• Title/Summary/Keyword: Side Population Cells

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Application of Optimized Gompertz Algorithm for Estimation of Controlled Drug Release (Gompertz modeling을 이용한 약물유출 예측시스템의 최적화)

  • Choe, Se-Woon;Woo, Young Woon
    • Journal of the Korea Society of Computer and Information
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    • v.19 no.12
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    • pp.219-225
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    • 2014
  • A Gompertz modeling, sigmoid in shape, is a widely used application for social science, natural science, engineering, and medical research to allow confident approximation and accurate analysis and has been applied to estimate an elderly population on aging of population. Due to the high toxicity of currently available drug delivery vehicles, various efforts have been made to reduce side-effects in clinical fields, but its application to preclinical and clinical studies is limited and there are some difficulties to optimize the parameters of Gompertz modeling applicable to preclinical studies. Therefore, in this study, we demonstrated the ability of sickle red blood cells loaded by hypotonic dialysis then photosensitized and light-activated ex vivo for controlled release and simultaneously optimized Gompertz function to evaluate controlled drug release properties of photosensitized sickle red blood cells to reduce pain-related treatments in cancer patients.

MethA Fibrosarcoma Cells Expressing Membrane-Bound Forms of IL-2 Enhance Antitumor Immunity

  • Sonn, Chung-Hee;Yoon, Hee-Ryung;Seong, In-Ock;Chang, Mi-Ra;Kim, Yong-Chan;Kang, Han-Chul;Suh, Seok-Cheol;Kim, Young-Sang
    • Journal of Microbiology and Biotechnology
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    • v.16 no.12
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    • pp.1919-1927
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    • 2006
  • Tumor cells genetically engineered to secrete cytokines are effective in tumor therapy, but various unexpected side effects are observed, which may result from the bulk activation of various bystander cells. In this study, we tested tumor vaccines expressing various membrane-bound forms of IL-2 (mbIL-2) on MethA fibrosarcoma cells to focus antitumor immune responses to CTL. Chimeric forms of IL-2 with whole CD4, deletion forms of CD4, and TNF were expressed on the tumor cell surface, respectively. Tumor clones expressing mbIL-2 or secretory form of IL-2 were able to support the cell growth of CTLL-2, an IL-2-dependent T cell line, and the proliferation of spleen cells from 2C TCR transgenic mice that are responsive to the $p2Ca/L^d$ MHC class I complex. Expression of mbIL-2 on tumor cells reduced the tumorigenicity of tumor cells, and the mice that once rejected the live IL-2/TNF tumor clone acquired systemic immunity against wild-type MethA cells. The IL-2/TNF clone was inferior to other clones in tumor formation, and superior in the stimulation of the CD8+ T cell population in vitro. These results suggest that the IL-2/TNF clone is the best tumor vaccine, and may stimulate CD8+ T cells by direct priming. Expression of IL-2/TNF on tumor cells may serve as an effective gene therapy method to ameliorate the side effects encountered in the recombinant cytokine therapy and the conventional cytokine gene therapy using the secretory form of IL-2.

Expression Analyses Revealed Thymic Stromal Co-Transporter/Slc46A2 Is in Stem Cell Populations and Is a Putative Tumor Suppressor

  • Kim, Ki Yeon;Lee, Gwanghee;Yoon, Minsang;Cho, Eun Hye;Park, Chan-Sik;Kim, Moon Gyo
    • Molecules and Cells
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    • v.38 no.6
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    • pp.548-561
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    • 2015
  • By combining conventional single cell analysis with flow cytometry and public database searches with bioinformatics tools, we extended the expression profiling of thymic stromal cotransporter (TSCOT), Slc46A2/Ly110, that was shown to be expressed in bipotent precursor and cortical thymic epithelial cells. Genome scale analysis verified TSCOT expression in thymic tissue- and cell type- specific fashion and is also expressed in some other epithelial tissues including skin and lung. Coexpression profiling with genes, Foxn1 and Hoxa3, revealed the role of TSCOT during the organogenesis. TSCOT expression was detected in all thymic epithelial cells (TECs), but not in the $CD31^+$endothelial cell lineage in fetal thymus. In addition, ABC transporter-dependent side population and Sca-$1^+$ fetal TEC populations both contain TSCOT-expressing cells, indicating TEC stem cells express TSCOT. TSCOT expression was identified as early as in differentiating embryonic stem cells. TSCOT expression is not under the control of Foxn1 since TSCOT is present in the thymic rudiment of nude mice. By searching variations in the expression levels, TSCOT is positively associated with Grhl3 and Irf6. Cytokines such as IL1b, IL22 and IL24 are the potential regulators of the TSCOT expression. Surprisingly, we found TSCOT expression in the lung is diminished in lung cancers, suggesting TSCOT may be involved in the suppression of lung tumor development. Based on these results, a model for TEC differentiation from the stem cells was proposed in context of multiple epithelial organ formation.

Combination of Poly-Gamma-Glutamate and Cyclophosphamide Enhanced Antitumor Efficacy Against Tumor Growth and Metastasis in a Murine Melanoma Model

  • Kim, Doo-Jin;Kim, Eun-Jin;Lee, Tae-Young;Won, Ji-Na;Sung, Moon-Hee;Poo, Haryoung
    • Journal of Microbiology and Biotechnology
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    • v.23 no.9
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    • pp.1339-1346
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    • 2013
  • Conventional chemotherapeutic regimens often accompany severe side effects and fail to induce complete regression of chemoresistant or relapsing metastatic cancers. The need for establishing more efficacious anticancer strategies led to the development of a combined modality treatment of chemotherapy in conjunction with immunotherapy or radiotherapy. It has been reported that poly-gamma-glutamate (${\gamma}$-PGA), a natural polymer composed of glutamic acids, increases antitumor activity by activating antigen-presenting cells and natural killer (NK) cells. Here, we investigated the antitumor effect of ${\gamma}$-PGA in combination with cyclophosphamide in a murine melanoma model. Whereas cyclophosphamide alone directly triggered apoptosis of tumor cells in vitro, ${\gamma}$-PGA did not show cytotoxicity in tumor cells. Instead, it activated macrophages, as reflected by the upregulation of surface activation markers and the secretion of proinflammatory factors, such as nitric oxide and tumor necrosis factor ${\alpha}$. When the antitumor effects were examined in a mouse model, combined treatment with cyclophosphamide and ${\gamma}$-PGA markedly suppressed tumor growth and metastasis. Notably, ${\gamma}$-PGA treatment dramatically increased the NK cell population in lung tissues, coinciding with decreased metastasis and increased survival. These data collectively suggest that ${\gamma}$-PGA can act as an immunotherapeutic agent that exhibits a synergistic antitumor effect in combination with conventional chemotherapy.

Influence of rutin on the effects of neonatal cigarette smoke exposure-induced exacerbated MMP-9 expression, Th17 cytokines and NF-κB/iNOS-mediated inflammatory responses in asthmatic mice model

  • Liu, Li-Li;Zhang, Yan;Zhang, Xiao-Fang;Li, Fu-Hai
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.5
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    • pp.481-491
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    • 2018
  • Allergic asthma is one of the most enduring diseases of the airway. The T-helper cells and regulatory T-cells are critically involved in inflammatory responses, mucus hypersecretion, airway remodelling and in airway hyper-responsiveness. Cigarette smoke (CS) has been found to aggravate inflammatory responses in asthma. Though currently employed drugs are effective, associated side effects demand identification and development of novel drugs with negligible or no adverse effects. Rutin, plant-derived flavonoid has been found to possess antioxidant and anti-inflammatory effects. We investigated the ability of rutin to modulate T-cells and inhibit inflammation in experimentally-induced asthma in cigarette smoke exposed mice. Separate groups of neonatal mice were exposed to CS for 10 days from post-natal days 2 to 11. After 2 weeks, the mice were sensitized and challenged with ovalbumin (OVA). Treatment group were given rutin (37.5 or 75 mg/kg body weight) during OVA sensitization and challenge. Rutin treatment was found to significantly inhibit cellular infiltration in the airways and Th2 and Th17 cytokine levels as well. Flow cytometry revealed effectively raised $CD4^+CD25^+Fox3^+$ Treg cells and supressed Th17 cell population on rutin treatment. Airway hyper-responsiveness observed following CS and OVA challenge were inhibited by rutin. $NF-{\kappa}B$ and iNOS, chief regulators of inflammatory responses robustly activated by CS and OVA were down-regulated by rutin. Rutin also inhibited the expression of matrix metalloproteinase 9, thereby aiding in prevention of airway remodelling in asthma thereby revealing to be a potent candidate in asthma therapy.

Action Pattern of Anti-Yeast Substance Originated from Rahnella aquatilis Strain AY2000 (Rahnella aquatilis AY2000균 유래의 항 효모물질의 작용양상)

  • Park, Hae-Ji;Kang, Min-Jung;Lee, Jong-Hwan;Kim, Kwang-Hyeon
    • Korean Journal of Microbiology
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    • v.47 no.2
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    • pp.163-166
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    • 2011
  • For reduction of side effects by anti-fungal agents, a less toxic anti-fungal substance or a synergistic substance with a new mechanism is needed. The anti-yeast substance (AYS) originated from Rahnella aquatilis strain AY2000 is like to be a heterogeneous protein. The AYS inhibited the growth of Candida albicans in culture broth, and AYS-treated cells were arrested in each phase during cell cycle. Among AYS-treated cells, the population of the cells belonging to sub-G1 phase was not increased during cell cycle. Therefore, AYS has rather yeaststatic than yeastcidal effect to C. albicans. Moreover, with combination of itraconazole or fluconazole, AYS had a synergistic anti-yeast activity against Saccharomyces cerevisiae based on the analysis of fractional inhibitory concentration index.

Consequence of Floral Herbivory in Vicia cracca (Leguminosae)

  • Gang, Hye-Sun
    • Animal cells and systems
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    • v.2 no.1
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    • pp.55-63
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    • 1998
  • The effects of inflorescence herbivory and flowering time on plant architecture and reproductive yields were examined with a perennial herbacious species, Vicia cracca, occurring in Natick, Massachusetts, USA. Natural herbivory on inflorescences was observed among the total of 157 plants during a growing season. Vegetative and reproductive characters were measured in the field as well as in the lab depending on the characters. Approximately 64% of the plants were subjected to herbivory on inflorescences. Plants were classified into three groups; unbrowsed plants, partially browsed, and totally browsed plants, according to the level of herbivory on inflorescences of each plant. Plants were also categorized by their flowering time such as early vs late flowering plants. Herbivores tended to favor inflorescences on rather small plants, resulting in a pattern of totally contact or partially intact inflorescences on taller plants. The mean number of stems, which was assumed to be a direct result of severe herbivory in this population, differed among herbivory groups. There also was a tendency that plants flowering late in the season had more nodes with more leaves, suggesting that herbivory on stem tips early in the season before flowering might have induced growth of side branches or branchlets along the main stems. Comparison between unbrowsed and partially browsed plants showed that the latter compensated for browsing in terms of numbers of inflorescences, fruits, seeds and seed size (weight), though they did not compensate in flower number. The probability of fruit production (presence vs absence of fruits) and seed weight declined toward the end of the season. These results suggest that resources are deficient at the end of the season. Almost complete reproductive failure in totally browsed plants is attributed to the destruction of inflorescence display and the disadvantage of small vegetative size of those plants. After all, in this population, a moderate level of herbivory on inflorescences did not reduce the maternal fitness of the plants. However, severe herbivory on inflorescences resulted in antagonistic interactions between plants and herbivores.

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Distribution of Alexandrium tamarense in Drake Passage and the Threat of Harmful Algal Blooms in the Antarctic Ocean

  • Ho, King-Chung;Kang, Sung-Ho,;Lam Ironside H.Y.;Ho, dgkiss I.John
    • Ocean and Polar Research
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    • v.25 no.4
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    • pp.625-631
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    • 2003
  • While phytoplankton diversity and productivity in the Southern Ocean has been widely studied in recent years, most attention has been given to elucidating environmental factors that affect the dynamics of micro-plankton (mainly diatoms) and nano-plankton (mainly Phaeocystis antarctica). Only limited effects have been given to studying the occurrence and the potential risks associated with the blooming of dinoflagellates in the relevant waters. This study focused on the appearance and toxicological characteristics of a toxic dinoflagellate, Alexandrium tamarense, identified and isolated from the Drake Passage in a research cruise from November to December 2001 The appearance of A. tamarense in the Southern Ocean indicates the risk of a paralytic shellfish poisoning (PSP) outbreak there and is therefore of scientific concern. Results showed that while the overall quantity of A. tamarense in water samples from 30meters below the sea surface often comprised less than 0.1% of the total population of phytoplankton, the highest concentration of A. tamarense (20 cells $L^{-1}$) was recorded in the portion of the Southern Ocean between the southern end of South America and the Falkland Islands. Waters near the Polar Front contained the second highest concentrations of 10-15 cells $L^{-1}$. A. tamarense was however rarely found in waters near the southern side of the Polar Front, indicating that cold sea temperatures near the Antarctic ice does not favor the growth of this dinoflagellate. One strain of A. tamarense from this cruise was isolated and cultured for further study in the laboratory. Experiments showed that this strain of A. tamarense has a high tolerance to temperature variations and could survive at temperatures ranging from $5-26^{\circ}C$. This shows the cosmopolitan nature off. tamarense. With regard to the algal toxins produced, this strain of A. tamarense produced mainly C-2 toxins but very little saxitoxin and gonyailtoxin. The toxicological property of this A. tamarense strain coincided with a massive death of penguins in the Falkland Islands in December 2002 to January 2003.

Effect of ethanol extract from Achyranthis Radix on hair growth (우슬의 에탄올 추출물이 모발 성장에 미치는 영향)

  • Lee, Mi-Ja;Choi, Moon-Yeol;Kim, Yoo Jin;Kim, Mi Ryeo;Yoo, Wang Keun
    • The Korea Journal of Herbology
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    • v.36 no.4
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    • pp.1-7
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    • 2021
  • Objective : As more and more people are interested in appearance in modern society, the increasing number of hair loss population can have an important impact on psychological and social problems such as depression and inappropriate interpersonal symptoms. Therefore, much research is being done on treatments for alopecia using herbal extracts with relatively few side effects. This study was investigated about the effect of Achyranthis Radix (AR) extract with ethanol solvent on hair growth. Methods : We determined the promoting efficacy of AR-ethanol extract compared with minoxidil (MNXD) on the growth of human hair dermal papilla cells (HDPCs). Cell viability was measured by MTT assay and cell proliferation was confirmed by cell cycle analysis from flow cytometry in HDPCs. Also, we monitored the safe concentration range through MTT assay. And protein expression of hair growth-related genes (insulin-like growth factor 1 (IGF-1), Wnt3a, Protein kinase B (Akt), Extracellular signal-regulated kinase (Erk)) was monitored by western blot. Results : On cell cycle analysis, the G2/M phase was higher than that of the DW group in AR ethanol extract group at 0.05 and 0.1 mg/㎖. All protein expression levels of HDPCs were increased in AR ethanol extract groups and the MNXD group, compared to the DW group, respectively. Conclusion : As mentioned above, AR extract increased cell proliferation and the protein expression of IGF-1, Wnt3a, Akt, Erk in HDPCs. These results suggest that AR ethanol extract has promoted hair growth and it might be potential hair growth supplement.

Derivation of MSC Like-Cell Population from Feeder Free Cultured hESC and Their Proteomic Analysis for Comparison Study with BM-MSC (Feeder Free 상태에서 배양된 인간 배아 줄기세포를 이용한 중간엽 줄기세포 분화 및 단백체학을 이용한 골수 유래 중간엽 줄기세포와의 비교)

  • Park, Soon-Jung;Jeon, Young-Joo;Kim, Ju-Mi;Shin, Jeong-Min;Chae, Jung-Il;Chung, Hyung-Min
    • Reproductive and Developmental Biology
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    • v.34 no.3
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    • pp.143-151
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    • 2010
  • Pluripotency of human embryonic stem cell (hESC) is one of the most valuable ability of hESCs for applying cell therapy field, but also showing side effect, for example teratoma formation. When transplant multipotent stem cell, such as mesnchymal stem cell (MSC) which retains similar differentiation ability, they do not form teratoma in vivo, but there exist limitation of cellular source supply. Accordingly, differentiation of hESC into MSC will be promising cellular source with strong points of both hESC and MSC line. In this study, we described the derivation of MSC like cell population from feeder free cultured hESC (hESC-MSC) using direct differentiation system. Cells population, hESC-MSC and bone marrow derived MSC (BM-MSC) retained similar characteristics in vitro, such as morphology, MSC specific marker expression and differentiation capacity. At the point of differentiation of both cell populations, differentiation rate was slower in hESC-MSC than BM-MSC. As these reason, to verify differentially expressed molecular condition of both cell population which bring out different differentiation rate, we compare the molecular condition of hESC-MSC and BM-MSC using 2-D proteomic analysis tool. In the proteomic analysis, we identified 49 differentially expressed proteins in hESC-MSC and BM-MSC, and they involved in different biological process such as positive regulation of molecular function, biological process, cellular metabolic process, nitrogen compound metabolic process, macromolecule metabolic process, metabolic process, molecular function, and positive regulation of molecular function and regulation of ubiquitin protein ligase activity during mitotic cell cycle, cellular response to stress, and RNA localization. As the related function of differentially expressed proteins, we sought to these proteins were key regulators which contribute to their differentiation rate, developmental process and cell proliferation. Our results suggest that the expressions of these proteins between the hESC-MSC and BM-MSC, could give to us further evidence for hESC differentiation into the mesenchymal stem cell is associated with a differentiation factor. As the initial step to understand fundamental difference of hESC-MSC and BM-MSC, we sought to investigate different protein expression profile. And the grafting of hESC differentiation into MSC and their comparative proteomic analysis will be positively contribute to cell therapy without cellular source limitation, also with exact background of their molecular condition.