• 대한한의학회지
• /
• 제40권1호
• /
• pp.63-77
• /
• 2019

Objectives: The purpose of this study is to examine the effect of water and fermentation extracts of KMS (Kami-Mihudeongsikjang-tang) on AD (atopic dermatitis). Additionally, by applying the fermentation extracts of KMS at the first sensitization and latency period, I investgated whether it could prevent AD. Methods: In this study, to test the effect and preventive efficacy of KMSs on AD. DNCB-induced BALB/c mice of AD model was used. Through histological observation, epidermis and dermis thickness, the infiltration of eoshiphils and mast cells in epidermis and dermis were examined. We measured the serum level of IgE and IL-6, TNF-alpha, and the expressions of $NF-{\kappa}B$ and MAPK protein. In order to examine the effect of KMSs on keratinocyte, HaCaT cells were treated TNF-alpha and IFN-gamma to induce an inflammatory response. The KMSs were applied at various concentration in the experimental group. We investigated TARC expression. Results: The treatment groups were reduced epidermis and dermis thickness, inhibited the infiltration of eosinophils and mast cells, reduced the serum level of IL-6. Moreover, sfKMS group reduced serum level of TNF-alpha, inhibited the protein expressions of $NF-{\kappa}B$ and the phosphoryllation of ERK, JNK and p38. Especially sfKMS-pre group were reduced the serum level of IgE, show significant inhibition on the protein expression of $NF-{\kappa}B$ and the phosphoryllation of ERK, JNK and p38. In the experiment on HaCaT cells, sfKMS group were reduced expression of TARC. Conclusions: These result suggest that wKMS and sfKMS was effective in the treament on AD, and sfKMS would prevent AD.

• Journal of Microbiology and Biotechnology
• /
• 제31권5호
• /
• pp.667-675
• /
• 2021

Streptococcus agalactiae is an important bacterial pathogen and causative agent of diseases including neonatal sepsis and meningitis, as well as infections in healthy adults and pregnant women. Although antibiotic treatments effectively relieve symptoms, the emergence and transmission of multidrug-resistant strains indicate the need for an effective immunotherapy. Effector T helper (Th) 17 cells are a relatively newly discovered subpopulation of helper CD4⁺ T lymphocytes, and which, by expressing interleukin (IL)-17A, play crucial roles in host defenses against a variety of pathogens, including bacteria and viruses. However, whether S. agalactiae infection can induce the differentiation of CD4⁺ T cells into Th17 cells, and whether IL-17A can play an effective role against S. agalactiae infections, are still unclear. In this study, we analyzed the responses of CD4⁺ T cells and their defensive effects after S. agalactiae infection. The results showed that S. agalactiae infection induces not only the formation of Th1 cells expressing interferon (IFN)-γ, but also the differentiation of mouse splenic CD4⁺ T cells into Th17 cells, which highly express IL-17A. In addition, the bacterial load of S. agalactiae was significantly increased and decreased in organs as determined by antibody neutralization and IL-17A addition experiments, respectively. The results confirmed that IL-17A is required by the host to defend against S. agalactiae and that it plays an important role in effectively eliminating S. agalactiae. Our findings therefore prompt us to adopt effective methods to regulate the expression of IL-17A as a potent strategy for the prevention and treatment of S. agalactiae infection.

• 병원약사회지
• /
• 제35권4호
• /
• pp.453-462
• /
• 2018

Background : The prevalence of chronic hepatitis C virus (HCV) tends to be higher in the elderly. Pegylated interferon and ribavirin therapy (Peg-IFN/RBV) was recommended as the first-line treatment in the past decades, but this regimen showed unsatisfactory results in terms of safety and efficacy especially in elderly patients. Recently, it was demonstrated that dual therapy with daclatasvir and asunaprevir was well tolerated and led to high sustained virological response (SVR) rates, irrespective of age. We conducted a study to evaluate the efficacy and safety of daclatasvir plus asunaprevir by involving elderly patients aged above 65 years. Methods : We retrospectively analyzed clinical data from chronic hepatitis C virus (HCV) genotype 1b patients treated with daclatasvir plus asunaprevir from September 2015 to December 2016 at Seoul St. Mary's hospital. The patients were divided into two groups as elderly patients (older than 65 years) and non-elderly patients (younger than 65 years) and compared the efficacy and safety. Results : A total of 112 patients were treated with daclatasvir plus asunaprevir for chronic hepatitis C. Among them, 101 patients completed the whole treatment, and in 88 patients the amount of HCV RNA was measured after 12 weeks of treatment. There was no significant difference in SVR at 12 weeks between both the groups (p=0.68). Typically, 91.4%(32/35) of elderly patients and 94.3%(50/53) of non-elderly patients achieved SVR12. Common adverse events included elevation in transaminase level, headache, and gastrointestinal disorders. There was no statistical difference in the symptoms between the two groups. Conclusions : The combination therapy with daclatasvir plus asunaprevir exhibited similar rates of SVR12 in HCV elderly patients without leading to further adverse events compared to non-elderly patients. Therefore, it is proposed that daclatasvir plus asunaprevir therapy could be considered as an effective and safe treatment, even in patients aged over 65 years.

• 한국식품영양학회지
• /
• 제33권6호
• /
• pp.692-701
• /
• 2020

Centella asiatica (CA) has been widely used as herbal plants. It is a valuable resources. The aim of the present study was to evaluate physiological activities of solvent extracts from CA cultivated in Chungju, Korea (Good tiger care). After preparing water (cold-water, CA-WE; hot-water, CA-HWE) and EtOH extracts (50% EtOH, CA-50E; 70% EtOH, CA-70E), their total polyphenol, flavonoid, and triterpenoid contents, and anti-oxidant activities, and anti-inflammatory activities were examined and compared. CA-70E showed the most potent anti-oxidant activity based on ABTS radical scavenging activity and reducing ability assays, while CA-50E and CA-70E showed the highest DPPH radical scavenging activity. Among major triterpenoid glycosides present in CA, madecassoside and asiaticoside contents were found to be the highest in CA-70E, and madecassic acid and asiatic acid were the highest in CA-50E. In LPS-stimulated RAW 264.7 cells, CA-70E showed the highest TNF-α inhibitory activity, although CA-50E and CA-70E similarly inhibited nitric oxide production. Ethanol extracts significantly inhibited IL-6 and IL-8 production more than water extracts using TNF-α/IFN-γ-stimulated HaCaT cells, indicating its better inhibitory against skin inflammation. Therefore, Chungju-CA EtOH extract, especially 70% EtOH extract, has high physiologically active ingredients and potent anti-oxidant and anti-inflammatory activities, suggesting its industrial application as a functional material.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• 제24권4호
• /
• pp.377-383
• /
• 2021

Purpose: We investigated the association of effector memory (EM) CD8⁺ T cell and CD4⁺ T cell immunity with metabolic syndrome (MS). Methods: Surface and intracellular staining of peripheral blood mononuclear cells was performed. Anti-interleukin-7 receptor-alpha (IL-7Rα) and CX3CR1 antibodies were used to stain the subsets of EM CD8⁺ T cells, while anti-interferon-gamma (IFN-γ), interleukin-17 (IL-17), and forkhead box P3 (FOXP3) antibodies were used for CD4⁺ T cell subsets. Results: Of the 47 obese children, 11 were female. Children with MS had significantly higher levels of serum insulin (34.8±13.8 vs. 16.4±6.3 µU/mL, p<0.001) and homeostasis model assessment of insulin resistance (8.9±4.1 vs. 3.9±1.5, p<0.001) than children without MS. Children with MS revealed significantly higher frequencies of IL-7Rα^low CD8⁺ T cells (60.1±19.1% vs. 48.4±11.5%, p=0.047) and IL-7Rα^lowCX3CR1⁺ CD8⁺ T cells (53.8±20.1% vs. 41.5±11.9%, p=0.036) than children without MS. As the serum triglyceride levels increased, the frequency of IL-7Rα^lowCX3CR1⁺ and IL-7Rα^highCX3CR1^- CD8⁺ T cells increased and decreased, respectively (r=0.335, p=0.014 and r=-0.350, p=0.010, respectively), in 47 children. However, no CD4⁺ T cell subset parameters were significantly different between children with and without MS. Conclusion: In obese children with MS, the changes in immunity due to changes in EM CD8⁺ T cells might be related to the morbidity of obesity.

• 한국가금학회지
• /
• 제47권4호
• /
• pp.229-235
• /
• 2020

가금산업에서 전염성 질병은 농장의 생산성에 악영향을 미치는 중요한 요인이다. 그 중 저병원성 조류인플루엔자는 산란율과 증체율에 영향을 준다. 본 연구에서는 육계에서 저병원성 조류인플루엔자 감염시 혈청 단백질 및 사이토카인의 변화 양상을 조사하였다. 1일령의 육계를 1주령부터 4주령까지 각 주령마다 저병원성 조류인플루엔자를 공격 접종 후 혈중 chDBP, Chicken Ovotransferrin, chIL-1β, chIL-6, chIFN-γ의 양을 비교하였다. 어린 주령에 저병원성 조류인플루엔자를 공격접종한 그룹에서는 4주령에 음성대조군과 비교해 chIL-1β, chIL-6가 유의성 있는 낮은 값을 보이는 것을 확인하였다. 추가적인 연구를 통하여 chIL-1β, chIL-6가 질병의 경과를 확인할 수 있는 보조적인 감염 지표로 활용될 수 있을 것으로 판단된다.

• Journal of Microbiology and Biotechnology
• /
• 제32권9호
• /
• pp.1126-1133
• /
• 2022

This study investigated the contribution of lipoxygenase (LOX) inhibitors, nordihydroguaiaretic acid (NDGA), tetra-O-methyl nordihydroguaiaretic acid (M₄N) and zileuton (ZIL), and thromboxane A2 (TXA₂) inhibitor 4,5-diphenylimidazole (DPI) in the proliferation of Brucella abortus infection. None of the compounds affected the uptake of Brucella into the macrophages. We determined the effect of neutralizing leukotriene B4 (LTB4) receptor and showed that the uptake of the bacteria was inhibited at 30 min post-infection. M₄N treatment attenuated intracellular survival of Brucella at 2 h post-incubation but it was not observed in the succeeding time points. DPI treatment showed reduced survival of Brucella at 24 h post-incubation while blocking LTB4 receptor was observed to have a lower intracellular growth at 48 h post-incubation suggesting different action of the inhibitors in the course of the survival of Brucella within the cells. Reduced proliferation of the bacteria in the spleens of mice was observed in animals treated with ZIL or DPI. Increased serum cytokine level of TNF-α and MCP-1 was observed in mice treated with M₄N or ZIL while a lower IFN-γ level in ZIL-treated mice and a higher IL-12 serum level in DPI-treated mice were observed at 7 d post-infection. At 14 d post-infection, ZIL-treated mice displayed reduced serum level of IL-12 and IL-10. Overall, inhibition of 5-LOX or TXA₂ or a combination therapy promises a potential alternative therapy against B. abortus infection. Furthermore, strong ligands for LTB4 receptor could also be a good candidate for the control of Brucella infection.

• 한국미생물·생명공학회지
• /
• 제49권1호
• /
• pp.75-87
• /
• 2021

Type I Interferons (IFNα) are known for their role as biological anticancer agents owing to their cell-apoptosis inducing properties. Development of an appropriate, cost-effective host expression system is crucial for meeting the increasing demand for proteins. Therefore, this study aims to develop codon-optimized IFNα-2b in L. lactis NZ3900. These cells express extracellular protein using the NICE system and Usp₄₅ signal peptide. To validate the mature form of the expressed protein, the recombinant IFNα-2b was screened in a human colorectal cancer cell line using the cytotoxicity assay. The IFNα-2b was successfully cloned into the pNZ8148 vector, thereby generating recombinant L. lactis pNZ8148-SP_Usp45-IFNα-2b. The computational analysis of codon-optimized IFNα-2b revealed no mutation and amino acid changes; additionally, the codon-optimized IFNα-2b showed 100% similarity with native human IFNα-2b, in the BLAST analysis. The partial size exclusion chromatography (SEC) of extracellular protein yielded a 19 kDa protein, which was further confirmed by its positive binding to anti-IFNα-2b in the western blot analysis. The crude protein and SEC-purified partial fraction showed IC₅₀ values of 33.22 ㎍/ml and 127.2 ㎍/ml, respectively, which indicated better activity than the metabolites of L. lactis NZ3900 (231.8 ㎍/ml). These values were also comparable with those of the regular anticancer drug tamoxifen (105.5 ㎍/ml). These results demonstrated L. lactis as a promising host system that functions by utilizing the pNZ8148 NICE system. Meanwhile, codon-optimized usage of the inserted gene increased the optimal protein expression levels, which could be beneficial for its large-scale production. Taken together, the recombinant L. lactis IFNα-2b is a potential alternative treatment for colorectal cancer. Furthermore, its activity was analyzed in the WiDr cell line, to assess its colorectal anticancer activities in vivo.

• 대한본초학회지
• /
• 제33권4호
• /
• pp.19-26
• /
• 2018

Objectives : The aim of this study was to investigate the immunopotentiating activity of combine extract that Silkworm and Cinnamomum cassia. Recently, acute epidemic diseases such as cold and viral respiratory diseases have been emerging. So, interested in immunity enhancement has been increasing, and research on natural products to promote immunity activity has been actively conducted. Methods : To confirm the immunopotentiating activity effect, Silkworm (SW), Cinnamomum cassia (CC), and SWCC combined extracts were treated 14 days at 300 mg/kg/day. The changes of glutamic oxalacetic transaminase (GOT), glutamic pyruvate transaminase (GPT) in serum were analyzed after experiment. The changes in the total spleen cell number were measured. Immune cells in spleen were analyzed using fluorescence activated cell sorter (FACS). also, analyzed the expression of cytokines in spleen. Results : Total number of cells in the spleen and FACS analysis of T lymphocytes activated in the spleen showed that the SWCC combined treated group had much higher frequency of active cells than both single groups. The ratio of CD4+CD8+, CD4+CD69+ and CD4+CD25+ T cells in spleen, SWCC is higher than other groups except Nor in CD4+, CD4+CD69+, CD4+CD25+ T cells. The results of this study suggest that SWCC can help immune function via IL-2, IL-10, IL-12, IFN-${\gamma}$ cytokine production, increased T lymphocytes and splenocyte proliferation. Conclusion : Therefore, these results suggested that the SWCC combined extracts administration increase stronger immunity enhancement than when SW and CC adminstration.

• 대한본초학회지
• /
• 제34권2호
• /
• pp.41-47
• /
• 2019

Objectives : A traditional herbal prescription, Kyung-Ok-Ko (KOK), has long been used in oriental medicine as an invigorant for age-related diseases, such as amnesia and stroke. However, the beneficial value of KOK for immune responses is largely unknown. Based on the above mentioned effects of KOK, other previous reports, and its use in traditional medicine, we hypothesized that KOK displays beneficial effects against methotrexate (MTX)-induced immune suppression. Methods : We investigated the effects of KOK (0.6 g/kg/day, oral (p.o.)) on deteriorated immunity caused by MTX (2 mg/kg/day, p.o.) in an immune suppression mouse model. MTX was fed to mice once a day for 7 days. After the immune responses of the mice deteriorated by MTX treatment, KOK in water was fed to the mice once a day for 14 days. We then measured the expression levels of various cytokines, such as T helper cell (Th1, Th2) cytokines, and the number of immune cells, such as spleen T cells, B cells, and macrophages. Results : The data showed that MTX decreased Th1 profiles (interferon $(IFN)-{\gamma}$, interleukin (IL)-2, IL-12) and the number of immune cells, and increased Th2 profiles (IL-4, IL-5, IL-13), which were normalized significantly by post-administration of KOK. However, there was no significant difference in body-weight gain between MTX- and KOK-treated mice. Conclusion : These results indicate that KOK has immune-enhancing functions and reduces immunotoxicity of MTX, suggesting that supplementation with KOK will improve immune responses clinically and be useful for the prevention of immune-related diseases.