• Toxicological Research
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• v.17
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• pp.329-333
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• 2001

Apoptosis is the normal physiological process of cell death essential for the maintenance of homeostasis. The function of nicotinamide adenine dinucleotide (NAD) and adenine diphosphate (ADP) ribosylation (transfer of ADP-ribose to proteins) reactions in modifying apoptosis have recently been of great interest. Recently. CD38. a type 2 transmembrane glycoprotein expressed in hematopoietic and non hematopoietic cell lines. has been reported to possess NAD glycohydrolase activity (Han. 1999) and PC-1 and CD38 NADase regulates T cells by inhibition of phosphodiesterase/pyrophosphatase activity of PC-1 by its association with glycosaminoglycan (Hozada et al., 1999). Sindhuphak et al. (2000) has reported that cervical cancer cells can be differentiated from normal cells by using FTIR (Fourier-Transformed Infrared) technique. which has characterized shifts to be due to the phosphodiester bond in nucleic acid. protein amide I&II. carbohydrate and glycogen bands. Mechanisms how phosphodiester bond shift in cervical cancer cells as compared to control cells remain to be elucidated. Suramana et al. (2000) as well as Lohitnavy and Sinhaseni (1998) have studied methomyl and colchicine effects in rat splenocytes. Lactate Dehydroge-nase Isozymes 3 (LDH3) and LDH4 were observed to increase transiently and subsided in plasma of rats exposed to 6~8 mg/kg methomyl after 48 hours. Phosphodiester bond shift of nucleic acid. detected by FTIR. was also reported (Suramana et al., 2000). We report here, after analysis of bond shift patterns. a similar bond shifts detected by FTIR spectrum observed in human cervical cells and splenocytes of rats exposed orally to 2~8 mg/kg methomyl as well as rats exposed to colchicine 2~6 mg/kg orally.

• Journal of Ginseng Research
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• v.40 no.4
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• pp.431-436
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• 2016

Background: Although numerous studies of the anticancer activities of Korean Red Ginseng (KRG) have been performed, the therapeutic effect of KRG on leukemia has not been fully elucidated. In this study, we investigated the antileukemia activities of KRG and its cellular and molecular mechanisms. Methods: An established leukemia tumor model induced by xenografted T cell lymphoma (RMA cells) was used to test the therapeutic activity of KRG water extract (KRG-WE). Direct cytotoxic activity of KRG-WE was confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The immunomodulatory activities of KRG-WE were verified by immunohistochemistry, nitric oxide production assay. The inhibitory effect of KRG-WE on cell survival signaling was also examined. Results: Orally administered KRG-WE reduced the sizes of tumor masses. Levels of apoptosis regulatory enzymes and cleaved forms of caspases-3 and -8 were increased by this extract. In addition, expression of matrix metalloproteinase-9, a metastasis regulatory enzyme, was decreased by KRG-WE treatment. The proportion of CD11c+ cells was remarkably increased in the KRG-treated group compared to the control group. However, KRG-WE did not show significant direct cytotoxicity against RMA cells. Conclusion: Our results strongly suggest that the KRG might have antileukemia activity through CD11c+ cell-mediated antitumor immunity.

• Journal of Ginseng Research
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• v.34 no.3
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• pp.219-226
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• 2010

In the present study, we investigated whether a gross deletion in the nef gene ($g{\Delta}nef$) is induced by Korean red ginseng (KRG) intake. Ten patients were treated with KRG powder for 3 years in the absence of antiretroviral drug therapy. On average, $3,555{\pm}1,042\;g$ KRG was administered per person over $36.1{\pm}2.4$ months. There was a mild decrease in CD4 T cell count ($75{\pm}110/{\mu}L$) over the $36.1{\pm}2.4$ months (p = 0.059). We obtained 355 nef amplicons using 71 peripheral blood mononuclear cell samples over a 3-year period. All ten patients exhibited g${\Delta}$nef (range, 3.2 to 45.9%). At baseline, 3 of 78 amplicons (3.8%) exhibited $g{\Delta}nef$, whereas 18.8% (52/277) revealed $g{\Delta}nef$ during KRG-intake (p<0.001). The proportion of $g{\Delta}nef$ was significantly correlated with monthly dose of KRG (r=0.89, p<0.001). The median time for first detection of $g{\Delta}nef$ was 13 months. In conclusion, our data show that $g{\Delta}nef$ is inducible by KRG intake and its proportion is dependent on the duration of KRG intake and dose of KRG.

• Journal of Microbiology and Biotechnology
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• v.29 no.1
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• pp.160-170
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• 2019

The lactic acid bacteria species Lactobacillus plantarum (L. plantarum) has been used extensively for vaccine delivery. Considering to the critical role of dendritic cells in stimulating host immune response, in this study, we constructed a novel CD11c-targeting L. plantarum strain with surface-displayed variable fragments of anti-CD11c, single-chain antibody (scFv-CD11c). The newly designed L. plantarum strain, named 409-aCD11c, could adhere and invade more efficiently to bone marrow-derived DCs (BMDCs) in vitro due to the specific interaction between scFv-CD11c and CD11c located on the surface of BMDCs. After incubation with BMDCs, the 409-aCD11c strain harboring a eukaryotic vector pValac-GFP could lead to more efficient expression of GFP compared with wild-type strains shown by flow cytometry analysis, indicating the enhanced translocation of pValac-GFP from L. plantarum to BMDCs. Similar results were also observed in an in vivo study, which showed that oral administration resulted in efficient expression of GFP in both Peyer's patches (PP) and mesenteric lymph nodes (MLNs) within 7 days after the last administration. In addition, the CD11c-targeting strain significantly promoted the differentiation and maturation of DCs, the differentiation of $IL-4^+$ and $IL-17A^+$ T helper (Th) cells in MLNs, as well as production of $B220^+$ $IgA^+$ B cells in the PP. In conclusion, this study developed a novel DC-targeting L. plantarum strain which could increase the ability to deliver eukaryotic expression plasmid to host cells, indicating a promising approach for vaccine study.

• 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.

• Archives of Pharmacal Research
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• v.29 no.3
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• pp.235-240
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• 2006

The oral administration of extracts of young radishes cultivated with sulfur after intravenous tumor cell injection achieved a marked reduction of pulmonary colonization in mice. Treatment of the mice with extracts of young radish cultivated with sulfur did not show any increase in the number of CD8+ or NK T cells in the spleen, indicating no influence on host immunity. Sulforaphane, which could be a candidate for an active compound from young radishes cultivated with sulfur, inhibited cell growth of B16-F10 melanoma cells. In addition, extracts of the young radish cultivated with sulfur-fed group showed enhanced quinine reductase (QR) activities in the liver and lung and a slight increase of glutathione S-transferase (GST) activity in the liver. These results suggested that the administration of extracts of young radishes cultivated with sulfur suppressed pulmonary tumorigenesis, possibly due to increased activity of detoxification enzymes in the liver and lung, and partly due to cell cytotoxicity.

• IMMUNE NETWORK
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• v.22 no.1
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• pp.5.1-5.22
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• 2022

The approval of immunotherapies such as checkpoint inhibitors (CPIs), adoptive cell therapies and cancer vaccines has revolutionized the way cancer treatment is approached. While immunotherapies have improved clinical outcome in a variety of tumor types, some cancers have proven harder to combat using single agents, underscoring the need for multi-targeted immunotherapy approaches. Efficacy of CPIs and cancer vaccines requires patients to have a competent immune system with adequate cell numbers while the efficacy of adoptive cellular therapy is limited by the expansion and persistence of cells after infusion. A promising strategy to overcome these challenges is combination treatment with common gamma-chain cytokines. Gamma-chain cytokines play a critical role in the survival, proliferation, differentiation and function of multiple immune cell types, including CD8 T-cells and NK cells, which are at the center of the anti-tumor response. While the short halflife of recombinant cytokines initially limited their application in the clinic, advancements in protein engineering have led to the development of several next-generation drug candidates with dramatically increased half-life and bioactivity. When combining these cytokines with other immunotherapies, strong evidence of synergy has been observed in preclinical and clinical cancer settings. This promising data has led to the initiation of 70 ongoing clinical trials including IL-2, IL-7, IL-15 and IL-21. This review summarizes the recent advancements of common gamma-chain cytokines and their potential as a cancer immunotherapy.

• Biomolecules & Therapeutics
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• v.32 no.5
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• pp.556-567
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• 2024

β-glucan, a polysaccharide found in various sources, exhibits unique physicochemical properties, yet its high polymerization limits clinical applications because of its solubility. Addressing this limitation, we introduce PPTEE-glycan, a highly purified soluble β-1,3/1,6-glucan derived from Aureobasidium pullulans. The refined PPTEE-glycan demonstrated robust immune stimulation in vitro, activated dendritic cells, and enhanced co-stimulatory markers, cytokines, and cross-presentation. Formulated as a PPTEE + microemulsion (ME), it elevated immune responses in vivo, promoting antigen-specific antibodies and CD8+ T cell proliferation. Intratumoral administration of PPTEE + ME in tumor-bearing mice induced notable tumor regression, which was linked to the activation of immunosuppressive cells. This study highlights the potential of high-purity Aureobasidium pullulans-derived β-glucan, particularly PPTEE, as promising immune adjuvants, offering novel avenues for advancing cancer immunotherapy.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.28 no.4
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• pp.92-110
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• 2015

Objectives : The water extract of Bowon-tang composited with thePanax, AstragalusandGlycyrrhiza Radixhas been traditionally used for treatment of a sickly child and smallpox in oriental medicine. However, little is known about the regulatory effects of Bowon-tang on the production, expression and activity of immune mediators [nitric oxide, prostaglandin E2, inducible nitric oxide synthetase, cyclooxygenase-2], the macrophage activation factor production, the proliferation, subset expression, the killing activity, and the capping in immune cells.Methods : In this study, we investigated the effects of water extracts from Bowon-tang,Panax, AstragalusorGRin mouse immune cells or human Jurkat T cells. Each extract (25-200 ㎍/㎖)perse had no cytotoxic effect in unstimulated macrophages, but concentration-dependently regulated NO and PGE₂production, iNOS expression, and COX-2 activity in mouse peritoneal macrophages with MAF stimulation. These regulatory effects were synergistically increased by their combination (Bowon-tang).Results : The extract of Bowon-tang concentration-dependently regulated T cell proliferation, CD4⁺and CD8⁺expression, and NK killing activity in mouse splenocytes and capping in Jurkat T cells.Conclusions : These results suggest that the water extract of Bowon-tang composited with thePanax, AstragalusandGRmay be useful for therapeutic drugs against a sickly constitution and immune diseases, probably by regulating the production of immune mediators.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.1
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• pp.59-65
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• 2004

Hot water-extracts prepared from Cordyceps militaris of silkworm pupa (CMP) or Cordyceps militaris of silkworm larva (CML) were tested for tumor growth inhibitory and immunomodulatory activities in ICR mice bearing sarcoma-180 cells solid tumor, and compared with those of the known compound, cordycepin, found in Cordyceps militaris. Mice were subcutaneously injected with sarcoma-180 cells, and i.p. injected with either saline (Control), 50 mg/kg or 100 mg/kg of CMP (CMP50 or CMP100, respectively), or CML (CML50 or CML100, respectively), or 1 or 2 mg/kg of cordycepin (C1 or C2, respectively) for 10 days. Mice injected with CMP50 or CMP100 showed a 47.3% or 57.6% inhibition in the solid tumor growth (P<0.05), while those injected with CML50 or CML100 exhibited a 35.5% or 37.1% reduction (p<0.05) in solid tumor size compared to the value for control mice treated with saline. Animals injected with corcycepin showed a 26∼30% inhibition in the solid tumor growth (P<0.05). Mice bearing solid tumor and injected with CMP or CML showed a significantly increased thymus weight (38∼44% increase), lymphocyte percentages of CD4+ T-cell, CD8+ T-cell, and NK-cell (63∼110% increase) in the spleen, and interleukin-2 excretion (33∼51% increase) by the isolated splenocytes compared to those in control mice (p<0.05). These results indicate that the anti-tumor activity of hot water extracts of Cordyceps militaris, raised on both silkworm pupa and silkworm larva, appears to be associated with their immunomodulatory activity, and these activities found in Cordyceps militaris are superior to those for the single compound, cordycepin.