• Title/Summary/Keyword: immunology

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Modulated Gene Expression of Toxoplasma gondii Infected Retinal Pigment Epithelial Cell Line (ARPE-19) via PI3K/Akt or mTOR Signal Pathway

  • Zhou, Wei;Quan, Juan-Hua;Gao, Fei-Fei;Ismail, Hassan Ahmed Hassan Ahmed;Lee, Young-Ha;Cha, Guang-Ho
    • Parasites, Hosts and Diseases
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    • v.56 no.2
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    • pp.135-145
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    • 2018
  • Due to the critical location and physiological activities of the retinal pigment epithelial (RPE) cell, it is constantly subjected to contact with various infectious agents and inflammatory mediators. However, little is known about the signaling events in RPE involved in Toxoplasma gondii infection and development. The aim of the study is to screen the host mRNA transcriptional change of 3 inflammation-related gene categories, PI3K/Akt pathway regulatory components, blood vessel development factors and ROS regulators, to prove that PI3K/Akt or mTOR signaling pathway play an essential role in regulating the selected inflammation-related genes. The selected genes include PH domain and leucine- rich-repeat protein phosphatases (PHLPP), casein kinase2 (CK2), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), glutamate-cysteine ligase (GCL), glutathione S-transferase (GST), and NAD(P)H: quinone oxidoreductase (NQO1). Using reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), we found that T. gondii up-regulates PHLPP2, $CK2{\beta}$, VEGF, GCL, GST and NQO1 gene expression levels, but down-regulates PHLPP1 and PEDF mRNA transcription levels. PI3K inhibition and mTOR inhibition by specific inhibitors showed that most of these host gene expression patterns were due to activation of PI3K/Akt or mTOR pathways with some exceptional cases. Taken together, our results reveal a new molecular mechanism of these gene expression change dependent on PI3K/Akt or mTOR pathways and highlight more systematical insight of how an intracellular T. gondii can manipulate host genes to avoid host defense.

Interaction between Trichomonas vaginalis and the Prostate Epithelium

  • Kim, Jung-Hyun;Han, Ik-Hwan;Kim, Sang-Su;Park, Soon-Jung;Min, Duk-Young;Ahn, Myoung-Hee;Ryu, Jae-Sook
    • Parasites, Hosts and Diseases
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    • v.55 no.2
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    • pp.213-218
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    • 2017
  • Most men infected with Trichomonas vaginalis are asymptomatic and can remain undiagnosed and untreated. This has been hypothesized to result in chronic persistent prostatic infection. Adhesion of the protozoan organisms to mucosal cells is considered a first and prerequisite step for T. vaginalis infection. Adhesion of T. vaginalis to prostate epithelial cells has not yet been observed; however, there are several reports about inflammation of prostate epithelial cells induced by T. vaginalis. The aim of this study was to investigate whether adhesion and cytotoxicity of T. vaginalis are involved in inflammation of prostate epithelial cells. When RWPE-1 cells were infected with T. vaginalis (1:0.4 or 1:4), adhesion of T. vaginalis continuously increased for 24 hr or 3 hr, respectively. The cytotoxicity of prostate epithelial cells infected with T. vaginalis (RWPE-1: T. vaginalis=1:0.4) increased at 9 hr; at an infection ratio of 1:4, cytotoxicity increased after 3 hr. When the RWPE-1 to T. vaginalis ratio was 1:0.4 or 1:4, production of IL-$1{\beta}$, IL-6, CCL2, and CXCL8 also increased. Epithelial-mesenchymal transition (EMT) was verified by measuring decreased E-cadherin and increased vimentin expression at 24 hr and 48 hr. Taken together, the results indicate that T. vaginalis adhered to prostate epithelial cells, causing cytotoxicity, pro-inflammatory cytokine production, and EMT. Our findings suggest for the first time that T. vaginalis may induce inflammation via adhesion to normal prostate epithelial cells.

Distribution of Human Rotavirus Genotypes in a Tertiary Hospital, Seoul, Korea During 2009-2013 (2009년부터 2013년까지 서울의 일개 대학병원에서 동정된 로타바이러스 유전형의 분포)

  • Han, Tae Hee;Park, Sang-Hun;Chung, Ju-Young;Hwang, Eung-Soo
    • Pediatric Infection and Vaccine
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    • v.22 no.2
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    • pp.81-90
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    • 2015
  • Purpose: Group A rotavirus (RV) is most common etiologic agent of acute gastroenteritis (AGE) in children worldwide. Recently, vaccination has been introduced in several countries to reduce the disease burden caused by RV infections, but continuous surveillance of RV strains is necessary to detect the emergence of potential variants induced by vaccine-immune pressure. This study aimed to investigate the changing pattern of RV genotypes in children with AGE, following the introduction of vaccination in Korea. Methods: Genotyping of RVs by RT-PCR on the basis of VP7 and VP4 gene segment sequence was carried out on 201 rotavirus-positive stool samples, from children hospitalized with AGE between August 2009 and June 2013. We have directly sequenced PCR products and analyzed the phylogenetic tree. Results: The most prevalent G genotype was G9 (33.3%), followed by G1 (22.4%), G3 (15.9%), G2 (6.0%), G4 (3.0%), G10 (1.5%), and mixed G-type (15.4%), with some nontypeable cases (2.5%). The detected P genotypes were P[4] (45.3%), P[8] (43.8%), mixed P-type (10.4 %), and P[2] (0.5%). The G9P[4] genotype was predominantly observed in hospitalized cases in Seoul in 2010/2011, however G1P[8] has been re-emerged as the predominant genotype in the following season (P =0.004). Conclusions: It seems that the periodic fluctuation in predominance of the G1, G3, and G9 strains occurred in Korea during 2009-2013, following the introduction of RV vaccination.

Changes in Effective Components of Ginseng by Puffing (팽화에 의한 인삼 유효성분의 변화)

  • Kim, Ji-Hye;Ahn, Soon-Cheol;Choi, Sung-Won;Hur, Nam-Youn;Kim, Byung-Yong;Baik, Moo-Yeol
    • Applied Biological Chemistry
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    • v.51 no.3
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    • pp.188-193
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    • 2008
  • This study was conducted to investigate the effect of moisture content and pressure on extraction yield, crude saponins and ginsenoside contents of puffed Korean ginseng. Puffed ginsengs showed relatively higher extraction yield ($50.0{\sim}62.1%$) and amounts of crude saponins ($19.6{\sim}48.8$ mg/g ginseng) than no-puffed ginseng ($37.6{\pm}0.8%$ and $11.0{\pm}1.0$ mg/g ginseng), respectively. The highest extraction yield and amounts of crude saponins were obtained in 8.0% moisture content sample puffed at 10 $kg_f/cm^2$. In HPLC analysis, amounts of measured major ginsenosides (Rb1, Rb2, Rc, Rd, Re, and Rg1) decreased with increasing puffing pressure, yet contents of almost all major gin senosides were higher than control (no-puffed). On the other hand, ginsenoside Rg3 were produced after puffing suggesting that chemical structure of some ginsenosides might be altered during the puffing process. These results indicate that puffing can increase the extraction yield and crude saponin contents and it could influence the ginsenoside composition.

Development of a Guidelines of the Herbal Medicine Treatment for Gastric Cancer on the Use of Systemic Review and Delphi Technique (체계적 문헌 고찰과 델파이 기법을 활용한 위암의 한약 치료에 관한 한의표준임상진료 지침 개발)

  • Song, Si Yeon;Ban, Kyung-tae;Ha, Su-jeung;Park, So-jung;Lee, Yeon-weol;Cho, Chong-kwan;Cho, Seung-Hun;Yoo, Hwa-Seung
    • Journal of Korean Traditional Oncology
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    • v.23 no.1
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    • pp.1-14
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    • 2018
  • Objectives: This study was conducted towards developing guidelines of herbal medicine treatment for gastric cancer. Methods: We performed a systematic review and meta-analysis designed to investigate the efficacy of herbal medicine treatment for gastric cancer on four cancer questions; survival rate, metastasis, immune function, and quality of life. Based on the findings, we utilized a two-round delphi process with panel of 22 experts for their level of agreement. Results: Combined therapy group, herbal medicine treated with chemotherapy, was significantly higher in the 1-year survival rate (RR=1.27, 95% CI: 1.14 to 1.40, P=0.005, $I^2=71%$) and 3-years survival rate (RR=1.41, 95% CI: 1.16 to 1.71, P=0.91, $I^2=0%$) than chemotherapy group. The suppression of metastasis was higher in the combined therapy group (RR=0.62, 95% CI: 0.45 to 0.84, P=0.09, $I^2=54%$). The immunology function was higher in the combined therapy group compared with the chemotherapy group (MD=16.43, 95% CI: 13.25 to 29.61, P<0.001, $I^2=99%$). The quality of life score was higher in the combined therapy group compared with the chemotherapy group (RR=1.55, 95% CI: 1.21 to 2.00, P<0.66, $I^2=0%$). Conclusions: Among the Randomized controlled trials (RCT) included, the levels of survival rates, suppression of metastasis, immune function, and quality of life of the group treated with chemotherapy were lower compared to those treated with herbal medicine in addition to chemotherapy.

Characterization of food allergies in patients with atopic dermatitis

  • Kwon, Jaryoung;Kim, Jungyun;Cho, Sunheui;Noh, Geunwoong;Lee, Sang Sun
    • Nutrition Research and Practice
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    • v.7 no.2
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    • pp.115-121
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    • 2013
  • We examined the characteristics of food allergy prevalence and suggested the basis of dietary guidelines for patients with food allergies and atopic dermatitis. A total of 2,417 patients were enrolled in this study. Each subject underwent a skin prick test as well as serum immunoglobulin E (IgE) measurement. A double-blind, placebo-controlled food challenge was conducted using milk, eggs, wheat, and soybeans, and an oral food challenge was performed using beef, pork, and chicken. Food allergy prevalence was found among 50.7% in patients with atopic dermatitis. Among patients with food allergies (n = 1,225), the prevalence of non-IgE-mediated food allergies, IgE-mediated food allergies, and mixed allergies was discovered in 94.9%, 2.2%, and 2.9% of the patients, respectively. Food allergy prevalence, according to food item, was as follows: eggs = 21.6%, milk = 20.9%, wheat = 11.8%, soybeans = 11.7%, chicken = 11.7%, pork = 8.9% and beef = 9.2%. The total number of reactions to different food items in each patient was also variable at 45.1%, 30.6%, 15.3%, 5.8%, 2.2%, and 1.0% for 1 to 6 reactions, respectively. The most commonly seen combination in patients with two food allergies was eggs and milk. The clinical severity of the reactions observed in the challenge test, in the order of most to least severe, were wheat, beef, soybeans, milk, pork, eggs, and chicken. The minimum and maximum onset times of food allergy reactions were 0.2-24 hrs for wheat, 0.5-48 hrs for beef, 1.0-24 hrs for soybeans, 0.7-24 hrs for milk, 3.0-24 hrs for pork, 0.01-72 hrs for eggs, and 3.0-72 hrs for chicken. In our study, we examined the characteristics of seven popular foods. It will be necessary, however, to study a broader range of foods for the establishment of a dietary guideline. Our results suggest that it may be helpful to identify food allergies in order to improve symptoms in patients with atopic dermatitis.

Extrusion Processing of Low-Inhibitor Soybeans Improves Growth Performance of Early-Weaned Pigs

  • Kim, I.H.;Hancock, J.D.;Jones, D.B.;Reddy, P.G.
    • Asian-Australasian Journal of Animal Sciences
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    • v.12 no.8
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    • pp.1251-1257
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    • 1999
  • Two experiments were conducted to determine the effects of roasting and extrusion on nutritional value of conventional and low-inhibitor soy beans for nurser-age pigs. In Exp. 1, 100 weaning pigs (7.5 kg average initial BW) were used in a 35-d growth assay to determine the effects of processing method (roasting in a Rast-A-Tron$^{TM}$ raster vs extrusion in an Insta-Pro$^{TM}$ extruder) on the nutritional value of Williams 82 soybeans with (+K) and without (-K) gene expression for the Kunitz trypsin inhibitor. Treatments were 48% soybean meal with added soybean oil, +K roasted, +K extruded, -K roasted and -K extruded. All diets were formulated to contain 3.5 Mcal DE/kg, with 0.92% lysine for d 0 to 14 and 0.76% lysine for d 14 to 35 of the experiment. The lysine concentrations were 80% of NRC (1988) recommendations to accentuate difference in response to protein quality and lysine availability. For d 0 to 14, pigs fed extruded soybeans (+K and -K) had greater ADG (p<0.001), ADFI (p<0.09) and gain/feed (p<0.01) than pigs fed roasted soybeans. For d 14 to 35 and overall, the same effects were noted, i.e., pigs fed extruded soybeans had greater ADG, ADFI and gain/feed than pigs fed roasted soybeans (p<0.03). Also, pigs fed -K soybeans were more efficient (p<0.008) than pigs fed +K soybeans. In Exp. 2, 150 weanling pigs (7.0 kg average initial BW) were used in a 35-d growth assay. All diets were formulated to contain 3.5 Mcal DE/kg, with 1.25% lysine for d 0 to 14 and 1.10% lysine for d 14 to 35 of the experiment. The lysine concentrations were formulated to be in excess of NRC recommendation to determine if differences in nutritional value of the soybean preparations could be detected in protein-adequate diets. For d 0 to 14 (p<0.06), 14 to 35 (p<0.03) and 0 to 35 (p<0.02), pigs fed extruded soybeans had greater ADG and gain/feed than pigs fed roasted soybeans. Apparent digestibilities of DM, N and GE were greater for diets with extruded soybeans than diets with roasted soybeans and diets with soybean meal and soybean oil were intermediate. The response to extrusion processing was greater with -K than +K soybeans, with pigs fed extruded -K soybeans having the greatest growth performance and nutrient digestibilities and lowest skin-fold thickness of any treatment. In conclusion, extrusion yielded a full-fat soy product of greater nutritional value than roasting. Also, selection against genetic expression of the Kunitz trypsin inhibitor improved nutritional value of the resulting soybean preparations.

ST6Gal-I Predicts Postoperative Clinical Outcome for Patients with Localized Clear-cell Renal Cell Carcinoma

  • Liu, Hai-Ou;Wu, Qian;Liu, Wei-Si;Liu, Yi-Dong;Fu, Qiang;Zhang, Wei-Juan;Xu, Le;Xu, Jie-Jie
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10217-10223
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    • 2015
  • Hyperactivated ${\alpha}2$-6-sialylation on N-glycans due to overexpression of the Golgi enzyme ${\beta}$-galactoside: ${\alpha}2$-6-sialyltransferase (ST6Gal-I) often correlates with cancer progression, metastasis, and poor prognosis. This study was aimed to determine the association between ST6Gal-I expression and the risk of recurrence and survival of patients with localized clear-cell renal cell carcinoma (ccRCC) following surgery. We retrospectively enrolled 391 patients (265 in training cohort and 126 in validation cohort) with localized ccRCC underwent nephrectomy at a single center. Tissue microarrays were constructed for immunostaining of ST6Gal-I. Prognostic value and clinical outcomes were evaluated. High ST6Gal-I expression was associated with Fuhrman grade (p<0.001 and p=0.016, respectively) and the University of California Los-Angeles Integrated Staging System (UISS) score (p=0.004 and p=0.017, respectively) in both cohorts. Patients with high ST6Gal-I expression had significantly worse overall survival (OS) (p<0.001 and p<0.001, respectively) and recurrence free survival (RFS) (p<0.001 and p=0.002, respectively) than those with low expression in both cohorts. On multivariate analysis, ST6Gal-I expression remained associated with OS and RFS even after adjusting for the UISS score. Stratified analysis suggested that the association is more pronounced among patients with low and intermediate-risk disease defined by the UISS score. High ST6Gal-I expression is a potential independent adverse predictor of survival and recurrence in ccRCC patients, and the prognostic value is most prominent in those with low and intermediate-risk disease defined by the UISS score.

Efficacy of First-line Chemotherapy Affects the Second-Line Setting Response in Patients with Advanced Non-Small Cell Lung Cancer

  • Cao, Wa;Li, Ai-Wu;Ren, Sheng-Xiang;Chen, Xiao-Xia;Li, Wei;Gao, Guang-Hui;He, Ya-Yi;Zhou, Cai-Cun
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6799-6804
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    • 2014
  • Background: Chemotherapy is the mainstay of treatment for the majority of patients with advanced non-small cell lung cancer (NSCLC) without driver mutations and many receive therapies beyond first-line. Second-line chemotherapy has been disappointing both in terms of response rate and survival and we know relatively little about the prognostic factors. Materials and Methods: One thousand and eight patients with advanced NSCLC who received second-line chemotherapy after progression were reviewed in Shanghai Pulmonary Hospital, China, from September 2005 to July 2010. We analyzed the effects of potential prognostic factors on the outcomes of second-line chemotherapy (overall response rate, ORR; progression free survival, PFS; overall survival, OS). Results: The response and progression free survival of first-line chemotherapy affects the ORR, PFS and OS of second-line chemotherapy (ORR: CR/PR 15.4%, SD 10.1%, PD2.3%, p<0.001; PFS: CR/PR 3.80 months, SD 2.77 months, PD 2.03 months, p<0.001; OS: CR/PR 11.60 months, SD 10.33 months, PD 6.57 months, p=0.578, p<0.001, p<0.001, respectively). On multivariate analysis, better response to first-line therapy (CR/PR: HR=0.751, p=0.002; SD: HR=0.781, p=0.021) and progression within 3-6 months (HR=0.626, p<0.001), together with adenocarcinoma (HR=0.815, p=0.017), without liver metastasis (HR=0.541, p=0.001), never-smoker (HR=0.772, p=0.001), and ECOG PS 0-1 (HR=0.745, p=0.021) were predictors for good OS following second-line chemotherapy. Conclusions: Patients who responded to first-line chemotherapy had a better outcome after second-line therapy for advanced NSCLC, and the efficacy of first-line chemotherapy, period of progression, histology, liver metastasis, smoking status and ECOG PS were independent prognostic factors for OS.

A Bacterial Metabolite, Compound K, Induces Programmed Necrosis in MCF-7 Cells via GSK3β

  • Kwak, Chae Won;Son, Young Min;Gu, Min Jeong;Kim, Girak;Lee, In Kyu;Kye, Yoon Chul;Kim, Han Wool;Song, Ki-Duk;Chu, Hyuk;Park, Byung-Chul;Lee, Hak-Kyo;Yang, Deok-Chun;Sprent, Jonathan;Yun, Cheol-Heui
    • Journal of Microbiology and Biotechnology
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    • v.25 no.7
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    • pp.1170-1176
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    • 2015
  • Ginsenosides, the major active component of ginseng, are traditionally used to treat various diseases, including cancer, inflammation, and obesity. Among these, compound K (CK), an intestinal bacterial metabolite of the ginsenosides Rb1, Rb2, and Rc from Bacteroides JY-6, is reported to inhibit cancer cell growth by inducing cell-cycle arrest or cell death, including apoptosis and necrosis. However, the precise effect of CK on breast cancer cells remains unclear. MCF-7 cells were treated with CK ($0-70{\mu}M$) for 24 or 48 h. Cell proliferation and death were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Changes in downstream signaling molecules involved in cell death, including glycogen synthase kinase $3\beta$ ($GSK3\beta$), $GSK3\beta$, $\beta$-catenin, and cyclin D1, were analyzed by western blot assay. To block $GSK3\beta$ signaling, MCF-7 cells were pretreated with $GSK3\beta$ inhibitors 1 h prior to CK treatment. Cell death and the expression of $\beta$-catenin and cyclin D1 were then examined. CK dose- and time-dependently inhibited MCF-7 cell proliferation. Interestingly, CK induced programmed necrosis, but not apoptosis, via the $GSK3\beta$ signaling pathway in MCF-7 cells. CK inhibited $GSK3\beta$ phosphorylation, thereby suppressing the expression of $\beta$-catenin and cyclin D1. Our results suggest that CK induces programmed necrosis in MCF-7 breast cancer cells via the $GSK3\beta$ signaling pathway.