Background: Ergothioneine (EGT) is a natural amino acid derivative in various animal organs and is a bioactive compound recognized as a food and medicine. Objectives: This study examined the effects of EGT supplementation during the in vitro maturation (IVM) period on porcine oocyte maturation and subsequent embryonic development competence after in vitro fertilization (IVF). Methods: Each EGT concentration (0, 10, 50, and 100 µM) was supplemented in the maturation medium during IVM. After IVM, nuclear maturation, intracellular glutathione (GSH), and reactive oxygen species (ROS) levels of oocytes were investigated. In addition, the genes related to cumulus function and antioxidant pathways in oocytes or cumulus cells were investigated. Finally, this study examined whether EGT could affect embryonic development after IVF. Results: After IVM, the EGT supplementation group showed significantly higher intracellular GSH levels and significantly lower intracellular ROS levels than the control group. Moreover, the expression levels of hyaluronan synthase 2 and Connexin 43 were significantly higher in the 10 µM EGT group than in the control group. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and NAD(P)H quinone dehydrogenase 1 (NQO1) were significantly higher in the oocytes of the 10 µM EGT group than in the control group. In the assessment of subsequent embryonic development after IVF, the 10 µM EGT treatment group improved the cleavage and blastocyst rate significantly than the control group. Conclusions Supplementation of EGT improved oocyte maturation and embryonic development by reducing oxidative stress in IVM oocytes.

The efficiency of somatic cell nuclear transfer (NT) in pigs is low and requires enhancement. We identified the most efficient method for zona pellucida (ZP) removal and blastomere aggregation in pigs and investigated whether the aggregation of NT and parthenogenetic activation (PA) of blastomeres could reduce embryonic apoptosis and improve the quality of NT-derived embryos by investigating. Embryonic developmental competence after ZP removal using acid Tyrode's solution or protease (pronase E). The embryonic developmental potential of NT-derived blastomeres was also investigated using well-of-the-well or phytohemagglutinin-L. We analyzed apoptosis in aggregate-derived blastocysts. The aggregation rate of protease-treated embryos was lower than that of Tyrode’s solution-treated embryos (69.2% vs. 88.3%). No significant difference was observed between phytohemagglutinin-L and well-of-the-well (35.7%–38.5%). However, 2P1N showed a higher number of blastocysts compared to 3N (73.8% vs. 24.3%) and an increased blastocyst diameter compared to the control and 1P2N (274 μm vs. 230–234 μm). In blastomeres aggregated using phytohemagglutinin-L, the apoptotic cell ratio was significantly higher in 1P2N and 3N than in 3P (5.91%–6.46% vs. 2.94%, respectively). Our results indicate that aggregation of one NT embryo with two PA embryos improved the rate of blastocysts with increased blastocyst diameter.

Objectives: . This study was conducted to determine whether patients with allergic rhinitis might be more susceptible to human rhinovirus (HRV) infection and whether the effects of infection on the elicited immune responses are different in allergic and non-allergic patients with chronic rhinosinusitis (CRS). Methods: . Uncinate process tissues were obtained from 61 CRS patients (of whom 39 had allergies and 22 did not) and were infected with HRV-16 using an air-liquid interface organ culture system. The expression levels of programmed cell death-ligand (PD-L)1, PD-L2, intracellular adhesion molecule 1, interferon-gamma (IFN-γ), interleukin (IL)-4, IL-5, and IL-10 were evaluated in the infected nasal mucosa. Results: . The HRV infection rates were not significantly different between the allergy (74.4%) and non-allergy (72.7%) groups. In the allergy group, the expression of PD-L1 (P=0.013) and IL-10 (P=0.040) was significantly elevated in the HRV-infected tissues, and there was a strong correlation between PD-L1 and IL-10 (r=0.868, P<0.001). In contrast, infected tissues from the non-allergy group displayed increased levels of IL-4 (P=0.039), IL-5 (P=0.023), and IFN-γ (P=0.031), as well as an increased IL-4/IFN-γ ratio, after HRV infection (P=0.043). Conclusion . This study showed that HRV infection rates were similar in the nasal mucosa of patients with CRS regardless of the presence of allergic rhinitis. HRV infection enhanced the Th2 environment by modulating PD-L1 and PD-L2 expression levels in allergic mucosa and by increasing the IL-4/IFN-γ ratio in non-allergic mucosa.

Objectives: . This study was conducted to determine whether patients with allergic rhinitis might be more susceptible to human rhinovirus (HRV) infection and whether the effects of infection on the elicited immune responses are different in allergic and non-allergic patients with chronic rhinosinusitis (CRS). Methods: . Uncinate process tissues were obtained from 61 CRS patients (of whom 39 had allergies and 22 did not) and were infected with HRV-16 using an air-liquid interface organ culture system. The expression levels of programmed cell death-ligand (PD-L)1, PD-L2, intracellular adhesion molecule 1, interferon-gamma (IFN-γ), interleukin (IL)-4, IL-5, and IL-10 were evaluated in the infected nasal mucosa. Results: . The HRV infection rates were not significantly different between the allergy (74.4%) and non-allergy (72.7%) groups. In the allergy group, the expression of PD-L1 (P=0.013) and IL-10 (P=0.040) was significantly elevated in the HRV-infected tissues, and there was a strong correlation between PD-L1 and IL-10 (r=0.868, P<0.001). In contrast, infected tissues from the non-allergy group displayed increased levels of IL-4 (P=0.039), IL-5 (P=0.023), and IFN-γ (P=0.031), as well as an increased IL-4/IFN-γ ratio, after HRV infection (P=0.043). Conclusion . This study showed that HRV infection rates were similar in the nasal mucosa of patients with CRS regardless of the presence of allergic rhinitis. HRV infection enhanced the Th2 environment by modulating PD-L1 and PD-L2 expression levels in allergic mucosa and by increasing the IL-4/IFN-γ ratio in non-allergic mucosa.

The explosive growth of next-generation sequencing data has resulted in ultra-large-scale datasets and ensuing computational problems. In Korea, the amount of genomic data has been increasing rapidly in the recent years. Leveraging these big data requires researchers to use large-scale computational resources and analysis pipelines. A promising solution for addressing this computational challenge is cloud computing, where CPUs, memory, storage, and programs are accessible in the form of virtual machines. Here, we present a cloud computing-based system, Bio-Express, that provides user-friendly, cost-effective analysis of massive genomic datasets. Bio-Express is loaded with predefined multi-omics data analysis pipelines, which are divided into genome, transcriptome, epigenome, and metagenome pipelines. Users can employ predefined pipelines or create a new pipeline for analyzing their own omics data. We also developed several web-based services for facilitating downstream analysis of genome data. Bio-Express web service is freely available at https://www.bioexpress.re.kr/.

The explosive growth of next-generation sequencing data has resulted in ultra-large-scale datasets and ensuing computational problems. In Korea, the amount of genomic data has been increasing rapidly in the recent years. Leveraging these big data requires researchers to use large-scale computational resources and analysis pipelines. A promising solution for addressing this computational challenge is cloud computing, where CPUs, memory, storage, and programs are accessible in the form of virtual machines. Here, we present a cloud computing-based system, Bio-Express, that provides user-friendly, cost-effective analysis of massive genomic datasets. Bio-Express is loaded with predefined multi-omics data analysis pipelines, which are divided into genome, transcriptome, epigenome, and metagenome pipelines. Users can employ predefined pipelines or create a new pipeline for analyzing their own omics data. We also developed several web-based services for facilitating downstream analysis of genome data. Bio-Express web service is freely available at https://www.bioexpress.re.kr/.

PURPOSE: Vitamin D is a potent immunomodulator. However, its role in the pathogenesis of allergic rhinitis is unclear. METHODS: The aim of this study was to evaluate the antiallergic effect of intranasally applied vitamin D in an allergic rhinitis mouse model. BALB/c mice were intraperitoneally sensitized with ovalbumin (OVA) and alum before they were intranasally challenged with OVA. Then, they were intranasally administered 1, 25-dihydroxyvitamin D3 (0.02 μg) or solvent. Allergic symptom scores, eosinophil infiltration, cytokine mRNA levels (interleukin [IL]-4, IL-5, IL-10, IL-13 and interferon-γ) in the nasal tissue, and serum total immunoglobulin E (IgE) and OVA-specific IgE, IgG1, and IgG2a were analyzed and compared with negative and positive control groups. Cervical lymph nodes (LNs) were harvested for flow cytometry analysis and cell proliferation assay. RESULTS: In the treatment group, allergic symptom scores, eosinophil infiltration, and mRNA levels of IL-4 and IL-13 were significantly lower in the nasal tissue than in the positive control group. The IL-5 mRNA level, serum total IgE, and OVA-specific IgE and IgG1 levels decreased in the treatment group; however, the difference was not significant. In the cervical LNs, CD86 expression had been down-regulated in CD11c+major histocompatibility complex II-high (MHCIIhigh) in the treatment group. Additionally, IL-4 secretion in the lymphocyte culture from cervical LNs significantly decreased. CONCLUSIONS: The results confirm the antiallergic effect of intranasal 1,25-dihydroxyvitamin D3. It decreases CD 86 expression among CD11c+MHCIIhigh cells and T-helper type 2-mediated inflammation in the cervical LNs. Therefore, topically applied 1,25-dihydroxyvitamin D3 can be a future therapeutic agent for allergic rhinitis.
Administration, Intranasal ; Animals ; Anti-Allergic Agents ; Calcitriol ; Cell Proliferation ; Dendritic Cells ; Eosinophils ; Flow Cytometry ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins ; Inflammation ; Interleukin-10 ; Interleukin-13 ; Interleukin-4 ; Interleukin-5 ; Lymph Nodes ; Lymphocytes ; Major Histocompatibility Complex ; Mice ; Models, Animal ; Ovalbumin ; Ovum ; Rhinitis, Allergic ; RNA, Messenger ; Vitamin D

PURPOSE: Whereas the majority of nasal polyps observed in Western populations are eosinophilic, non-eosinophilic nasal polyps are significantly more frequent in Asian countries. Given the importance of nuclear factor-kappa B (NF-κB) in inflammation, this study focused on the role of NF-κB in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNPs) in Asian patients. METHODS: A total of 46 patients were enrolled in this study (22 diagnosed with CRSwNPs, 10 with chronic rhinosinusitis without nasal polyps [CRSsNP], and 14 control subjects). Nasal polyps and uncinate tissues (UTs) were collected and the tissues prepared for hematoxylin-eosin staining and immunohistochemistric (IHC) analysis. Total RNA was isolated for real-time polymerase chain reaction for p65, interleukin (IL)-6, IL-8, intracellular adhesion molecule (ICAM)-1, IL-1β, tumor necrosis factor (TNF)-α, and eotaxin. RESULTS: In the CRSwNPs group, 50% of nasal polyps were non-eosinophilic. IHC revealed a significantly higher fraction of NF-κB p65-positive cells in nasal polyps of the CRSwNPs group than in the UTs of control and CRSsNP groups. No difference in NF-κB p65-positive cell fraction was observed between eosinophilic and non-eosinophilic nasal polyps. The mRNA expression of p65, IL-6, IL-8, and eotaxin was significantly higher in nasal polyps of the CRSwNPs than in the UTs of control and CRSsNP group. However, no difference in expression was observed between eosinophilic and non-eosinophilic nasal polyps, with the exception of IL-1β expression. CONCLUSIONS: Elevated expression of NF-κB- and NF-κB-associated inflammatory cytokines suggests NF-κB as the key factor for CRSwNPs pathogenesis in Asian patients. Understanding NF-κB-associated mechanisms will provide a deeper insight into CRSwNPs pathogenesis and ultimately improve therapeutic strategies for CRSwNPs.
Asian Continental Ancestry Group ; Cytokines ; Eosinophils ; Humans ; Immunohistochemistry ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Nasal Polyps ; Real-Time Polymerase Chain Reaction ; RNA ; RNA, Messenger ; Sinusitis ; Transcription Factors ; Tumor Necrosis Factor-alpha

The 2017 China (Lianyungang) International Medical Technology Conference was held in Lianyungang,Jiangsu Province during November 15-17,2017.During this conference,the Division for Traditional Chinese Medicine and Natural Products Pharmacology of Chinese Pharmacological Society (CNPHARS) and Jiangsu Kanion Pharmaceutical Co. Ltd.jointly held the Forum on R&D and Interna-tionalization of New Drugs and Health Products of Traditional Chinese Medicine.The forum was co-chaired by Professor ZHANG Yong-xiang, President of CNPHARS, Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Chair of the Natural Product Section of Inter-national Union of Basic&Clinical Pharmacology(IUPHAR), Professor DU Guan-hua,former President of CNPHARS and Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Dr.XIAO Wei,Chairman of the Board of Jiangsu Kanion Pharmaceutical Co. Ltd. And Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS. More than 70 scholars attended the forum, including four foreign experts [Michael SPEDDING, Secretary-General of IUPHAR; Professor Valérie B. SCHINI-KERTH, Vice-Chair of the Natural Product Section of IUPHAR; Professor Cherry WAINWRGHT, Director of Centre for Natural Product Drugs of Robert Gordon University; Professor InKyeom KIM, Director of the Korean Society of Pharmacology], members of the Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS and leading researchers at Jiangsu Kanion Pharmaceutical Co.,Ltd.GU Jin-hui,Director of the Division of National Science and Technology Major Project for Drug Innovation,Department of Health Science,Technology and Education,National Health and Family Planning Commission of the People's Republic of China was also invited to attend the forum. Representatives discussed the R&D and internationalization of new drugs and health products of traditional Chinese medicine.The summary of views and advice of some experts was published here for the purpose of promoting domestic and overseas academic exchange, and playing an active role in improving the level of R&D and internationalization of new drugs and health products of traditional Chinese medicine in China.

PURPOSE: It remains unknown whether local inhibition of Nuclear factor-kappa B (NF-κB) could have therapeutic value in the treatment of allergic rhinitis (AR). This study aimed to evaluate the effect of selective NF-κB inhibition using NF-κB decoy oligodeoxynucleotides (ODNs) for the local treatment of AR in ovalbumin (OVA)-sensitized wild-type mice. METHODS: BALB/c mice were sensitized with OVA and alum, and then challenged intranasally with OVA. NF-κB decoy ODNs were given intranasally to the treatment group, and NF-κB scrambled ODNs were given to the sham treatment group. Allergic symptom scores, eosinophil infiltration, cytokine levels in the nasal mucosa, nasal lavage fluid, and spleen cell culture, serum total and OVA-specific immunoglobulins, as well as intercellular adhesion molecure-1 (ICAM-1) in the nasal mucosa, were analyzed. RESULTS: NF-κB decoy ODNs significantly reduced allergic symptoms and eosinophil infiltration in the nasal mucosa. They also suppressed serum levels of total IgE, OVA-specific IgE, and IgG1. IL-5 and TNF-α levels and the expression of ICAM-1 were decreased in the nasal mucosa of the treatment group compared to the positive control and sham treatment groups. In addition, IL-6 levels were significantly decreased in the nasal lavage fluid of the treatment group. Furthermore, NF-κB decoy ODNs significantly reduced expression of the systemic Th2 cytokines, IL-4 and IL-5 in spleen cell culture. CONCLUSIONS: This study demonstrates for the first time that local NF-κB inhibition using NF-κB decoy ODNs suppressed the allergic response in a murine AR model. This shows the therapeutic potential of local NF-κB inhibition in the control of AR.
Animals ; Anti-Allergic Agents ; Cell Culture Techniques ; Cytokines ; Eosinophils ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins ; Intercellular Adhesion Molecule-1 ; Interleukin-4 ; Interleukin-5 ; Interleukin-6 ; Mice ; Nasal Lavage Fluid ; Nasal Mucosa ; NF-kappa B ; Oligodeoxyribonucleotides* ; Ovalbumin ; Ovum ; Placebos ; Rhinitis, Allergic* ; Spleen