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      • KCI등재

        Altered microRNA Expression Profiles of Extracellular Vesicles in Nasal Mucus From Patients With Allergic Rhinitis

        Geping Wu,Guanghai Yang,Ruxin Zhang,Guangyin Xu,Ling Zhang,Wu Wen,Jianbing Lu,Jianyong Liu,Yan Yu 대한천식알레르기학회 2015 Allergy, Asthma & Immunology Research Vol.7 No.5

        Purpose: Allergic rhinitis (AR) is an inflammatory disorder of the upper airway. Exosomes or extracellular vesicles are nanosized vesicles of endosomal origin released from inflammatory and epithelial cells that have been implicated in allergic diseases. In this study, we characterized the microRNA (miRNA) content of exosomes in AR. Methods: Extracellular vesicles were isolated from nasal mucus from healthy control subjects (n=10) and patients with severe AR (n=10). Vesicle RNA was analyzed by using a TaqMan microRNA assays Human Panel-Early Access kit (Applied Biosystems, Foster City, CA, USA) containing probes for 366 human miRNAs, and selected findings were validated with quantitative RT-PCR. Target prediction and pathway analysis for the differentially expressed miRNAs were performed using DIANA-mirPath. Results: Twenty-one vesicle miRNAs were up -regulated and 14 miRNAs were under-regulated significantly (P<0.05) in nasal mucus from AR patients when compared to healthy controls. Bioinformatic analysis by DIANA-mirPath demonstrated that 32 KEGG biological processes were significantly enriched (P<0.05, FDR corrected) among differentially expressed vesicle miRNA signatures. Among them, the B-cell receptor signaling pathway (P=3.709E-09), the natural killer cell-mediated cytotoxicity (P=8.466E-05), the T-cell receptor signaling pathway (P=0.00075), the RIG-I-like receptor signaling pathway (P=0.00127), the Wnt signaling pathway (P=0.00130), endocytosis (P=0.00440), and salivary secretion (P=0.04660) were the most prominent pathways enriched in quantiles with differential vesicle miRNA patterns. Furthermore, miR-30-5p, miR-199b-3p, miR-874, miR-28-3p, miR-203, and miR-875-5p, involved in B-cell receptor and salivary secretion signaling pathways, were selected for validation using independent samples from 44 AR patients and 20 healthy controls. MiR-30-5p and miR-199b-3p were significantly increased in extracellular vesicles from nasal mucus when compared to healthy controls, while miR-874 and miR-28-3p were significantly down-regulated. In addition, miRNA-203 was significantly increased in AR patients, while miRNA-875-5p was found to be significantly decreased in AR patients. Conclusions: This study demonstrated that vesicle miRNA may be a regulator for the development of AR.

      • KCI등재

        ZL-2, a cathelicidin-derived antimicrobial peptide, has a broad antimicrobial activity against gram-positive bacteria and gram-negative bacteria in vitro and in vivo

        Jiancheng Tu,Shusheng Wang,Geping Wu,Yun Zuo,Lei Zhao 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.10

        Alloferons are a group of naturally occurringpeptides primarily isolated from insects that are capable ofstimulating mouse and human NK cell cytotoxicity towardcancer cells. In this study, we found that a modified antibacterialpeptide had a broad range of action against bothgram-positive and gram-negative bacteria. A time-courseexperiment showed that CFU counts rapidly decreasedafter ZL-2 treatment, with the bacteria nearly eliminatedwithin 4 h. We also examined the synergy between thepeptide and antibiotics. The peptide ZL-2 resulted in asignificant synergistic improvement in the potencies ofampicillin, erythromycin and ceftazidime against methicillin-resistant bacteria. In addition, ZL-2 had no detectablecytotoxicity in mouse spleen cells or a mouse animalmodel. In the mouse model by i.p. inoculation with Escherichiacoli, timely treatment of i.p. injection with ZL-2resulted in 100-fold reduction in bacteria load in blood aswell as 80 % protection from death in the inoculated animals. In conclusion, we successfully identified a modifiedpeptide with maximal bactericidal activity. This study alsoprovides a potential therapeutic for the treatment of E. colisepticemia by increasing the activity of antimicrobials.

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        Protein Kinase C Mediates the Corticosterone-induced Sensitization of Dorsal Root Ganglion Neurons Innervating the Rat Stomach

        ( Meng Li ),( Lu Xue ),( Hong-yan Zhu ),( Hongjun Wang ),( Xue Xu ),( Ping-an Zhang ),( Geping Wu ),( Guang-yin Xu ) 대한소화기기능성질환·운동학회 2017 Journal of Neurogastroenterology and Motility (JNM Vol.23 No.3

        Background/Aims Gastric hypersensitivity contributes to abdominal pain in patients with functional dyspepsia. Recent studies showed that hormones induced by stress are correlated with visceral hypersensitivity. However, the precise mechanisms underlying gastric hypersensitivity remain largely unknown. The aim of the present study was designed to investigate the roles of corticosterone (CORT) on excitability of dorsal root ganglion (DRG) neurons innervating the stomach. Methods DRG neurons innervating the stomach were labeled by DiI injection into the stomach wall. Patch clamp recordings were employed to examine neural excitability and voltage-gated sodium channel currents. Electromyograph technique was used to determine the responses of neck muscles to gastric distension. Results Incubation of acutely isolated DRG neurons with CORT significantly depolarized action potential threshold and enhanced the number of action potentials induced by current stimulation of the neuron. Under voltage-clamp mode, incubation of CORT enhanced voltage-gated sodium current density of the recorded neurons. Pre-incubation of GF109203X, an inhibitor of protein kinase C, blocked the CORT-induced hyperexcitability and potentiation of sodium currents. However, pre-incubation of H-89, an inhibitor of protein kinase A, did not alter the sodium current density. More importantly, intraperitoneal injection of CORT produced gastric hypersensitivity of healthy rats, which was blocked by pre-administration of GF109203X but not H-89. Conclusions Our data strongly suggest that CORT rapidly enhanced neuronal excitability and sodium channel functions, which is most likely mediated by protein kinase C but not protein kinase A signaling pathway in DRG neurons innervating the stomach, thus underlying the gastric hypersensitivity induced by CORT injection. (J Neurogastroenterol Motil 2017;23:464-476)

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