New product innovation is a process of embodying new knowledge in a product and technology licensing is getting popular as a means to innovations and introduction of new product to the market in today's competitive global market environment. Incumbents often rely on technology licensing to access new product opportunities created by other firms. Prior research has examined various aspects of technology licensing agreements such as specific contract terms of licensing agreements, e.g., distribution of control rights, exclusivity of licensing agreements, cross-licensing, and the scope of licensing agreements. This study aims to provide answers to an important, but under-researched question: why do some incumbents initiate more licensing agreement for exploratory learning while others do it for exploitative learning along the innovation process? We attempt to extend our knowledge of licensing agreements from an organizational learning perspective. Technology licensing as a specific form of interfirm linkages can be initiated with different learning objectives along the process of new product innovation. The exploratory stages of the innovation process such as discovery or research stages involve extensive searches to create new knowledge or capabilities, whereas the exploitative stages of the innovation process such as application or test stages near the commercialization are more focused on developing specific applications or improving their efficiency or reliability. Thus, different stages of the innovation process generate different types of learning and the resulting technological resources. We examine when incumbents as licensees initiate more licensing agreements for exploratory learning objectives and when more for exploitative learning objectives, focusing on two factors that may influence a firm's formation of exploratory and exploitative licensing agreements: 1) its past radical and incremental innovation experience and 2) its internal investments in R&D and marketing. We develop and test our hypotheses regarding the relationship between a firm's radical and incremental new product experience, R&D investment intensity and marketing investment intensity, and the likelihood of engaging in exploratory and exploitive licensing agreements. Using data collected from various secondary sources (Recap database, Compustat database, and FDA website), we analyzed technology licensing agreements initiated in the biotechnology and pharmaceutical industries from 1988 to 2011. The results of this study show that incumbents initiate exploratory rather than exploitative licensing agreements when they have more radical innovation experience and when they invest in R&D activities more intensively; in contrast, they initiate exploitative rather than exploratory licensing agreements when they have more incremental innovation experience and when they invest in marketing activities more intensively. The findings of this study contribute to the licensing and interfirm cooperation studies. First, this study lays a foundation to understand the organizational learning aspect of technology licensing agreements. Second, this study sheds lights on how a firm's internal investments in R&D and marketing are linked to its tendency to initiate licensing agreements along the innovation process. Finally, the findings of this study provide important insight to managers regarding which technologies to gain via licensing agreements. This study suggests that firms need to consider their internal investments in R&D and marketing as well as their past innovation experiences when they initiate licensing agreements along the process of new product innovation.
This study aims to elucidate the effect of glycyrrhizic acid on smooth muscle contraction and to determine the detailed mechanism incorporated. We hypothesized that glycyrrhizic acid played a role in the agonist-sensitive management of smooth muscle contraction. Stripped smooth muscles of Sprague-Dawley rats were prepared in organ baths and isometric tensions were converted, stored and analyzed by using isometric transducers, a physiograph and one way ANOVA. Interestingly, glycyrrhizic acid attenuated the thick filament regulating agonist (fluoride or thromboxane mimetic)-sensitive contraction (p=0.113, 0.008, 0.004 (Student's t-test), p=0.113, 0.008, 0.004 (One way ANOVA) at 0.01, 0.03, 0.1 mM fluoride, and p=0.156, 0.004, 0.003 (Student's t-test), p=0.156, 0.004, 0.003 (One way ANOVA) at 0.01, 0.03, 0.1 mM thromboxane mimetic) and did not attenuate the thin filament regulating agonist (phorbol ester)-induced contraction (p=0.392, 0.086, 0.065 (Student's t-test), p=0.392, 0.086, 0.065 (One way ANOVA) at 0.01, 0.03, 0.1 mM phorbol ester). It is suggesting that endothelial EDRF (NO) synthesis and accessory pathways besides endothelial EDRF (NO) synthesis such as ROCK restriction might be incorporated in the glycyrrhizic acid-induced modulation of smooth muscle contraction inhibiting acto-myosin interaction.
Jong Min Choi;Yongwei Piao;Kyong Hoon Ahn;Seok Kyun Kim;Jong Hoon Won;Jae Hong Lee;Ji Min Jang;In Chul Shin;Zhicheng Fu;Sung Yun Jung;Eui Man Jeong;Dae Kyong Kim
Molecules and Cells
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v.46
no.9
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pp.545-557
/
2023
Sphingomyelinase (SMase) catalyzes ceramide production from sphingomyelin. Ceramides are critical in cellular responses such as apoptosis. They enhance mitochondrial outer membrane permeabilization (MOMP) through self-assembly in the mitochondrial outer membrane to form channels that release cytochrome c from intermembrane space (IMS) into the cytosol, triggering caspase-9 activation. However, the SMase involved in MOMP is yet to be identified. Here, we identified a mitochondrial Mg2+-independent SMase (mt-iSMase) from rat brain, which was purified 6,130-fold using a Percoll gradient, pulled down with biotinylated sphingomyelin, and subjected to Mono Q anion exchange. A single peak of mt-iSMase activity was eluted at a molecular mass of approximately 65 kDa using Superose 6 gel filtration. The purified enzyme showed optimal activity at pH of 6.5 and was inhibited by dithiothreitol and Mg2+, Mn2+, Ni2+, Cu2+, Zn2+, Fe2+, and Fe3+ ions. It was also inhibited by GW4869, which is a non-competitive inhibitor of Mg2+-dependent neutral SMase 2 (encoded by SMPD3), that protects against cytochrome c release-mediated cell death. Subfractionation experiments showed that mt-iSMase localizes in the IMS of the mitochondria, implying that mt-iSMase may play a critical role in generating ceramides for MOMP, cytochrome c release, and apoptosis. These data suggest that the purified enzyme in this study is a novel SMase.
Journal of the Korean Applied Science and Technology
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v.40
no.5
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pp.965-976
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2023
Reynoutria japonica is a perennate plant belonging to Polygonaceae and grows wild in East Asia containing Korea. Roots of Reynoutria japonica (R. japonica), part of roots of Reynoutria japonica, has been used for anti-inflammation and antispasmodics and contains emodin as active compound. Epidermis of skin is crucial roles to defense our body against stimulants, harmful substance and prevent water loss. In this study, we examined the effect of R. japonica and emodin, its active compound, on skin-barrier and moisturizing on HaCaT cells. First, antioxidant effect of R. japonica was prominent by scavenging ABTS+ radicals. Next, we conducted real time PCR and expression of filaggrin mRNA which is crucial role in differentiation of keratinocyte increased by R. japonica and emodin dose-dependently. In addition, R. japonica and emodin significantly elevated the expression of HAS-2 mRNA which play a role in hyaluronic acid synthesis on HaCaT cells. Taken together, R. japonica containing emodin, as active compound has potential as a cosmetic material for enhancing the function of skin-barrier and moisturizing in epidermis.
Photobacterium sp. YW2207 was isolated from rainbow trout raised in a fish farm located in Yeongwol-gun, Gangwon Province, South Korea. Based on 16S rRNA sequence analysis and phylogenetic analysis, it was confirmed that Photobacterium sp. YW2207 showed 100% similarity with Photobacterium piscicola and Photobacterium phosphoreum, and 94.6% similarity with P. damselae subsp. damselae. Biochemical analysis revealed that Photobacterium sp. YW2207 is a Gram-negative, motile bacterium with a cell size of 1.5~3×3~5 ㎛. The bacteria were cultured on nutrient agar, brain heart infusion agar, Muller-Hinton agar, tryptic soy agar, and thiosulfate citrate bile sucrose agar with NaCl concentrations ranging from 0 to 2.5%. The API50CHE and API20E tests indicated lower utilization capabilities compared to the P. damselae strains provided in the API database. Furthermore, unlike most Photobacterium species, Photobacterium sp. YW2207 presented negative for catalase test. Results from the flow cytometric measurement indicated that Photobacterium sp. YW2207 exhibited a more diverse distribution of cell sizes and had larger cell sizes compared with P. damselae subsp. damselae. Minimum inhibitory concentration tests showed that Photobacterium sp. YW2207 had low susceptibility to β-Lactam and aminoglycoside antibiotics, while having high susceptibility to tetracycline, doxycycline, and quinolone antibiotics. Pathogenicity on rainbow trout revealed that an immersion of 1×105 CFU/ml did not cause mortality or clinical symptoms.
This study was conducted to determine the conditions for breaking dormancy in the seeds of the North Korean plant resource, Trollius macropetalus, and to investigate its germination characteristics. The morphological characteristics and viability of T. macropetalus seeds were examined. Germination characteristics were investigated based on temperature conditions (15/6℃ & 25/15℃), cold stratification treatment, and GA3 treatment. The results showed that cold stratification treatment had no effect on breaking the dormancy of T. macropetalus. GA3 treatment significantly increased the germination rate of T. macropetalus and also improved the mean germination days and germination speed. However, compared to the 15/6℃ condition, the effectiveness of GA3 treatment for T. macropetalus decreased under the 25/15℃ condition. It was determined that T. macropetalus have a nondeep-type morpho-physiological dormancy. The most effective conditions for breaking dormancy were found to be the 15/6℃ temperature condition and GA3 treatment at 500 mg·L-1. The findings of this study are expected to provide valuable information for the mass propagation of T. macropetalus, which has potential applications in landscaping and pharmaceutical materials.
Plantago asiatica L. (P. asiatica) is a perennial plant belonging to the plantaginaceae and is useful in treating a various diseases such as wounds, bronchitis, and chronic constipation. The bioactive effects of P. asiatica extract was evaluated to determine its potential for use as a variety materials in the food, pharmaceutical, and agricultural industries. Polyphenol and flavonoid contents, free radical scavenging, reducing power activity, and reactive oxygen species (ROS) expression were measured to identify the antioxidative activity. Anti-inflammatory effects were evaluated via analysis of nitric oxide (NO) and pro-inflammatory protein expression in LPS-induced RAW 264.7 cell. As a result of measuring the antioxidant activities of the P. asiatica extract, the total polyphenol content was 50.91±0.78 mg gallic acid equivalents/g and the flavonoid content was 100.99±0.44 mg rutin equivalents/g, and both DPPH and ABTS radical scavenging activities and reducing power increased depending on the concentration. Also, intracellular ROS production was inhibited by the P. asiatica extract. No cytotoxicity was observed when P. asiatica extract was treated, and NO and inflammatory protein expression were inhibited, and nuclear factor kappa B (NF-κB) phosphorylation was also inhibited in a concentration-dependent manner. In conclusion, P. asiatica is a functional natural resources of antioxidant and anti-inflammatory agents that can be used in various industries, including food and agriculture.
Yi Zheng;Yunlong Si;Xuejiao Xu;Hongming Gu;Zhen He;Zihan Zhao;Zhangkai Feng;Jiyong Su;Kevin H. Mayo;Yifa Zhou;Guihua Tai
Journal of Ginseng Research
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v.48
no.2
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pp.202-210
/
2024
Background: Panax ginseng Meyer polysaccharides exhibit various biological functions, like antagonizing galectin-3-mediated cell adhesion and migration. Galectin-8 (Gal-8), with its linker-joined N- and C-terminal carbohydrate recognition domains (CRDs), is also crucial to these biological processes, and thus plays a role in various pathological disorders. Yet the effect of ginseng-derived polysaccharides in modulating Gal-8 function has remained unclear. Methods: P. ginseng-derived pectin was chromatographically isolated and enzymatically digested to obtain a series of polysaccharides. Biolayer Interferometry (BLI) quantified their binding affinity to Gal-8, and their inhibitory effects on Gal-8 was assessed by hemagglutination, cell migration and T-cell apoptosis. Results: Our ginseng-derived pectin polysaccharides consist mostly of rhamnogalacturonan-I (RG-I) and homogalacturonan (HG). BLI shows that Gal-8 binding rests primarily in RG-I and its β-1,4-galactan side chains, with sub-micromolar KD values. Both N- and C-terminal Gal-8 CRDs bind RG-I, with binding correlated with Gal-8-mediated function. Conclusion: P. ginseng RG-I pectin β-1,4-galactan side chains are crucial to binding Gal-8 and antagonizing its function. This study enhances our understanding of galectin-sugar interactions, information that may be used in the development of pharmaceutical agents targeting Gal-8.
Han Kyu Chae;Nayoung Suh;Myong Jin Jang;Yu Seon Kim;Bo Hyun Kim;Joomin Aum;Ha Chul Shin;Dalsan You;Bumsik Hong;Hyung Keun Park;Choung-Soo Kim
International Journal of Stem Cells
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v.16
no.1
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pp.66-77
/
2023
Background and Objectives: We compared the efficacy and safety of human bone marrow-derived mesenchymal stem cells (hBMSC), delivered at different doses and via different injection routes in an animal model of chronic kidney disease. Methods and Results: A total of ninety 12-week-old rats underwent 5/6 nephrectomy and randomized among nine groups: sham, renal artery control (RA-C), tail vein control (TV-C), renal artery low dose (RA-LD) (0.5×106 cells), renal artery moderate dose (RA-MD) (1.0×106 cells), renal artery high dose (RA-HD) (2.0×106 cells), tail vein low dose (TV-LD) (0.5×106 cells), tail vein moderate dose (TV-MD) (1.0×106 cells), and tail vein high dose (TV-HD) (2.0×106 cells). Renal function and mortality of rats were evaluated after hBMSC injection. Serum blood urea nitrogen was significantly lower in the TV-HD group at 2 weeks (p<0.01), 16 weeks (p<0.05), and 24 weeks (p<0.01) than in the TV-C group, as determined by one-way ANOVA. Serum creatinine was significantly lower in the TV-HD group at 24 weeks (p<0.05). At 8 weeks, creatinine clearance was significantly higher in the TV-MD and TV-HD groups (p<0.01, p<0.05) than in the TV-C group. In the safety evaluation, we observed no significant difference among the groups. Conclusions: Our findings confirm the efficacy and safety of high dose (2×106 cells) injection of hBMSC via the tail vein.
Sang Mi Park;Dae Hwa Jung;Byung Gu Min;Kyung Hwan Jegal;Sung Hui Byun;Jae Kwang Kim;Sang Chan Kim
Herbal Formula Science
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v.31
no.4
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pp.231-243
/
2023
Objectives : Jasminum officinale L. var. grandiflorum is used as a traditional or folk remedy in China to treat arthritis, hepatitis, duodenitis, conjunctivitis, gastritis, and diarrhea. In this study, we aimed to study the hepatocyte protective activity and molecular mechanism of Jasminum officinale L. var. grandiflorum aqueous extract (JGW) using HepG2 hepatocyte cell lines. Methods : HepG2 cells were pretreated with diverse concentrations of JGW, and then the cells were exposed to tert-butyl hydroperoxide (tBHP) for inducing oxidative stress. Hydrogen peroxide (H2O2) production, glutathione (GSH) concentration, mitochondrial membrane potential (MMP) and cell viability were measured to investigate hepato-protective effects of JGW. Phosphorylation of AMP-activated protein kinases (AMPK), acetyl coenzyme A carboxylase (ACC) and effects of compound C on cell viability were examined to observe the role of AMPK on JGW-mediated cytoprotection. Results : Pretreatment with JGW (10-300 ㎍/mL) significantly suppressed cytotoxicity induced by tBHP in a concentration dependent manner and reduced the expression of cleaved PARP and cleaved caspase-3 proteins related to apoptosis in HepG2 cells. In addition, pretreatment with JGW significantly prevented the increase in H2O2 production, GSH depletion, and lower MMP induced by tBHP. Treatment with JGW (30 minutes of incubation and concentrations of 100 and 300 ㎍/mL) increased the phosphorylation of AMPK and ACC and treatment with compound C, a chemical inhibitor of AMPK, inhibited the cytoprotective effect of JGW. Conclusions : Our results demonstrated that JGW may protect hepatocytes from oxidative stress via activation of AMPK.
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