• Korean Journal of Clinical Laboratory Science
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• v.55 no.2
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• pp.105-112
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• 2023

Leucine-rich repeat kinase 2 (LRRK2) is known to play a crucial role in the pathophysiology of neurodegenerative disorders such as Parkinson's disease. LRRK2 is predominantly expressed in the lung as well as the brain. However, it is unclear whether LRRK2 expression correlates with the pathogenesis of lung squamous cell carcinoma (LUSC). This study analyzes the prognostic significance of LRRK2 in LUSC using the Kaplan-Meier plotter tool. High expression of LRRK2 is known to be associated with a bad prognosis in patients with LUSC. Patients with high LRRK2 expression, tumor mutational burden, high neoantigen load, and even gender correlation reportedly have the worse survival rates. In the gene expression profiling interactive analysis (GEPIA) database, the severity of pathogenesis in LUSC with high LRRK2 expression positively corresponds to a high expression of anti-inflammatory cytokines but not inflammatory cytokines. Similarly, the increased expression of interleukin (IL)10-related genes was shown to be significantly linked in LRRK2-high LUSC patients having a poor prognosis. Moreover, the tumor immune estimation resource (TIMER) database suggests that macrophages are one of the cellular sources of IL10 in LRRK2-high LUSC patients. Collectively, our results demonstrate that the postulated LRRK2-IL10 axis is a potential therapeutic target and prognostic biomarker for LUSC.

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.7
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• pp.1035-1043
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• 2014

To investigate the effect of dietary Acanthopanax senticosus polysaccharide (ASPS) on growth performance, immunity, blood parameters and mRNA expression of pro-inflammatory cytokines in immunologically challenged piglets, an experiment employing $2{\times}2$ factorial arrangement concerning dietary ASPS treatment (0 or 800 mg/kg) and immunological challenge (lipopolysaccharide [LPS] or saline injection) was conducted with 64 crossbred piglets (weaned at 28 d of age, average initial body weight of $7.25{\pm}0.21kg$) assigned to two dietary ASPS treatments with 8 replicates of 4 pigs each. Half of the piglets of per dietary treatment were injected with LPS or saline on d 14. Blood samples were obtained at 3 h after immunological injection on d 14 and piglets were slaughtered to obtain spleen samples on d 21. Dietary ASPS did not affect average daily gain (ADG) (p = 0.634), average daily feed intake (ADFI) (p = 0.655), and gain:feed (p = 0.814) prior to LPS challenge. After LPS challenge, for LPS-challenged pigs those fed ASPS had higher ADG and ADFI than the non-supplemented group (p<0.05), and an interaction between $LPS{\times}ASPS$ was observed on the two indices (p<0.05). Dietary ASPS improved lymphocyte proliferation among saline-injected and LPS-injected pigs (p<0.05). Interaction between $LPS{\times}ASPS$ was also revealed on lymphocyte proliferation (p<0.05). Circulatory concentration of IgG was influenced neither by ASPS (p = 0.803) or LPS (p = 0.692), nor their interaction (p = 0.289). Plasma concentration and spleen mRNA expression of interleukin-1beta (IL-$1{\beta}$), interleukin-6 (IL-6), and tumor necrosis factor (TNF)-${\alpha}$ were induced to increase (p<0.05) by LPS challenge, in contrast, these indices were decreased by dietary ASPS (p<0.05), and interactions were found on these cytokines (p<0.05). For LPS-challenged pigs, dietary ASPS also reduced the circulating concentration and spleen mRNA expression of IL-$1{\beta}$, IL-6 as well as TNF-${\alpha}$ (p<0.05). The interaction between $LPS{\times}ASPS$ was also observed on the circulating concentration of insulin-like growth factor-I, ${\alpha}$-acid glycoprotein (${\alpha}$-AGP), nonesterified fatty acid, and glucose (p<0.05). The results of this study demonstrate that dietary ASPS can modulate the release of pro-inflammatory cytokines during immunological challenge, which might enable piglets to achieve better growth performance.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.5
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• pp.705-711
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• 2018

Objective: This experiment was conducted to evaluate the effects of golden needle mushroom (Flammulina velutipes) stem waste (FVW), on organic eggs production, calcium utilization, antibody response, serum immunoglobulin, and serum cytokine concentration at early phase of production in laying hens. Methods: A total 210, 19 weeks old aged ISA Brown layers were randomly assigned into 5 equal treatment groups, with 7 replications of 6 hens each. Dietary treatment included a standard basal diet as control; antibiotic (0.05% flavomycin); 2% FVW; 4% FVW; and 6% FVW. The experimental duration was 10 weeks. Results: There was no significant differences (p>0.05) on hen day egg production, egg weight, egg mass, feed intake, and feed conversion ratio (FCR) among experimental groups. Unmarketable eggs were significantly lower (p<0.05) both in 4% FVW and 6% FVW fed groups than control group. The calcium retention and calcium in egg shell deposition were significantly higher (p<0.05) in FVW inclusion groups than control and antibiotic groups. Antibody titers against Newcastle diseases were significantly higher (p<0.05) in 6% FVW fed group (except combined with 4% FVW at day 147) and infectious bronchitis were significantly higher (p<0.05) in FVW fed groups (except 2% FVW and 4% FVW at day 161) than control and antibiotic groups. Serum immunoglobulin sIgA was significantly higher (p<0.05) in all levels of FVW and IgG was significantly higher (p<0.05) in 4% FVW than control and antibiotic groups. Serum cytokine concentration interleukin-2 (IL-2) was significantly higher (p<0.05) in 6% FVW; IL-6 and tumor necrotic $factor-{\alpha}$ were significantly higher (p<0.05) both in 4% FVW and 6% FVW than control and antibiotic groups; IL-4 was significantly higher (p<0.05) in antibiotic, 2% FVW and 4% FVW fed groups than control. Conclusion: F. velutipes mushroom waste can be used as a novel substitute for antibiotic for organic egg production and sound health status in laying hens.

• Journal of Life Science
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• v.30 no.3
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• pp.267-277
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• 2020

This study was conducted to assess the effect of highly concentrated onion intake on rodents. The experimental animals were divided two groups as follows; water administered group (CON) and Allium cepa administered group (ACE). The ACE group showed a slightly increases in the number of erythrocytes (RBC), hemoglobin (HGB), hematocrit (Hct) levels compared to the control group (p<0.05). Hemoglobin, monocyte, lymphocyte and neutrophil had no significant change (p>0.05) in ACE group and control group. The analysis of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels showed a significant decrease in ACE group compared to the control group (p<0.05). The blood glucose, total protein, HDL-cholesterol were slightly high in ACE group, while triglyceride, total cholesterol levels were lower in ACE group compared to the control group (p<0.05). The levels of cytokines (interluekin-1α (IL-1α), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon-γ (INF-γ), interleukin-18 (IL-18), interleukin-2 (IL-2), granulocyte-macrophage colony-stimulating factor (GM-CSF)) involved in immunity and inflammation in liver tissue and blood have all been confirmed to be within normal range. These findings could be used as basic data to show that highly concentrated dietary onion extract is not toxic to hematological indicators and immune functions.

• Korean Journal of Food Science and Technology
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• v.50 no.4
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• pp.444-450
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• 2018

Dendritic cells (DCs) are potent antigen-presenting cells that play a pivotal role in modulating both innate and adaptive immunity. This study examined the immunomodulatory activities of hot-water extracts of bee pollen (BPW) in bone-marrow derived DCs (BMDC) and mice splenocytes. BMDCs isolated from mice were treated with 250 and $500{\mu}g/mL$ BPW for 24 h. BPW, up to $500{\mu}g/mL$, did not display any cellular toxicity against BMDCs. In fact, it functionally induced BMDC activation via augmentation of CD80, CD86, and major histocompatibility complex (MHC) class I/II expression and pro-inflammatory cytokine (tumor necrosis factor; $TNF-{\alpha}$, interleukin; IL-6, and $IL-1{\beta}$) production. Interestingly, BPW treatment significantly increased the production of interferon $(IFN)-{\gamma}$ in splenocytes, suggesting its possible contribution to Th1 polarization in immune response. Taken together, these findings suggest that BPW may regulate innate and adaptive immunity via DC activation and Th1 polarization in immune responses.

• Journal of Microbiology and Biotechnology
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• v.27 no.6
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• pp.1071-1077
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• 2017

A rise in the occurrence of allergic diseases is attributed to the dysregulated balance of type 1/type 2 immunity, where type 2 T-helper (Th2) cells predominate over type 1 T-helper (Th1) cells, leading to an abnormally increased production of IgE in response to unharmful antigens. Kimchi, a traditional Korean fermented food, is a rich source of beneficial lactic acid bacteria. In this study, we investigated the ability of Enterococcus faecium FC-K derived from kimchi to induce type I immunity in the presence of Th2 polarizing conditions in vitro and in vivo. Stimulation of mouse peritoneal macrophages with E. faecium FC-K induced the production of tumor necrosis factor alpha, interleukin (IL)-6, and IL-12. Under the in vitro Th2 conditions in which splenic T cells were activated in the presence of IL-4, E. faecium FC-K enhanced the ability of T cells to produce interferon $(IFN)-{\gamma}$. Using the ovalbumin (OVA)-induced allergy model, male BALB/c mice receiving E. faecium FC-K reduced the serum level of total IgE, but not that of OVA-specific IgE. Furthermore, the population of activated splenic B cells during OVA immunization was decreased in E. faecium FC-K-treated mice, accounting for a reduction of total IgE in the serum. Restimulating splenocytes from OVA-immunized mice with OVA ex vivo resulted in an increased production of $IFN-{\gamma}$, with no effect on IL-4, in E. faecium FC-K-treated mice. These observations provide the evidence that E. faecium FC-K can be a beneficial probiotic strain that can modulate the Th2-mediated pathologic response.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.9
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• pp.1453-1461
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• 2007

This study was conducted to test the hypothesis that dietary supplementation with an herbal extract of Acanthopanax senticosus (AS) enhances the immune response in weaned piglets. Sixty piglets weaned at 21 days of age were randomly assigned to 3 treatment groups representing the addition of 0 or 1 g/kg of the AS extract or 0.2 g/kg of colistin (an antibiotic) to maize- and soybean meal-based diets (n = 20 per group). On days 7, 14 and 28 after initiation of the addition, total and differential counts of leucocytes, proliferating activity of peripheral lymphocytes, serum levels of immunoglobulins (Ig) and cytokines and the spleen index were determined. The AS extract decreased (p<0.05) the number of neutrophils on days 7 and 28 in comparison with the control group and reduced (p<0.05) serum interleukin-$1{\beta}$ level on day 28 compared with the other 2 groups. Dietary supplementation with the AS extract increased (p<0.05) the lymphocyte/leukocyte ratio on day 28 compared with the control group and increased the proliferating activity of lymphocytes on days 14 and 28 compared with the other 2 groups. The AS extract increased (p<0.05) the serum content of IgG on day 7 and of IgG and IgM on day 28 compared with the other 2 groups, as well as increasing the serum content of tumor necrosis factor on day 7 and spleen index on days 7 and 28 compared with the control group. Collectively, these findings suggest that the AS extract as a dietary additive enhances the cellular and humoral immune responses of weaned piglets by modulating the production of immunocytes, cytokines and antibodies.

• The Journal of Internal Korean Medicine
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• v.39 no.6
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• pp.1244-1255
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• 2018

Objectives: The purpose of this study is to determine the stimulatory effects of herbal medicines extracts on cytokines release of immune response in immune cells, RAW 264.7 and TK-1 cell. Methods: In a total of 18 extracts, 9 water extracts and 9 ethanol extracts, of herbal medicines, the quantities of polyphenolic compounds were measured and anti-oxidation activities were determined by colorimetric assay. The herbal medicine extracts were treated on RAW 264.7 and TK-1, respectively, and then the releasing changes of tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$), interleukin-6, and interleukin-10 from both immune cells were determined by the enzyme-linked immunosorbent assay. Results: The polyphenol contents were measured to be 1.56~0.64 mg/g of solids in the two types of extracts with 9 kinds of herbal medicines, while antioxidant activities were found to be 95.62~31.46% as compared with ascorbic acid control. In RAW 264.7 cells treated with herbal medicines extracts, the secretion of $TNF-{\alpha}$ increased to 1.31~1.18 fold, and the amounts of IL-6 were 68.4~97.9% compared with the control group treated with LPS alone. In particular, the secretion amount of anti-inflammatory cytokine IL-10 was suppressed by treatment using herbal medicine extracts. In the case of TK-1 cells, $TNF-{\alpha}$ secretion was suppressed according to the concentrations of herbal extract. The released amounts of IL-10 were shown at 10~40 pg/ml, and increased in a dose-dependent manner. Conclusions: Herbal medicines extracts act on macrophages inducing the secretion of inflammatory cytokine, thereby enhancing the activity of innate immunity. When acting on T cells involved in adaptive immunity, the secretion of anti-inflammatory cytokine is increased to induce the inhibition of the innate immune response.

• Journal of Life Science
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• v.31 no.8
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• pp.745-754
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• 2021

Deterioration of the immune function weakens the body's resistance to various infections, leading to a series of diseases. Immunomodulatory biomaterials have been used to reduce the side effects of immunosuppressants or to enhance immunity. Agarwood is the aromatic resinous portion of Aquilaria trees that has been traditionally used as a medicinal herb for the treatment of various diseases. Although previous studies have shown that agarwood can improve the body's immunity, evidence for this claim is still lacking. In this study, the immune-enhancing effects of the agarwood methanol extracts of Aquilaria malaccensis Lamk were evaluated in a RAW 264.7 macrophage model. Based on the results, the agarwood extracts markedly enhanced phagocytosis in the absence of cytotoxicity. The agarwood extract-treated RAW 264.7 cells exhibited the typical morphology of activated macrophages, which are spindle-shaped with elongated filopodia. Agarwood extract also significantly increased the production of nitric oxide (NO), which is associated with the increased expression of inducible NO synthase. Moreover, the secretion and expression levels of cytokines, such as tumor necrosis factor-α and interleukin (IL)-1β and IL-6, were increased by agarwood treatment. Notably, these are also associated with a mitogen-activated protein kinase signaling pathway. Taken together, our findings provide scientific evidence that agarwood has potential immune-enhancing effects in vitro.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.27 no.1
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• pp.26-36
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• 2024

Purpose: We investigated the role of CD8⁺T cells as host immune factors in pediatric patients with Helicobacter pylori gastritis. Methods: Gastric mucosal tissue and blood samples were collected from 39 children, including 11 children with H. pylori infection and 28 children as controls. Anti-CD8 and anti-T-bet antibodies were used for immunohistochemistry of the gastric mucosa. For the cell surface and intracellular staining, peripheral blood mononuclear cells were stained with anti-IL7Rα, anti-CX3CR1, anti-CD8, anti-T-bet, and anti-IFN-γ antibodies. Cytokines of sera such as tumor necrosis factor alpha (TNF-α) and CX3CL1 were analyzed using enzyme- linked immunosorbent assay (ELISA). Results: In the immunohistochemistry of gastric mucosa, the frequency of CD8⁺ and T-bet⁺ T cells cells was higher in the H. pylori-positive group than in the control group (26.9± 7.8% vs. 16.9±3.3%, p<0.001; 5.0±2.5% vs. 2.2±0.7%, p=0.001). Between the control and H. pylori-positive groups, the frequency of IL-7Rα^lowCX3CR1⁺ CD8⁺ and T-bet⁺ INF-γ⁺ CD8⁺ T cells were not significantly different between surface and intracellular staining, respectively (40.4±24.0% vs. 38.2±17.8%, p=0.914; 40.4±24.0% vs. 38.2±17.8%, p=0.914). In the ELISA, no significant differences in TNF-α and CX3CL1 concentrations were observed between the control and H. pylori-positive groups (34.3±12.1 pg/mL vs. 47.0±22.6 pg/mL, p=0.114/0.5± 0.1 pg/mL vs. 0.5±0.1 pg/mL, p=0.188). Conclusion: CD8⁺ T and Th1 cells, which secrete IFN-γ, might play important roles in the mucosal immunity of the stomach in children with H. pylori infection.