucleozid reduces α-synuclein protein levels by decreasing the amount of SNCA mRNA loaded into polysomes, mechanistically providing a cytoprotective effect in cells. Proteome- and transcriptome-wide studies showed that the compound’s selectivity makes Synucleozid suitable for further development. Importantly, transcriptome-wide analysis of mRNAs that encode intrinsically disordered proteins revealed that each has structured regions that could be targeted with small molecules. These findings demonstrate the potential for targeting undruggable proteins at the level of their coding mRNAs. This approach, as applied to SNCA, is a promising disease-modifying therapeutic strategy for PD and other α-synucleinopathies.

α-Synuclein (α-Syn) is a key pathogenic protein in α-synucleinopathies including Parkinson disease (PD) and Dementia with Lewy Bodies. Accumulating evidence from studies of postmortem human brains, rodent models and cultured neurons show that misfolded fibrillar α-Syn is transmitted from cell-to-cell, a phenomenon that correlates with clinical progression and emergence of additional neuropsychiatric manifestations as the disease advances. We previously showed that deleting the MAP3 kinase Apoptosis Signal-Regulating Kinase 1 (ASK1), which is a central player linking oxidative stress with neuroinflammation, mitigates the phenotype of α-Syn transgenic mice. However, whether ASK1 impacts pathology and disease progression induced by recombinant α-Syn preformed fibrils (PFF) remains unknown. Here, we compared the neuropathological and behavioral phenotype of ASK1 knock-out mice with that of wild-type mice following intrastriatal injections of α-Syn PFF. At six months post-injections, ASK1 null mice exhibited reduced amount of phosphorylated α-Syn aggregates in the striatum and cortex, and less pronounced degeneration of the nigrostriatal pathway. Additionally, the neuroinflammatory reaction to α-Syn PFF injection and propagation seen in wild-type mice was attenuated in ASK1 knock-out animals. These neuropathological markers of diminished toxicity of α-Syn PFF in the absence of ASK1 was associated with better behavioral performance on the Rotarod and nesting behavior compared to wild-type mice. These data suggest that ASK1 plays an important role in pathological α-Syn fibril transmission and, consequently, may impact disease progression. These findings collectively support inhibiting ASK1 as a disease modifying therapeutic strategy for PD and related α-synucleinopathies.

A Grignard reagent containing pyrene, 1-pyrenylmethylmagnesium bromide (PMgBr), was explored as a novel reactive compatibilizer for producing aliphatic polyketone (PK) composites with multi-walled carbon nanotube (MWCNT) that had improved interfacial adhesion and mechanical strength. 1-Bromomethylpyrene (PBr) was adsorbed on MWCNTs and reacted with Mg to produce PMgBr on MWCNTs (MWCNT-PMgBr). PK-grafted MWCNT (PK-g-MWCNT) was prepared by reacting MWCNT-PMgBr with PK, and its composite with PK was fabricated by melt extrusion. The formation of PK-g-MWCNT was examined by spectroscopy, electron microscopy, and thermal analysis. The PK interfacial adhesion energies with MWCNTs were quantified, and the mechanical strengths of their composites examined. PK-g-MWCNT had the highest interfacial adhesion energy with PK among the MWCNTs. The PK/PK-g-MWCNT composite showed better MWCNT dispersion in PK and interfacial adhesion between MWCNT and PK than the PK/pristine MWCNT composite. Consequently, the PK/PK-g-MWCNT composite exhibited higher mechanical strength than the PK/pristine MWCNT composite when the composite contained the same amount of MWCNTs.

(Sr1-xCax)0.95Ga2S4:0.05Eu (x = 0, 0.25, 0.50, 0.75, 1) and Sr1-yGa2S4:yEu (y = 0.05, 0.25, 0.50, 0.75, 1) phosphors were synthesized from CaS, SrS, EuS, and Ga2S3 by carrying out solid-state reactions. X-ray diffraction (XRD) results indicated that the (Sr1-xCax)0.95Ga2S4:0.05Eu and Sr1-yGa2S4:yEu phosphors formed solid solutions between SrGa2S4 and CaGa2S4, and between SrGa2S4 and EuGa2S4, respectively. The photoluminescence excitation (PLE) and photoluminescence (PL) spectra of these phosphors were examined. The wavelength at maximum intensity (λmax) of the PL spectra changed gradually from 537 to 559 nm as the calcium ion mole fraction (x) increased in the (Sr1-xCax)0.95Ga2S4:0.05Eu phosphors. λmax changed from 537 to 545 nm as the europium mole fraction (y) in the Sr1-yGa2S4:yEu phosphors increased. The luminescence parameters, such as the zero phonon line energy (E0), Stokes shift (ΔS), and red shift (D), were calculated from the PLE and PL spectra of these phosphors. The origins of the wavelength changes were deduced from the luminescence parameters of these phosphors. The three-band white light emitting diode (WLED) was fabricated by coating the (Sr0.5Ca0.5)0.95Ga2S4:0.05Eu as a greenish yellow-emitting phosphor and K2SiF6:Mn4+ as a red-emitting phosphor onto a commercial blue LED. The photoluminescence property of the three-band WLED was investigated.

본 연구에서는 층꽃나무와 L. plantarum으로 발효한 층꽃나무를 각각 80% ethanol로 추출하여 추출물들이 LPS로 유도된 Raw 264.7 cell의 염증반응에 미치는 영향을 비교 검증하여 항염증 소재 개발 가능성을 검토하였다. HPLC를 이용하여 L. plantarum에 의한 층꽃나무 발효 추출물의 유용성분 변화를 확인한 결과, 발효를 통해 유용성분의 profile 변화가 있는 것을 확인할 수 있었다. Raw 264.7 cell에서 세포 독성을 측정하기 위해 MTT assay를 실시한 결과, 층꽃나무 80% ethanol 추출물은 5, 10, 15 μg/mL의 농도에서 발효 층꽃나무 80% ethanol 추출물의 경우 10, 20, 30, 40 μg/mL의 농도에서 90.0% 이상의 세포 생존율을 나타내었다. 항염증 효능을 검정하기 위해 iNOS 단백질 발현량, COX-2 단백질 발현량, NO 생성, PGE2 생성, pro-inflammatory cytokine 발현량을 측정하였다. NO 생합성 효소인 iNOS 단백질의 발현량을 측정한 결과, 층꽃나무와 발효 층꽃나무 80% ethanol 추출물은 각각 15, 40 μg/mL의 농도에서 약 50.0% 가까운 발현 억제 효과를 나타내었으며, 농도 의존적으로 감소하는 것을 확인할 수 있었다. PGE2 생합성 효소인 COX-2 단백질의 발현량을 측정한 결과, 층꽃나무 80% ethanol 추출물은 15 μg/mL 농도에서 50.0%, 발효 층꽃나무 80% ethanol 추출물은 40 μg/mL 농도에서 83.0%의 발현 억제효과를 보여주었다. NO 생성 억제 효과를 측정한 결과 층꽃나무 80% ethanal 추출물은 15 μg/mL 농도에서 62.0%, 발효 층 꽃나무는 40 μg/mL 농도에서 81.0%로 control군과 비교하였을 때 NO 생성이 크게 억제되었다. PGE2 생성 억제 효과를 측정한 결과, 층꽃나무와 발효 층꽃나무 80% ethanal 추출물은 각각 15, 30 μg/mL의 농도에서 약 70.0%의 발현 억제 효과를 나타내었다. 또한, pro-inflammatory cytokine의 경우, 층꽃나무 80% ethanol 추출물 15 μg/mL 농도에서 TNF-α는 43.6%, IL-6는 64.3%, IL-1β는 58.7%의 저해율을 나타냈으며, 발효 층꽃나무 80% ethanol 추출물 40 μg/mL 농도에서 TNF-α는 75.4%, IL-6는 64.3%, IL-1β는 37.7%의 발현 억제 효과를 나타내었다. 이상의 결과를 통해 층꽃나무는 매우 우수한 항염증 효과를 나타내는 소재임을 확인할 수 있었으며, L. plantarum균을 이용한 발효를 통해 층꽃나무가 가진 세포 독성을 낮추어 안전성하고 우수한 효능을 가진 새로운 항염증제로 개발 가능한 소재로 활용될 수 있을 것으로 기대되었다.

Recently, a digital fabrication technique has been recognized as one of requisite processing methods that can realize large-area, low-cost, form-factor free optoelectronics applications. Digitally printed conductive layers are implemented in practical device layouts for electrically interconnecting active/passive components. In terms of high conductivity, printing processability, and cost-effectiveness, printable Cu fluids are most appropriate to generate highly conductive printed features. To resolve critical issues in printed Cu conductors, we propose a selective green-laser-sintering process with a usage of a mixture of Cu nanoparticles and flakes. Surface oxide-free Cu nanoparticles and sub-micron Cu particles are synthesized through highly concentrated solvothermal synthetic methods. Sub-micron spherical Cu particles are transformed into disc-shaped Cu flakes by a subsequent mechanical milling process. The printable Cu fluids including the mixed particles and a photo-reactive polymer, enable the formation of printed particle assemblies that can be sintered by highly energetic green-wavelength photons. It is demonstrated that highly conductive printed layers are generated with values in resistivity and resistance as low as 16 μΩ cm and 1.9 Ω/cm, respectively, by the combined approach of mask-free printing and selective green-laser sintering processes.

와송에 함유된 phenol성 물질은 50% ethanol을 용매로 하여 추출하였을 때 $10.56{\pm}0.32mg/g$의 함량을 나타내었다. 와송 추출물의 항산화력을 측정한 결과 전자공여능은 $200{\mu}g/mL$ phenolic 농도에서 열수 추출물과 50% ethanol 추출물 모두 80.0% 이상으로 높은 효과가 확인되었다. ABTS radical cation decolorization을 측정한 결과에서 와송 열수와 50% ethanol 추출물 모두 95.0% 이상의 높은 항산화 활성이 측정되었다. Antioxidant protection factor (PF)는 열수 추출물이 50% ethanol 추출물에 비해 높은 PF값을 나타내었으며, thiobarbituric acid reactive substance (TBARs) 저해효과는 50% ethanol 추출물이 열수 추출물 보다 높은 항산화력을 나타내었다. 와송 추출물의 항고혈압 효과를 살펴보기 위하여 angiotensin converting enzyme 저해활성을 측정한 결과 $200{\mu}g/mL$ phenolic의 처리농도에서 열수와 50% ethanol 추출물이 각각 6.67%과 7.98%로 낮게 나타났다. 와송 추출물의 XOase 저해활성은 50% ethanol 추출물 $200{\mu}g/mL$ phenolic 농도에서 60.85%의 저해율을 나타내었으며, tyrosinase 억제활성은 50% ethanol 추출물 $200{\mu}g/mL$ phenolic 농도에서 64.59%로 나타나 대조구인 kojic acid 보다 미백 효과가 더 우수함을 입증하였다. 주름 생성과 관련된 collagenase 억제효과는 50% ethanol 추출물의 $50200{\mu}g/mL$ phenolic 농도에서 75.9585.02%로 매우 우수하였으며, 대조구인 epigallocatechin-gallate의 68.9176.64% 보다 다소 높았다. Elastase 저해활성도 50% ethanol 추출물 $200{\mu}g/mL$ phenolic 농도에서 최대 63.65%의 저해효과를 나타내어 와송 50% ethanol 추출물의 주름개선 효과가 매우 우수함을 확인하였다. 이상의 결과를 통해 와송 추출물의 항산화 활성, 통풍 억제효능, 미백 및 주름개선 등의 기능성 검증을 위한 기초 연구 자료로 활용이 가능할 것으로 예상되며, 향후 추가적인 연구를 통해 와송 추출물을 기능성 식품 및 화장품, 의약품 소재로 적용이 가능할 것으로 판단되었다.

Hyperphosphorylated tau aggregates are characteristic of tauopathies including progressive supranuclear palsy (PSP) and Alzheimer disease (AD), but factors contributing to pathologic tau phosphorylation are not well understood. Here, we studied the regulation of the major tau phosphatase, the heterotrimeric AB55αC protein phosphatase 2 A (PP2A), in PSP and AD. The assembly and activity of this PP2A isoform are regulated by reversible carboxyl methylation of its catalytic C subunit, while the B subunit confers substrate specificity. We sought to address whether the decreases in PP2A methylation and its methylating enzyme, leucine carboxyl methyltransferase (LCMT-1), which are reported in AD, relate to tau pathology or to concomitant amyloid pathology by comparing them in the relatively pure tauopathy PSP. Immunohistochemical analysis of frontal cortices showed that methyl-PP2A is reduced while demethyl-PP2A is increased, with no changes in total PP2A or B55α subunit, resulting in a reduction in the methyl/demethyl PP2A ratio of 63% in PSP and 75% in AD compared to controls. Similarly, Western blot analyses showed a decrease of methyl-PP2A and an increase of demethyl-PP2A with a concomitant reduction in the methyl/demethyl PP2A ratio in both PSP (74%) and AD (76%) brains. This was associated with a decrease in LCMT-1 and an increase in the demethylating enzyme, protein phosphatase methylesterase (PME-1), in both diseases. These findings suggest that PP2A dysregulation in tauopathies may contribute to the accumulation of hyperphosphorylated tau and to neurodegeneration.

Eclalbasaponin II derived from Eclipta prostrata L. (Asteraceae) has been reported to have anti-fibrotic, anti-bacterial and autophagic activities, but its effect on cognitive function has not been investigated. We studied the effect of eclalbasaponin II on cholinergic blockade-induced memory impairment in mice using the passive avoidance, Y-maze, and Morris water maze tasks. Eclalbasaponin II (10 or 20 mg/kg, p.o.) significantly ameliorated the cognitive dysfunction induced by scopolamine in the passive avoidance, Y-maze, and the Morris water maze tasks. To identify the mechanism of the memory-ameliorating effect of eclalbasaponin II, acetylcholinesterase (AChE) activity assay, Western blot analysis and electrophysiology were conducted. Eclalbasaponin II inhibited the AChE activity in ex vivo study, and the administration of eclalbasaponin II and its metabolite, echinocystic acid, increased the phosphorylation levels of memory-related signaling molecules, including protein kinase B (Akt) and glycogen synthase kinase-3β (GSK-3β), in the hippocampus. Although eclalbasaponin II did not affect hippocampal long term potentiation (LTP), echinocystic acid significantly enhanced hippocampal LTP formation (30 μM). These results suggest that eclalbasaponin II ameliorates cholinergic blockade-induced cognitive impairment via AChE inhibition, LTP formation and the activation of Akt-GSK-3β signaling, and that eclalbasaponin II may be a useful to treat cognitive impairment derived from cholinergic dysfunction.

Cordyceps militaris (C. militaris) has various biomedical applications in traditional oriental medicine for different diseases including inflammatory and immune-dysregulated diseases. It is a reservoir of nutritional components such as cordycepin, polysaccharides, and antioxidants. To improve its bioactivity, we fermented C. militaris with a Pediococcus pentosaceus strain isolated from a salted small octopus (SC11). The current study aimed to evaluate whether P. pentosaceus (SC11) fermentation could enhance the anti-allergic potential of C. militaris cultured on germinated Rhynchosia nulubilis (GRC) against a type I hypersensitive reaction in in vitro and in vivo studies. Total antioxidant capacity and cordycepin content were significantly increased in GRC after SC11 fermentation. GRC-SC11 showed significantly enhanced anti-allergic responses by inhibiting immunoglobulin E (IgE)/antigen-induced degranulation in RBL-2H3 cells, compared to GRC. The results demonstrated the significant inhibition of phosphorylated spleen tyrosine kinase (Syk)/ p38/GRB2-associated binding protein 2 (Gab2)/c-jun in IgE/Ag-triggered RBL-2H3 cells. Furthermore, suppressed mRNA levels of interleukin-4 (IL-4) and tumor necrosis factor-α (TNF-α) in IgE/Ag-activated RBL-2H3 cells were observed. GRC-SC11 significantly ameliorated IgE-induced allergic reactions by suppressing the ear swelling, vascular permeability, and inflammatory cell infiltration in passive cutaneous anaphylaxis (PCA) BALB/c mice. In conclusion, GRC fermented with P.pentosaceus exerted enhanced anti-allergic effects, and increased the cordycepin content and antioxidants potential compared to GRC. It can be used as bio-functional food in the prevention and management of type I allergic diseases.

In this study, the effect of GBR fermented with the Pediococcus pentosaceus SP024 strain on IgE/Ag mediated passive cutaneous anaphylaxis (PCA) was investigated. Protocatechuic acid and trans-ferulic acid levels in GBR-SP024 increased more than those in unfermented GBR, respec-tively. The inhibitory activity of GBR-SP024 on β-hexosaminidase release and the level of proin-flammatory cytokine mRNA expression (tumor necrosis factor-α (TNF-α) and interleukin 4 (IL-4)) was observed in IgE/Ag-stimulated RBL-2H3 cells. Western blot analysis showed that GBR-SP024 significantly inhibited the phosphorylation of the linker for activation of T cell (LAT) and nuclear factor-κB (NF-κB) in IgE/Ag-stimulated RBL-2H3 cells. Further, we investigated the anti-allergic effect of GBR-SP024 using PCA murine model. The number of infiltrated immune cells and degranulated mast cells in GBR-SP024 treated dermis was lower than that in the GBR-treated mice. In addition, mRNA expression of 5-lipoxygenase (5-LOX) in the dermis of ear tissue declined in the GBR-SP024–treated group, compared to that in the GBR group. GBR-SP024 was also more effective than GBR at reducing the levels of IL-33 protein expression in IgE/Ag-stimulated BALB/c mice. Our study suggests the potential usage of GBR-SP024 as a dietary supplement or an adjuvant for treating IgE-dependent-allergic diseases.

Global aging has led to growing health concerns posed by Alzheimer’s disease (AD), the most common type of dementia. Aripiprazole is an atypical FDA-approved anti-psychotic drug with potential against AD. To investigate its therapeutic effects on AD pathology, we administered aripiprazole to 5xFAD AD model mice and examined beta-amyloid (βA)-induced AD-like phenotypes, including βA production, neuroinflammation, and cerebral glucose metabolism. Aripiprazole administration significantly decreased βA accumulation in the brains of 5xFAD AD mice. Aripiprazole significantly modified amyloid precursor protein processing, including carboxyl-terminal fragment β and βA, a disintegrin and metalloproteinase domain-containing protein 10, and beta-site APP cleaving enzyme 1, as determined by Western blotting. Neuroinflammation, as evidenced by ionized calcium binding adapter molecule 1 and glial fibrillary acidic protein upregulation was dramatically inhibited, and the neuron cell layer of the hippocampal CA1 region was preserved following aripiprazole administration. In 18F-fluorodeoxyglucose positron emission tomography, after receiving aripiprazole, 5xFAD mice showed a significant increase in glucose uptake in the striatum, thalamus, and hippocampus compared to vehicle-treated AD mice. Thus, aripiprazole effectively alleviated βA lesions and prevented the decline of cerebral glucose metabolism in 5xFAD AD mice, suggesting its potential for βA metabolic modification and highlighting its therapeutic effect over AD progression.

소나무 뿌리(동송근)로부터 phenolic compounds를 추출 후 미용식품활성을 검정하여 기능성 소재로 활용가능성을 살펴보았다. 동송근에 함유된 페놀성 물질의 tyrosinase 저해효과를 측정한 결과 50 μg/mL phenolics 농도에서 ethanol 추출물이 92%의 tyrosinase 저해효과를 나타내었다. Elastase와 collagenase 저해효과를 측정한 결과 200 μg/mL phenolics 농도에서 ethanol추출물이 각각 61, 78%의 높은 저해력을 나타내어 주름개선효과가 높았다. 수렴효과는 50 μg/mL phenolics의 저농도 ethanol추출물에서 82%의 저해효과를 나타내었다. 염증억제효과를 나타내는 hyaluronidase 저해효과를 측정한 결과 100-200 μg/mL phenolic 농도의 ethanol 추출물에서 74-94%의 매우 높은 염증억제효과를 나타내었다. 이러한 결과로 보아 동송근 추출물이 미용식품활성 또는 기능성 소재로서 활용이 가능할 것으로 판단되었다.