The Antioxidant Activity and Their Major Antioxidant Compounds from Acanthopanax senticosus and A. koreanum

The antioxidant activity and chlorogenic acid and caffeic acid contents were investigated from different parts of Acanthopanax senticosus and A. koreanum. Antioxidant activity was assessed by various in vitro assays such as DPPH, ABTS, FRAP, reducing power assays and ORAC, and the chlorogenic acid and caffeic acid were validated by HPLC chromatography. Among the various extracts, the fruit extracts of A. senticosus and A. koreanum exhibited strongest antioxidant activities including ABTS, FRAP, reducing power and ORAC, however, strongest DPPH radical scavenging activity was observed from the leaf extract of A. senticosus. In addition, the antioxidant activities of various extracts were correlated with total phenolic and proanthocyanidin contents. The major phenolic contents from various parts of these plants observed that leaf extract of A. senticosus expressed higher levels of chlorogenic acid (14.86 mg/dry weigh g) and caffeic acid (3.09 mg/dry weigh g) than other parts. Therefore, these results suggest that the leaf of A. senticosus may be an excellent natural source for functional foods and pharmaceutical agents, and the validated method was useful for the quality control of A. senticosus

Differentially Expressed Potassium Channels Are Associated with Function of Human Effector Memory CD8+T cells

The voltage-gated potassium channel, Kv1.3, and the Ca2+-activated potassium channel, KCa3.1, regulate membrane potentials in T cells, thereby controlling T cell activation and cytokine production. However, little is known about the expression and function of potassium channels in human effector memory ( EM) CD8+ T cells that can be further divided into functionally distinct subsets based on the expression of the interleukin ( IL)-7 receptor alpha ( IL-7R alpha) chain. Herein, we investigated the functional expression and roles of Kv1.3 and KCa3.1 in EM CD8+ T cells that express high or low levels of the IL-7 receptor alpha chain ( IL-7R alpha(high) and IL-7R alpha(low), respectively). In contrast to the significant activity of Kv1.3 and KCa3.1 in IL-7Rahigh EM CD8+ T cells, IL-7Ralow EM CD8+ T cells showed lower expression of Kv1.3 and insignificant expression of KCa3.1. Kv1.3 was involved in the modulation of cell proliferation and IL-2 production, whereas KCa3.1 affected the motility of EM CD8+ T cells. The lower motility of IL-7Ralow EM CD8+ T cells was demonstrated using transendothelial migration and motility assays with intercellular adhesion molecule 1-and/or chemokine stromal cell-derived factor-1 alpha-coated surfaces. Consistent with the lower migration property, IL-7Ralow EM CD8+ T cells were found less frequently in human skin. Stimulating IL-7Ralow EM CD8+ T cells with IL-2 or IL-15 increased their motility and recovery of KCa3.1 activity. Our findings demonstrate that Kv1.3 and KCa3.1 are differentially involved in the functions of EM CD8+ T cells. The weak expression of potassium channels in IL-7Ralow EM CD8+ T cells can be revived by stimulation with IL-2 or IL-15, which restores the associated functions. This study suggests that IL-7Rahigh EM CD8+ T cells with functional potassium channels may serve as a reservoir for effector CD8+ T cells during peripheral inflammation.112Ysciescopu

Subspecific Status of the Korean Tiger Inferred by Ancient DNA Analysis

The tiger population that once inhabited the Korean peninsula was initially considered a unique subspecies (Panthera tigris coreensis), distinct from the Amur tiger of the Russian Far East (P. t. altaica). However, in the following decades, the population of P. t. coreensis was classified as P. t. altaica and hence forth the two populations have been considered the same subspecies. From an ecological point of view, the classification of the Korean tiger population as P. t. altaica is a plausible conclusion. Historically, there were no major dispersal barriers between the Korean peninsula and the habitat of Amur tigers in Far Eastern Russia and northeastern China that might prevent gene flow, especially for a large carnivore with long-distance dispersal abilities. However, there has yet to be a genetic study to confirm the subspecific status of the Korean tiger. Bone samples from four tigers originally caught in the Korean peninsula were collected from two museums in Japan and the United States. Eight mitochondrial gene fragments were sequenced and compared to previously published tiger subspecies\u27 mtDNA sequences to assess the phylogenetic relationship of the Korean tiger. Three individuals shared an identical haplotype with the Amur tigers. One specimen grouped with Malayan tigers, perhaps due to misidentification or mislabeling of the sample. Our results support the conclusion that the Korean tiger should be classified as P. t. altaica, which has important implications for the conservation and reintroduction of Korean tigers

Nasal commensal Staphylococcus epidermidis enhances interferon-λ-dependent immunity against influenza virus

Background Staphylococcus epidermidis is one of the most abundant colonizers of healthy human mucosa including that in the respiratory tract. As the respiratory microbiome has been linked to host immune responses, this study sought to determine the role of nasal mucosa-associated S. epidermidis in innate immune responses against the influenza A virus (IAV). S. epidermidis strains were isolated from nasal mucus samples of healthy individuals. The effects of these mucosa-derived commensal strains on interferon (IFN)-dependent innate immunity and IAV infection dynamics were tested in vitro using normal human nasal epithelial (NHNE) cells and human turbinate mucosa. The effects of S. epidermidis on antiviral immunity were also tested in vivo using an acute IAV infection mouse model. Results Exposure of NHNE cells to nasal mucosa-derived S. epidermidis increased IFN-λ mRNA and secreted protein levels in the absence of viral stimulation. In the context of IAV infection, NHNE exposure to S. epidermidis prevented an increase in the viral burden, as revealed by IAV PA mRNA abundance, IAV nucleoprotein levels, and viral titers. S. epidermidis also enhanced transcription of IFN-stimulated genes independently of Toll-like receptor 2 and further induced IFN-λ production in IAV-infected cells by promoting phosphorylation of interferon regulatory factor 7. In a murine infection model, S. epidermidis prevented the spread of IAV to the lungs by stimulating IFN-λ innate immunity and suppressing IAV replication in the nasal mucosa. Conclusion The human nasal commensal S. epidermidis mediates front-line antiviral protection against IAV infection through modulation of IFN-λ-dependent innate immune mechanisms in the nasal mucosa, thereby demonstrating the role of host-bacterial commensalism in shaping human antiviral responses.This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Kim et al. Microbiome (2019) 7:80 Page 10 of 12 Education (2016R1D1A1B01014116 to H.J.K.) and (2017M3A9F3041233 to S.S.Y.). This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI18C1337 to H.J.K), and the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2014M3A9D5A01073865 to J.Y.C

The acidic tumor microenvironment enhances PD-L1 expression via activation of STAT3 in MDA-MB-231 breast cancer cells

Abstract Tumor acidosis, a common phenomenon in solid cancers such as breast cancer, is caused by the abnormal metabolism of cancer cells. The low pH affects cells surrounding the cancer, and tumor acidosis has been shown to inhibit the activity of immune cells. Despite many previous studies, the immune surveillance mechanisms are not fully understood. We found that the expression of PD-L1 was significantly increased under conditions of extracellular acidosis in MDA-MB-231 cells. We also confirmed that the increased expression of PD-L1 mediated by extracellular acidosis was decreased when the pH was raised to the normal range. Gene set enrichment analysis (GSEA) of public breast cancer patient databases showed that PD-L1 expression was also highly correlated with IL-6/JAK/STAT3 signaling. Surprisingly, the expression of both phospho-tyrosine STAT3 and PD-L1 was significantly increased under conditions of extracellular acidosis, and inhibition of STAT3 did not increase the expression of PD-L1 even under acidic conditions in MDA-MB-231 cells. Based on these results, we suggest that the expression of PD-L1 is increased by tumor acidosis via activation of STAT3 in MDA-MB-231 cells.This work was supported by grants from the National Research Foundation of Korea (NRF) funded by the Korean government (NRF-2018R1A5A2025964) and the Seoul National University Hospital (SNUH) Research Fund (04–20200230). This study was also carried out with support from the R&D Program for Forest Science Technology (Project No. 2020195A00–2122-BA01) of the Korea Forest Service (Korea Forestry Promotion Institute) and Cooperative Research Program for the Agriculture Science and Technology Development (Project No. PJ01589402 and No. PJ016202022) Rural Development Administration, Republic of Korea

Clinical Characteristics of Allergic Rhinitis According to Allergic Rhinitis and Its Impact on Asthma Guidelines

ObjectivesThe Allergic rhinitis and its impact on asthma (ARIA) guidelines were suggested for use to classify allergic rhinitis (AR). However, few studies have been performed in Asians. The objective of this study is to identify the clinical characteristics of AR in Korean patients according to the ARIA guidelines.MethodsFor the study, 610 patients who had been diagnosed with allergic rhinitis at Seoul National University Bundang Hospital and 545 patients who had been diagnosed with allergic rhinitis at 3 local clinics were included. All the patients were categorized into 4 groups, such as the mild intermittent, mild persistent, moderate-severe intermittent and moderate-severe persistent groups. The patients were given a questionnaire on allergic rhinitis-related symptoms and they underwent blood tests, including the blood eosinophil count and the serum total IgE level.ResultsThe most prevalent type was the moderate-severe persistent group (34.7%), and the moderate-severe intermittent group (17.1%) was the rarest. There were significant differences among the 4 groups for olfaction (P<0.001), self-awareness of rhinitis (P=0.013), a previous history of AR (P<0.001), self-awareness of asthma (P=0.001) and allergic conjunctivitis (P<0.001). On the allergy laboratory tests, there was a significant difference between the groups for the eosinophi count (P=0.004). The number of blood eosinophil was more in the persistent groups than in the intermittent groups.ConclusionAccording to the ARIA guidelines, the moderate-severe persistent group was the most prevalent for Korean patients. Blood eosinophilia and olfactory dysfunction were the most severe in the moderate-severe persistent group

The inhibitory effect of quercitrin gallate on iNOS expression induced by lipopolysaccharide in Balb/c mice

Quercetin 3-O-β-(2"-galloyl)-rhamnopyranoside (QGR) is a naturally occurring quercitrin gallate, which is a polyphenolic compound that was originally isolated from Persicaria lapathifolia (Polygonaceae). QGR has been shown to have an inhibitory effect on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. Therefore, this study was conducted to investigate the inhibitory effect of QGR on nitric oxide production and inducible nitric oxide synthases (iNOS) expression in LPS-stimulated Balb/c mice. To accomplish this, 10 mg/kg of QGR was administered via gavage once a day for 3 days. iNOS was then induced by intraperitoneal injection of LPS. Six hours after the LPS treatment the animals were sacrificed under ether anethesia. The serum levels of NO were then measured to determine if QGR exerted an inhibitory effect on NO production in vivo. LPS induced an approximately 6 fold increase in the expression of NO. However, oral administration of QGR reduced the LPS induced increase in NO by half. Furthermore, RT-PCR and western blot analysis revealed that the increased levels of iNOS expression that occurred in response to treatment with LPS were significantly attenuated in response to QGR pretreatment. Histologically, LPS induced the infiltration of polymorphonuclear neutrophils in portal veins and sinusoids and caused the formation of a large number of necrotic cells; however, pretreatment with QGR attenuated these LPS induced effects. Taken together, these results indicate that QGR inhibits iNOS expression in vivo as well as in vitro and has antiinflammatory potentials