• Journal of Venture Innovation
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• v.5 no.1
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• pp.107-127
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• 2022

Global challenges such as the corona pandemic, climate change and the war-on-tech ensure that the demand who the technologies of the future develops and monitors prominently for will be on the agenda. Development of, and applications in, agrifood, biotech, high-tech, medtech, quantum, AI and photonics are the basis of the future earning capacity of the Netherlands and contribute to solving societal challenges, close to home and worldwide. To be like the Netherlands and Europe a strategic position in the to obtain knowledge and innovation chain, and with it our autonomy in relation to from China and the United States insurance, clear choices are needed. Brainport Eindhoven: Building on Philips' knowledge base, there is create an innovative ecosystem where more than 7,000 companies in the High-tech Systems & Materials (HTSM) collaborate on new technologies, future earning potential and international value chains. Nearly 20,000 private R&D employees work in 5 regional high-end campuses and for companies such as ASML, NXP, DAF, Prodrive Technologies, Lightyear and many others. Brainport Eindhoven has a internationally leading position in the field of system engineering, semicon, micro and nanoelectronics, AI, integrated photonics and additive manufacturing. What is being developed in Brainport leads to the growth of the manufacturing industry far beyond the region thanks to chain cooperation between large companies and SMEs. South-Holland: The South Holland ecosystem includes companies as KPN, Shell, DSM and Janssen Pharmaceutical, large and innovative SMEs and leading educational and knowledge institutions that have more than Invest €3.3 billion in R&D. Bearing Cores are formed by the top campuses of Leiden and Delft, good for more than 40,000 innovative jobs, the port-industrial complex (logistics & energy), the manufacturing industry cluster on maritime and aerospace and the horticultural cluster in the Westland. South Holland trains thematically key technologies such as biotech, quantum technology and AI. Twente: The green, technological top region of Twente has a long tradition of collaboration in triple helix bandage. Technological innovations from Twente offer worldwide solutions for the large social issues. Work is in progress to key technologies such as AI, photonics, robotics and nanotechnology. New technology is applied in sectors such as medtech, the manufacturing industry, agriculture and circular value chains, such as textiles and construction. Being for Twente start-ups and SMEs of great importance to the jobs of tomorrow. Connect these companies technology from Twente with knowledge regions and OEMs, at home and abroad. Wageningen in FoodValley: Wageningen Campus is a global agri-food magnet for startups and corporates by the national accelerator StartLife and student incubator StartHub. FoodvalleyNL also connects with an ambitious 2030 programme, the versatile ecosystem regional, national and international - including through the WEF European food innovation hub. The campus offers guests and the 3,000 private R&D put in an interesting programming science, innovation and social dialogue around the challenges in agro production, food processing, biobased/circular, climate and biodiversity. The Netherlands succeeded in industrializing in logistics countries, but it is striving for sustainable growth by creating an innovative ecosystem through a regional industry-academic research model. In particular, the Brainport Cluster, centered on the high-tech industry, pursues regional innovation and is opening a new horizon for existing industry-academic models. Brainport is a state-of-the-art forward base that leads the innovation ecosystem of Dutch manufacturing. The history of ports in the Netherlands is transforming from a logistics-oriented port symbolized by Rotterdam into a "port of digital knowledge" centered on Brainport. On the basis of this, it can be seen that the industry-academic cluster model linking the central government's vision to create an innovative ecosystem and the specialized industry in the region serves as the biggest stepping stone. The Netherlands' innovation policy is expected to be more faithful to its role as Europe's "digital gateway" through regional development centered on the innovation cluster ecosystem and investment in job creation and new industries.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.6
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• pp.837-843
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• 2013

Sasa borealis is a major source of bamboo leaves used for traditional medicine in Korea. Obesity is a serious health problem in industrialized countries that has been implicated in various diseases, including type 2 diabetes, hypertension, cancer, and coronary heart disease. Recent reports have proposed mechanisms to reduce obesity by decreasing preadipocyte differentiation, and proliferation in 3T3-L1 preadipocyte. The preadipocytes play a key role by differentiation into mature adipocytes and increasing fat mass. In this study, we investigated whether ethanol-soluble extracts and ethyl acetate-soluble fractions from Sasa borealis inhibits intracellular accumulation of lipid droplets in a dose-dependent manner in 3T3-L1 cells (an important model system for studying adipogenesis). The down-regulation of PPAR${\gamma}$ and C/EBP${\alpha}$ (key adipogenic transcription factors) were confirmed by the reverse transcription polymerase chain reaction (RT-PCR). Ethyl acetate-soluble fractions from Sasa borealis attenuated the expression of PPAR${\gamma}$ and C/EBP${\alpha}$. These results suggest that Sasa borealis inhibits adipogenic differentiation by regulating adipogenic transcription factors in 3T3-L1 cells. Therefore, Sasa borealis extracts may be a good candidate for the management of obesity.

• The Korea Journal of Herbology
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• v.35 no.6
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• pp.11-19
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• 2020

Objective : The genus Glycyrrhiza has been used in food and traditional herbal medicine. Glycyrrhiza new varieties Wongam and Sinwongam have been developed by Korea Rural Development Administration and investigated to register on Korean Pharmacopoeia of the Ministry of Food and Drug Safety. The aim of this study is to investigate the immunomodulatory effect of Wongam and Sinwongam comparing with listed Glycyrrhiza species (Glycyrrhiza uralensis Fischer and G. glabra Linne) for evaluations about pharmacological effect of Glycyrrhiza new varieties. Methods : We studied the immunomodulatory effect of Wongam and Sinwongam compared with G. uralensis and G. glabra using THP-1 cell in vitro model. The cells were treated with phorbol 12-myristate 13-acetate (PMA) for differentiation and stimulated with lipopolysaccharides (LPS) to induce immune activation. We analyzed and compared the effects Glycyrrhiza new varieties and listed Glycyrrhiza species using nitric oxide (NO) assay, western blot, and reverse transcription-quantitative polymerase chain reaction analysis. 1) Results : Wongam and Sinwongam showed no cytotoxicity in THP-1 cells. Wongam and Sinwongam, and listed Glycyrrhiza species increased NO production, and cyclooxygenase (COX)-2 expression with or without LPS in differentiated THP-1 macrophages. Furthermore, Wongam and Sinwongam and listed Glycyrrhiza species upregulated the mRNA expressions of T helper type 1 (Th 1)-associated cytokines in LPS-stimulated THP-1 macrophages. Conclusion : These results indicated that Wongam and Sinwongam would have effect of enhancing immune response through the increase of NO and COX-2 expression, and activate Th1-associated cytokines. The findings of this study suggest the wide applicability of Glycyrrhiza new varieties.

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.10.1-10.8
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• 2016

Objectives Aromatase inhibitors that block estrogen synthesis are a proven first-line hormonal therapy for postmenopausal breast cancer. Although it is known that standardized extract of Ginkgo biloba (EGb761) induces anti-carcinogenic effects like the aromatase inhibitors, the effects of EGb761 on steroidogenesis have not been studied yet. Therefore, the effects of EGb761 on steroidogenesis and aromatase activity was studied using a H295R cell model, which was a good in vitro model to predict effects on human adrenal steroidogenesis. Methods Cortisol, aldosterone, testosterone, and $17{\beta}$-estradiol were evaluated in the H295R cells by competitive enzyme-linked immunospecific assay after exposure to EGb761. Real-time polymerase chain reaction were performed to evaluate effects on critical genes in steroid hormone production, specifically cytochrome P450 (CYP11/ 17/19/21) and the hydroxysteroid dehydrogenases ($3{\beta}$-HSD2 and $17{\beta}$-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis. Results H295R cells exposed to EGb761 (10 and $100{\mu}g/mL$) showed a significant decrease in $17{\beta}$-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and $17{\beta}$-HSD1) related to the estrogen steroidogenesis were significantly decreased by EGb761. EGb761 treatment of H295R cells resulted in a significant decrease of aromatase activity as measured by the direct and indirect assays. The coding sequence/Exon PII of CYP19 gene transcript and protein level of CYP19 were significantly decreased by EGb761. Conclusions These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and $17{\beta}$-HSD1, and lead to a decrease in $17{\beta}$-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer.

• Journal of Veterinary Science
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• v.23 no.5
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• pp.74.1-74.16
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• 2022

Background: Previous studies have presented evidence to support the significant association between red meat intake and colon cancer, suggesting that heme iron plays a key role in colon carcinogenesis. Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, exhibits anti-oxidative and anti-cancer effects. However, the effect of EGCG on red meat-associated colon carcinogenesis is not well understood. Objectives: We aimed to investigate the regulatory effects of hemin and EGCG on colon carcinogenesis and the underlying mechanism of action. Methods: Hemin and EGCG were treated in Caco2 cells to perform the water-soluble tetrazolium salt-1 assay, lactate dehydrogenase release assay, reactive oxygen species (ROS) detection assay, real-time quantitative polymerase chain reaction and western blot. We investigated the regulatory effects of hemin and EGCG on an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colon carcinogenesis mouse model. Results: In Caco2 cells, hemin increased cell proliferation and the expression of cell cycle regulatory proteins, and ROS levels. EGCG suppressed hemin-induced cell proliferation and cell cycle regulatory protein expression as well as mitochondrial ROS accumulation. Hemin increased nuclear factor erythroid-2-related factor 2 (Nrf2) expression, but decreased Keap1 expression. EGCG enhanced hemin-induced Nrf2 and antioxidant gene expression. Nrf2 inhibitor reversed EGCG reduced cell proliferation and cell cycle regulatory protein expression. In AOM/DSS mice, hemin treatment induced hyperplastic changes in colon tissues, inhibited by EGCG supplementation. EGCG reduced the hemin-induced numbers of total aberrant crypts and malondialdehyde concentration in the AOM/DSS model. Conclusions: We demonstrated that EGCG reduced hemin-induced proliferation and colon carcinogenesis through Nrf2-inhibited mitochondrial ROS accumulation.

• Korean Journal of Animal Reproduction
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• v.25 no.4
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• pp.389-397
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• 2001

Cocaine-amphetamine regulated transcript (CART), a satiety factor regulated by leptin, is associated with food intake and motor behavior. In knock out studies, Leu34Phe mutation of human CART gene resulted in obese phenotype but mice carrying a targeted deletion of the CART gene exhibited no dramatic increase of body weight on normal fat diet. To establish a new transgenic mouse model for determining the function of CART on feeding behavior in vivo, we constructed the fusion gene, CART gene under the control of neurofilament light chain promoter, which regulates gene expression at the stage of neuronal differentiation. Transgenic mice were generated by microinjection method and screened by PCR and Southern blot analyses. In these transgenic mice, overexpression of CART was detected by in situ hybridization in spinal cords and brains at 13.5 days post-coitum embryos. At six weeks of age, RT-PCR analysis showed that exogenous CART mRNA was expressed strongly in brains and spinal cords, but not much in other tissues. Our results suggest that these transgenic mice provide a new model to investigate the function of CART gene in neuronal network associated with feeding behavior.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.7
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• pp.929-937
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• 2016

The purpose of this study was to investigate the effect of Acanthopanax senticosus extract (ASE) (ethanol : DW=1:1, v/v) on inhibition of type 2 diabetes using an OLETF rat model via regulation of HbA1c and AGEs levels. Supplementation with ASE 0.1% and 0.5% effectively lowered levels of glucose, insulin, oral glucose tolerance test, and Homa-insulin resistance, suggesting reduced insulin resistance. Blood levels of HbA1c and AGEs were significantly reduced in a dose-dependent manner. As oxidative stress plays a key role in accelerating production of HbA1c and AGEs, which worsen symptoms of type 2 diabetes, levels of malonaldehyde and pro-inflammatory cytokines were measured. Lipid peroxidation in both blood and liver tissues was significantly reduced, and induction of pro-inflammatory cytokines interleukin-${\beta}$ and tumor necrosis factor-${\alpha}$, which elevate production of HbA1c and AGEs, was inhibited (P<0.05). To evaluate the possible cellular events after AGEs receptor activation, genetic expression of protein kinase C (PKC)-${\delta}$ and transforming growth factor (TGF)-${\beta}$ was measured by real-time polymerase chain reaction. Supplementation with both ASE 0.1% and 0.5% significantly inhibited mRNA expression of PKC-${\delta}$ and TGF-${\beta}$, indicating that ASE may have beneficial effects on preventing insulin-resistant cells or tissues from progressing to diabetic complications. Taken together, ASE has potential to improve type 2 diabetes by inhibiting insulin resistance and protein glycosylation, including production of HbA1c and AGEs. Anti-oxidative activities of ASE are a main requisite for reducing production of HbA1c and AGEs and are also related to regulation of the PKC signaling pathway, resulting in suppression of TGF-${\beta}$, which increases synthesis of collagen, prostaglandin, and disease-related proteins.

• The Journal of Internal Korean Medicine
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• v.30 no.2
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• pp.257-269
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• 2009

Objective : Obesity is an important cause of diabetes, and lipotoxicity causes insulin resistance. Recently a lot of research is being done on PPAR-${\alpha}$. TNF-${\alpha}$. adiponectin, and leptin, which are important obesity related factors. In this study, we investigated the effects of Supungsunki-hwan on high fat. high carbohydrate diet-induced obese type 2 diabetic mouse models. Methods: Diabetes was induced in ICR male mouse (30${\pm}$5g) with Surwit's high fat, high sucrose diet. Mice were divided into 4 groups(n=10) of Normal. Control. Supungsunkj-hwan group. and acarbose group. The Supungsunki-hwsn group was given 10% Supungsunkj-hwan in their diet. and the acarbose group was given 0.5% acarbose in their diet. After 6 weeks. body weight. food intake, FBS and OGTT. lipid profile and liver enzymes, epididymal fat weight, and gene expression of leptin, adiponectin, TNF-${\alpha}$ and PPAR-${\alpha}$ were measured. Leptin. adiponectin. tumor necrosis factor(TNF)-${\alpha}$ and peroxisome proliferator-activated receptor (PPAR)-${\alpha}$ were evaluated by reverse transcription-polymerase chain reaction. Results : Supungsunkj-hwan increased the gene expression of PPAR-${\alpha}$, which reduces lipotoxicity and insulin resistance. Supungsunkj-hwan also significantly reduced triglyceride. AST. ALT serum levels. and 1 hour oral glucose tolerance levels. Conclusion : These results show that Supungsunkj-hwan improves insulin resistance in the liver and muscles, by reducing triglyceride levels and lipotoxicity through increased PPAR-${\alpha}$ gene expression. This is supported by the fact that Supungsunkj-hwan significantly reduces 1 hour oral glucose tolerance levels. Therefore we suggest that Supungsunkj-hwan would be an effective treatment for obese type 2 diabetic patients.

• Journal of Microbiology and Biotechnology
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• v.13 no.3
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• pp.348-353
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• 2003

Generally, two different types of fructose polymer are found in nature. One is inulin, whose fructosyl residues are linked mainly by a ${\beta}-(2,1)-linkage$, while the other is high-molecular-weight levan, whose fructosyl residues are linked mainly by a ${\beta}-(2,6)-linkage$. In contrast to the extensive studies on the prebiotic properties of inulin, there has been no report on the effect of levan on the large bowel microflora in viva. Therefore, to examine whether dietary levan can be used as a prebiotic, Sprague-Dawley male rats were fed one of two diets for 3 weeks: 1) basal diet plus sucrose; 2) basal diet plus 10% (wt/wt) levan. The cecal bowel mass, cecal and colon short-chain fatty acids (SCFAs), pH, and microflora were then compared. The intake of the levan-containing diet significantly increased the total cecal weight and wall weight. The analyses of the SCFAs in the cecal and colonic contents revealed that levan was converted into acetate, butyrate, and lactate, which resulted in acidic conditions. The intake of levan also significantly increased the total number of microorganisms by 5-fold and lactic acid-producing bacteria (LAB) 30-fold in the feces. Accordingly, the current work shows that levan can be used as a prebiotic for stimulating the growth of LAB in an animal model.

• Journal of Ginseng Research
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• v.44 no.6
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• pp.833-842
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• 2020

Background: Ulcerative colitis (UC) is a commonly encountered large intestine disease in the contemporary world that terminates into colorectal cancer; therefore, the timely treatment of UC is of major concern. Panax ginseng Meyer is an extensively consumed herbal commodity in South East Asian countries, especially Korea. It exhibits a wide range of biologically beneficial qualities for almost head-to-toe ailments in the body. Epimedium koreanum Nakai (EKN) is also a widely used traditional Korean herbal medicine used for treating infertility, rheumatism, and cardiovascular diseases. Materials and methods: Separately the anti-inflammatory activities of both red ginseng extracts (RGEs) and EKNs had been demonstrated in the past in various inflammatory models; however, we sought to unravel the anti-inflammatory activities of the combination of these two extracts in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice model because the allopathic remedies for UC involve more side effects than benefits. Results: Our results have shown that the combination of RGE + EKN synergistically alleviated the macroscopic lesions in DSS-induced colitic mice such as colon shortening, hematochezia, and weight loss. Moreover, it restored the histopathological lesions in mice and decreased the levels of proinflammatory mediators and cytokines through the repression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP-3) expression. In vitro, this combination also reduced the magnitude of nitric acid (NO), proinflammatory mediators and cytokine through NF-κB and mitogen-activated protein kinase (MAPK) pathways in RAW 264.7 mouse macrophage cells. Conclusion: In the light of these findings, we can endorse this combination extract as a functional food for the prophylactic as well as therapeutic treatment of UC in humans together with allopathic remedies.