• Biomolecules & Therapeutics
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• 제21권1호
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• pp.35-41
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• 2013

Metformin is widely used for T2D therapy but its cellular mechanism of action is undefined. Recent studies on the mechanism of metformin in T2D have demonstrated involvement of the immune system. Current immunotherapies focus on the potential of immunomodulatory strategies for the treatment of T2D. In this study, we examined the effects of metformin on the antigen-presenting function of antigen-presenting cells (APCs). Metformin decreased both MHC class I and class II-restricted presentation of OVA and suppressed the expression of both MHC molecules and co-stimulatory factors such as CD54, CD80, and CD86 in DCs, but did not affect the phagocytic activity toward exogenous OVA. The class II-restricted OVA presentation-regulating activity of metformin was also confirmed using mice that had been injected with metformin followed by soluble OVA. These results provide an understanding of the mechanisms of the T cell response-regulating activity of metformin through the inhibition of MHC-restricted antigen presentation in relation to its actions on APCs.

• 동의생리병리학회지
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• 제38권1호
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• pp.32-37
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• 2024

The aim of this study was to investigate the role of Daesiho-tang (Da Chai Hu-Tang) water extract (DSTE) in regulating chronic stress-induced cancer progression, focusing on its activity in modulating tumor-associated macrophages (TAMs). Different stimuli can polarize TAMs into immune-stimulating M1 macrophages or immunosuppressive M2 macrophages. During cancer progression, M2 phenotype increases and supports tumor growth, angiogenesis and metastasis. Notably, chronic stress-induced catecholamines promote M2 macrophage polarization. In this study, we investigated whether DSTE regulates norepinephrine (NE)-induced M2 macrophage polarization in RAW 264.7 mouse macrophage cells. Even though NE itself did not increase the expression of M2 markers, the conditioned media of NE-treated 4T1 mouse breast cancer cells (NE CM) significantly up-regulated M2 markers in RAW 264.7 cells, suggesting that NE-regulated cancer cell secretome stimulated M2 polarization. However, such increase was abrogated by DSTE. NE CM also induced phosphorylation of signal transducer and activator of transcription 6 (STAT6) in RAW 264.7 cells, which was clearly reversed by pretreatment with DSTE, demonstrating that DSTE inhibited M2 polarization by inactivating STAT6. Finally, M2-polarized RAW264.7 cells by NE CM markedly increased the migration of 4T1 cells. However, such increase was completely reversed by co-treating RAW264.7 cells with NE CM and DSTE, indicating that DSTE attenuated cancer cell migration by blocking M2 polarization. Taken together, our results suggest a probable use of DSTE for cancer patients under chronic stress by regulating M2 macrophage polarization.

• Journal of Microbiology and Biotechnology
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• 제21권10호
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• pp.1026-1035
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• 2011

Vibrio parahaemolyticus, which owes its origin to the marine environment, is considered as one of the most common causes of infectious diarrhea worldwide. The present study investigated the pathogenicity of V. parahaemolyticus against the model organism, Caenorhabditis elegans. Infection in the host was localized with GFP-tagged V. parahaemolyticus using confocal laser scanning microscopy. The times required for causing infection, bacterial load in intestine, chemotactic response, and alteration in pharyngeal pumping were analyzed in the host system. In addition, the regulation of innate immune-related genes, lys-7, clec- 60, and clec-87, was analyzed using real-time PCR. The role of immune-responsible pmk-1 was studied using mutant strains. The pathogenicity of environmental strain CM2 isolated from the Gulf of Mannar, India was compared with that of a reference strain obtained from ATCC. The pathogen infected animals appeared to ward off infection by up-regulating candidate antimicrobial genes for a few hours after the exposure, before succumbing to the pathogen. For the first time, the pathogenicity of V. parahaemolyticus at both the physiological and molecular levels has been studied in detail using the model organism C. elegans.

• 한국식품영양학회지
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• 제19권3호
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• pp.327-331
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• 2006

Zingiber officinale and Hizikia fusiforme(sea weed fusiforme) have long been used for food sources in Korea. The present study was performed to investigate the ex vivo effect of Zingiber officinale and Hizikia fusiforme on NO production in macrophage of mice. Seven to eight week old mices(Balb/c) were fed chew diet ad libitum and water extract of Zingiber officinale and Hizikia fusiforme was administrated orally at two different concentrations (50 and 500 mg/kg B.W.). every other day for two or four weeks NO(nitric oxide) production by activated macrophage was assessed by measuring nitrite, the stable NO metabolite, using Griess reaction assay. NO production were significantly enhanced in Zingiber officinale group at 500 mg/kg B.W. and in Hizikia fusiforme group at 50 mg/kg B.W. compared to the coresponding control groups. In conclusion, this study may suggest that Zingiber officinale and Hizikia fusiforme(sea weed fusiforme) extracts enhance the immune function by regulating NO production in macrophages of mice.

• 한국식품영양학회지
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• 제23권2호
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• pp.135-140
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• 2010

Acorns have been used as a traditional remed as well as food source. However, few studies on their immunomodulating effects have been reported. In this study, the combined immunomodulative effect of a water extract of acorns was tested on seven to eight weeks old mice(balb/c). The mice were fed ad libitum on a chow diet, and a water extract of the plant mixture was orally administered every other day for four weeks at two different concentrations(50 and 500 mg/kg B.W.). The production of cytokine(IL-$1{\beta}$, IL-6, IL-2, IL-10, IFN-$\gamma$), secreted by macrophages stimulated with LPS or not, detected by ELISA assay using cytokine kit. After 48 h of incubation with mitogen(ConA or LPS) ex vivo study showed that cytokine (IL-$1{\beta}$, IL-6, IL-2, IL-10, IFN-$\gamma$) was detected in both of the 50 and 500 mg/kg B.W. supplementation groups with LPS stimulation. The results of this study may suggest that supplementation with acorn water extract increase immune function by regulating cytokine production capacity by activated macrophages.

• Journal of Microbiology and Biotechnology
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• 제19권6호
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• pp.610-615
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• 2009

As a provirus, polydnavirus has a segmented DNA genome on chromosome(s) of host wasp. It contains several genes in each segment that presumably play critical roles in regulating physiological processes of target insect parasitized by the wasp. A cysteine-rich protein 1 (CRP1) is present in the polydnavirus Cotesia plutellae bracovirus (CpBV) genome, but its expression and physiological function in Plutella xylostella parasitized by the viral host C. plutellae is not known. This CpBV-CRP1 encoding 189 amino acids with a putative signal peptide (20 residues) was persistently expressed in parasitized P. xylostella with gradual decrease at the late parasitization period. Expression of CpBV-CRP1 was tissue-specific in the fat body/epidermis and hemocyte, but not in the gut. Its physiological function was analyzed by inducing transient expression of a CpBV segment containing CpBV-CRP1 and its promoter, which caused significant reduction in hemocyte -spreading and delayed larval development. When the treated larvae were co-injected with double-stranded RNA of CpBV-CRP1, the expression of CpBV-CRP1 disappeared, whereas other genes encoded in the CpBV segment was expressed. These co-injected larvae significantly recovered the hemocyte-spreading capacity and larval development rate. This study reports that CpBV-CRP1 is expressed in P. xylostella parasitized by C. plutellae and its physiological function is to alter the host immune and developmental processes.

• 대한한방소아과학회지
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• 제34권4호
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• pp.31-42
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• 2020

Objectives The purpose of this study is to perform a review on recent researches of Hataedock, a traditional method of removing fetal toxin by dropping herbal extracts in the mouth, to appraise its preventive and therapeutic effects of diseases. Methods Studies of Hataedock were extracted from both Chinese and Korean medical journals published within 10 years, from January 2010 to January 2020. Clinical studies and experimental researches were analyzed and categorized to skin disease, allergic rhinitis, intestinal mucosa inflammation and anal fistula for further evaluation. Results Among 194 studies were searched and screened, 22 met designated criteria. Hataedock showed the effectiveness in treating skin disease, allergic rhinitis, intestinal mucosa inflammation and anal fistula by maintaining skin barrier and regulating immune system. Coptis japonica, Glycyrrhiza uralensis, and Fermented Glycine max were mainly used as herbal extracts in Hataedock. Conclusion This study shows the recent research trends of Hataedock and suggests that Hataedock can be considered as a method of treatment or prevention to some of the incurable chronic diseases.

• 동의생리병리학회지
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• 제20권4호
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• pp.1036-1043
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• 2006

The present study was conducted to investigate the effect of Gamisamul-tang (GSMT) on atopic dermatitis (AD). AD was induced in NC/Nga mutant mice by DNCB treatment. GSMT administration reduced levels of skin severity scores. Serum levels of IgE, IgG, IgM, and inflammatory cytokines including IL-4, IL-4 and 1L-13 were significantly decreased by GSMT treatment. Levels of mRNA's encoding IL-4, IL-6, IL-13, $TNF-{\alpha}$, and $interferon-{\gamma}$ in the dermal tissue and draining lymph node (DLN) by real time RT-PCR analysis showed decrease by GSMT testament. Moreover, the number of CD4+ and CD8+ cells was significantly decreased in the spleen and DLN tissues. Histological examination showed that infiltration levels of immune cells in ear, skin, and DLN of AD-induced NC/Nga mice were much improved by GSMT treatment. The present data suggest that GSMT may play an important role in recovering AD symptoms by regulating immune reactivity.

• Molecules and Cells
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• 제44권9호
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• pp.670-679
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• 2021

Vesicle-associated membrane proteins 721 and 722 (VAMP721/722) are secretory vesicle-localized arginine-conserved soluble N-ethylmaleimide-sensitive factor attachment protein receptors (R-SNAREs) to drive exocytosis in plants. They are involved in diverse physiological processes in plants by interacting with distinct plasma membrane (PM) syntaxins. Here, we show that synaptotagmin 5 (SYT5) is involved in plant defense against Pseudomonas syringae pv tomato (Pst) DC3000 by regulating SYP132-VAMP721/722 interactions. Calcium-dependent stimulation of in vitro SYP132-VAMP722 interaction by SYT5 and reduced in vivo SYP132-VAMP721/722 interaction in syt5 plants suggest that SYT5 regulates the interaction between SYP132 and VAMP721/722. We interestingly found that disease resistance to Pst DC3000 bacterium but not to Erysiphe pisi fungus is compromised in syt5 plants. Since SYP132 plays an immune function to bacteria, elevated growth of surface-inoculated Pst DC3000 in VAMP721/722-deficient plants suggests that SYT5 contributes to plant immunity to Pst DC3000 by promoting the SYP132-VAMP721/722 immune secretory pathway.

• Journal of Microbiology and Biotechnology
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• 제29권6호
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• pp.989-998
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• 2019

Autophagy is crucial for immune defense against Mycobacterium tuberculosis (Mtb) infection. Mtb can evade host immune attack and survival within macrophages by manipulating the autophagic process. MicroRNAs (miRNAs) are small, non-coding RNAs that are involved in regulating vital genes during Mtb infection. The precise role of miRNAs in autophagy with the exits of Mtb remains largely unknown. In this study, we found miR-1958, a new miRNA that could regulate autophagy by interacting with 3'UTR of autophagy-related gene 5 (Atg5). In addition, Mtb infection triggered miR-1958 expression in RAW264.7 cells. What's more, miR-1958 overexpression blocked autophagic flux by impairing the fusion of autophagosomes and lysosomes. Overexpression of miR-1958 reduced Atg5 expression and LC3 puncta while inhibition of miR-1958 brought an increase of Atg5 and LC3 puncta; the opposite results were observed in detection of p62. The survival of Mtb in RAW264.7 cells transfected with mimic of miR-1958 was enhanced. Taken together, our research demonstrated that a novel miR-1958 could inhibit autophagy by interacting with Atg5 and favored intracellular Mtb survival in RAW264.7 cells.