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Atopic dermatitis (AD) is one of major skin inflammatory diseases characterized by excessive Th2-mediated immune responses. Recent evidence provides that interlukin-13 (IL-13) plays the role of a key Th2 cytokine that drives the inflammation underlining AD. Due to adverse effects of commercially available synthetic drugs, the need for treatments based on natural products is gaining much attention. Sargassum horneri is an edible brown algae known for beneficial bioactivities including anti-inflammation. We investigated if polyphenol-rich S. horneri extracts (SHE) could suppress AD-like skin lesions in NC/Nga mice and if that involved inhibition of the infiltration of Th2-mediated cytokine IL-13. We observed markedly increased infiltration of IL-13 positive cells in AD-like skin lesions of mice but SHE treatments decreased it. Also, the dermal expression of IL-13 was sufficient to cause inflammatory responses in mice skin resembling human AD. SHE suppressed the dermal infiltration of inflammatory cells where IL-13 plays a crucial role in skin tissues and in the recruitment of inflammatory cells. Furthermore, it was confirmed that SHE reduced T cell, dendritic cell, and macrophage populations in spleen. Moreover, SHE decreased the collagen deposition in skin and ear dermis resulting in reduced fibrosis that occurs in AD due to excessive collagen. Taken together, our results reveal that SHE suppressed the infiltration of inflammatory cells into skin dermis by decreasing the infiltration of IL-13 positive cells. Therefore, SHE could be taken as a useful therapeutic agent to alleviate AD.

Neurological complications attributed to coronavirus disease-19 (COVID-19) infection have been reported including acute disseminated encephalomyelitis, Guillain-Barré syndrome, and so on. Herein, we report a 49-year-old woman presented with acute encephalopathy and paraplegia simultaneously after COVID-19 infection. Brain magnetic resonance imaging (MRI) showed symmetric hyperintense basal ganglia lesions on T2-weighted imaging. Cerebrospinal fluid pleocytosis, motor axonal neuropathy and enhancement of conus medullaris nerve roots on spine MRI were observed. We treated her with high-dose corticosteroid and intravenous immunoglobulin.

The Geostationary Environment Monitoring Spectrometer (GEMS) onboard the Geostationary Korea Multi-Purpose Satellite-2B (GEO-KOMPSAT-2B) satellite observes the hourly volcanic SO2 over Asia. In this study, the various physical characteristics of volcanic plumes have been investigated based on hourly volcanic SO2 measurements. The transport direction, path and speed, and altitude of volcanic SO2 plume emitted from Nishinoshima in Japan, Etna in Italy, and Dukono located in Halmahera, Indonesia were calculated. The SO2 plume from Nishinoshima, Japan, moved westward at a maximum speed of 57 km/h on August 4, 2020. The SO2 plume generated from Etna was observed to move over China using both GEMS and TROPOMI, and moved at an altitude of 11–14 km and a speed of 162–190 km/h. In the case of the SO2 plume from the Dukono volcano flowed into an average of 3.6 Mg of SO2 per hour to the cities of nearby islands. GEMS can be utilized for an improvement in the prediction accuracy of SO2 plume transport using a chemical transport model due to the availability of hourly volcanic SO2 height information. In addition, hourly observations of SO2 concentrations are expected to protect SO2 exposure through rapid forecasting for people in cities around the volcano.

In this study, nanocomplexes composed of glycyrrhizic acid (GA) derived from the root of the licorice plant (

The initiation of antiviral treatment in chronic hepatitis B (CHB) patients with compensated cirrhosis and low-level viremia (LLV; HBV DNA 15-2,000 IU/mL) remains controversial. We sought to compare the long-term outcomes of these untreated patients according to their viremic status.627 CHB untreated patients with compensated cirrhosis were analyzed retrospectively. The risk of hepatocellular carcinoma (HCC) and liver-related clinical events, including hepatic decompensation, were compared between patients with LLV and undetectable HBV DNA. Patients who received antiviral treatment were censored at the time of treatment initiation.The mean age of the patients was 54.7 years, 64.4 % of whom were male. During the study period, 59 patients developed HCC (20 and 39 in the undetectable and LLV groups, respectively) with an annual incidence of 2.44/100 person-years (PYs). Multivariable analysis revealed that the LLV group was associated with a significantly higher risk of HCC (adjusted hazard ratio [HR]: 2.36, p=0.002) than the undetectable group. In the 204 propensity-score (PS) matched cohort, the LLV group had a 2.16-fold greater risk of HCC than the undetectable group (p=0.014). Liver-related clinical events occurred in 121 patients with an annual incidence of 5.25/100 PYs. Despite not reaching statistical significance, the LLV group tended to have a higher risk of liver-related events in the PS-matched cohort (HR: 1.14, p=0.50).Compared with patients with undetectable HBV DNA, those with compensated cirrhosis and LLV had a significantly higher risk of HCC. Antiviral treatment should be advised for these patients.

Background: Pain and autonomic dysfunction are prominent symptoms in some patients with carpal tunnel syndrome (CTS). Infrared thermography (IRT) has been used to evaluate CTS by measuring the cutaneous temperature and sympathetic vasomotor function.Methods: This study enrolled the 66 hands of 33 subjects, some of which had clinical CTS and the others were healthy. The enrolled patients completed the Boston Carpal Tunnel Questionnaire (BCTQ) and Historical-Objective scale, and underwent nerve conduction studies (NCSs) and IRT. Skin temperature was measured at the fingertips and the thenar and hypothenar regions in each hand. We analyzed (1) the correlations between self-reported severity, physician-assessed severity, and test results, and (2) the sensitivity and specificity of IRT in diagnosing CTS.Results: No significant correlation was observed between the results of the BCTQ, NCS, and IRT. IRT had a low sensitivity and high specificity in diagnosing CTS.Conclusions: IRT cannot replace NCS in diagnosing CTS, nor did it provide an advantage in combination with NCS. However, lower temperatures at the median nerve in some hands with moderate-to-severe CTS suggested the involvement of sympathetic nerve fiber function. Follow-up studies with a larger-scale and complementary design are required to elucidate the relationships.

Despite ongoing research on factors affecting stress, there is a shortage of research on genetic variation using single nucleotide polymorphisms (SNPs). Thus, this study aims to identify genes that may affect the risk of stress in a large-scale Korean cohort. The stress survey used in this study consisted of 40 questions, organized into the following four categories: 10 questions on General Stress (GenST); 10 questions on Mental Stress (MenST); 10 questions on Physical Stress (PhyST); and 10 questions on Activity Stress (ActST). An overall stress score was calculated as the sum of the survey scores from each category, with a high stress score defined as a stress score in which the proportion of insomnia was large. Genome-wide association studies of approximately 320,000 SNPs acquired from the Korea Centers for Disease Control and Prevention (KCDC) were conducted to explore the risk of stress in the four categories. As a result, three loci were identified for GenST, no significant loci were observed for MenST, four loci were identified for PhyST, and two loci were identified for ActST. The most significant SNP of GenST (rs9353437) was located in an epidermal growth factor gene (eyes shut homolog, EYS) and expressed in the photoreceptor layer of the retina. The genome-wide association studies' (GWAS) results of PhyST showed a significant SNP (rs4924370) in a spliceosomal factor (Aquarius intron-binding spliceosomal factor, AQR). Notably, the second most significant SNP (rs1991002) was located in an oxidoreductase gene (NADH:Ubiquinone Oxidoreductase Subunit S4, NDUFS4) and was also marginally associated with GenST, MenST, and ActST (p-value < 0.05). A bioinformatics analysis of the genes linked to the identified SNPs demonstrated the presence of many genes that could be associated with neurotransmission or stress. Although the stress survey or classification criteria for stress scores used in this study were ambiguous, such results may be the first to expand upon the understanding of the genetic variations and the molecular mechanisms that may cause vulnerabilities to stress.

Considering the potent immune stimulation by CpG oligodeoxynucleotides (CpGs), the development of CpG carriers is a prerequisite for efficient cancer immunotherapy. In this study, we conjugated 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[hydroxyl succinimidyl (polyethylene glycol)] (DSPE-PEG-NHS) with polyethylenimine (PEI) to develop a PEI-PEG-DSPE conjugate that can serve as a biocompatible and efficient CpG carrier. Five types of PEIPEG-DSPE conjugates were developed, each with different molecular weights of PEI and different degrees of DSPEPEG modification, and all exhibited significantly lower cytotoxicity. In particular, compared to CpG delivery via natural PEI, delivery with PEI (25 kDa)-PEG-DSPE and DSPE-PEG-NHS/(amine groups of PEI) at a molar ratio of 0.1 resulted in a higher uptake of CpGs into RAW264.7 cells, probably because of the presence of a hydrophobic lipid moiety. In addition, PEI-PEG-DSPE/CpG complexes triggered significant cytokine secretion (TNF-α) from RAW264.7 cells, comparable to that triggered by PEI/CpG complexes. Thus, PEI-PEG-DSPE conjugates could serve as biocompatible and efficient carriers of the immune stimulator CpG to the macrophages.

Background: Neurology in Korea is a field of clinical practice and research that has been developing for over 30 years, but due to its relatively short history, public awareness is low compared to other clinical fields. The Korean Neurological Association conducted a survey to evaluate the Korean public’s awareness of neurology and the necessity of a name change. This study details the second survey conducted on the topic, with the first being conducted in 2013. The two surveys were compared to identify how the public’s awareness of neurology has improved since 2013 and determine how this can be improved.Methods: The survey was conducted by Gallup Korea, where 1,000 participants were randomly selected and interviewed through telephone surveys.Results: Of the 1,000 participants, 78.5% were familiar with Neurology, similar to the results of the 2013 survey. Meanwhile, when asked about neurological diseases, only 27.9% of the participants recognized neurological diseases correctly. The most accurately recognized symptoms related to Neurology were tremors (57.8%), strokes (55.5%), and dizziness (49.7%). In 2013, 61.7% of the participants thought a name change was necessary. In comparison, only 38.4% responded it needed to change in the recent survey.Conclusions: The preference for Neurology’s current name in Korea has improved since 2013 despite no significant change in the public’s awareness of neurology. More active public relations activities are needed to improve awareness of neurology in the future.

In the fight against cancer, immunotherapies are one of the largest growing therapeutics in development. Immunotherapeutics are designed to boost or harness the power of the immune system to prevent, control, or eliminate cancer; while many immune therapies have been found to be safe others have induced severe toxicities. For instance, even compounds that target the same molecule/antigen can have dramatically differing safety profiles. Current preclinical models evaluating these therapies are underequipped to assess the safety of these compounds: in vitro assays fail to predict systemic responses and traditional animal models often fail to correlate with human responses. To better meet the needs of assessing preclinical toxicity we developed a PBMC-humanized mouse model to test a variety of therapeutics, including both monoclonal and bispecific antibodies and induce human cytokine release responses which can manifest within hours or days later resulting in tissue damage and lethality of the mice. To date we have tested a variety of therapeutics, including Blinatumomab, Rituximab, EGFRxCD3 BiTE, CAR-T, and others in our platform while evaluating the ability of the therapeutic to induce human cytokines, bodyweight loss, clinical symptom assessment, and survival in the context of toxicity alone or along with the evaluation with efficacy. We found that many of the therapeutics tested in our platform showed similarities to clinical data in humans. For example, urelumab and utomilumab are both fully humanized monoclonal antibodies against 4-1BB (CD137). However, during clinical trials, urelumab was shown to induce severe liver toxicities while utomilumab was well tolerated. In our huPBMC mouse model, we likewise showed that huPBMC mice dosed with 10 mpk of urelumab experienced body weight loss, showed liver necrosis, and met the clinical criteria for early euthanasia compared to mice treated with 10 mpk utomilumab and PBS treated controls. Serum levels of enzymes associated with liver damage: AST, ALT and GLDH were significantly higher in urelumab treated mice and terminal serum cytokine analysis revealed similarities with those found to be increased in urelumab clinical trials, including elevated IFNγ, IP-10, MIG, and MIP-1α and MIP-1β. Further, HuPBMC mice are also capable of detecting variability among donors. We have screened well over 60 human PBMC donors in huPBMC mice treated with OKT3 and αCD28 and while we always see an increase in cytokines such as IFNγ - the range of induction varies greatly among donors. Further, we see PBMC-donor variability in body weight loss and survival rate after OKT3 and αCD28 treatments. We demonstrate that the PBMC humanized mouse model shows clinical relevance. The use of these models for preclinical safety assessments has the potential to become an important part of novel immunotherapeutic development for patient safety and reducing drug development costs. Citation Format: Destanie Rose, Won Lee, Guoxiang Yang, Jiwon Yang, Mingshan Cheng, Wenqian He, Bernard Buetow, Allison Vitsky, Maggie Liu, Bart Jessen, James Keck. The use of PBMC humanized mice to test the efficacy and safety of antibody and cell-based cancer immunotherapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB349.

Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a revolutionary therapeutic to fight cancer. However, side effects such as cytokine-release syndrome and neurotoxicity often accompany and remain unpredictable. While autologous CAR-Ts are FDA-approved, allogeneic CAR-Ts are in active development in pursuit of “off-the-shelf” availability and reduced manufacturing costs. However, the same concern for adverse events applies. Importantly, how the immune characteristics of the patient may predispose towards toxicity is not well modeled. Further, it is unclear how autologous versus allogeneic products interact with the patient immune system. Toxicity does not correlate with in vitro characterization of the CAR-Ts, adding unpredictability to the toxicity and efficacy. These highlight the need for in vivo mouse models to explore biological variation, predictive biomarkers, and therapeutic intervention. Therefore, we developed a humanized mouse model using NSG™-MHC Class I/II double knock-out (DKO) mice engrafted with human PBMCs to access individual variability in CAR-T-induced toxicity and efficacy. DKO mice are optimal for assessing human cytokine induction from CAR-Ts as they show delayed onset of GvHD and low baseline cytokine levels. To test donor variation in autologous CAR-T toxicity, we humanized mice and treated with autologous CD19 CAR-Ts containing the CD28 costimulatory domain and CD3z chain from two human PBMC donors (Donor A and B). CAR-T successfully eliminated human B cells from both PBMC donors in vivo. We observed drastic body weight loss and 83% of Donor A mice (engrafted with 17M PBMCs) reached the humane endpoint. In contrast, Donor B mice did not experience body weight loss. CAR-T induced human cytokines such as IFN-ꝩ, IL-2, IL-4, IL-6, IL-10, TNFα, MIG, MIP-1a, and IP-10, recapturing clinical data. To test donor variation in allogeneic CAR-T toxicity, we engrafted mice with 10M PBMCs from 6 healthy donors and treated with allogeneic CAR-Ts from Donor A or B. Allogenic efficacy was greater in Donor B CAR- than Donor A CAR-Ts. Donor-specific variability was observed; mice humanized with one of the six donors, experienced significant body weight loss only from the Donor B CAR-Ts but not from Donor A CAR-Ts. Principal component analysis of cytokine data revealed that Donor B CAR-Ts induced more distinguished cytokine responses than Donor A CAR-Ts, driven by IFN-ꝩ and IL-10. Lastly, the data indicates that the CAR-T cells show poor expansion in allogeneic treatment, corresponding to the current literature. PBMC-humanized mice provide an in vivo platform to assess the toxicity and efficacy of autologous and allogeneic CAR-T treatment. This platform can be used to preclinically assess cytokine induction from the interaction between the patient immune system and allogeneic CAR-Ts from healthy donors. Citation Format: Won Lee, Destanie Rose, Katelyn Burleigh, Blair Armstrong, Heather Gustafson, Rebecca Gardner, James G. Keck, Jiwon Yang. Assessing individual variability in efficacy and toxicity of autologous and allogeneic chimeric antigen receptor T-cell immunotherapy using a PBMC-humanized mouse model. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4096.

Glucose and galactose are monosaccharides obtained from Gloiopeltis furcata (Red algae). A total monosaccharide yield of 62.3 g/L was obtained from G. furcata using thermal acid hydrolysis and enzymatic saccharification. Activated carbon was used to eliminate hydroxymethylfurfural (HMF) from the hydrolysate. Previously obtained monosaccharides are used for ethanol production by Saccharomyces cerevisiae. S. cerevisiae consumes glucose first, then galactose. The methods for reducing fermentation time and increasing the ethanol yield coefficient using the simultaneous consumption of glucose and galactose have been evaluated. Gal3p and Gal80p of S. cerevisiae act as signal transducers that govern the galactose inducer Gal4p mediated transcriptional activation of the Gal gene family. Gal80p binds to Gal4p for transcription deactivation. Therefore, Gal80p was deleted for Gal4p expression without interruption.

Because of the environmental issues associated with thermoset or network polymers, recyclable polymers are highly in demand, and the use of sustainable biomass-derived ingredients is also becoming ...

In this study, we examined cellular responses to acute and chronic IRA irradiation at mild and natural levels of exposure in two types of human fibroblasts, each isolated from a different donor, at physiological temperature (34°C).Two types of human dermal fibroblasts (derived from a 20- and 50-year-old women, respectively) were exposed to different repeat numbers of IRA exposure (3, 6, 10, and 14 times; 42 mW/cmWe demonstrated that chronic IRA irradiation-induced severe cellular damage, including prolonged cell proliferation, increased intracellular ROS levels, activated cellular apoptosis, and elongated cell morphology, whereas acute IRA irradiation had negligible effects at 34°C. In addition, it was evident that the degree of cellular damage due to IRA irradiation differed according to the type of fibroblasts.Considering the severe cellular damage induced by chronic IRA irradiation without heat, continuous exposure of skin to IRA irradiation during daily life may be harmful enough to induce photoaging.

The Geostationary Environment Monitoring Spectrometer (GEMS) onboard the Geostationary Korea Multi-Purpose Satellite-2B (GEO-KOMPSAT-2B) satellite was launched in February 2020 and observes the hourly volcanic SO2 in geostationary orbit. We For the first time show the hourly changes in volcanic SO2 distributions emitted and transported from several volcanoes over Asia. The various physical characteristics of volcanic plumes have been investigated based on hourly volcanic SO2 measurements. We estimated transport direction, path and speed, and altitude of volcanic SO2 plume emitted from Nishinoshima in Japan, Etna in Italy, Taal volcano in the Philippines and Dukono located in Halmahera, Indonesia. Before the eruption, Taal volcanic SO2 plumes, which were found to present within PBL, were transported mostly less than 100 km in various azimuth directions. Gradual increase in SO2 column densities was observed for about two months before a volcanic eruption from Taal. It implies that it might be possible to warn a volcanic eruption in advance which is subject to further investigation. GEMS can be further utilized for an improvement in prediction accuracy of SO2 plume transport using chemical transport model due to the availability of hourly volcanic SO2 height information.

Nitrogen dioxide (NO2) is generally emitted from the anthropogenic source such as fossil fuel combustion and natural sources such as lightning, forest fires, and soil emission. These NO2 have adverse effects on human health and are known to affect regional climate as a short lived climate forcer. In addition, it is a precursor of aerosol nitrate and plays a key role the photochemistry of tropospheric Ozone. Up to date, NO2 observation has been possible only once a day using low earth orbit satellite sensors such as GOME, SCIAMACHY, GEMS-2, OMI, OMPS, and TROPOMI. However, hourly NO2 monitoring is expected to provide better understanding of atmospheric chemistries and climate effects related with NOx in regional and global scales. From February, 2020, it is possible, for the first time, to observe the diurnal NO2 variations using Geostationary Environment Monitoring Spectrometer (GEMS). Here, we present first results of diurnal changes in total and tropospheric NO2 columns observed over Asia with high temporal and spatial resolutions using the GEMS operational NO2 algorithm. NIER of Ministry of Environment in South Korea plans to release the GEMS NO2 data in real-time. The GEMS operational NO2 algorithm based on DOAS technique and LUT based NO2 AMF to retrieve the total NO2 columns. We, in addition, retrieve the GEMS tropospheric NO2 columns by subtracting stratospheric NO2 columns from the total NO2 columns. The stratospheric NO2 columns are calculated from scaling stratospheric NO2 from SLIMCAT model using the real GEMS observation data over Pacific ocean. In this present study, we introduce diurnal characteristics at various major cities including, ports, and industrial regions. We also evaluate the performance of the GEMS NO2 retrieval algorithm by comparing GEMS NO2 columns and those observed from ground based Pandora at Seosan in South Korea and MAX-DOAS at Xianghe in China. The comparisons also are made between the total and tropospheric GEMS NO2 data and that of TROPOMI. The validation results show good agreements of GEMS data against those from others.