• Title/Summary/Keyword: $\beta-cell$ function

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Cell Biological Function of Secretome of Adipose-Derived Stem Cells on Human Dermal Fibroblasts and Keratinocytes (인체 섬유아세포 및 케라티노사이트에 대한 지방줄기세포 분비물의 세포생물학적 기능)

  • Lee, Jae-Seol;Lee, Jong-Hwan
    • Microbiology and Biotechnology Letters
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    • v.40 no.2
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    • pp.117-127
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    • 2012
  • The beneficial effects of adipose-derived stem cell conditioned media (ADSC-CM) for skin regeneration have previously been reported, despite the precise mechanism of how ADSC-CM promotes skin regeneration remaining unclear. ADSC-CM contains various secretomes and this may be a factor in it being a good resource for the treatment of skin conditions. It is also known that ADSC-CM produced in hypoxia conditions, in other words Advanced Adipose-Derived Stem cell Protein Extract (AAPE), has excellent skin regenerative properties. In this study, a human primary skin cell was devised to examine how AAPE affects human dermal fibroblast (HDF) and human keratinocyte (HK), which both play fundamental roles in skin regeneration. The promotion of collagen formation by HDFs was observed at 0.32 mg/ml of AAPE. AAPE treatment significantly stimulated stress fiber formation. DNA gene chips demonstrated that AAPE in HKs (p<0.05) affected the expression of 133 identifiable transcripts, which were associated with cell proliferation, migration, cell adhesion, and response to wounding. Twenty five identified proteins, including MMP, growth factor and cytokines such as CD54, FGF-2, GM-CSF, IL-4, IL-6, VEGF, TGF-${\beta}2$, TGF-${\beta}3$, MMP-1, MMP-10, and MMP-19, were contained in AAPE via antibody arrays. Thus, AAPE might activate the HK biological function and induce the collagen synthesis of HDF. These results demonstrate that AAPE has the potential to be used for clinic applications aimed at skin regeneration.

Aloe-Emodin Protects RIN-5F (Pancreatic β-cell) Cell from Glucotoxicity via Regulation of Pro-Inflammatory Cytokine and Downregulation of Bax and Caspase 3

  • Alshatwi, Ali A;Subash-Babu, P.
    • Biomolecules & Therapeutics
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    • v.24 no.1
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    • pp.49-56
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    • 2016
  • To determine the protective effect of aloe-emodin (AE) from high glucose induced toxicity in RIN-5F (pancreatic ${\beta}$-cell) cell and restoration of its function was analyzed. RIN-5F cells have been cultured in high glucose (25 mM glucose) condition, with and without AE treatment. RIN-5F cells cultured in high glucose decreased cell viability and increased ROS levels after 48 hr compared with standard medium (5.5 mM glucose). Glucotoxicity was confirmed by significantly increased ROS production, increased pro-inflammatory (IFN-${\gamma}$, IL-$1{\beta}$,) & decreased anti-inflammatory (IL-6&IL-10) cytokine levels, increased DNA fragmentation. In addition, we found increased Bax, caspase 3, Fadd, and Fas and significantly reduced Bcl-2 expression after 48 hr. RIN-5F treated with both high glucose and AE ($20{\mu}M$) decreased ROS generation and prevent RIN-5F cell from glucotoxicity. In addition, AE treated cells cultured in high glucose were transferred to standard medium, normal responsiveness to glucose was restored within 8hr and normal basal insulin release within 24 hr was achieved when compared to high glucose.

The Role of Tripartite Motif Family Proteins in TGF-β Signaling Pathway and Cancer

  • Lee, Ho-Jae
    • Journal of Cancer Prevention
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    • v.23 no.4
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    • pp.162-169
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    • 2018
  • $TGF-{\beta}$ signaling plays a tumor suppressive role in normal and premalignant cells but promotes tumor progression during the late stages of tumor development. The $TGF-{\beta}$ signaling pathway is tightly regulated at various levels, including transcriptional and post-translational mechanisms. Ubiquitination of signaling components, such as receptors and Smad proteins is one of the key regulatory mechanisms of $TGF-{\beta}$ signaling. Tripartite motif (TRIM) family of proteins is a highly conserved group of E3 ubiquitin ligase proteins that have been implicated in a variety of cellular functions, including cell growth, differentiation, immune response, and carcinogenesis. Recent emerging studies have shown that some TRIM family proteins function as important regulators in tumor initiation and progression. This review summarizes current knowledge of TRIM family proteins regulating the $TGF-{\beta}$ signaling pathway with relevance to cancer.

Modulation of Cell Proliferation and Hypertrophy by Gangliosides in Cultured Human Glomerular Mesangial Cells

  • Lee Seoul;Ahn Seon Ho;Baek Seung Hoon;Song Ju Hung;Choo Young Kug;Kwon Oh Deog;Choi Bong Kyu;Jung Kyu Yong
    • Archives of Pharmacal Research
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    • v.28 no.8
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    • pp.948-955
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    • 2005
  • Glomerular mesangial cells (GMCs) in diverse renal diseases undergo cell proliferation and/or hypertrophy, and gangliosides have been reported to play an important role in modulating cell structure and function. This study compared the effects of transforming growth $factor-\beta\; (TGF­\beta1)$ and the effects of the application of exogenous gangliosides on GMCs and investigated whether the application of exogenous gangliosides regulated cellular proliferation and hypertrophy. Human GMCs were cultured with exogenous gangliosides and $TGF-\beta1$ in a media containing $10\%$ fetal bovine serum and in a media without the fetal bovine serum. Exogenous gangliosides biphasically changed the proliferation of human GMCs (0.1-1.0 mg/mL). A low concentration (0.1 mg/mL) of gangliosides mainly increased the number of human GMCs, whereas cellular proliferation was significantly reduced by raising the concentration of exogenous gangliosides. $TGF-\beta1$ greatly reduced the number of human GMCs in a concentration­dependent manner (1-10 ng/mL). Serum deprivation accelerated the gangliosides- and $TGF­\beta1-induced$ inhibition of mesangial cell proliferation to a greater extent. Gangliosides (1.0 mg/ mL) and $TGF-\beta1$ (10 ng/mL) both caused a significant increase in the incorporation of $[^3H]leucine$ per cell in the serum-deprived condition, whereas it was completely reversed in serum­supplemented condition. Similar results to the $[^3H]leucine$ incorporation were also observed in the changes in cell size measured by flow cytometric analysis. These results show that exogenous gangliosides modulate cell proliferation and hypertrophy in cultured human GMCs, and these cellular responses were regulated differently based on whether the media contained serum or not. Results from the present study raise new possibilities about the potential involvement of gangliosides in the development of mesangial cell proliferation and hypertrophy.

Estrogenic and Antiestrogenic Insecticides in MCF7-BUS Cell Line (피레스로이드계 살충제의 MCF7-BUS세포에 대한 에스트로겐 및 항에스트로겐 효과)

  • 오승민;정규혁
    • YAKHAK HOEJI
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    • v.45 no.6
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    • pp.694-700
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    • 2001
  • Synthetic pyrethroids are analysis of a natural chemical moiety, pyrethrin derived from the pyrethrum plant Chrysanthemum. The natural pyrethrin structure has been modified to be highly lipophilic and photostable, creating an effective pesticide and resulting in an increased presence in the environment. Worldwide, they are commonly used insecticides against ticks, mites, mosquitoes, and as treatment for human head lice and scabies. Therefore, human exposure to their compounds in extensive. Several studies on the effects of pyrethroids on thyroid hormone regulation, estrogen and androgen function have been reported and yet little has been done try assess their potential hormonal activities. Among humans, a pyrethroid compound was suggested to be the causal agent for gynecomastia in a group of Haitian men. The reports suggest that some pyrethroid compounds are capable of disrupting endocrine function. Therefore, we examined estrogenic/antiestrogenic potential of three pyrethroid insecticides, that is permethrin, allethrin and fenvalerate in human breast cancer cell and action mechanism mediated by the estrogen receptor. Fenvalerate showed weak estrogenic activity but aallethrin and permethrin showed no effect. In combination with high levels (10$^{-10}$ M, 10$^{-11}$ M) of 17$\beta$-estradiol and three synthetic pyrethroids inhibited cert proliferations in MCF7-BUS cell by 17$\beta$-estradiol. Whereas, fenvalerate increased cell proliferative activity at lower level of estradiol (10$^{-12}$ M, 10$^{-13}$ M). The relative affinities to the estrogen receptor were observed by allethrin and permethrin treatment, but not by fenvalerate. These results indicated that some of pyrethroid insecticides may modulate estrogen functions in human breast cancer cell. The action mechanisms of estrogen receptor mediated antiestrogenicity by allethrin and permethrin were postulated.

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Suppression of ASKβ(AtSK32), a Clade III Arabidopsis GSK3, Leads to the Pollen Defect during Late Pollen Development

  • Dong, Xiangshu;Nou, Ill-Sup;Yi, Hankuil;Hur, Yoonkang
    • Molecules and Cells
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    • v.38 no.6
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    • pp.506-517
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    • 2015
  • Arabidopsis Shaggy-like protein kinases (ASKs) are Arabidopsis thaliana homologs of glycogen synthase kinase 3/SHAGGY-like kinases (GSK3/SGG), which are comprised of 10 genes with diverse functions. To dissect the function of $ASK{\beta}$ (AtSK32), $ASK{\beta}$ antisense transgenic plants were generated, revealing the effects of $ASK{\beta}$ down-regulation in Arabidopsis. Suppression of $ASK{\beta}$ expression specifically interfered with pollen development and fertility without altering the plants' vegetative phenotypes, which differed from the phenotypes reported for Arabidopsis plants defective in other ASK members. The strength of these phenotypes showed an inverse correlation with the expression levels of $ASK{\beta}$ and its co-expressed genes. In the aborted pollen of $ASK{\beta}$ antisense plants, loss of nuclei and shrunken cytoplasm began to appear at the bicellular stage of microgametogenesis. The in silico analysis of promoter and the expression characteristics implicate $ASK{\beta}$ is associated with the expression of genes known to be involved in sperm cell differentiation. We speculate that $ASK{\beta}$ indirectly affects the transcription of its co-expressed genes through the phosphorylation of its target proteins during late pollen development.

Function and use of silkworm dpp gene (누에 유래의 dpp 유전자의 기능 및 유전체 연구를 통한 식의약용 신소재로서 활용)

  • Park, Seung Wong
    • Journal of Sericultural and Entomological Science
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    • v.54 no.1_2
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    • pp.1-5
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    • 2016
  • The dpp gene originated from the silkworms is an important gene that is well conserved in the genome of humans, cattle, rodents, poultry and Drosophila. The dpp gene belonging to the TGF-beta (Transforming Growth Factor-beta) superfamily is known to play an important role in several developmental stages. The $TGF-{\beta}$ gene family is a genetically well-conserved and playing an important role gene family in various species such as determining cell proliferation and differentiation, apoptosis and cell fate. In this review, we have confirmed the following studies data. The recent studies on the silkworm dpp gene have confirmed for the first time the biological functions such as promoting osteogenesis activity. In addition, previous data shows that dpp have developmental functions such as morphogenetic materials at the blastophyllum stage, induction of the mesoblast at the late embryonic stage and involved in the proliferation and morphogenesis of imaginal disc in adult development. We found the splice variant of the dpp gene originated from the wildtype silkworm by using comparative genomics. It has provided important data for basic research based on genetics studies of these processes may promote a better understanding of evolution. Silkworm is a medicinal insect and is approved for its safety. It is used as a natural antibiotic for promoting growth as a medical material, a health functional food, and a feed additive. Therefore, it is necessary to present various data to obtain more value of functional insect.

Comparison of Inhibitory Effects of 17-AAG Nanoparticles and Free 17-AAG on HSP90 Gene Expression in Breast Cancer

  • Ghalhar, Masoud Gandomkar;Akbarzadeh, Abolfazl;Rahmati, Mohammad;Mellatyar, Hassan;Dariushnejad, Hassan;Zarghami, Nosratallah;Barkhordari, Amin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7113-7118
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    • 2014
  • Background: HSP90 may be overexpressed in cancer cells which are greatly dependent on Hsp90 function. Geldanamycin derivative 17 allylamino-17-demethoxygeldanamycin (17-AAG) inhibits the function and expression of HSP90. 17-AAG has poor water-solubility which is a potential problem for clinical practice. In this study for improving the stability and solubility of molecules in drug delivery systems we used a ${\beta}$-cyclodextrin-17AAG complex. Materials and Methods: To assess cytotoxic effects of ${\beta}$-cyclodextrin-17AAG complexes and free 17AAG, colorimetric cell viability (MTT) assays were performed. Cells were treated with equal concentrations of ${\beta}$-cyclodextrin- 17AAG complex and free 17AAG and Hsp90 gene expression levels in the two groups was compared by real-time PCR. Results: MTT assay confirmed that ${\beta}$-cyclodextrin- 17AAG complex enhanced 17AAG cytotoxicity and drug delivery in T47D breast cancer cells. The level of Hsp90 gene expression in cells treated with ${\beta}$-cyclodextrin- 17AAG complex was lower than that of cells treated with free 17AAG (P=0.001). Conclusions: The results demonstrated that ${\beta}$-cyclodextrin- 17AAG complexes are more effective than free 17AAG in down-regulating HSP90 expression due to enhanced ${\beta}$-cyclodextrin-17AAG uptake by cells. Therefore, ${\beta}$-cyclodextrin could be superior carrier for this kind of hydrophobic agent.

Effects of Job's Tears(Yul-Moo) Extracts on Mouse Splenocyte and Macrophage Cell Activation (율무 추출물의 마우스 비장세포와 대식세포 활성 효과)

  • Ryu, Hye-Sook
    • The Korean Journal of Food And Nutrition
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    • v.21 no.1
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    • pp.1-6
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    • 2008
  • Job's Tears(Yul-Moo) is a grass crop long-used as a traditional medicine; it is also a nourishing food. There are reports of its anti-inflammatory, stomachic, antiallergic activity, and antispastic effects and Job's Tears has been used in China to treat rheumatism, and neuralgia although its warts, rheumanism remains unclear. Thus, the present study was performed to investigate the in vitro effect of Job's Tears extracts on immune function. Here mouse splenocyte proliferation and cytokine production$(IL-1{\beta},\;IL-6,\;TNF-{\alpha})$ by peritoneal macrophages cultured with ethanol and water extracts of Job's Tears were examined. splenocytes proliferation increased with Job's Tears water extracts supplement at concentrations investigated The cytokine production$(IL-1{\beta},\;IL-6,\;TNF-{\alpha})$ by ELISA using a cytokine kit And $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production increased water extracts supplementation. This in vitro study suggests that supplementation with Job's Tears water extracts may enhance immune function by regulating the splenocyte proliferation and enhancing cytokine production of activated macrophages.

Proliferative and Synthetic Responses of Airway Smooth Muscle in Asthma (천식에서 기도평활근의 증식과 합성 반응에 대한 최신지견)

  • Shim, Jung Yeon
    • Clinical and Experimental Pediatrics
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    • v.48 no.6
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    • pp.580-587
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    • 2005
  • New evidence is emerging that airway smooth muscle(ASM) may act as an immunomodulatory cell by providing pro-inflammatory cytokines and chemokines, polypeptide growth factors, extracellular matrix proteins, cell adhesion receptors and co-stimulatory molecules. ASM can promote the formation of the interstitial extracellular matrix, and potentially contribute to the alterations within the extracellular matrix in asthma. In addition, extracellular matrix components can alter the proliferative, survival, and cytoskeletal synthetic function of ASM cells through integrin-directed signaling. Increased ASM mass is one of the most important features of the airway wall remodeling process in asthma. Three different mechanisms may contribute to the increased ASM mass : cell proliferation, increased migration and decreased rate of apoptosis. The major signaling pathways of cell proliferation activated by ASM mitogens are those dependent on extracellular signal-regulated kinase and phosphoinositide 3'-kinase. The key signaling mechanisms of cell migration have been identified as the p38 mitogen-activated protein kinase and the p21-activated kinase 1 pathways. ASM cells contain ${\beta}2$-adrenergic receptors and glucocorticoid receptors. They may represent a key target for ${\beta}2$-adrenergic receptor agonist/corticosteroid interactions which have antiproliferative activity against a broad spectrum of mitogens.