• Title/Summary/Keyword: In Vivo and In Vitro Function

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Improvement of Lipid Homeostasis Through Modulation of Low-density Lipoprotein Receptor Family by Functional Ingredients (천연 기능성 물질(Functional Ingredients)을 활용한 LDL 수용체과(科) 조절과 지질항상성 개선)

  • Jeong, Jeongho;Ryu, Yungsun;Park, Kibeum;Go, Gwang-woong
    • Food Engineering Progress
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    • v.21 no.1
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    • pp.1-11
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    • 2017
  • Dyslipidemia, defined as elevated triglyceride (TG), total- and LDL-C, and/or decreased HDL-C levels, is considered a principal risk factor for cardiovascular disease. The low-density lipoprotein receptor (LDLR) family has been considered a key player in the prevention of dyslipidemia. The LDLR family consists of cytoplasmic membrane proteins and plays an important role not only in ligand-receptor binding and uptake, but also in various cell signaling pathways. Emerging reports state that various functional ingredients dynamically modulate the function of the LDLR family. For instance, oats stimulated the LDLR function in vivo, resulting in decreased body weight and improved serum lipid profiles. The stimulation of LRP6 by functional ingredients in vitro activated the Wnt/${\beta}-catenin$ pathway, subsequently suppressing the intracellular TG via inhibition of SREBP1, $PPAR{\gamma}$, and $C/EBP{\alpha}$. Furthermore, the extract of Cistanchetubulosa enhanced the expression of the mRNA of VLDLR, followed by a reduction in the serum cholesterol level. In addition, fermented soy milk diminished TG and total cholesterol levels while increasing HDL-C levels via activation of LRP1. To summarize, modulating the function of the LDLR family by diverse functional ingredients may be a potent therapeutic remedy for the treatment of dyslipidemia and cardiovascular diseases.

Chitinase 3-like-1, a novel regulator of Th1/CTL responses, as a therapeutic target for increasing anti-tumor immunity

  • Kim, Do-Hyun;Choi, Je-Min
    • BMB Reports
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    • v.51 no.5
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    • pp.207-208
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    • 2018
  • Chitinase-Like Proteins (CLPs) are an evolutionarily conserved protein which lose their enzymatic activity for degrading chitin macromolecules. Chitinase-3-like-1 (Chi3l1) is a type of CLP that is highly expressed in epithelial cells, macrophages, etc., and is known to have correlations with type 2 inflammation and cancer. Although the increased level of Chi3l1 in the blood was reported in various disease patients, the function of Chi3l1 in adaptive immunity has been totally unknown. Recently, we found that Chi3l1 is expressed in T cells and has a negative regulatory role in T-cell activation and proliferation. A genetic ablation study of Chi3l1 in T cells showed hyperresponsiveness to TcR stimulation, which increased proliferation and Th1 differentiation. A significant increase of $IFN{\gamma}$ signaling in Chi3l1-deficient T cells synergistically increased Th1 and CTL functions against melanoma cells in vitro and in vivo. In addition, targeted knockdown by Chi3l1 siRNA complexed with the cell-penetrating peptide dNP2, which showed decreased pulmonary melanoma metastasis with increased infiltration of Th1 and CTL in the lung. This study first suggests that Chi3l1 is a novel regulator of Th1/CTL responses and could be a target for treating cancer to increase tumor immunity.

In vivo Metabolism of Endosulfan in Carp (Cyprinus carpio) (In vivo 시험에 의한 잉어체내 $^{14}C-endosulfan$의 대사)

  • Lee, K.B.;Shim, J.H.;Suh, Y.T.
    • Applied Biological Chemistry
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    • v.37 no.3
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    • pp.203-209
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    • 1994
  • When $^{14}C-{\alpha}-endosulfan$ was incubated with carp liver, kidney and gut preparations, it was metabolized to water soluble and organosoluble metabolites. In an in vitro test, endosulfan was converted to endosulfan ${\alpha}-hydroxyether$ (EHE), endosulfan alcohol (EA) and endosulfan ether (EE). The addition of NADPH resulted in rapid conversion of endosulfan to the metabolites in 105,000 g soluble fraction and microsomes. However, the rate of metabolism of endosulfan in liver, kidney and gut supplemented with NADPH as a cofactor was higher in the 105,000 g soluble fraction than that in the microsomes of carp under incubation conditions. The enzymes probably involved in the metabolism of endosulfan include the glutathione S-transferase (GST) and the mixed function oxidases (MFO), based on the evidence that addition of either GSH or NADPH increased the degradation of endosulfan.

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Antioxidant and Anti-hyperglycemic Activity of Polysaccharide Isolated from Dendrobium chrysotoxum Lindl

  • Zhao, Yaping;Son, Young-Ok;Kim, So-Soon;Jang, Yong-Suk;Lee, Jeong-Chae
    • BMB Reports
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    • v.40 no.5
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    • pp.670-677
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    • 2007
  • Although polysaccharide is believed to play an important role in the medicinal effect of Dendrobium chrysotoxum Lindl (DCL), its role as an antioxidant and in anti-hyperglycemic induction was not reported. In this study, polysaccharide with molecular weight of approximately 150 kDa, herein named DCLP, was isolated from the stem of DCL, and its antioxidative, hypoglycemic and immune stimulating effects were evaluated using various in vitro and in vivo assay systems. DCLP inhibited hydroxyl radicals ($^{\cdot}$OH)-mediated deoxyribose degradation by scavenging hydroxyl radicals directly as well as by chelating iron ions. DCLP also showed dose-dependent scavenging activity on superoxide anions ($O_2^{{\cdot}-}$) and offered significant protection (p < 0.001) against glucose oxidase-mediated cytotoxicity in Jurkat cells. DCLP had immune stimulating effects, as evidenced by the DCLP-mediated increases in the level of DNA synthesis, viability, and cytokine secretion in mouse lymphocytes. Moreover, oral administration of DCLP produced a significant reduction in blood glucose level in alloxan-induced diabetic mice. These findings suggest that DCLP has a potential utility in treating patients who require enhanced antioxidation, immune function and/or hypoglycemic activity.

Inhibitory Effects of Opuntia humifusa on 7, 12-Dimethyl-benz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate Induced Two-stage Skin Carcinogenesis

  • Lee, Jin-A;Jung, Bock-Gie;Lee, Bong-Joo
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4655-4660
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    • 2012
  • Opuntia humifusa, member of the Cactaceae family, was previously demonstrated to have radical scavenging, anti-inflammatory and anti-proliferative effects in in vitro models. It was suggested that O. humifusa could function in the prevention of carcinogenesis. To investigate the in vivo chemopreventive effect of O. humifusa, mice were fed a diet containing either 1% or 3% following 7, 12-dimethylbenz[a] anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) induction of skin carcinogenesis. Significant decrease in the numbers of papilloma and epidermal hyperplasia were observed in mice fed with O. humifusa, compared to the control group. O. humifusa also upregulated high total antioxidant capacity and level of phase II detoxifying enzyme such as superoxide dismutase and glutathione S-transferase activity in the skin. Lipid peroxidation activity level was measured in skin cytosol and significantly inhibited in 3% OH fed group compared to the control group. These results suggest that O. humifusa exerts chemopreventive effects on chemical carcinogenesis in mouse skin and that prevention effects are associated with reduction of oxidative stress via the modulation of cutaneous lipid peroxidation, enhancing of total antioxidant capacity especially in phase II detoxifying enzyme system and partial apoptotic influence.

Swiprosin-1 Regulates Cytokine Expression of Human Mast Cell Line HMC-1 through Actin Remodeling

  • Ramesh, T.P.;Kim, Young-Dae;Kwon, Min-Sung;Jun, Chang-Duk;Kim, Sang-Wook
    • IMMUNE NETWORK
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    • v.9 no.6
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    • pp.274-284
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    • 2009
  • Background: Swiprosin-1 was identified in human CD8+ lymphocytes, mature B cells and non-lymphonoid tissue. We have recently reported that swiprosin-1 is expressed in mast cells and up-regulated in both in vitro and in vivo. Methods: The expression of cytokines and swiprosin-1 were determined by by real time PCR and conventional PCR. Pharmacological inhibitors were treated to investigate potential mechanism of swiprosin-1 in mast cell activation. Actin content was evaluated by confocal microscopy and flow cytometry. Results: The swiprosin-1 augmented PMA/A23187-induced expression of cytokines and release of histamine. However, knock-down of swiprosin-1 showed only a modest effect on PMA/A23187-induced cytokine expression, suggesting that swiprosin-1 has gain-of-function characteristics. Swiprosin-1 was found in microvilli-like membrane protrusions and highly co-localized with F-actin. Importantly, either disruption of actin by cytochalasin B or inhibition of PI3 kinase, an enzyme involved in actin remodeling, by wortmannin blocked cytokine expression only in swiprosin-1-overexpressing cells. Conclusion: These results suggest that swiprosin-1 modulates mast cell activation potentially through actin regulation.

A review on the medicinal potentials of ginseng and ginsenosides on cardiovascular diseases

  • Lee, Chang Ho;Kim, Jong-Hoon
    • Journal of Ginseng Research
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    • v.38 no.3
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    • pp.161-166
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    • 2014
  • Ginseng is widely used for its promising healing and restorative properties as well as for its possible tonic effect in traditional medicine. Nowadays, many studies focus on purified individual ginsenoside, an important constituent in ginseng, and study its specific mechanism of action instead of whole-plant extracts on cardiovascular diseases (CVDs). Of the various ginsenosides, purified ginsenosides such as Rb1, Rg1, Rg3, Rh1, Re, and Rd are the most frequently studied. Although there are many reports on the molecular mechanisms and medical applications of ginsenosides in the treatment of CVDs, many concerns exist in their application. This review discusses current works on the countless pharmacological functions and the potential benefits of ginseng in the area of CVDs. Results: Both in vitro and in vivo results indicate that ginseng has potentially positive effects on heart disease through its various properties including antioxidation, reduced platelet adhesion, vasomotor regulation, improving lipid profiles, and influencing various ion channels. To date, approximately 40 ginsenosides have been identified, and each has a different mechanism of action owing to the differences in chemical structure. This review aims to present comprehensive information on the traditional uses, phytochemistry, and pharmacology of ginseng, especially in the control of hypertension and cardiovascular function. In addition, the review also provides an insight into the opportunities for future research and development on the biological activities of ginseng.

Telomere association of Oryza sativa telomere repeat-binding factor like 1 and its roles in telomere maintenance and development in rice, Oryza sativa L.

  • Byun, Mi Young;Cui, Li Hua;Lee, Hyoungseok;Kim, Woo Taek
    • BMB Reports
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    • v.51 no.11
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    • pp.578-583
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    • 2018
  • Telomeres are specialized nucleoprotein complexes that function to protect eukaryotic chromosomes from recombination and erosion. Several telomere binding proteins (TBPs) have been characterized in higher plants, but their detailed in vivo functions at the plant level are largely unknown. In this study, we identified and characterized OsTRFL1 (Oryza sativa Telomere Repeat-binding Factor Like 1) in rice, a monocot model crop. Although OsTRFL1 did not directly bind to telomere repeats $(TTTAGGG){_4}$ in vitro, it was associated with telomeric sequences in planta. OsTRFL1 interacted with rice TBPs, such as OsTRBF1 and RTBP1, in yeast and plant cells as well as in vitro. Thus, it seems likely that the association of OsTRFL1 with other TBPs enables OsTRFL1 to bind to telomeres indirectly. T-DNA inserted OsTRFL1 knock-out mutant rice plants displayed significantly longer telomeres (6-25 kb) than those (5-12 kb) in wild-type plants, indicating that OsTRFL1 is a negative factor for telomere lengthening. The reduced levels of OsTRFL1 caused serious developmental defects in both vegetative and reproductive organs of rice plants. These results suggest that OsTRFL1 is an essential factor for the proper maintenance of telomeres and normal development of rice.

Circular RNAs in and out of Cells: Therapeutic Usages of Circular RNAs

  • Mingyu Ju;Dayeon Kim;Geurim Son;Jinju Han
    • Molecules and Cells
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    • v.46 no.1
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    • pp.33-40
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    • 2023
  • RNAs are versatile molecules that are primarily involved in gene regulation and can thus be widely used to advance the fields of therapeutics and diagnostics. In particular, circular RNAs which are highly stable, have emerged as strong candidates for use on next-generation therapeutic platforms. Endogenous circular RNAs control gene regulatory networks by interacting with other biomolecules or through translation into polypeptides. Circular RNAs exhibit cell-type specific expression patterns, which can be altered in tissues and body fluids depending on pathophysiological conditions. Circular RNAs that are aberrantly expressed in diseases can function as biomarkers or therapeutic targets. Moreover, exogenous circular RNAs synthesized in vitro can be introduced into cells as therapeutic molecules to modulate gene expression networks in vivo. Depending on the purpose, synthetic circular RNA sequences can either be identical to endogenous circular RNA sequences or artificially designed. In this review, we introduce the life cycle and known functions of intracellular circular RNAs. The current stage of endogenous circular RNAs as biomarkers and therapeutic targets is also described. Finally, approaches and considerations that are important for applying the available knowledge on endogenous circular RNAs to design exogenous circular RNAs for therapeutic purposes are presented.

A Potent Medicinal Plant: Polygala Tenuifolia

  • Anvi, RANA
    • The Korean Journal of Food & Health Convergence
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    • v.9 no.1
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    • pp.1-9
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    • 2023
  • Polygala Tenuifolia, also described as Yuan Zhi, is a conventional botanic plant found in Korea and China. It's most well- known promise is to improve cognition and guard against mental disorders, cure sputum, anxiety, and sleeplessness, and keep the central nervous system health. The pharmacological aspects of Polygala Tenuifolia's genesis and component compounds reveal the neuroprotective potential in connection to Alzheimer's disease. It contains three herbs: Bokshin, Sukchangpo, and Wongi. P. Tenuifolia's primary ingredients are Xanthone glycosides, Triterpenoid saponins, and Oligosaccharides. Polygalasaponins and Etrahydrocolumbamine are the major components, and they've been widely used for more than a century to relieve mood and psychological illnesses, particularly in North Asian countries such as Korea, China, Japan, and Taiwan. P. Tenuifolia extract eliminates allergic illnesses such as eczema and contact dermatitis by modulating Protein kinase-A and Mitogen-protein kinase-38. In vitro and in vivo studies linking P. tenuifolia root ingredients to a variety of pharmacological effects pertinent to AD show that this species' isolates may function through polyvalency. In great health, people can take up to 250-300 mg per day. It was given in peer-reviewed studies at dosages of 100-150 mg many times each day. There is minimal evidence that it improves verbal memory in experimental animals.