• 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.

• 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.

• 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.

• 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.

• The Journal of Korean Obstetrics and Gynecology
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• v.31 no.4
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• pp.89-109
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• 2018

Objectives: The purpose of this systematic review is to assess the effects of herbal medicine with in vitro fertilization-embryo transfer (IVF-ET) based on the current evidence. Methods: Eligible randomized controlled trials (RCT) searched from Pubmed which compared a combination of herbal medicine and IVF with IVF alone were included. Results: Sixteen trials, in which 2025 women involved, were included in this review. The review results showed that the effect of traditional herbal medicine can improve the clinical pregnancy rate (herbal medicine intervention: 30.36~63.64%, Control: 9.38~47.5%) and rate of high quality oocytes and embryos. The mechanism may be through regulating follicular fluid to improve microenvironment for oocytes which would lead to a successful embryo implantation. Conclusions: This analysis showed that combination of IVF and traditional herbal medicine used in the included trials improve clinical pregnancy rate and IVF success. During in vitro fertilization, TCM can regulate the microenvironment in the follicular fluid to mature the oocyte, improve the quality of the embryo, and help the development and implantation of the embryo. Further large randomized placebo controlled trials are needed to confirm the effectiveness of traditional herbal medicine with concurrent IVF.

• IMMUNE NETWORK
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• v.14 no.6
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• pp.296-306
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• 2014

There is growing evidence that crosstalk between mantle cell lymphoma (MCL) cells and stromal microenvironments, such as bone marrow and secondary lymphoid tissues, promotes tumor progression by enhancing survival and growth as well as drug resistance of MCL cells. Recent advances in the understanding of lymphoma microenvironment have led to the identification of crucial factors involved in the crosstalk and subsequent generation of their targeted agents. In the present study, we evaluated the combinatory effect of blocking antibodies (Ab) targeting CXCR4 and VLA-4, both of which were known to play significant roles in the induction of environment-mediated drug resistance (EMDR) in MCL cell line, Jeko-1. Simultaneous treatment with anti-CXCR4 and anti-VLA-4 Ab not only reduced the migration of Jeko-1 cells into the protective stromal cells, but also enhanced sensitivity of Jeko-1 to a chemotherapeutic agent to a greater degree than with either Ab alone. These combinatorial effects were associated with decreased phosphorylation of ERK1/2, AKT and NF-${\kappa}B$. Importantly, drug resistance could not be overcome once the adhesion of Jeko-1 to the stromal occurred despite the combined use of Abs, suggesting that the efforts to mitigate migration of MCLs should be attempted as much as possible. Our results provide a basis for a future development of therapeutic strategies targeting both CXCR4 and VLA-4, such as Ab combinations or bispecific antibodies, to improve treatment outcomes of MCL with grave prognosis.

• Molecules and Cells
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• v.41 no.7
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• pp.631-638
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• 2018

Spermatogonial stem cells (SSCs) derived from mouse testis are unipotent in regard of spermatogenesis. Our previous study demonstrated that SSCs can be fully reprogrammed into pluripotent stem cells, so called germline-derived pluripotent stem cells (gPS cells), on feeder cells (mouse embryonic fibroblasts), which supports SSC proliferation and induction of pluripotency. Because of an uncontrollable microenvironment caused by interactions with feeder cells, feeder-based SSC reprogramming is not suitable for elucidation of the self-reprogramming mechanism by which SSCs are converted into pluripotent stem cells. Recently, we have established a Matrigel-based SSC expansion culture system that allows longterm SSC proliferation without mouse embryonic fibroblast support. In this study, we developed a new feeder-free SSC self-reprogramming protocol based on the Matrigel-based culture system. The gPS cells generated using a feeder-free reprogramming system showed pluripotency at the molecular and cellular levels. The differentiation potential of gPS cells was confirmed in vitro and in vivo. Our study shows for the first time that the induction of SSC pluripotency can be achieved without feeder cells. The newly developed feeder-free self-reprogramming system could be a useful tool to reveal the mechanism by which unipotent cells are self-reprogrammed into pluripotent stem cells.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.6
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• pp.463-468
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• 2012

Type 1 diabetes (T1D) is caused by dysregulation of the immune system in the pancreatic islets, which eventually leads to insulin-producing pancreatic ${\beta}$-cell death and destabilization of glucose homeostasis. One of the major characteristics of T1D pathogenesis is the production of inflammatory mediators by macrophages that result in destruction or damage of pancreatic ${\beta}$-cells. In this study the inflammatory microenvironment of T1D was simulated with RAW264.7 cells and MIN6 cells, acting as macrophages and pancreatic ${\beta}$-cells respectably. In this setting, peroxiredoxin-1, an anti-oxidant enzyme was knocked down to observe its functions in the pathogenesis of T1D. RAW264.7 cells were primed with lipopolysaccharide and co-cultured with MIN6 cells while PRX-1 was knocked down in one or both cell types. Our results suggest that hindrance of PRX-1 activity or the deficiency of this enzyme in inflammatory conditions negatively affects pancreatic ${\beta}$-cell survival. The observed decrease in viability of MIN6 cells seems to be caused by nitric oxide production. Additionally, it seems that PRX-1 affects previously reported protective activity of IL-6 in pancreatic ${\beta}$ cells as well. These results signify new, undiscovered roles for PRX-1 in inflammatory conditions and may contribute toward our understanding of autoimmunity.

• Molecules and Cells
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• v.43 no.9
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• pp.763-773
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• 2020

Recently, tumor microenvironment (TME) and its stromal constituents have provided profound insights into understanding alterations in tumor behavior. After each identification regarding the unique roles of TME compartments, non-malignant stromal cells are found to provide a sufficient tumorigenic niche for cancer cells. Of these TME constituents, adipocytes represent a dynamic population mediating endocrine effects to facilitate the crosstalk between cancer cells and distant organs, as well as the interplay with nearby tumor cells. To date, the prevalence of obesity has emphasized the significance of metabolic homeostasis along with adipose tissue (AT) inflammation, cancer incidence, and multiple pathological disorders. In this review, we summarized distinct characteristics of hypertrophic adipocytes and cancer to highlight the importance of an individual's metabolic health during cancer therapy. As AT undergoes inflammatory alterations inducing tissue remodeling, immune cell infiltration, and vascularization, these features directly influence the TME by favoring tumor progression. A comparison between inflammatory AT and progressing cancer could potentially provide crucial insights into delineating the complex communication network between uncontrolled hyperplastic tumors and their microenvironmental components. In turn, the comparison will unravel the underlying properties of dynamic tumor behavior, advocating possible therapeutic targets within TME constituents.

• Journal of Veterinary Science
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• v.22 no.3
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• pp.25.1-25.16
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• 2021

Background: Malignant lymphoma is the most common hematopoietic malignancy in dogs, and relapse is frequently seen despite aggressive initial treatment. In order for the treatment of these recurrent lymphomas in dogs to be effective, it is important to choose a personalized and sensitive anticancer agent. To provide a reliable tool for drug development and for personalized cancer therapy, it is critical to maintain key characteristics of the original tumor. Objectives: In this study, we established a model of hybrid tumor/stromal spheroids and investigated the association between canine lymphoma cell line (GL-1) and canine lymph node (LN)-derived stromal cells (SCs). Methods: A hybrid spheroid model consisting of GL-1 cells and LN-derived SC was created using ultra low attachment plate. The relationship between SCs and tumor cells (TCs) was investigated using a coculture system. Results: TCs cocultured with SCs were found to have significantly upregulated multidrug resistance genes, such as P-qp, MRP1, and BCRP, compared with TC monocultures. Additionally, it was revealed that coculture with SCs reduced doxorubicin-induced apoptosis and G2/M cell cycle arrest of GL-1 cells. Conclusions: SCs upregulated multidrug resistance genes in TCs and influenced apoptosis and the cell cycle of TCs in the presence of anticancer drugs. This study revealed that understanding the interaction between the tumor microenvironment and TCs is essential in designing experimental approaches to personalized medicine and to predict the effect of drugs.