• Journal of Marine Bioscience and Biotechnology
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• v.15 no.2
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• pp.33-40
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• 2023

This study aimed to investigate the immunomodulatory function of Pyropia yezoensis hydrothermal (water) extract (PYWE) in comparison to the group treated only with lipopolysaccharides (LPS) in RAW264.7 cells. LPS is known to be an inflammatory mediator that activates macrophages, leading to the secretion of nitric oxide (NO), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) as defense responses. Through enzyme-linked immunoassay and western blot analyses, it was observed that PYWE increased the expression levels of NO, iNOS, TNF-α, and IL-6 in RAW264.7 cells in a dose-dependent manner, although to a lesser extent compared with the group treated with LPS alone. In addition, the study examined the mitogen-activated protein kinases (MAPKs) pathway, which regulates various cellular activities, including gene expression, mitosis, cell differentiation, transformation, survival, and death. The western blot analysis confirmed that PYWE also regulated the MAPKs pathway. Furthermore, the expression levels of immunomodulatory-related factors increased in the group treated with PYWE compared with the control group. Even though the effects of PYWE were usually less strong than those of LPS, the effects of PYWE increased with increasing doses compared to the control group. This suggests that PYWE could be used to control the immune system.

• Genomics & Informatics
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• v.21 no.4
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• pp.44.1-44.10
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• 2023

Tumor hypoxia, oxygen deprivation state, occurs in most cancers and promotes angiogenesis, enhancing the potential for metastasis. The vascular endothelial growth factor (VEGF) family genes play crucial roles in tumorigenesis by promoting angiogenesis. To investigate the malignant processes triggered by hypoxia-induced angiogenesis across pan-cancers, we comprehensively analyzed the relationships between the expression of VEGF family genes and hypoxic microenvironment based on integrated bioinformatics methods. Our results suggest that the expression of VEGF family genes differs significantly among various cancers, highlighting their heterogeneity effect on human cancers. Across the 33 cancers, VEGFB and VEGFD showed the highest and lowest expression levels, respectively. The survival analysis showed that VEGFA and placental growth factor (PGF) were correlated with poor prognosis in many cancers, including kidney renal cell and liver hepatocellular carcinoma. VEGFC expression was positively correlated with glioma and stomach cancer. VEGFA and PGF showed distinct positive correlations with hypoxia scores in most cancers, indicating a potential correlation with tumor aggressiveness. The expression of miRNAs targeting VEGF family genes, including hsa-miR-130b-5p and hsa-miR-940, was positively correlated with hypoxia. In immune subtypes analysis, VEGFC was highly expressed in C3 (inflammatory) and C6 (transforming growth factor β dominant) across various cancers, indicating its potential role as a tumor promotor. VEGFC expression exhibited positive correlations with immune infiltration scores, suggesting low tumor purity. High expression of VEGFA and VEGFC showed favorable responses to various drugs, including BLU-667, which abrogates RET signaling, an oncogenic driver in liver and thyroid cancers. Our findings suggest potential roles of VEGF family genes in malignant processes related with hypoxia-induced angiogenesis.

• The Korea Journal of Herbology
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• v.30 no.5
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• pp.23-28
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• 2015

Objectives : The aim of this study is to investigate cell viability, anti-inflammatory, antioxidant, immunoenhancing activity using various extracts of Yeonsan Ogye.Methods : In order to evaluate cytotoxicity, MTT assay was performed. We investigated production levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-αand interleukin (IL)-6, and nitric oxide(NO) in LPS-induced RAW 264.7 cells. NO production in RAW 264.7 cells was measured by using Griess reagent. Cytokines including IL-6 and TNF-αwere measured by Luminex and ROS was measured by Flow cytometry.Results : No cytotoxicity of various extracts of Yeonsan Ogye was observed in RAW 264.7 cells. Productions of ROS in RAW 264.7 cells were increased from extraction of bones and decreased from extraction of skin. Also, productions of NO in RAW 264.7 cells were increased to bone extract and decreased at skin extract. In addition, productions of pro-inflammatory cytokines (IL-6 and TNF-α) in LPS-induced RAW 264.7 cells were decreased at skin, meat extracts, respectively. Finally, the levels of immune-related cytokines (IL-6 and TNF-α) were increased compared to those of the normal group.Conclusions : It is concluded that Yeonsan Ogye extracts seem to have significant biological activities likes anti-inflammatory, antioxidant, immuno-enhancing etc. These results may be developed as a raw material for new health food and new therapeutics to ease the symptoms related with inflammatory and oxidative stress. In terms of oriental traditional medicine, we expect that it contribute to building of EBM (Evidence-Based Medicine) from the this result.

• Journal of Veterinary Clinics
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• v.37 no.2
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• pp.61-66
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• 2020

Nickel is a nutritionally essential trace element that plays an important role in the immune system of several animal species. The aim of this study was to examine the effect of nickel chloride on chemotactic activity of peripheral blood polymorphonuclear cells (PMNs) and whether this effect is associated with interleukin (IL)-8 and a nuclear factor-kappa B (NF-κB)-dependent pathway. Peripheral blood mononuclear cells (PBMCs) and PMNs were isolated by Percoll solution (Specific gravity; 1.080) and 1.5% dextran treatment, respectively. A modified Boyden chamber assay was used to measure the chemotactic activity of PMNs. The level of IL-8 in culture supernatant from PBMCs was measured by enzyme-linked immunosorbent assay (ELISA). Both of PBMCs and PMNs exhibited a low viability when cultured with concentration of greater than 1,000 μM of nickel chloride for 24 h. Thus, nickel chloride was used at concentration of 500 μM, which preserved cell viability. Treatment with nickel did not directly affect the chemotactic activity of PMNs. However, the chemotactic activity of PMNs was remarkably increased by culture supernatant from PBMCs treated with nickel chloride (500 μM) for 24 h. Recombinant porcine IL-8 polyclonal antibody (pAb) neutralized the enhancing effect on the chemotactic activity of PMNs by culture supernatant from PBMCs treated with nickel and this culture supernatant had higher IL-8 levels than the culture supernatant from untreated PBMCs. In addition, n-tosyll-phenylalanine chloromethyl ketone (TPCK), a NF-κB inhibitor, antagonized the enhancing effect on the chemotactic activity of PMNs by the culture supernatant from PBMCs treated with nickel. These results suggested that nickel stimulates porcine PBMCs to produce IL-8, which increases the chemotaxis of PMNs via NF-κB-dependent pathway.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.5
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• pp.671-676
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• 2008

Forty-eight Naemi lambs (avg. BW 31.7 kg) were transported by truck for a distance of 1,450 km from Al-Jouf to Riyadh, Saudi Arabia. On arrival day, the lambs were randomly allocated to four groups receiving diets supplemented with 0.0, 0.3, 0.6 and 0.9 ppm organic chromium (Cr). Each group consisted of four separately housed replicates of three lambs each. The animals were fed ad libitum on a grower diet for 84 days. Blood samples were obtained shortly before transportation, upon arrival and at weekly intervals thereafter from all lambs for analysis of plasma and serum. Plasma glucose and serum cortisol, total protein, albumin, urea-N and total cholesterol concentrations were determined. A cursory clinical examination of the lambs, along with rectal temperature, was undertaken at different intervals during the experiment. The lambs were inoculated each with 2 ml i.v. chicken red blood cells (CRBC) on days 0, 21, and 42. Serum total, IgG and IgM antibody titers were determined at weekly intervals post-immunization. An in vivo intradermal hypersensitivity test was carried out on 6 lambs from each group on days 10 and 70. Transportation of the lambs resulted in a significant (p<0.001) elevation of serum cortisol, total protein and albumin levels, as well as increased plasma glucose concentration, with corresponding decrease in total cholesterol, while blood urea-N remained largely unchanged. These constituents returned to normal levels during subsequent weeks, with no significant differences in their concentrations being observed between the Cr-supplemented groups and controls. Rise in rectal temperature after transportation was reduced to a greater extent (p<0.05) in Cr-supplemented versus control lambs. Total, IgG and IgM antibody titers against CRBC rose significantly (p<0.05) during immunizations in all groups, with significantly and linearly higher (p<0.05) total and IgG titers in Cr-supplemented versus control lambs. By contrast, no significant effect due to Cr supplementation was recorded in IgG titers, which increased equally in Cr-fed and control groups. Skin thickness in response to intradermal inoculation of phytohaemagglutinin (PHA) was also significantly (p<0.01) increased as a result of Cr supplementation. These results indicate that dietary Cr supplementation might be useful during stress especially for enhancing immune responses in transport-stressed lambs.

• Journal of Acupuncture Research
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• v.19 no.4
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• pp.56-73
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• 2002

Objective : We need to develop a new treatment method which can curve cancer growth and enhance immunity of patients with various kinds of cancer more safely and effectively, for conventional anticancer treatment has lots of problems to be overcomed, in other words, Its efficacy can be recognizible but it doesn't actually give aid to patients due to its side effects. This study was taken up to evaluate the anticancer and immune-enhancing effect of Scutellariae Barbatae Herba, Alli bulbus, Oldenlandiae Herba(SAO) Herbal acupuncture. Methods : SAO Herbal acupuncture solution was made from Scutellariae Barbatae Herba, Alli bulbus, Oldenlandiae Herba by decoction. Experimental group was divided into normal(N), control(TC, cancer group induced by S 180), high and low concentration SAO complex Herbal acupuncture group. In the high and low concentration SAO complex Herbal acupuncture group, SAO Herbal acupuncture solution was injected, on the left and right Chok-samni(足三里, ST36) of ICR-male S 180 rats alternatively, by 200mg/kg and 100mg/kg respectively. In vitro, S 180 was cultured with $200{\mu}g$ and $500{\mu}g$ of SAO Herbal acupuncture solution. In each experimental group, we examined the effect of SAO complex Herbal acupuncture on body weight, antitumor, organ weight, activity of macrophage, activity of B cell, spleen cell division, IL-2 production and population of lymphocytes. Results : 1. In Body weight, no significant change was shown, but In solid cancer weight, the high concentration SAO complex Herbal acupuncture group showed signigicant(P<0.05) decrease and significant(P<0.05) increase in the weight of kidney, compared with control group. 2. In activity of macrophage, low concentration SAO complex Herbal acupuncture group showed significant(P<0.01) increase, but in vitro, there was no significant increase, compared with control group. 3. In activity of B cell, high and low concentration SAO complex Herbal acupuncture group showed no significant decrease, but in vitro, low concentration SAO complex Herbal acupuncture group showed significant(P<0.01) increase, compared with control group. 4. In spleen cell division, high and low concentration SAO complex Herbal acupuncture group had no significant influence on spleen cell division induced by Co A, meanwhile, it was found that macrophge promote spleen cell division in low concentration SAO complex Herbal acupuncture group(P<0.05), compared with control group. 5. In IL-2 production, high concentration SAO complex Herbal acupuncture group showed significant((P<0.05) increase, compared with control group. 6. In population of lymphocytes, high concentration SAO complex Herbal acupuncture group showed significant increase of CD3+(P<0.05), CD4+(P<0.05), CD3+ and CD4+ T cell(P<0.01) and B cell(P<0.05), while low concentration SAO complex Herbal acupuncture group showed significant increase of CD4+(P<0.05), CD8+ T cell(P<0.05) and B cell(P<0.01), compared with control group. Conclusion : SAO Herbal acupuncture inhibited cancer growth and enhanced immunity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.9
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• pp.1256-1263
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• 2015

Citrus junos Sieb. ex Tanaka has been traditionally called Yuza in Korea and is used as a cuisine material or tea as well as medicinal herb. In this study, we evaluated the immune-enhancing effect of Citrus junos ethanol extract (CJE) on RAW264.7 mouse macrophage and primary immunocytes. CJE treatment showed increased macrophage activity in a dose-dependant manner. CJE also enhanced natural killer (NK) cell activity. We measured lactate dehydrogenase (LDH) level as a measurement of NK cell cytotoxicity against YAC-1 lymphoma cells. CJE treatment showed an increased LDH level in a dose-dependent manner. Finally, we evaluated the effect of CJE on mouse primary splenocyte proliferation. CJE treatment slightly increased splenocyte proliferation compared to the control. The results of this study suggest that CJE can help immune function via macrophage cytokine production, increased NK cell activity, and splenocyte proliferation.

• The Korea Journal of Herbology
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• v.35 no.6
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• pp.11-19
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• 2020

Objective : The genus Glycyrrhiza has been used in food and traditional herbal medicine. Glycyrrhiza new varieties Wongam and Sinwongam have been developed by Korea Rural Development Administration and investigated to register on Korean Pharmacopoeia of the Ministry of Food and Drug Safety. The aim of this study is to investigate the immunomodulatory effect of Wongam and Sinwongam comparing with listed Glycyrrhiza species (Glycyrrhiza uralensis Fischer and G. glabra Linne) for evaluations about pharmacological effect of Glycyrrhiza new varieties. Methods : We studied the immunomodulatory effect of Wongam and Sinwongam compared with G. uralensis and G. glabra using THP-1 cell in vitro model. The cells were treated with phorbol 12-myristate 13-acetate (PMA) for differentiation and stimulated with lipopolysaccharides (LPS) to induce immune activation. We analyzed and compared the effects Glycyrrhiza new varieties and listed Glycyrrhiza species using nitric oxide (NO) assay, western blot, and reverse transcription-quantitative polymerase chain reaction analysis. 1) Results : Wongam and Sinwongam showed no cytotoxicity in THP-1 cells. Wongam and Sinwongam, and listed Glycyrrhiza species increased NO production, and cyclooxygenase (COX)-2 expression with or without LPS in differentiated THP-1 macrophages. Furthermore, Wongam and Sinwongam and listed Glycyrrhiza species upregulated the mRNA expressions of T helper type 1 (Th 1)-associated cytokines in LPS-stimulated THP-1 macrophages. Conclusion : These results indicated that Wongam and Sinwongam would have effect of enhancing immune response through the increase of NO and COX-2 expression, and activate Th1-associated cytokines. The findings of this study suggest the wide applicability of Glycyrrhiza new varieties.

• Korean Journal of Veterinary Research
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• v.52 no.3
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• pp.183-191
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• 2012

The maintenance of peripheral immune tolerance and prevention of chronic inflammation and autoimmune disease require $CD4^{+}CD25^{+}$ T cells (regulatory T cells). The transcription factor Foxp3 is essential for the development of functional, regulatory T cells, which plays a prominent role in self-tolerance. Retroviral vectors can confer high level of gene transfer and transgene expression in a variety of cell types. Here we observed that following retroviral vector-mediated gene transfer of Foxp3, transductional Foxp3 expression was increased in the liver, lung, brain, heart, muscle, spinal cord, kidney and spleen. One day after vector administration, high levels of transgene and gene expression were observed in liver and lung. At 2 days after injection, transductional Foxp3 expression level was increased in brain, heart, muscle and spinal cord, but kidney and spleen exhibited a consistent low level. This finding was inconsistent with the increase in both $CD4^{+}CD25^{+}$ T cell and $CD4^{+}Foxp3^{+}$ T cell frequencies observed in peripheral immune cells by fluorescence-activated cell-sorting (FACS) analysis. Retroviral vector-mediated gene transfer of Foxp3 did not lead to increased numbers of $CD4^{+}CD25^{+}$ T cell and $CD4^{+}Foxp3^{+}$ T cell. These results demonstrate the level and duration of transductional Foxp3 gene expression in various tissues. A better understanding of Foxp3 regulation can be useful in dissecting the cause of regulatory T cells dysfunction in several autoimmune diseases and raise the possibility of enhancing suppressive functions of regulatory T cells for therapeutic purposes.

• Advances in Traditional Medicine
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• v.5 no.3
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• pp.216-230
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• 2005

Although the field of study in immune enhancing compounds is relatively new, natural products from plants represent a rich and promising source of novel molecules with immunomodulating properties, Microglial cells, the main immune effector cells of the brain, usually display a ramified morphology and low expression levels of immunologically relevant antigens such as MHC class I and class II. Since any compound which participates in activation of phagocytic cells contributes to the production of potentially toxic factors, the search for convenient in vitro test-systems and study of mechanisms of action of these agents are of great interest. Human blood polymorphonuclear (PMN) cells and primary microglial cells isolated from Sprague-Dawley rats were used as cellular screening tests for study of phagocytosis-stimulating action of immunomodulating agents. Numbers of phagocytic activity were evaluated by the phagocyte ingestion of yeast cells and NO-synthase activity, nitrite production, and nitroblue tetrazolium test were determined after phagocyte stimulation. It was possible to demonstrate that indexes of phagocytic activity can be used as quantitative indicators for measurement immunomodulating activity. As a positive control, Zymosan A-induced phagocytosis in both PMN cells and primary microglial cells was used. $IFN-{\gamma}$ (0.1 -1 U/ml) stimulated phagocytosis in PMN cells 1.2 times after 2 - 3 h incubation, although at higher concentrations (10 - 100 U/ml) it strongly inhibited phagocytosis. In a similar way, at higher concentrations, $IFN-{\gamma}$ (100 - 500 U/ml) suppressed phagocytosis in zymosan-A stimulated microglial cells. When Polypodium leucotomus, cambricum and vulgare extracts were tested alone, increased levels of phagocytosis were observed in PMN. In addition, microglial cells showed both increased phagocytosis and MHC class-II antigen expressions. Surprisingly, when PMN and microglia were treated with a combination of Polypodium and $IFN-{\gamma}$, phagocytosis was not inhibited. We did not find changes in NO-synthase activity and nitrite production in both microglia and PMN cells activated by different immunomodulating agents. These results indicate that primary microglial cell cultures as well as human PMN cells can provide reproducible quantitative results in screening phagocytic activity of different immunoactive compounds. Furthermore, both inhibitory or activation mechanisms might be studied using these in vitro experimental approaches.