• Title/Summary/Keyword: Microenvironment

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Amelioration of colitis progression by ginseng-derived exosome-like nanoparticles through suppression of inflammatory cytokines

  • Jisu Kim;Shuya Zhang ;Ying Zhu;Ruirui Wang;Jianxin Wang
    • Journal of Ginseng Research
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    • v.47 no.5
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    • pp.627-637
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    • 2023
  • Background: Damage to the healthy intestinal epithelial layer and regulation of the intestinal immune system, closely interrelated, are considered pivotal parts of the curative treatment for inflammatory bowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironment in the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecological balance and may have therapeutic potential in colitis. However, there have been only a few reports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlying mechanism in colitis. This study aimed to assess the therapeutic effect of PENs from Panax ginseng, ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus on the intestinal immune microenvironment. Method: To evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of proinflammatory cytokines and anti-inflammatory cytokines such as TNF-α, IL-6, and IL-10 by real-time PCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alteration of gut microbiota composition in DSS-induced colitis mice after administration of GENs through 16S rRNA gene sequencing analysis. Result: GENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which could lead to effective suppression of pro-inflammatory cytokines such as TNF-α and IL-6 production through inhibition of NF-κB in DSS-induced colitis. As a result, it showed longer colon length and suppressed thickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression of DSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days compared to 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidota was decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would be expected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis by preventing bacterial dysbiosis. Conclusion: GENs have a therapeutic effect on colitis through modulation of the intestinal microbiota and immune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine by downregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinal barrier and thereby improve the digestive system.

Influence of microenvironment on the spatial distribution of Himantormia lugubris (Parmeliaceae) in ASPA No. 171, maritime Antarctic

  • Choi, Seung Ho;Kim, Seok Cheol;Hong, Soon Gyu;Lee, Kyu Song
    • Journal of Ecology and Environment
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    • v.38 no.4
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    • pp.493-503
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    • 2015
  • This study analyzed how spatial distribution of Himantormia lugubris is affected by the microenvironment in the Antarctic Specially Protected Area (ASPA) No. 171 located in the Barton Peninsula of King George Island that belongs to the maritime Antarctic. In order to determine the population structure of H. lugubris growing in Baekje Hill within ASPA No. 171, we counted the individuals of different size groups after dividing the population into 5 growth stages according to mean diameter as follows: ≤ 1 cm, 1-3 cm, 3-5 cm, 5-10 cm, and ≥ 10 cm. The count of H. lugubris individuals in each growth stage was converted into its percentage with respect to the entire population, which yielded the finding that stages 1 through 5 accounted for 32.8%, 25.3%, 15.9%, 22.5%, and 3.5%, respectively. This suggests that the population of H. lugubris in ASPA No. 171 has a stable reverse J-shaped population structure, with the younger individuals outnumbering mature ones. The mean density of H. lugubris was 17.6/0.25 m2, mean canopy cover 13.3%, and the mean dry weight 37.8 g/0.25 m2. It began to produce spore in the sizes over 3 cm, and most individuals measuring 5-10 cm were adults with sexually mature apothecia. The spatial distribution of H. lugubris was highly heterogeneous. The major factors influencing its distribution and performance were found to be the period covered by snow, wind direction, moisture, size of the substrate, and canopy cover of Usnea spp. Based on these factors, we constructed a prediction model for estimating the spatial distribution of H. lugubris. Conclusively, the major factors for the spatial distribution of H. lugubris were snow, wind, substrate and the competition with Usnea spp. These results are important for understanding of the distribution in the maritime Antarctic and evolution of H. lugubris that claims a unique life history and ecological niche.

Associations Between Infiltrating Lymphocyte Subsets and Hepatocellular Carcinoma

  • Guo, Cun-Li;Yang, Hai-Chao;Yang, Xiu-Hua;Cheng, Wen;Dong, Tian-Xiu;Zhu, Wen-Jing;Xu, Zheng;Zhao, Liang
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5909-5913
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    • 2012
  • Aims: We aimed to analyze the phenotype of tumor-infiltrating lymphocytes (TILs) and non-tumor infiltrating lymphocytes (NILs) in HCC and non-tumor tissues, and evaluate relationships between changes in these cells and the prognosis of HCC. Methods: Lymphocytes were isolated from HCC and corresponding non-tumor tissues and tested by flow cytometry. For comparison, clinical parameters were analyzed. Results: Compared with the non-tumor tissue, tumor tissue had a lower intensity of NK, NKT andCD8+T cell infiltration. TILs had higher intensity of CD4+CD25+Foxp3+regulatory T cell (Treg cells) infiltration compared with that in NILs. The prevalence of Treg cells was associated with fewer CD8 + T lymphocytes in the HCC immune microenvironment. The frequencies of NK cells and CD8+T cells in TILs of HCC patients with metastasis less than 12 months were lower than those without metastasis. However, the frequency of Treg cells was higher than those without metastasis. Conclusion: These results suggest that the frequencies of CD8+T, NK and NKT cells as well as Treg cells in the tumor tissue of HCC are significantly associated with patient survival, and could be applied as predictive indicators for HCC prognosis.

Potential Mechanisms of Benzyl Isothiocyanate Suppression of Invasion and Angiogenesis by the U87MG Human Glioma Cell Line

  • Zhu, Yu;Zhang, Ling;Zhang, Guo-Dong;Wang, Hong-Ou;Liu, Ming-Yan;Jiang, Yuan;Qi, Li-Sha;Li, Qi;Yang, Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8225-8228
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    • 2014
  • Glioma is one of the most common tumors in China and chemotherapy is critical for its treatment. Recent studies showed that benzyl isothiocyanate (BITC) could inhibit the growth of glioma cells, but the mechanisms are not fully understood. This study explored the inhibitory effect of BITC on invasion and angiogenesis of U87MG human glioma cells in vitro and in vivo, as well as potential mechanisms. It was found that BITC could inhibit invasion and angiogenesis of human glioma U87MG cells by inducing cell cycle arrest at phase G2/M. It also was demonstrated that BITC decreased expression of cyclin B1, p21, MMP-2/9, VE-cadherin, CD44, CXCR4 and MTH1, the activity of the telomerase and $PKC{\zeta}$ pathway. Microarray analysis was thus useful to explore the potential target genes related to tumorigenic processes. BITC may play important roles in the inhibition of invasion and angiogenesis of human glioma cells.

Effects of Extracellular Matrix Protein-derived Signaling on the Maintenance of the Undifferentiated State of Spermatogonial Stem Cells from Porcine Neonatal Testis

  • Park, Min Hee;Park, Ji Eun;Kim, Min Seong;Lee, Kwon Young;Hwang, Jae Yeon;Yun, Jung Im;Choi, Jung Hoon;Lee, Eunsong;Lee, Seung Tae
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.10
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    • pp.1398-1406
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    • 2016
  • In general, the seminiferous tubule basement membrane (STBM), comprising laminin, collagen IV, perlecan, and entactin, plays an important role in self-renewal and spermatogenesis of spermatogonial stem cells (SSCs) in the testis. However, among the diverse extracellular matrix (ECM) proteins constituting the STBM, the mechanism by which each regulates SSC fate has yet to be revealed. Accordingly, we investigated the effects of various ECM proteins on the maintenance of the undifferentiated state of SSCs in pigs. First, an extracellular signaling-free culture system was optimized, and alkaline phosphatase (AP) activity and transcriptional regulation of SSC-specific genes were analyzed in porcine SSCs (pSSCs) cultured for 1, 3, and 5 days on non-, laminin- and collagen IV-coated Petri dishes in the optimized culture system. The microenvironment consisting of glial cell-derived neurotrophic factor (GDNF)-supplemented mouse embryonic stem cell culture medium (mESCCM) (GDNF-mESCCM) demonstrated the highest efficiency in the maintenance of AP activity. Moreover, under the established extracellular signaling-free microenvironment, effective maintenance of AP activity and SSC-specific gene expression was detected in pSSCs experiencing laminin-derived signaling. From these results, we believe that laminin can serve as an extracellular niche factor required for the in vitro maintenance of undifferentiated pSSCs in the establishment of the pSSC culture system.

Resveratrol Inhibits IL-6-Induced Transcriptional Activity of AR and STAT3 in Human Prostate Cancer LNCaP-FGC Cells

  • Lee, Mee-Hyun;Kundu, Joydeb Kumar;Keum, Young-Sam;Cho, Yong-Yeon;Surh, Young-Joon;Choi, Bu Young
    • Biomolecules & Therapeutics
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    • v.22 no.5
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    • pp.426-430
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    • 2014
  • Prostate cancer is the most frequently diagnosed cancer. Although prostate tumors respond to androgen ablation therapy at an early stage, they often acquire the potential of androgen-independent growth. Elevated transcriptional activity of androgen receptor (AR) and/or signal transducer and activator of transcription-3 (STAT3) contributes to the proliferation of prostate cancer cells. In the present study, we examined the effect of resveratrol, a phytoalexin present in grapes, on the reporter gene activity of AR and STAT3 in human prostate cancer (LNCaP-FGC) cells stimulated with interleukin-6 (IL-6) and/or dihydrotestosterone (DHT). Our study revealed that resveratrol suppressed the growth of LNCaP-FGC cells in a time- and concentration-dependent manner. Whereas the AR transcriptional activity was induced by treatment with either IL-6 or DHT, the STAT3 transcriptional activity was induced only by treatment with IL-6 but not with DHT. Resveratrol significantly attenuated IL-6-induced STAT3 transcriptional activity, and DHT- or IL-6-induced AR transcriptional activity. Treatment of cells with DHT plus IL-6 significantly increased the AR transcriptional activity as compared to DHT or IL-6 treatment alone and resveratrol markedly diminished DHT plus IL-6-induced AR transcriptional activity. Furthermore, the production of prostate-specific antigen (PSA) was decreased by resveratrol in the DHT-, IL-6- or DHT plus IL-6-treated LNCaP-FGC cells. Taken together, the inhibitory effects of resveratrol on IL-6- and/or DHT-induced AR transcriptional activity in LNCaP prostate cancer cells are partly mediated through the suppression of STAT3 reporter gene activity, suggesting that resveratrol may be a promising therapeutic choice for the treatment of prostate cancer.

Affecting Factors of Personal Exposure to Toluene according to Sociodemographic Characterization and Time-activity Pattern (사회·인구학적 요인과 시간활동양상에 따른 톨루엔 개인노출의 영향요인 분석)

  • Jung, Soon-Won;Lee, Seok-Yong;Kim, Hyun jeong;Choi, Wookhee;Kim, Suejin;Yu, Seungdo;Yang, Wonho
    • Journal of Environmental Health Sciences
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    • v.43 no.2
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    • pp.157-166
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    • 2017
  • Objectives: Exposure to hazardous air pollutants could be affected by sociodemographic factors such as age, gender and more. Information on time spent in microenvironments has a critical role in exposure assessment. The purpose of this study was to analyze the exposure pathways which influence personal exposure through time-activity patterns and sociodemographic factors. Methods: A total of 379 subjects were collected from the second term of the Korean National Environmental Health Survey. A questionnaire survey in relation to sociodemographic factors and a time-activity diary were carried out for personal exposure to toluene. Focusing on personal exposure to toluene, factors affecting personal exposure were analyzed using multiple regression analysis. Results: Participants spent their time in an indoor house for $16.8{\pm}4.0hr$, workplace or school $2.3{\pm}3.5hr$, and other indoor $2.1{\pm}2.2hr$. Sociodemographic factors were significantly different among each personal exposure and microenvironment. Time of staying at an office turned out to be a main factor from point of exposure in exposure pathway using multiple regression analysis. As a result, this means that exposure may be different according to the time of staying in each microenvironment. Conclusions: Personal exposure to air pollutants might be decided by time-activity pattern indicating when, where, and which activities people pursue, as well as individual sociodemographic factors.

Overexpression of Semaphorin4D Indicates Poor Prognosis and Prompts Monocyte Differentiation toward M2 Macrophages in Epithelial Ovarian Cancer

  • Chen, Ying;Zhang, Lei;Lv, Rui;Zhang, Wen-Qi
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5883-5890
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    • 2013
  • Previously, we demonstrated overexpression of semaphorin4D (SEMA4D, CD100) to be closely related to tumor angiogenesis in epithelial ovarian cancers (EOCs). However, the function and expression of SEMA4D in the EOC microenvironment has yet to be clarified in detail. In this study, we confirmed that overexpression of SEMA4D in primary tumors and ascites was related to low differentiation, platinum resistance and a refractory status (P<0.05), while high M2 macrophage count and percentage were evident in EOC patients with advanced FIGO stage and platinum resistance (P<0.05), using immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and fluorescence-activated cell sorting (FACS), respectively. The data showed correlations of SEMA4D expression and M2 macrophage counts in primary tumors and M2 macrophage percentage in ascites (r=0.281 and 0.355, each P<0.05). In the Cox proportional hazard mode, SEMA4D expression was an independent indicator of overall survival (OS) and progression-free survival (PFS) for EOC patients. Furthermore, higher expression of SEMA4D in ovarian cancer cell lines (SKOV3, A2780, and SW626) and their supernatants were found than that in a human primary cultured ovarian cell and its supernatant by reversed transcript PCR (RT-PCR), Western blotting and ELISA, respectively. Interestingly, peripheral blood monocytes (MOs) tended towards the M2-polarized macrophage phenotype ($CD163^{high}$) in vitro after human recombined soluble SEMA4D protein stimulation. These findings suggest that SEMA4D might possibly serve as a reliable tool for early and accurate prediction of EOC poor prognosis and could playan important role in promoting tumor dissemination and metastasis in the EOC microenvironment. Thus SEMA4D and its role in macrophage polarization in EOC warrants further study.

An Intelligent Wireless Sensor and Actuator Network System for Greenhouse Microenvironment Control and Assessment

  • Pahuja, Roop;Verma, Harish Kumar;Uddin, Moin
    • Journal of Biosystems Engineering
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    • v.42 no.1
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    • pp.23-43
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    • 2017
  • Purpose: As application-specific wireless sensor networks are gaining popularity, this paper discusses the development and field performance of the GHAN, a greenhouse area network system to monitor, control, and access greenhouse microenvironments. GHAN, which is an upgraded system, has many new functions. It is an intelligent wireless sensor and actuator network (WSAN) system for next-generation greenhouses, which enhances the state of the art of greenhouse automation systems and helps growers by providing them valuable information not available otherwise. Apart from providing online spatial and temporal monitoring of the greenhouse microclimate, GHAN has a modified vapor pressure deficit (VPD) fuzzy controller with an adaptive-selective mechanism that provides better control of the greenhouse crop VPD with energy optimization. Using the latest soil-matrix potential sensors, the GHAN system also ascertains when, where, and how much to irrigate and spatially manages the irrigation schedule within the greenhouse grids. Further, given the need to understand the microclimate control dynamics of a greenhouse during the crop season or a specific time, a statistical assessment tool to estimate the degree of optimality and spatial variability is proposed and implemented. Methods: Apart from the development work, the system was field-tested in a commercial greenhouse situated in the region of Punjab, India, under different outside weather conditions for a long period of time. Conclusions: Day results of the greenhouse microclimate control dynamics were recorded and analyzed, and they proved the successful operation of the system in keeping the greenhouse climate optimal and uniform most of the time, with high control performance.