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Aspergillus fumigatus-derived demethoxyfumitremorgin C inhibits proliferation of PC3 human prostate cancer cells through p53/p21-dependent G1 arrest and apoptosis induction

  • Kim, Young-Sang;Park, Sun Joo
    • Fisheries and Aquatic Sciences
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    • v.24 no.1
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    • pp.1-9
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    • 2021
  • Human prostate cancer is the second most frequently diagnosed cancer worldwide, and its incidence rate continues to increase. Advanced prostate cancer is more difficult to treat than early forms due to its chemotherapy resistance. There is need for more effective agents that can inhibit the progression of advanced prostate cancer. Demethoxyfumitremorgin C (DMFTC) was isolated from the fermentation extract of the marine fungus Aspergillus fumigatus. Antiproliferative activity of DMFTC against human prostate cancer PC3 cells was examined through cell cycle analysis by flow cytometry, the fluorescent nuclear imaging analysis with propidium iodide (PI), and proteins expression related to cell cycle arrest and apoptosis were investigated via Western blotting. DMFTC inhibited PC3 cells growth through G1 phase cell cycle arrest and apoptosis induction. It activated the tumor suppressor p53 and the Cdk inhibitor p21, which regulate the cell progression into the G1 phase. Additionally, PI-positive late apoptotic non-viable cells were increased and the expression levels of the G1-positive downstream regulators cyclin D, cyclin E, Cdk2, and Cdk4 were decreased by DMFTC treatment. These results suggest that DMFTC induces G1 arrest and apoptosis induction through regulation of p53/p21-dependent cyclin-Cdk complexes, and it may be a useful therapeutic agent for the treatment of human advanced prostate cancer.

Opportunities and Future Directions of Human-Metaverse Interaction (휴먼-메타버스 인터랙션의 기회와 발전방향)

  • Yoon, Hyoseok;Park, ChangJu;Park, Jung Yeon
    • Smart Media Journal
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    • v.11 no.6
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    • pp.9-17
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    • 2022
  • In the COVID-19 pandemic era, non-contact services were demanded and the use of extended reality and metaverse services increased rapidly in various applications. In this paper, we analyze Gather.town, ifland, Roblox, and ZEPETO metaverse platforms in terms of user interaction, avatar-based interaction, and virtual world authoring. Especially, we distinguish interactions among user input techniques that occur in the real world, avatar representation techniques to represent users in the virtual world, and interaction types that create a virtual world through user participation. Based on this work, we highlight the current trends and needs of human-metaverse interaction and forecast future opportunities and research directions.

Deep Brain Photoreceptors and Photoperiodism in Vertebrates

  • Oishi, Tadashi;Haida, Yuka;Okano, Keiko;Yoshikawa, Tomoko;Kawano, Emi;Nagai, Kiyoko;Fukada, Yoshitaka;Tsutsui, Kazuyoshi;Tamotsu, Satoshi
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.5-8
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    • 2002
  • Photoperiodism is an important adaptive phenomenon in various physiological parameters including reproduction to cope with seasonal changes. Involvement of extraretinal photoreceptors in the photoperiodism in non-mammalian vertebrates has been well established. In addition, circadian clock system is known to be involved in the photoperiodic time measurement. The pathway consists of light-input system, time measurement system (circadian clock), gonadotropin releasing hormone (GnRH) production in the hypothalamus, luteinizing hormone (LH) and follicle stimulating hormone (FSH) production in the pituitary, and final gonadal development. Recently, several laboratories reported photopigments newly cloned in the pineal, eyes and deep brain in addition to already known visual pigments in the retina. These are pinopsin, parapinopsin, VA-opsin, melanopsin, etc. All these photopigments belong to the opsin family having retinal as the chromophore. However, the function of these photopigments remains unknown. I reviewed the studies on the location of the photopigments by immunocytochemistry. I also discussed the results on the action spectra for induction of gonadal development in relation with the location of the photoreceptors. Various physiologically active substances distribute in the vertebrate brain. Such substances are GnRH, GnIH, neuropeptide Y, vasoactive intestinal peptide, c-Fos, galanin, neurosteroids, etc. I summarized the immunhistochemical studies on the distribution and the photoperiodic changes of these substances and discussed the route from the deep brain photoreceptor to GnRH cells.

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Global Absolute Quantitation of Proteins in Human Whole Saliva by nLC-QIMS-TOF Employing MSE

  • Cho, Ha Ra;Jin, Sung Giu;Park, Jun Seo;Kim, Han Sol;Choi, Yong Seok
    • Mass Spectrometry Letters
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    • v.8 no.4
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    • pp.114-118
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    • 2017
  • While saliva can be considered as good biological fluid for monitoring biomarkers due to many advantages including its communication with blood and the non-invasive nature during its sampling, its applications to that purpose is still limited. As a part of efforts to expand the applications of saliva to the protein biomarker research, we carried out global absolute quantitation of proteins in human whole saliva (WS) by bottom-up proteomics techniques mainly based on nLC-Q-IMS-TOF employing $MS^E$. From the analyses of a pooled WS sample collected from 22 healthy Korean volunteers, 93 proteins ranging from $5.89{\times}10^1ng/mL$ (immunoglobulin heavy chain) to $1.59{\times}10^4ng/mL$ (${\alpha}-amylase$ 1) were confirmed. For the validation of the present results, human serum albumin in the same sample was quantitated by ELISA and its result was compared with that from the nLC-Q-IMS-TOF study. As a result, there was no significant difference between two results from individual approaches ($1.18{\times}10^4{\pm}0.03{\times}10^4 ng/mL$ from nLC-Q-IMS-TOF experiments vs. $1.23{\times}10^4{\pm}0.07{\times}10^4ng/mL$ from ELISA experiments, n=3, p=0.309). To our knowledge, this is the first global absolute quantitation of proteins in human whole saliva and information from the present study can be widely used as the first level reference for the discovery of new protein biomarkers from human whole saliva as well as for quantitative applications of human whole saliva proteins.

Talin-1 Correlates with Reduced Invasion and Migration in Human Hepatocellular Carcinoma Cells

  • Fang, Kun-Peng;Zhang, Jian-Lin;Ren, Yan-Hong;Qian, Ye-Ben
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2655-2661
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    • 2014
  • Background: Talin-1 is a cytoskeleton protein that participates in cell migration and plays a role in tumor formation, migration, and metastasis in different types of cancer. Chinese investigators have observed that the levels of Talin-1 protein and mRNA expression in HCC tissues are significantly lower than in the adjacent non-cancerous tissue. However, Japanese investigators have reported that Talin-1 is upregulated in HCC. Tln2 as homologous gene of Tln-1, which encodes a very similar protein, but the role of Talin-2 is very little known in primary liver cancer (PLC). We investigated whether the expression of Talin-1 in PLC may be associated with the histological subtype as well as the role of Talin-1 in tumor cell invasion and migration using human hepatocellular carcinoma cell lines. Materials and Methods: We measured the mRNA expression levels of Talin-1 and Talin-2 in five human liver cancer cell lines and normal human liver cell ($LO_2$ cell line) by real-time PCR and the protein expression levels of Talin-1 by Western blot. Migration and invasion of the cells were assessed using transwell assays and cell scratch experiments, respectively, and proliferation was assessed by soft AGAR colony formation. Results: Talin-1 and Talin-2 expression differed significantly between the five human liver cancer cell lines and $LO_2$ cell line (p<0.05). Compared with the $LO_2$ cell line, the invasion and migration capabilities of the five cancer cell lines differed significantly (p<0.05). Similarly, the colony-forming ability differed (p<0.05). Conclusions: High levels of Talin-1 expression are correlated with reduced invasion and migration as well as decreased malignancy in human liver cancer cell lines; the suppression of Talin-1 promotes invasion and migration. In addition, Talin-2 may be correlated with invasion and migration in human hepatocellular carcinoma.

POTENT INHIBITION OF HUMAN CYTOCHROME P450 1 ENZYMES BY DIMETHOXYPHENYL VINYL THIOPHENE

  • Lee, Sang-Kwang;Kim, Sang-Hee;Kim, Mie-Young;Chun, Young-Jin
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.312.3-313
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    • 2002
  • Recently we have reported that various hydroxystilbenes show strong inhibition of human P450 1 activity. A series of synthetic trans-stilbene derivatives were prepared and their inhibitory potentials were evaluated with the bacterial membrane of recombinant human P450 1A1, 1A2 or 1B1 coexpressed with human NADPH-P450 reductase to find new candidates for cancer chemoprevention, Of the compounds tested. SY-021 (3.5-dimethoxyphenyl vinyl thiophene) exhibited a potent inhibition of human P450 181 with an IC$_{50}$ value of 2 nM. SY-021 also showed the inhibitrion of P450 1A1 with IC$_{50}$ value of 61 nM and P450 1A2 with IC$_{50}$ value of 11 nM. SY-021 showed 31-fold selectivity for P450 1B1 over P450 1A1 and 6-fold selectivity for P450 1B1 over 1A2. We have further investigated the inhibition kinetics of P450 1A1. 1A2 and 1B1 by SY-021. The modes of inhibition by SY-021were non-compeitive for all three P450 1 enzymes. Effect of preincubation with NADPH on inhibition of P450 1B1 by SY-021 was determined. These results suggest that SY-021 is one of the mostj potent inhibitor of human P450 1 enzymes and may be considered as a good candidate for a cancer chemopreventive agent in human

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Analysis on the Kinematics and Dynamics of Human Arm Movement Toward Upper Limb Exoskeleton Robot Control - Part 2: Combination of Kinematic and Dynamic Constraints (상지 외골격 로봇 제어를 위한 인체 팔 동작의 기구학 및 동역학적 분석 - 파트 2: 제한조건의 선형 결합)

  • Kim, Hyunchul;Lee, Choon-Young
    • Journal of Institute of Control, Robotics and Systems
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    • v.20 no.8
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    • pp.875-881
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    • 2014
  • The redundancy resolution of the seven DOF (Degree of Freedom) upper limb exoskeleton is key to the synchronous motion between a robot and a human user. According to the seven DOF human arm model, positioning and orientating the wrist can be completed by multiple arm configurations that results in the non-unique solution to the inverse kinematics. This paper presents analysis on the kinematic and dynamic aspect of the human arm movement and its effect on the redundancy resolution of the seven DOF human arm model. The redundancy of the arm is expressed mathematically by defining the swivel angle. The final form of swivel angle can be represented as a linear combination of two different swivel angles achieved by optimizing two cost functions based on kinematic and dynamic criteria. The kinematic criterion is to maximize the projection of the longest principal axis of the manipulability ellipsoid of the human arm on the vector connecting the wrist and the virtual target on the head region. The dynamic criterion is to minimize the mechanical work done in the joint space for each of two consecutive points along the task space trajectory. The contribution of each criterion on the redundancy was verified by the post processing of experimental data collected with a motion capture system. Results indicate that the bimodal redundancy resolution approach improved the accuracy of the predicted swivel angle. Statistical testing of the dynamic constraint contribution shows that under moderate speeds and no load, the dynamic component of the human arm is not dominant, and it is enough to resolve the redundancy without dynamic constraint for the realtime application.

Osteogenic Potency of Nacre on Human Mesenchymal Stem Cells

  • Green, David W.;Kwon, Hyuk-Jae;Jung, Han-Sung
    • Molecules and Cells
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    • v.38 no.3
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    • pp.267-272
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    • 2015
  • Nacre seashell is a natural osteoinductive biomaterial with strong effects on osteoprogenitors, osteoblasts, and osteoclasts during bone tissue formation and morphogenesis. Although nacre has shown, in one study, to induce bridging of new bone across large non-union bone defects in 8 individual human patients, there have been no succeeding human surgical studies to confirm this outstanding potency. But the molecular mechanisms associated with nacre osteoinduction and the influence on bone marrow-derived mesenchymal stem cells (BMSC's), skeletal stem cells or bone marrow stromal cells remain elusive. In this study we highlight the phenotypic and biochemical effects of Pinctada maxima nacre chips and the global nacre soluble protein matrix (SPM) on primary human bone marrow-derived stromal cells (hBMSCs) in vitro. In static co-culture with nacre chips, the hBMSCs secreted Alkaline phosphatase (ALP) at levels that exceeded bone morphogenetic protein (rhBMP-2) treatment. Concentrated preparation of SPM applied to Stro-1 selected hBMSC's led to rapid ALP secretions, at concentrations exceeding the untreated controls even in osteogenic conditions. Within 21 days the same population of Stro-1 selected hBMSCs proliferated and secreted collagens I-IV, indicating the premature onset of an osteoblast phenotype. The same SPM was found to promote unselected hBMSC differentiation with osteocalcin detected at 7 days, and proliferation increased at 7 days in a dose-dependent manner. In conclusion, nacre particles and nacre SPM induced the early stages of human bone cell differentiation, indicating that they may be promising soluble factors with osteoinductive capacity in primary human bone cell progenitors such as, hBMSC's.

Impact Analysis of nonverbal multimodals for recognition of emotion expressed virtual humans (가상 인간의 감정 표현 인식을 위한 비언어적 다중모달 영향 분석)

  • Kim, Jin Ok
    • Journal of Internet Computing and Services
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    • v.13 no.5
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    • pp.9-19
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    • 2012
  • Virtual human used as HCI in digital contents expresses his various emotions across modalities like facial expression and body posture. However, few studies considered combinations of such nonverbal multimodal in emotion perception. Computational engine models have to consider how a combination of nonverbal modal like facial expression and body posture will be perceived by users to implement emotional virtual human, This paper proposes the impacts of nonverbal multimodal in design of emotion expressed virtual human. First, the relative impacts are analysed between different modals by exploring emotion recognition of modalities for virtual human. Then, experiment evaluates the contribution of the facial and postural congruent expressions to recognize basic emotion categories, as well as the valence and activation dimensions. Measurements are carried out to the impact of incongruent expressions of multimodal on the recognition of superposed emotions which are known to be frequent in everyday life. Experimental results show that the congruence of facial and postural expression of virtual human facilitates perception of emotion categories and categorical recognition is influenced by the facial expression modality, furthermore, postural modality are preferred to establish a judgement about level of activation dimension. These results will be used to implementation of animation engine system and behavior syncronization for emotion expressed virtual human.

Effects Of Nicotine And PDGF On The Cell Activity Of Human Gingival Fibroblasts And Periodontal Ligament Cells. (니코틴과 PDGF-AB가 배양인체 치은섬유모세포 및 치주인대세포의 활성에 미치는 영향)

  • Kim, Deok-Kyu;Kong, Young-Hwan;You, Hyung-Keun;Shin, Hyung-Shik
    • Journal of Periodontal and Implant Science
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    • v.26 no.1
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    • pp.176-187
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    • 1996
  • The ability of fibroblasts attached to teeth is paramount important in reestablishing the lost connective tissue attachment after periodontal therapy. The migration and proliferation of periodontal ligament cells are desired goal of periodontal regeneration therapy. PDGF is well known to regulate the cell activity of mesenchymal origin cell. Tobacco contains a complex mixture of substance including nicotine, various nitrosamines, trace elements, and variety of poorly characterized substances. Human gingival fibroblasts and periodontal ligament cells were cultured from extracted tooth for non-periodontal reason. Cultured human gingival fibroblasts and periodontal ligament cells in vitro were treated with PDGF, nicotine in time dependent manner. Cellular activities were determined by MTT assay. The purpose of this study was to determine the effects of Nicotine and PDGF, respectively and the effect of PDGF presence of nicotine on human gingival fibroblasts and periodontal ligament cells. The results were as follows : 1. In the cell activities of human gingival fibroblasts and periodontal ligament cells were similar or decreased to control value at 1st day. At 2nd day, cellular activities of both group were increased to control value. At 3rd day, cellular activities of both group were returned to the control value. 2. In the cell activities of PDGF on human gingival fibroblasts and periodontal ligament cells, cell activities significantly increase from control group on periodontal ligament cells compared to gingival fibroblast group at 3rd day. 3. In the cell activities of PDGF and nicotine combined application on human gingival fibroblasts and periodontal ligament cells, it seems likely that the nicotinic effect of gingival fibroblasts were higher than periodontal ligament cells and the PDGF effect of periodontal ligament cells were higher than gingival fibroblasts. This results suggested that PDGF might stimulate the selective growth on periodontal ligament cells.

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