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A new ultra-hydrophilic elastic sponge composite has been proposed. Medicinal herbs, commonly used in herbal medicine and subsequently discarded, are rich in natural polymer substances, making them promising candidates for various material industries. TEMPO-oxidized cellulose was extracted from medicinal herb residue, and the physicochemical properties of an ultra-hydrophilic elastic sponge, prepared through a PVA and CA impregnate cross-linking process, were investigated. The fabricated composite sponge exhibited an increase in compressive stress-strain proportional to the PVA cross-linking concentration, and its water retention capability was assessed through retention tests. Swelling tests for various solvents were conducted to evaluate the potential use of the sponge in diverse industries, revealing the highest swelling ratio in water. Pressure distribution measurements using prescale film indicated that the sponge's shock absorption capacity was enhanced by PVA cross-linking, leading to improved pressure dispersion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: This review aimed to evaluate the effects of gamification on academic motivation and confidence among undergraduate nursing students and identify the game design elements contributing to these effects., Design: Systematic review and meta-analysis., Data Sources: Comprehensive systematic searches were conducted to retrieve randomized controlled trials (RCTs) and quasi-experimental studies (QES) with control groups published in English and Korean from inception to January 31, 2024, using PubMed, Embase, CINAHL Plus, ERIC, ProQuest Central, Cochrane Library, and RISS., Review Methods: Eligible studies, including grey literature, were selected. The quality of the selected studies was evaluated using the Joanna Briggs Institute Critical Tool. Meta-analyses based on a random-effects model were conducted to estimate the standardized pooled effects (SMD). Subgroup analyses were conducted to identify the effect size moderators and game design elements that contributed to the effect size. The grading of recommendations, assessment, development, and evaluation approach (GRADE) was used to evaluate the certainty of evidence., Results: A total of 22 studies were selected for the systematic review, and 18 studies were included in the meta-analysis. The SMD for academic motivation (SMD of RCTs = 0.86, 95 % CI [0.27, 1.45]; SMD of QES = 1.22, 95 % CI [0.17, 2.26]) and confidence (SMD of RCTs = 1.11, 95 % CI [0.54, 1.68]; SMD of QES = 0.79, 95 % CI [0.40, 1.19]) revealed moderate-to-large effects. The subgroup analysis revealed significant differences in effect sizes across academic years, measurement scales, study areas, study quality, game duration, and game design elements. GRADE assessments for academic motivation and confidence were rated as moderate and low, respectively., Conclusion: This review provides convincing evidence for the positive effects of gamification interventions on academic motivation and confidence among undergraduate nursing students. However, the limited number of RCTs and moderate-to-low certainty of the evidence underscore the need for additional research., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Nitrogen oxides represent one of the main threats for the environment. Despite decades of intensive research efforts, a sustainable solution for NO x removal under environmental conditions is still undefined. Using theoretical modelling, material design, state-of-the-art investigation methods and mimicking enzymes, it is found that selected porous hybrid iron(II/III) based MOF material are able to decompose NO x , at room temperature, in the presence of water and oxygen, into N 2 and O 2 and without reducing agents. This paves the way to the development of new highly sustainable heterogeneous catalysts to improve air quality., (© 2024 Wiley‐VCH GmbH.)

Background: Major depressive disorder (MDD) occurs more often in women than that in men due to various complex causes. This study aimed to evaluate the effectiveness and safety of Yukwool-tang (YWT) for MDD in women., Methods: A total of 72 patients diagnosed with MDD and Korean version of the Hamilton Depression Rating Scale (K-HDRS) ≥ 14 points were randomly assigned to the YWT or placebo group, and 1 bottle (30 mg) of No-S solution and placebo was administered to the YWT and placebo groups, respectively, orally thrice a day for 8 weeks. The evaluation was conducted through K-HDRS, Korean version of the Beck Depression Inventory (BDI-K), Korean version of the Beck Hopelessness Scale (K-BHS), Korean version of the Insomnia Severity Index (ISI-K), State-Trait Anxiety Inventory (STAI-K), EuroQol-5 dimension (EQ-5D), and Pattern Identifications Tool for Depression (PITD). Fifty patients completed the trial., Results: In the YWT group, the K-HDRS, BDI-K, K-BHS, ISI-K, STAI-K, and EQ-5D scores changed significantly at the 8th week, but there were no significant differences with the placebo. In subgroup analysis, the K-BHS score with an initial K-HDRS score < 18 points was significantly decreased compared to placebo at the 12th week (P < .05). In the YWT group, the ratio of Stagnation of Liver Gi () was the highest, but Dual Deficiency of the Heart and Spleen () became the highest after administration, which was also the highest in the placebo group both before and after administration., Conclusion: YWT improved depression and accompanying symptoms in women with MDD, although it was not significant compared to placebo, and it might be effective in improving the degree of hopelessness. The effect of YWT will become relatively clear through further research that can overcome certain limitations., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Industrial cities are hotspots for many hazardous air pollutants (HAPs), which are detrimental to human health. We devised an identification method to determine priority HAP monitoring areas using a comprehensive approach involving monitoring, modeling, and demographics. The methodology to identify the priority HAP monitoring area consists of two parts: (1) mapping the spatial distribution of selected categories relevant to the target pollutant and (2) integrating the distribution maps of various categories and subsequent scoring. The identification method was applied in Ulsan, the largest industrial city in South Korea, to identify priority HAP monitoring areas. Four categories related to HAPs were used in the method: (1) concentrations of HAPs, (2) amount of HAP emissions, (3) the contribution of industrial activities, and (4) population density in the city. This method can be used to select priority HAP monitoring areas for intensive monitoring campaigns, cohort studies, and epidemiological studies., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Industrial cities are strongly influenced by primary emissions of PM 2.5 from local industries. In addition, gaseous precursors, such as sulfur oxides (SO X ), nitrogen oxides (NO X ), and volatile organic compounds (VOCs), emitted from industrial sources, undergo conversion into secondary inorganic and organic aerosols (SIAs and SOAs). In this study, the spatial distributions of primary and secondary PM 2.5 in Ulsan, the largest industrial city in South Korea, were visualized. PM 2.5 components (ions, carbons, and metals) and PM 2.5 precursors (SO 2 , NO 2 , NH 3 , and VOCs) were measured to estimate the concentrations of secondary inorganic ions (SO 4 2- , NO 3 - , and NH 4 + ) and secondary organic aerosol formation potential (SOAFP). The spatial distributions of SIAs and SOAs were then plotted by combining atmospheric dispersion modeling, receptor modeling, and monitoring data. Spatial distribution maps of primary and secondary PM 2.5 provide fundamental insights for formulating management policies in different districts of Ulsan. For instance, among the five districts in Ulsan, Nam-gu exhibited the highest levels of primary PM 2.5 and secondary nitrate. Consequently, controlling both PM 2.5 and NO 2 emissions becomes essential in this district. The methodology developed in this study successfully identified areas with dominant contributions from both primary emissions and secondary formation. This approach can be further applied to prioritize control measures during periods of elevated PM levels in other industrial cities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Skeletal muscle aging results in the gradual suppression of myogenesis, leading to muscle mass loss. However, the specific role of cardiolipin in myogenesis has not been determined. This study investigated the crucial role of mitochondrial cardiolipin and cardiolipin synthase 1 (Crls1) in age-related muscle deterioration and myogenesis. Our findings demonstrated that cardiolipin and Crls1 are downregulated in aged skeletal muscle. Moreover, the knockdown of Crls1 in myoblasts reduced mitochondrial mass, activity, and OXPHOS complex IV expression and disrupted the structure of the mitochondrial cristae. AAV9-shCrls1-mediated downregulation of Crls1 impaired muscle regeneration in a mouse model of cardiotoxin (CTX)-induced muscle damage, whereas AAV9-mCrls1-mediated Crls1 overexpression improved regeneration. Overall, our results highlight that the age-dependent decrease in CRLS1 expression contributes to muscle loss by diminishing mitochondrial quality in skeletal muscle myoblasts. Hence, modulating CRLS1 expression is a promising therapeutic strategy for mitigating muscle deterioration associated with aging, suggesting potential avenues for developing interventions to improve overall muscle health and quality of life in elderly individuals., (© 2024. The Author(s).)

Sterol regulatory element-binding protein (SREBP)-1c is involved in cellular lipid homeostasis and cholesterol biosynthesis and is highly increased in nonalcoholic steatohepatitis (NASH). However, the molecular mechanism by which SREBP-1c regulates hepatic stellate cells (HSCs) activation in NASH animal models and patients have not been fully elucidated. In this study, we examined the role of SREBP-1c in NASH and the regulation of LCN2 gene expression. Wild-type and SREBP-1c knockout (1cKO) mice were fed a high-fat/high-sucrose diet, treated with carbon tetrachloride (CCl 4 ), and subjected to lipocalin-2 (LCN2) overexpression. The role of LCN2 in NASH progression was assessed using mouse primary hepatocytes, Kupffer cells, and HSCs. LCN2 expression was examined in samples from normal patients and those with NASH. LCN2 gene expression and secretion increased in CCl 4 -induced liver fibrosis mice model, and SREBP-1c regulated LCN2 gene transcription. Moreover, treatment with holo-LCN2 stimulated intracellular iron accumulation and fibrosis-related gene expression in mouse primary HSCs, but these effects were not observed in 1cKO HSCs, indicating that SREBP-1c-induced LCN2 expression and secretion could stimulate HSCs activation through iron accumulation. Furthermore, LCN2 expression was strongly correlated with inflammation and fibrosis in patients with NASH. Our findings indicate that SREBP-1c regulates Lcn2 gene expression, contributing to diet-induced NASH. Reduced Lcn2 expression in 1cKO mice protects against NASH development. Therefore, the activation of Lcn2 by SREBP-1c establishes a new connection between iron and lipid metabolism, affecting inflammation and HSCs activation. These findings may lead to new therapeutic strategies for NASH., (© 2024. The Author(s).)

Purpose: This study evaluated the efficacy of a tube-shaped poly(ε) caprolactone - β tricalcium phosphate (PCL-TCP) scaffold with the incorporation of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) and platelet-rich plasma (PRP) for bone regeneration in the procedure of single-stage sinus augmentation and dental implantation in minipigs., Methods: Implants were placed in the bilateral sides of the maxillary sinuses of 5 minipigs and allocated to a PCL-TCP+hUCMSCs+PRP group (n=5), a PCL-TCP+PRP group (n=5), and a PCL-TCP-only group (n=6). After 12 weeks, bone regeneration was evaluated with soft X-rays, micro-computed tomography, fluorescence microscopy, and histomorphometric analysis., Results: Four implants failed (2 each in the PCL-TCP+hUCMSCs+PRP and PCL-TCP+hUCMSC groups). An analysis of the grayscale levels and bone-implant contact ratio showed significantly higher mean values in the PCL-TCP+hUCMSCs+PRP than in the PCL-TCP group ( P =0.045 and P =0.016, respectively). In fluoromicroscopic images, new bone formation around the outer surfaces of the scaffolds was observed in the PCL-TCP+hUCMSCs+PRP group, suggesting a tenting effect of the specially designed scaffolds. Bone regeneration at the scaffold-implant interfaces was observed in all 3 groups., Conclusions: Using a tube-shaped, honeycombed PCL-TCP scaffold with hUCMSCs and PRP may serve to enhance bone formation and dental implants' osseointegration in the procedure of simultaneous sinus lifting and dental implantation., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2023. Korean Academy of Periodontology.)

In this study, we investigated the effect of EMF exposure on the regulation of RANKL-induced osteoclast differentiation in Raw 264.7 cells. In the EMF-exposed group, the cell volume did not increase despite RANKL treatment, and the expression levels of Caspase-3 remained much lower than those in the RANKL-treated group. TRAP and F-actin staining revealed smaller actin rings in cells exposed to EMF during RANKL-induced differentiation, indicating that EMF inhibited osteoclast differentiation. EMF-irradiated cells exhibited reduced mRNA levels of osteoclastic differentiation markers cathepsin K (CTSK), tartrate-resistant acid phosphatase (TRAP), and matrix metalloproteinase 9 (MMP-9). Furthermore, as measured by RT-qPCR and Western blot, EMF induced no changes in the levels of p-ERK and p-38; however, it reduced the levels of TRPV4 and p-CREB. Overall, our findings indicate that EMF irradiation inhibits osteoclast differentiation through the TRPV4 and p-CREB pathway.

The accurate mapping and assessment of groundwater vulnerability index are crucial for the preservation of groundwater resources from the possible contamination. In this research, novel intelligent predictive Machine Learning (ML) regression models of k-Neighborhood (KNN), ensemble Extremely Randomized Trees (ERT), and ensemble Bagging regression (BA) at two levels of modeling were utilized to improve DRASTIC-LU model in the Miryang aquifer located in South Korea. The predicted outputs from level 1 (KNN and ERT models) were used as inputs for ensemble bagging (BA) in level 2. The predictive groundwater pollution vulnerability index (GPVI), derived from DRASTIC-LU model was adjusted by NO 3 -N data and was utilized as the target data of the ML models. Hyperparameters for all models were tuned using a Grid Searching approach to determine the best effective model structures. Various statistical metrics and graphical representations were used to evaluate the superior predictive performance among ML models. Ensemble BA model in level 2 was more precise than standalone KNN and ensemble ERT models in level 1 for predicting GPVI values. Furthermore, the ensemble BA model offered suitable outcomes for the unseen data that could subsequently prevent the overfitting issue in the testing phase. Therefore, ML modeling at two levels could be an excellent approach for the proactive management of groundwater resources against contamination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The skin aging process is governed by intrinsic and extrinsic factors causing skin wrinkles, sagging, and loosening. The 1-monoeicosapentaenoin (1-MEST) is a component isolated from Micractinium , a genus of microalgae (Chlorophyta, Trebouxiophyceae). However, the anti-wrinkle effects of 1-MEST are not yet known. This study aimed to evaluate the anti-wrinkle effects of 1-MEST in vitro and in clinical trials. The cytotoxicity of 1-MEST was investigated in vitro using the MTS assay in human epidermal keratinocytes (HEKs). Expression of matrix metalloproteinase (MMP)-1 and MMP-9 was determined by ELISA in HEKs irradiated with UVB after treatment with 1-MEST. A split-face randomized, double-blind, placebo-controlled study was conducted to evaluate the safety and efficacy of 1-MEST. The study evaluated wrinkle parameters and visual assessment, self-efficacy and usability questionnaires, and adverse events. The study showed that the 1-MEST was not cytotoxic in HEKs, suppressed MMP-1 secretion and MMP-9 protein expression in HEKs irradiated with UVB. The wrinkle parameters and mean visual assessment score were significantly decreased in the test group after 12 weeks and differed from the control group. There were no significant differences in efficacy and usability. Adverse effects were also not observed. The 1-MEST showed anti-wrinkle properties to slow down or prevent skin aging.

It is assumed that mood can be inferred from one's facial expression. While this association may prove to be an objective marker for mood disorders, few studies have explicitly evaluated this linkage. The facial movement responses of women with major depressive disorder (n = 66) and healthy controls (n = 46) under emotional stimuli were recorded using webcam. To boost facial movements, the naturalistic audio-visual stimuli were presented. To assess consistent global patterns across facial movements, scores for facial action units were extracted and projected onto principal component using principal component analysis. The associations of component for facial movements with functional brain circuitry was also investigated. Clusters of mouth movements, such as lip press and stretch, identified by principal component analysis, were attenuated in depressive patients compared to those in healthy controls. This component of facial movements was associated with depressive symptoms, and the strengths of resting brain functional connectivity between nucleus accumbens and both posterior insular cortex and thalamus. The evaluation of facial movements may prove to be a promising quantitative marker for assessing depressive symptoms and their underlying brain circuitry., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Renal fibrosis is an irreversible and progressive process that causes severe dysfunction in chronic kidney disease (CKD). The progression of CKD stages is highly associated with a gradual reduction in serum Klotho levels. We focused on Klotho protein as a key therapeutic factor against CKD. Urine-derived stem cells (UDSCs) have been identified as a novel stem cell source for kidney regeneration and CKD treatment because of their kidney tissue-specific origin. However, the relationship between UDSCs and Klotho in the kidneys is not yet known. In this study, we discovered that UDSCs were stem cells that expressed Klotho protein more strongly than other mesenchymal stem cells (MSCs). UDSCs also suppressed fibrosis by inhibiting transforming growth factor (TGF)-β in HK-2 human renal proximal tubule cells in an in vitro model. Klotho siRNA silencing reduced the TGF-inhibiting ability of UDSCs. Here, we suggest an alternative cell source that can overcome the limitations of MSCs through the synergetic effect of the origin specificity of UDSCs and the anti-fibrotic effect of Klotho.

Hair loss is a chronic disorder that affects many people; however, a complete treatment has not yet been developed. Therefore, new therapeutic agents for preventing hair loss must be developed, and electromagnetic field (EMF) therapy has been proven to be a promising medical treatment in various fields, including hair loss treatment. This study evaluated the effect of extremely low-frequency electromagnetic field (ELF-EMF) intensity and exposure time by analyzing the expression of cytokines and anagen-related molecules, which influence hair activation and growth, in hair bulb spheroid (HBS) and hair follicle (HF) organ cultures. ELF-EMFs did not induce toxicity in the HBSs, as verified via the lactate dehydrogenase (LDH) assay. Moreover, an ELF-EMF intensity of 5-20 G promoted the expression of ALP, versican, β-catenin, and several cytokines (VEGF, PDGF, FGF-10, and ET-1) in HBSs. Immunohistochemical staining showed that ELF-EMF at an intensity of 5-20 G upregulated ALP and β-catenin and decreased TUNEL staining in HBS. Moreover, HFs exposed to ELF-EMF for 60 min exhibited an increase in hair length and a 1.5-fold increase in IL-4, ICAM-1, ALP, and versican mRNA expression compared to the control. Immunohistochemical staining indicated that 60 min of ELF-EMF can increase the expression of ALP and β-catenin and decreases TUNEL staining in organ cultures. Collectively, our results demonstrated that ELF-EMF exposure at a 10 G intensity for 60 min promoted hair shaft growth in HFs due to the effect of cytokines and adhesion molecules via the Wnt/β-catenin pathway. Therefore, ELF-EMF is a promising treatment for hair loss.

Background: Skin aging is caused by exogenous and endogenous factors and is commonly manifested as wrinkling, sagging, and looseness of the skin. The herbal extract including Zingiber officinale Roscoe, Atractylodes chinensis (Bunge) Kodiz, Curcuma longa L., and Cinnamomum cassia (L.) J.Presl (ZACC extract), is widely used for So-eum (SE) Sasang constitutional type individuals. This study aimed to examine the protective effects of the ZACC extract against skin aging in 21 SE type subjects., Methods: The safety and clinical efficacy of herbal cream were evaluated after application on human skin in a split-face randomized, double-blind, placebo-controlled study. The Sasang Constitution Analysis Tool (SCAT) was used to select 21 SE type subjects, who applied herbal cream and placebo cream for 12 weeks. Visual assessment, wrinkle parameters, questionnaires, and skin safety were evaluated., Results: The visual assessment score was decreased by using of the herbal cream, but there were no significant differences between groups. Among the wrinkle parameters, R1 (skin roughness) and R4 (smoothness depth) values were significantly improved after the application of the herbal cream compared to those observed after application of the placebo cream for 12 weeks. No significant differences were observed in evaluation of the product efficacy and usability by questionnaires. There were no adverse dermatologic reactions in the SE type subjects during the evaluation period., Conclusion: The ZACC herbal cream may be used to prevent or slow skin aging, including wrinkle formation, in SE type individuals., (© 2021 Published by Elsevier B.V. on behalf of Korea Institute of Oriental Medicine.)

Background: Ginseng (Panax ginseng C.A. Mey.) has been used as a valuable ingredient in traditional medicine for thousands of years mostly in Asian countries due to its therapeutic effects in various diseases. Among the processed ginseng products, black ginseng is produced by a repeated steaming and drying process of ginseng roots and has been known for its superior efficacy based on high accumulation of minor ginsenosides as recently discovered. Despite its popularity and increasing use, the toxicity information on black ginseng still remained largely lacking, raising safety concerns. This study was therefore carried out to determine the repeated oral toxicity of black ginseng extract (BGE; CJ EnerG) with evaluation of cytotoxic activity as validation of its pharmacological activity for toxicity testing., Methods: Prior to the toxicity test, we examined the cytotoxicity of BGE in six cancer cell lines derived from distinct human tissues in comparison with red ginseng extract (RGE), ginsenosides Rg5 and 20(S)-Rg3, and then assessed 28-day repeated oral toxicity in Sprague-Dawley (SD) rats using daily administration of up to 2000 mg/kg BGE., Results: BGE showed higher cytotoxicity than RGE in all the cell lines used in this study. Interestingly, the efficacy of BGE closely resembled the cytotoxic pattern of Rg5, suggesting Rg5 as the main effector in the cytotoxic activity of BGE. During the toxicity study, BGE-treated groups showed no noticeable abnormality in clinical signs, body weight gain, food and water consumption and urinalysis. Furthermore, hematological, serum biochemical and histopathological analyses did not find any BGE-related toxicity., Conclusion: Our findings demonstrated that BGE has broad-spectrum in vitro cytotoxic activity, and that NOAEL of BGE in SD rats is > 2000 mg/kg, providing the essential safety information for human consumption., (© 2022. The Author(s).)

Human umbilical-cord-derived mesenchymal stem cells (hUC-MSC) are a type of mesenchymal stem cells and are more primitive than other MSCs. In this study, we identify novel genes and signal-activating proteins involved in the neural differentiation of hUC-MSCs induced by Low-Intensity Sub-Sonic Vibration (LISSV). RNA sequencing was used to find genes involved in the differentiation process by LISSV. The changes in hUC-MSCs caused by LISSV were confirmed by PLXNA4 overexpression and gene knockdown through small interfering RNA experiments. The six genes were increased among genes related to neurons and the nervous system. One of them, the PLXNA4 gene, is known to play a role as a guide for axons in the development of the nervous system. When the PLXNA4 recombinant protein was added, neuron-related genes were increased. In the PLXNA4 gene knockdown experiment, the expression of neuron-related genes was not changed by LISSV exposure. The PLXNA4 gene is activated by sema family ligands. The expression of SEMA3A was increased by LISSV, and its downstream signaling molecule, FYN, was also activated. We suggest that the PLXNA4 gene plays an important role in hUC-MSC neuronal differentiation through exposure to LISSV. The differentiation process depends on SEMA3A - PLXNA4 -dependent FYN activation in hUC-MSCs.

Stroke is among the leading causes of death worldwide, and stroke patients are more likely to live with permanent disabilities even after treatment. Several treatments are being developed to improve the quality of life of patients; however, these treatments still have important limitations. Our study thus sought to evaluate the neural differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) at various pulsed electromagnetic field (PEMF) frequencies. Furthermore, the effects of selected frequencies in vivo were also evaluated using a mouse ischemia stroke model. Cell proliferation decreased by 20% in the PEMF group, as demonstrated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, and lactate dehydrogenase (LDH) secretion increased by approximately 10% in an LDH release assay. Fluorescence-activated cell sorting (FACS) analysis demonstrated that CD73 and CD105 were downregulated in the PEMF group at 60 Hz. Moreover, microtubule-associated protein 2 (MAP-2) and neurofilament light chain (NF-L) were upregulated in cell cultures at 60 and 75 Hz. To assess the effects of PEMF in vivo, cerebral ischemia mice were exposed to a PEMF at 60 Hz. Neural-related proteins were significantly upregulated in the PEMF groups compared with the control and cell group. Upon conducting rotarod tests, the cell/PEMF group exhibited significant differences in motor coordination at 13 days post-treatment when compared with the control and stem-cell-treated group. Furthermore, the cell and cell/PEMF group exhibited a significant reduction in the expression of matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) in the induced ischemic area compared with the control. Collectively, our findings demonstrated that PEMFs at 60 and 75 Hz could stimulate hBM-MSCs neural differentiation in vitro, in addition to promoting neurogenesis to enhance the functional recovery process by reducing the post-stroke inflammatory reaction.

Objectives: This study aimed to investigate the in vitro osteoinductivity of the combination of bone morphogenetic protein-2 (BMP-2) and nanohydroxyapatite (nHAp) and the in vivo effects of implants coated with nHAp/BMP-2., Materials and Methods: To evaluate the in vitro efficacy of nHAp/BMP-2 on bone formation, bone marrow-derived mesenchymal stem cells (BMMSCs) were seeded onto titanium disks coated with collagen (Col), Col/nHAp, or Col/nHAp/BMP-2. Protein levels were determined by a biochemical assay and reverse transcriptase-polymerase chain reaction. Stem cell differentiation was analyzed by flow cytometry. For in vivo studies with mice, Col, Col/nHAp, and Col/nHAp/BMP-2 were injected in subcutaneous pockets. Titanium implants or implants coated with Col/nHAp/BMP-2 were placed bilaterally on rabbit tibias and evaluated for 4 weeks., Results: In the in vitro study, BM-MSCs on Col/nHAp/BMP-2 showed reduced levels of CD73, CD90, and CD105 and increased levels of glycosaminoglycan, osteopontin, and alkaline phosphatase activity. After 4 weeks, the Col/nHAp/BMP-2 implant showed greater bone formation than the control ( P =0.07), while no differences were observed in bone implant contact and removal torque., Conclusion: These results suggest that a combination of BMP-2 and an nHAp carrier would activate osseointegration on dental implant surfaces.

Mechanical/physical stimulations modulate tissue metabolism, and this process involves multiple cellular mechanisms, including the secretion of growth factors and the activation of mechano-physically sensitive kinases. Cells and tissue can be modulated through specific vibration-induced changes in cell activity, which depend on the vibration frequency and occur via differential gene expression. However, there are few reports about the effects of medium-magnitude (1.12 g) sonic vibration on the osteogenic differentiation of human dental pulp stem cells (HDPSCs). In this study, we investigated whether medium-magnitude (1.12 g) sonic vibration with a frequency of 30, 45, or 100 Hz could affect the osteogenic differentiation of HDPSCs. Their cell morphology changed to a cuboidal shape at 45 Hz and 100 Hz, but the cells in the other groups were elongated. FACS analysis showed decreased CD 73, CD 90, and CD 105 expression at 45 Hz and 100 Hz. Additionally, the proportions of cells in the G0/G1 phase in the control, 30 Hz, 45 Hz, and 100 Hz groups after vibration were 60.7%, 65.9%, 68.3%, and 66.7%, respectively. The mRNA levels of osteogenic-specific markers, including osteonectin, osteocalcin, BMP-2, ALP, and Runx-2, increased at 45 and 100 Hz, and the ALP and calcium content was elevated in the vibration groups compared with those in the control. Additionally, the western blotting results showed that p-ERK, BSP, osteoprotegerin, and osteonectin proteins were upregulated at 45 Hz compared with the other groups. The vibration groups showed higher ALP and calcium content than the control. Vibration, especially at 100 Hz, increased the number of calcified nodes relative to the control group, as evidenced by von Kossa staining. Immunohistochemical staining demonstrated that type I and III collagen, osteonectin, and osteopontin were upregulated at 45 Hz and 100 Hz. These results suggest that medium magnitude vibration at 45 Hz induces the G0/G1 arrest of HDPSCs through the p-ERK/Runx-2 pathway and can serve as a potent stimulator of differentiation and extracellular matrix production.

In skeletal-muscle regeneration, it is critical to promote efferocytosis of immune cells and differentiation of satellite cells/postnatal muscle stem cells at the damaged sites. With the optimized poloxamer 407 composition gelled at body temperature, the drugs can be delivered locally. The purpose of this study is to develop a topical injection therapeutic agent for muscle regeneration, sarcopenia, and cachexia. Herein, we construct an injectable, in situ hydrogel system consisting of CD146, IGF-1, collagen I/III, and poloxamer 407, termed CIC gel. The secreted CD146 then binds to VEGFR2 on the muscle surface and effectively induces efferocytosis of neutrophils and macrophages. IGF-1 promotes satellite cell differentiation, and biocompatible collagen evades immune responses of the CIC gel. Consequently, these combined molecules activate muscle regeneration via autophagy and suppress muscle inflammation and apoptosis. Conclusively, we provide an applicable concept of the myogenesis-activating protein formulation, broadening the thermoreversible hydrogel to protein therapeutics for damaged muscle recovery.

Odontoblasts produce proteins that form the dentinal extracellular matrix, which can protect the dental pulp from external stimuli and is required for tooth regeneration. This study showed that a pulsed electromagnetic field (PEMF) can regulate cell metabolism and induce cell differentiation. This study determined the frequency of PEMF that is effective for odontoblast differentiation. Human dental pulp stem cells (hDPSCs) were cultured in odontoblast differentiation medium containing dexamethasone, BMP2, TGF-β1, and FGF-2, and then exposed to 10 mT intensity of PEMF at 40, 60, 70, and 150 Hz for 15 min/day. The MTT assay, LDH assay, flow cytometry, protein and gene expression, and immunofluorescence were performed to check if hDPSCs differentiated into odontoblast-like cells. The hDPSCs showed frequency-dependent differences in protein and gene expression. The mesenchymal stem cell markers were reduced to a greater extent at 60 and 70 Hz than at other frequencies, and odontoblast-related markers, particularly β-catenin, p-GSK-3β, and p-p38, were increased at 60 and 70 Hz. Exposure to 10 mT intensity of PEMF at 70 Hz influenced the differentiation of hDPSCs considerably. Taken together, PEMF treatment can promote differentiation of hDPSCs into odontoblast-like cells by increasing p-GSK-3β and β-catenin expression.

Electromagnetic fields (EMFs) are widely used in a number of cell therapies and bone disorder treatments, and nanomagnetic particles (NMPs) also promote cell activity. In this study, we investigated the synergistic effects of EMFs and NMPs on the osteogenesis of the human Saos-2 osteoblast cell line and in a rat calvarial defect model. The Saos-2 cells and critical-size calvarial defects of the rats were exposed to EMF (1 mT, 45 Hz, 8 h/day) with or without Fe 3 O 4 NMPs. Biocompatibility was evaluated with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and LDH (lactate dehydrogenase) assays. This analysis showed that NMP and EMF did not induce cell toxicity. Quantitative reverse-transcription polymerase chain reaction indicated that the osteogenesis-related markers were highly expressed in the NMP-incorporated Saos-2 cells after exposure to EMF. Also, the expression of gene-encoding proteins involved in calcium channels was activated and the calcium concentration of the NMP-incorporated + EMF-exposed group was increased compared with the control group. In particular, in the NMP-incorporated + EMF-exposed group, all osteogenic proteins were more abundantly expressed than in the control group. This indicated that the NMP incorporation + EMF exposure induced a signaling pathway through activation of p-ERK and calcium channels. Also, in vivo evaluation revealed that rat calvarial defects treated with EMFs and NMPs had good regeneration results with new bone formation and increased mineral density after 6 weeks. Altogether, these results suggest that NMP treatment or EMF exposure of Saos-2 cells can increase osteogenic activity and NMP incorporation following EMF exposure which is synergistically efficient for osteogenesis., (© 2020 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

This study compared the topography of different titanium surface structures (TiO 2 nanotube and grain) with similar elemental compositions (TiO2 and fluorine [F]) on the Ti surface. High magnification indicated that the surfaces of the control and etching groups were similar to each other in a flat, smooth form. The group anodized for 1 h was observed with TiO 2 nanotubes organized very neatly and regularly. In the group anodized for 30 min after etching, uneven wave and nanopore structures were observed. In addition, MTT assay showed that the F of the surface did not adversely affect cell viability, and the initial cell adhesion was increased in the 2.8% F-incorporated TiO 2 nanograin. At the edge of adherent cells, filopodia were observed in spreading form on the surfaces of the anodizing and two-step processing groups, and they were observed in a branch shape in the control and etching groups. Moreover, cell adhesion molecule and osteogenesis marker expression was increased at the F-incorporated TiO 2 nanostructure. In addition, it was found that the expression of p-extracellular signal-regulated kinase (ERK) and p-cAMP response element-binding protein (CREB) increased in the TiO 2 nanograin with the nanopore surface compared to the micro rough and nanotube surfaces relative to the osteogenic-related gene expression patterns. As a result, this study confirmed that the topographic structure of the surface is more affected by osteogenic differentiation than the pore size and that differentiation by specific surface composition components is by CREB. Thus, the synergy effect of osteogenic differentiation was confirmed by the simultaneous activation of CREB/ERK., (© 2020 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

We previously reported that the duodenal-jejunal bypass (DJB) surgery altered transsulfuration and purine metabolism via flux changes in 1-carbon metabolism in the liver. In this study, we extended our study to gain further insight into mechanistic details of how the DJB-induced flux changes in 1-carbon metabolism contributes to the improvement of diet-induced nonalcoholic fatty liver disease. Rodents were subjected to surgical (sham operation and DJB) or dietary (reduced food supply to follow the weight changes in the DJB group) interventions. The microscopic features of the liver were examined by immunohistochemistry. The expressions of genes in lipid synthesis and in 1-carbon cycle in the liver were analyzed by real-time polymerase chain reaction and western blotting. Metabolic changes in the liver were determined. We observed that DJB reduces hepatic steatosis and improves insulin sensitivity in both high-fat diet-fed rats and mice. Metabolic analyses revealed that the possible underlying mechanism may involve decreased S-adenosylmethionine (SAM)-to-S-adenosylhomocysteine ratio via downregulation of SAM synthesizing enzyme and upregulation of SAM catabolizing enzyme. We also found in mice that DJB-mediated attenuation of hepatic steatosis is independent of weight loss. DJB also increased hepatic expression levels of GNMT while decreasing those of PEMT and BHMT, a change in 1-carbon metabolism that may decrease the ratio of SAM to S-adenosylhomocysteine, thereby resulting in the prevention of fat accumulation in the liver. Thus, we suggest that the change in 1-carbon metabolism, especially the SAM metabolism, may contribute to the improvement of diet-induced fatty liver disease after DJB surgery., (Copyright © 2021 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the efficacy and safety of radiofrequency ablation (RFA) for papillary thyroid microcarcinoma (PTMC) after > 10 years of follow-up., Materials and Methods: This study included five patients who underwent RFA to treat PTMCs (five lesions, mean diameter 0.5 cm, range 0.4-0.7 cm) between November 2006 and December 2009. The inclusion criteria were histopathologically confirmed PTMCs, a single PTMC lesion without extrathyroidal extension, no metastasis, and ineligibility or refusal to undergo surgery. RFA was performed by a single radiologist using a radiofrequency generator and an internally cooled electrode. We retrospectively analyzed the procedure-induced complications, serial changes in ablated tumors, recurrence, and local as well as lymph node metastasis based on data obtained from medical records and radiological images., Results: The mean follow-up period was 130.6 months (range 121-159 months). Three patients underwent a single RFA session, and two patients underwent two RFA sessions. We observed no procedure-induced complications. Three tumors completely disappeared after ablation, and ablation of the other two tumors resulted in the formation of a small scar that showed long-term stability (mean duration 16.8 months, range 12-27 months). At the last follow-up, no patient showed recurrence or lymph node metastasis, and serum thyroglobulin levels were within normal limits in all patients., Conclusion: RFA may be effective and safe to treat low-risk PTMC in patients who refuse or are ineligible for surgery., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2021 The Korean Society of Radiology.)

Purpose: The establishment of a preclinical model of the abscopal effect on hepatocellular carcinoma (HCC) and evaluation of whether the hypofractionated radiation therapy (RT) multitumor Hepa1-6 mouse HCC model could be used to suppress nonradiated tumor mass was performed in this study., Methods and Materials: Hepa1-6 mouse liver cancer cell lines were used to form tumors. Immunogenicity was analyzed using ELISpot and immune cell labeled antibody. Interferon (IFN) β expression was confirmed through polymerase chain reaction., Results: After investigation, the intratumoral transcription of type Ⅰ IFN increased by 2-fold. The antitumor immune response to Hepa 1-6 cells induced by radiation was increased. Moreover, the influx of activated CD8 + T cells was increased in nonirradiated tumors. The number of dendritic cells and activation status were evaluated by flow cytometry on the second day after irradiation. Flow cytometry revealed a significantly increased dendritic cell population expressing the CD11c molecule in tumor-draining lymph nodes. Furthermore, because irradiation leads to adaptation of immune resistance of tumor cells against RT, we sought to elucidate a potent tool to overcome the resistance and confirm the ability of PD-L1 antibody to survive late RT resistance., Conclusions: The immunologic mechanism of the abscopal effect was revealed and the application of PD-L1 inhibitor successfully performed as a breakthrough in late RT resistance in the Hepa1-6 tumor model., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Finding a material that supports bone regeneration is the concern for many investigators. We supposed that a composite scaffold of poly(ε) caprolactone and β-tricalcium phosphate (PCL-TCP) would entail desirable characteristics of biocompatibility, bioresorbability, rigidity, and osteoconductivity for a proper guided bone regeneration. Furthermore, the incorporation of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) would boost the bone regeneration. We conducted this study to evaluate the bone regeneration capacity of PCL-TCP scaffold that is loaded with MSCs and PRP., Materials and Methods: Five miniature pigs received 6 implants in 6 created-mandibular bony defects in the right and left lower premolar areas. The bony defects were managed according to the following three groups: the PCL-TCP scaffold loaded with MSCs and PRP (MSCs+PRP+PCL-TCP) group (n = 10), PCL-TCP scaffold loaded with PRP (PRP+PCL-TCP) group (n = 10), and PCL-TCP scaffold group (n = 10). After 12 weeks, the bone regeneration was assessed using fluorochrome bone labeling, μCT bone morphogenic analysis, and histomorphometric analysis., Results: All of the three groups supported the bone regeneration around the dental implants. However, the PCL-TCP scaffold loaded with MSCs and PRP (MSCs+PRP+PCL-TCP) group showed non-significant higher bone surface, bone specific surface, and bone surface density than the other two groups as revealed by the μCT bone morphogenic analysis. Histologically, the same group revealed higher bone-implant contact ratio (BIC) (p = 0.017) and new bone height formation (NBH, mm) (p = 0.0097) with statistically significant difference compared to the PCL-TCP scaffold group., Conclusions: PCL-TCP scaffold is compatible for bone regeneration in bone defects surrounding dental implants. Moreover, the incorporation of MSCs and PRP optimized the bone regeneration process with respect to the rate of scaffold replacement, the height of the regenerated bone, and implant stability.

Red ginseng (RG) and black ginseng (BG, CJ EnerG) were prepared from fresh ginseng using one and nine cycles of steaming and drying, respectively. This process reduces the molecular weight (MW) of ginsenoside-active compounds in ginseng by removing sugar moieties from their dammaranes. We compared the pharmacokinetic characteristics of ginsenosides between BG comprising mainly low-MW ginsenosides (Rg3, Rg5, Rk1, and Rh1) and RG that predominantly contains high-MW ginsenosides (Rb1, Rb2, Rc, Rd, Re, and Rg1). The safety profiles and tolerability were also studied using a randomized, double-blind, single-dose, crossover clinical trial. A combination of Rb1, Rg1, and Rg3, well-known representative and functional RG components, exhibited a 1 h faster absorption rate (T max ) and 58% higher exposure (24 h area under the concentration-time curve, AUC 24 ) in BG than in RG. Furthermore, the combination of Rg3, Rg5, and Rk1, the major and most efficient components in BG, displayed 824% higher absorption (AUC 24 ) in BG than in RG. The total ginsenoside showed a 5 h rapid intestinal absorption (T max ) and 79% greater systemic exposure (AUC 24 ) in BG than in RG. No clinically significant findings were observed in terms of safety or tolerability. Thus, BG extract was more effective than RG extract.

Purpose: Aromatase inhibitors (AIs) are widely prescribed for postmenopausal women with breast cancer and are known to cause musculoskeletal pain. This study aimed to identify factors associated with AI continuation intention among breast cancer survivors (BCS)., Methods: A cross-sectional survey was conducted on 123 BCS (stages I-III), who had been taking AIs for at least 6 weeks. Participants were recruited from a cancer center in Goyang, Korea, from September to November 2019. Descriptive statistics, Welch analysis of variance, Pearson correlation coefficients, and simple linear regression were used for the analysis., Results: Beliefs about endocrine therapy was a significant predictor of AI continuation intention (β=.66, p <.001). The majority of participants (87.0%) reported experiencing musculoskeletal pain since taking AIs and the score for the worst pain severity within 24 hours was 5.08±2.80 out of 10. Musculoskeletal pain, however, was not associated with AI continuation intention. Fear of cancer recurrence (FCR) was clinically significant (≥13) for 74.0% of the respondents (mean, 17.62±7.14). Musculoskeletal pain severity and pain interference were significantly associated with FCR (r=.21, p <.05; r=.35, p <.01, respectively). Pain interference was significantly associated with beliefs about endocrine therapy (r=-.18, p <.05)., Conclusion: AI continuation intention can be modified by reinforcing patients' beliefs about endocrine therapy. Musculoskeletal pain may have a negative effect on beliefs about endocrine therapy and increase FCR among BCS. Thus, awareness of musculoskeletal pain during AI therapy should be raised and further research is required to develop multidisciplinary pain management strategies and clinical guidelines to reinforce beliefs about endocrine therapy., Competing Interests: Conflict of interest Sue Kim has been editor-in-chief of the Korean Journal of Women Health Nursing since January 2020. She was not involved in the review process of this manuscript. Otherwise, there was no conflict of interest., (Copyright © 2021 Korean Society of Women Health Nursing.)

Abstract: The prevalence of obesity as well as cognitive impairment increases with age. Previous studies showed that obesity is associated with an increased risk of cognitive impairment and dementia. Body composition changes occur as part of the aging process; therefore, the assessment of obesity in elderly populations should include body composition as well as body weight. This study investigated the relationship between body mass index (BMI), body composition, and cognitive function in a community-dwelling elderly Korean population.This cohort-based cross-sectional analysis included 2386 elderly participants aged between 70 and 84 years from the Korean Frailty and Aging Cohort Study for 2016 to 2017. To investigate the relationship between body composition and cognitive function in community-dwelling individuals, BMI and body composition, including total and trunk fat mass and fat-free mass, were measured by dual-energy X-ray absorptiometry. Fat mass index (FMI), trunk fat mass index (TFMI), and fat-free mass index (FFMI) were used to represent the body composition. A short form of the Korean version of the Consortium to Establish a Registry for Alzheimer disease was used to assess cognitive function. To evaluate the relationship between variables, simple and fully adjusted multivariable analyses were performed using generalized linear regression models.The mean ages were 76.8 years for males and 76.1 years for females. The BMI of male participants was significantly lower than that of females (23.9 ± 2.89 vs 24.7 ± 3.02 kg/m2, P < .001). Among body composition parameters, the differences in FMI (6.44 ± 1.97 vs 9.29 ± 2.3 kg/m2), TFMI (3.68 ± 1.33 vs 5.03 ± 1.43 kg/m2), and FFMI (17.4 ± 1.64 vs 15.3 ± 1.39 kg/m2) were statistically significant. In linear regression analyses, BMI, FMI, and TFMI showed significant positive correlations with mini-mental state examination in the Korean version of the CERAD assessment packet; wordlist memory, recall, and recognition; and frontal assessment battery only in males. The significant positive correlations persisted even after fully adjusting for age, education periods, location of residence, depression, marriage, annual income, presence of diabetes mellitus, dyslipidemia, and hypertension. However, no significant correlations in either sex were observed between FFMI and cognitive functions in the fully adjusted models.In this study, BMI, and fat mass-related indexes including FMI and TFMI showed a positive linear correlation with cognitive functions but not FFMI. Moreover, the findings were significant only in men. Besides the difference between sexes, the results of this study showed a more apparent correlation in fat mass than in fat-free mass that comprises body weight., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Sterol regulatory element binding protein-2 (SREBP-2) is activated by cytokines or pathogen, such as virus or bacteria, but its association with diminished cholesterol levels in COVID-19 patients is unknown. Here, we evaluated SREBP-2 activation in peripheral blood mononuclear cells of COVID-19 patients and verified the function of SREBP-2 in COVID-19. Intriguingly, we report the first observation of SREBP-2 C-terminal fragment in COVID-19 patients' blood and propose SREBP-2 C-terminal fragment as an indicator for determining severity. We confirmed that SREBP-2-induced cholesterol biosynthesis was suppressed by Sestrin-1 and PCSK9 expression, while the SREBP-2-induced inflammatory responses was upregulated in COVID-19 ICU patients. Using an infectious disease mouse model, inhibitors of SREBP-2 and NF-κB suppressed cytokine storms caused by viral infection and prevented pulmonary damages. These results collectively suggest that SREBP-2 can serve as an indicator for severity diagnosis and therapeutic target for preventing cytokine storm and lung damage in severe COVID-19 patients.

The role of dental pulp stem cells (DPSCs) in dental tissue regeneration is gaining attention because DPSCs can differentiate into odontoblasts and other specialized cell types. Epigenetic modification has been found to play an important role in cell differentiation and regulation, among which histone deacetylase (HDAC) is involved in suppressing genes by removing histone acetyl groups. The use of HDAC inhibitor to control this is increasing and has been widely studied by many researchers. This study aimed to induce differentiation by causing epigenetic changes in odontoblast-related genes and the MAPK signaling pathway in human dental pulp stem cells. Western blot and immunofluorescence staining showed increased expression of DMP-1, ALP, DSPP, and RUNX2 compared to the control. However, activation of the MAPK signaling system was similar to but slightly different from the expression of odontoblast-related proteins. After 3 days, as shown by MTT and LDH assays, proliferation decreased overall, but cytotoxicity decreased at only a specific concentration. We confirmed that there was no change in mRNA expression of caspase 3 or 9 using real-time PCR. In addition, flow cytometry analysis confirmed that differentiation occurred due to the decrease in the expression of the CD73 and CD146. Although overall proliferation was reduced due to the G2/M inhibition of the cell cycle, the expression of BCL-2 protected the cells from cell death. Overall, cell proliferation decreased in response to MS-275, but it did not induce cytotoxicity in 5 nM and 10 nM concentration and induces differentiation into odontoblast-like cells.

The impact of industrial activities on atmospheric volatile organic compounds (VOCs) in the Sihwa-Banwol complexes, i.e., the largest industrial area in Korea, was investigated. More than 60 VOCs were determined from 850 samples collected from four sites in and around the complexes through a 2-year monitoring campaign from 2005 to 2007. The VOCs of particular concern found in the area were benzene, toluene, ethylbenzene, xylenes, trichloroethylene, and formaldehyde, given their toxicity, concentration, and detection frequency. Toluene was the most abundant one. The VOC concentration rankings were consistent with their emission rankings. Most VOCs had higher concentrations at the industrial sites than at residential sites, indicating a significant impact of industrial emissions. The ambient levels of benzene and formaldehyde were additionally affected by vehicular emissions and secondary formation, respectively. Overall, the VOC levels increased in winter and at night, because of the local weather conditions. In contrast, the formaldehyde concentration increased in summer, owing to its secondary formation in the atmosphere. The ambient VOC levels in Sihwa-Banwol were higher than those in other parts of Korea. Additionally, the cumulative cancer risks posed by the toxic VOCs exceeded a tolerable risk level of 1 × 10 -4 in not only the industrial areas but also the residential areas. The sum of the non-cancer risks in both areas significantly exceeded the threshold criterion of 1. The large amounts of aromatic compounds emitted from the industrial complexes are believed to play a crucial role in the elevated levels of surface ozone in the Seoul metropolitan area during the summer season. Therefore, comprehensive measures for controlling the VOC emissions in the Sihwa-Banwol area need to be prioritized to reduce the health risks for residents of not only this area but also the capital Seoul and its surrounding areas.

Background: For chronic kidney disease (CKD) patients, management of nutritional status is critical for delaying progression to end-stage renal disease. The purpose of this study is to provide the basis for personalized nutritional intervention in pre-dialysis patients by comparing the foods contributing to nutrients intake, nutritional status and potential dietary inflammation of CKD patients according to the diabetes mellitus (DM) comorbidity and CKD stage., Methods: Two hundred fifty-six outpatients referred to the Department of Nephrology at SNUH from Feb 2016 to Jan 2017 were included. Subjects on dialysis and those who had undergone kidney transplantation were excluded. Bioelectrical impedance analysis (BIA), subjective global assessment (SGA), dietary intake, and biochemical parameters were collected. Subjects were classified into 4 groups according to DM comorbidity (DM or Non-DM) and CKD stage (Early or Late) by kidney function. Two-way analysis of variance and multinomial logistic regression analysis were performed for statistical analysis., Results: Total number of malnourished patients was 31 (12.1%), and all of them were moderately malnourished according to SGA. The body mass index (BMI) of the DM-CKD group was significantly higher than the Non-DM-CKD group. The contribution of whole grains and legumes to protein intake in the DM-CKD group was greater than that in the Non-DM-CKD group. The DM- Early-CKD group consumed more whole grains and legumes compared with the Non-DM-Early-CKD group. The subjects in the lowest tertile for protein intake had lower phase angle, SGA score and serum albumin levels than those in the highest tertile. The potential for diet-induced inflammation did not differ among the groups., Conclusions: Significant differences in intakes of whole grains and legumes between CKD patients with or without DM were observed. Since contribution of whole grains and legumes to phosphorus and potassium intake were significant, advice regarding whole grains and legumes may be needed in DM-CKD patients if phosphorus and potassium intake levels should be controlled. The nutritional status determined by BIA, SGA and serum albumin was found to be different depending on the protein intake. Understanding the characteristics of food sources can provide a basis for individualized nutritional intervention for CKD patients depending on the presence of diabetes.

Sepsis is a potentially fatal complication of infections and there are currently no effective therapeutic options for severe sepsis. In this study, we revealed the secretion mechanism of transforming growth factor β-induced protein (TGFBIp) that was recently identified as a therapeutic target for sepsis, and designed TGFBIp acetylation inhibitory peptide (TAIP) that suppresses acetylation of lysine 676 in TGFBIp. To improve bioavailability and biodegradation of the peptide, TAIP was conjugated to polyamidoamine (PAMAM) dendrimers. Additionally, the cell-penetrating peptide (CPP) was conjugated to the TAIP-modified PAMAM dendrimers for the intracellular delivery of TGFBIp. The resulting nanostructures, decorated with TAIP and CPP via poly(ethylene glycol) linkage, improved the mortality and organ damage in the septic mouse model and suppressed lipopolysaccharide-activated severe vascular inflammatory responses in endothelial cells. Thus, the dendrimer-based nanostructures for delivery of TAIP using CPP show great promise in practical applications in sepsis therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Both glucose and free fatty acids (FFAs) are used as fuel sources for energy production in a living organism. Compelling evidence supports a role for excess fatty acids synthesized in intramuscular space or dietary intermediates in the regulation of skeletal muscle function. Excess FFA and lipid droplets leads to intramuscular accumulation of lipid intermediates. The resulting downregulation of the insulin signaling cascade prevents the translocation of glucose transporter to the plasma membrane and glucose uptake into skeletal muscle, leading to metabolic disorders such as type 2 diabetes. The mechanisms underlining metabolic dysfunction in skeletal muscle include accumulation of intracellular lipid derivatives from elevated plasma FFAs. This paper provides a review of the molecular mechanisms underlying insulin-related signaling pathways after excess accumulation of lipids.

Background: Timosaponin A-III (TA-III) is known to exist in the medicinal herb of Anemarrhena asphodeloides as one of major chemical components., Aims: The photoprotective properties of TA-III on UVB-exposed HaCaT cells were evaluated on the antiwrinkle effects and skin safety in terms of clinical trial., Methods: The level of matrix metalloproteinase (MMP)-1, tissue inhibitor of metalloproteinases (TIMPs), and pro-inflammatory cytokines were measured in HaCaT cells following UVB irradiation. To evaluate the clinical safety of an agent containing 0.25% of TA-III for use on human skin. Female subjects (n = 21) between the ages of 43 and 55 who met the criteria for subject selection were selected. They were beginning to form or had already formed wrinkles., Results: UVB irradiation increased MMP-1 expression and pro-inflammatory cytokines. These increases were attenuated by TA-III pretreatment of UVB-exposed HaCaT cells. We found that the agent containing 0.25% of TA-III ameliorated skin wrinkling. A comparison between groups showed that wrinkle parameters were significantly reduced after 12 weeks of product use (P < 0.05). According to skin safety result, TA-III showed no dermatological toxicity was found in participants., Conclusions: In conclusion, TA-III could provide protection against photoaging and daily application of TA-III for 12 weeks significantly reduced signs of facial aging by limiting wrinkle formation., (© 2019 The Authors. Journal of Cosmetic Dermatology Published by Wiley Periodicals, Inc.)

Background: Melanogenesis is a biological process resulting in the production of melanin pigment, which plays an important role in the prevention of sun-induced skin injury and determines the hair and skin color. Melanin has the ability to block ultraviolet radiation and scavenge free oxygen radicals, thus protecting the skin from their harmful effects. Agents that increase melanin synthesis in melanocytes may reduce the risk of photodamage and skin cancer. Hence, various approaches have been proposed to increase the synthesis of melanin., Methods: The current study aimed to develop a three-dimensional hair follicle-like tissue (HFLT) model with human dermal papilla, melanocytes, and outer root sheaths cells. This model showed enhanced melanogenesis-related protein expression after rice bran ash extract (RBE) treatment. Next, we investigated the melanogenic effect of RBE in the HFLT and compared the results to those of hair follicle (HF) organ culture model., Results: RBE was found to significantly increase the expression of microphthalmia-associated transcription factor, a key transcription factor involved in melanin production, in both HFLT and organ culture models. Results showed that melanogenesis-related protein expression levels were higher in the RBE group compared to those in the control group. Similar results were obtained by immunohistochemistry., Conclusion: Our data suggested that RBE promotes melanin biosynthesis. Taken together, this simple in vitro HFLT model system has the potential to provide significant insights into the underlying molecular mechanisms of HF melanogenesis, and hence can be used for controlled evaluation of the efficacy of new materials for melanogenesis.

It is well known that vitamin D (VitD) plays an important role in bone and calcium metabolism in the human body. VitD has additional roles in the body including modulation of cell growth, neurogenesis, neuroprotection, detoxification, immune function, and reduction of inflammation. Recent studies reveal insufficiency of VitD as a risk factor for cognitive decline or dementia. VitD has a role in normal brain function; insufficiency of VitD may lead to decreased memory and cognitive function.Using 2 years of baseline data from Korean frailty and aging cohort study, 2990 subjects (1415 men and 1575 women) were recruited. A short form of Korean version of the consortium to establish a registry for Alzheimer disease (CERAD-K), an assessment of cognitive status in patients with dementia was used. Among CERAD-K tests, we included word list memory/recall/recognition, digit span (forward, backward), trail making test (TMT) A, and mini-mental state examination in the Korean version of the CERAD assessment packet (MMSE-KC). Serum samples were collected and 25-hydroxyvitamin D (25(OH)D) was measured. Serum 25(OH)D concentrations were classified into clinically relevant categories as: deficient (<10 nmol/L), insufficient (10-30 nmol/L), and sufficient (≥30 nmol/L).The mean age of participants was 76.5 ± 3.9 years, and 52.7% were women. Among 2990 participants, 119 (4.0%) were classified as 25(OH)D deficient and 2253 (75.3%) as insufficient. Only 618 (20.7%) participants were sufficient for 25(OH)D. Among them performance in MMSE-KC, TMT A, and digit span tests was better in sufficient, insufficient, and deficient groups, which was statistically significant (P < .05). However, in multivariable regression analysis after adjusting for age, sex, body mass index, education, center, seasonality, physical activity, and alcohol use, association between 25(OH)D and cognitive function was not statistically significant.Although, when comparing VitD levels, there were differences in cognitive tests among the groups, fully adjusted analysis did not show any association. This result suggests that cognition was not affected by VitD levels alone but also population and sociological variables. In a fully adjusted model, there was no statistically significant association between VitD and cognitive function in the elderly Koreans in logistic regression analysis.

Background: Mild neurocognitive disorder (mNCD) is one of the degenerative diseases that results in memory deficit, and can progress to dementia. The effectiveness of drug therapy for mNCD is still debatable, but treatment of this disease has important implications for postponing or preventing dementia. Jujadokseo-hwan (JDH) is a traditional herbal medicine formulation that exhibits improvement in cognitive abilities and neuroprotective effects. In this study, we will evaluate the safety and efficacy of JDH compared to placebo in mNCD patients., Methods and Design: This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial. After obtaining informed consent from all participants and performing the screening process, the participants will be equally divided into an experimental group and a control group. Each participant will visit the trial center 7 times during the 12 weeks of intervention. The follow up study will be conducted 12 weeks after the intervention ends. The primary outcome is the variance in Seoul verbal learning test-elderly's version (SVLT-E) score from baseline to 12 weeks. Secondary outcomes include scores/values for the following variables: SVLT-E, Rey complex figure test, Digit span test, Korean-Boston naming test, calculation ability, controlled oral word association test, Korean-color word stroop test, digit symbol coding, Korean-trail making test-elderly's version, Korean version of mini mental state examination for dementia screening, euro-qol-5 dimension, pattern identifications tool for cognitive disorders, Korean version of Montreal cognitive assessment, Korean quality of life-Alzheimer disease, computerized tongue image analysis system, blood pressure pulse analyzer, bioelectrical impedance analyzer, wearable electroencephalogram device, functional near-infrared spectroscopy system, and cost analysis., Discussion: This is the first trial evaluating the efficacy of JDH for mNCD. We expect this trial will provide strong support for wide use of JDH for mNCD and lead to further research on herbal medicine treatments for mNCD., Trial Registration Number: KCT0003570 (Registered in Clinical Research Information Service of the Republic of Korea, https://cris.nih.go.kr/cris/search/search&#95;result&#95;st01.jsp?seq=12669).

Despite advances in medical treatments, the proportion of the population suffering from alopecia is increasing, thereby creating a need for new treatments to control hair loss and prevent balding. Human hair follicle dermal papilla cells (hDPCs), a type of specialized fibroblast in the hair bulb, play an essential role in controlling hair growth and in conditions like androgenic alopecia. This study aimed to evaluate the intensity-dependent effect of extremely low-frequency electromagnetic fields (ELF-EMFs) on the expression of anagen-related molecules in hDPCs in vitro. We examined the effect of ELF-EMF on hDPCs to determine whether activation of the GSK-3β/ERK/Akt signaling pathway improved hDPC activation and proliferation; hDPCs were exposed to ELF-EMFs at a frequency of 70 Hz and at intensities ranging from 5 to 100 G, over four days. Various PEMF intensities significantly increased the expression of anagen-related molecules, including collagen IV, laminin, ALP, and versican. In particular, an intensity of 10 G is most potent for promoting the proliferation of hDPC and expression of anagen-related molecules. Moreover, 10 G ELF-EMF significantly increased β-catenin and Wnt3α expression and GSK-3β/ERK/Akt phosphorylation. Our results confirmed that ELF-EMFs enhance hDPC activation and proliferation via the GSK-3β/ERK/Akt signaling pathway, suggesting a potential treatment strategy for alopecia., Competing Interests: The authors have no financial conflicts of interest.

Fibrous dysplasia (FD) is generally considered to be a benign disease that affects the bones, but it has potential to become malignant over time, generally several decades after its initial diagnosis. Radiation therapy can induce malignant transformation of FD; however, reports have indicated a few cases of malignant transformation of FD in the absence of radiation therapy. Angiosarcoma is a particularly rare type of cancer in the oral region, which accounts for less than 1% of all soft-tissue sarcomas. Herein, we reported a case of a 62-year-old man with monostotic FD of the left maxilla of over 50 years' duration that underwent malignant transformation into an epithelioid-type angiosarcoma. To the best of our knowledge, this is the first report of such case.

Background: Dysphagia and dysarthria tend to coexist in stroke patients. Dysphagia can reduce patients' quality of life, cause aspiration pneumonia and increased mortality., Objective: To evaluate correlations among swallowing function parameters and acoustic vowel space values in patients with stroke., Methods: Data from stroke patients with dysarthria and dysphagia were collected. The formant parameter representing the resonance frequency of the vocal tract as a two-dimensional coordinate point was measured for the /a/, /ae/, /i/, and /u/vowels, and the quadrilateral vowel space area (VSA) and formant centralization ratio (FCR) were measured. Swallowing function was evaluated by a videofluoroscopic swallowing study (VFSS) using the videofluoroscopic dysphagia scale (VDS) and penetration aspiration scale (PAS). Pearson's correlation and linear regression analyses were used to assess the correlation of VSA and FCR to VDS and PAS scores., Results: Thirty-one stroke patients with dysphagia and dysarthria were analyzed. VSA showed a negative correlation to VDS and PAS scores, while FCR showed a positive correlation to VDS score, but not to PAS score. VSA and FCR were significant factors for assessing dysphagia severity., Conclusions: VSA and FCR values were correlated with swallowing function and may be helpful in predicting dysphagia severity associated with stroke.