• Journal of Microbiology and Biotechnology
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• 제29권1호
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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.

• Biomolecules & Therapeutics
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• 제24권3호
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• pp.244-251
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• 2016

Understanding the developmental mechanisms of humoral immunity against intranasal antigens is essential for the development of therapeutic approaches against air-borne pathogens as well as allergen-induced pulmonary inflammation. Follicular helper T (Tfh) cells expressing CXCR5 are required for humoral immunity by providing IL-21 and ICOS costimulation to activated B cells. However, the regulation of Tfh cell responses against intranasal antigens remains unclear. Here, we found that the generation of Tfh cells and germinal center B cells in the bronchial lymph node against intranasal proteinase antigens was independent of $TGF-{\beta}$. In contrast, administration of STAT3 inhibitor STA-21 suppressed the generation of Tfh cells and germinal center B cells. Compared with wild-type OT-II T cells, STAT3-deficient OT-II T cells transferred into recipients lacking T cells not only showed significantly reduced frequency Tfh cells, but also induced diminished IgG as well as IgE specific for the intranasal antigens. Cotransfer study of wild-type OT-II and STAT3-deficient OT-II T cells revealed that the latter failed to differentiate into Tfh cells. These findings demonstrate that T cell-intrinsic STAT3 is required for the generation of Tfh cells to intranasal antigens and that targeting STAT3 might be an effective approach to ameliorate antibody-mediated pathology in the lung.

• Clinical and Experimental Pediatrics
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• 제63권8호
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• pp.291-300
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• 2020

Advances in autoimmune encephalitis studies in the past 10 years have led to the identification of new syndromes and biomarkers that have transformed the diagnostic approach to the disorder. The disorder or syndrome has been linked to a wide variety of pathologic processes associated with the neuron-specific autoantibodies targeting intracellular and plasma membrane antigens. However, current criteria for autoimmune encephalitis are quite dependent on antibody testing and responses to immunotherapy, which might delay the diagnosis. This form of encephalitis can involve the multifaceted presentation of seizures and unexpected behavioral changes. The spectrum of neuropsychiatric symptoms in children is less definitive than that in adults, and the incorporation of clinical, immunological, electrophysiological, and neuroradiological results is critical to the diagnostic approach. In this review, we document the clinical and immunologic characteristics of autoimmune encephalitis known to date, with the goal of helping clinicians in differential diagnosis and to provide prompt and effective treatment.

• Molecules and Cells
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• 제25권4호
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• pp.494-503
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• 2008

Many therapeutic glycoproteins have been successfully generated in plants. Plants have advantages regarding practical and economic concerns, and safety of protein production over other existing systems. However, plants are not ideal expression systems for the production of biopharmaceutical proteins, due to the fact that they are incapable of the authentic human N-glycosylation process. The majority of therapeutic proteins are glycoproteins which harbor N-glycans, which are often essential for their stability, folding, and biological activity. Thus, several glyco-engineering strategies have emerged for the tailor-making of N-glycosylation in plants, including glycoprotein subcellular targeting, the inhibition of plant specific glycosyltranferases, or the addition of human specific glycosyltransferases. This article focuses on plant N-glycosylation structure, glycosylation variation in plant cell, plant expression system of glycoproteins, and impact of glycosylation on immunological function. Furthermore, plant glyco-engineering techniques currently being developed to overcome the limitations of plant expression systems in the production of therapeutic glycoproteins will be discussed in this review.

• 한국발생생물학회지:발생과생식
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• 제24권2호
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• pp.101-111
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• 2020

Coiled-coil domain containing 110 (CCDC110, KM-HN-1) is a protein containing C-terminal coiled-coil domain (CCD) which was previously discovered as a member of the human cancer/testis antigen (CTA). In addition, CCDC110 has both nuclear localization signal sequence and the leucine zipper motif. Although the functional role of CCDC110 has yet to be fully identified, the mRNA expression levels of CCDC110 are known to be highly elevated in various cancer types including testis, implying its relevance to cancer pathogenesis. In this study, we first developed several monoclonal antibody (mAb) hybridoma clones targeting CCDC110 and further isolated clone by characterizing for its specificity using immunoblotting and immunoprecipitation approaches with basal parenchymal sperm cells in testis tissue. Next, using these mAbs, we showed that the Tet-inducible overexpression of CCDC110 protein delayed the entry of G2/M phase in U2-OS osteosarcoma cells. Based on these results, we propose that CCDC110 plays a crucial role in cell cycle progression.

• 한국동물학회지
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• 제35권2호
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• pp.161-172
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• 1992

In the short-term treahent of 12-0-tetradecanoylphorbol-13-acetate (TPA) or platelet-derived growth factor (PDGF), the'Wh and PDGF induced the Protein Kinase C (PKC) activation and migration from the cytoplasm to the peripheral nulcear membrane. And the activated PKC which was directly or indirectly stimulated by TPA or PDGF Phosphorylated many kinds of PKC's targeting proteins and induces various biological responses. Especially, the cytoplasmic PKC was phosphorylated within 1 hr and 10 min by TPA-and PDGF-treahent respectivelv. In the long-term treatment of TPA or PDGF, both of them induced the down-regulation and translocation of PKC in the mvoblasts. The down-regulation of PKC isozyrnes, the pattern of PKC I and ll was similar to the PKC 111 isozpnes in the cytoplasm. But in the nucleolus, the TPA did not induce and down-regulation or the inhibition of the immunoreactivity of PKC III antibody. This investigation indicates that each isozvmes of PKC mal be performed the different effects to the down-regulation of the cytoplasm or nucleolus. And douvn-regulated myoblasts contained low immunoreactivity of PKC antibodies.

• 한국동물위생학회지
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• 제37권2호
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• pp.97-100
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• 2014

This study was performed in Korea to get serological information for bovine herpesvirus 1 (BoHV-1), most commonly found in cattle. Antibodies against BoHV-1 were examined by targeting infectious bovine rhinotracheitis (IBR) in unvaccinated and vaccinated cattle, using viral neutralization (VN) test. In 2013, among 261 sera collected from IBR-unvaccinated herds, 7 sera (2.7%) were found seropositive and their VN titers were ranging from 1:4 to 1:32. Among 315 sera collected from IBR-vaccinated herds in large capacity farms, 303 sera (96.2%) were found to be seropositive for BoHV-1 and their VN titers were in the range of 1:4 to 1:2048. It was found that the IBR-vaccinated herds had higher levels of VN titer than IBR-unvaccinated herds. The results indicated that it may be due to heavy vaccination in vaccinated herds and no or a little infection in unvaccinated herds. At the end of the study it was concluded that although the seropositivity in IBR-unvaccinated herds was low, the monitoring of IBR should be continuously practiced to control and prevent the disease because of exportation of living cattle causing its nationwide outbreaks.

• Korean Circulation Journal
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• 제48권12호
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• pp.1097-1119
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• 2018

Although elevated serum low-density lipoprotein-cholesterol (LDL-C) is without any doubts accepted as an important risk factor for cardiovascular disease (CVD), the role of elevated triglycerides (TGs)-rich lipoproteins as an independent risk factor has until recently been quite controversial. Recent data strongly suggest that elevated TG-rich lipoproteins are an independent risk factor for CVD and that therapeutic targeting of them could possibly provide further benefit in reducing CVD morbidity, events and mortality, apart from LDL-C lowering. Today elevated TGs are treated with lifestyle interventions, and with fibrates which could be combined with omega-3 fatty acids. There are also some new drugs. Volanesorsen, is an antisense oligonucleotid that inhibits the production of the Apo C-III which is crucial in regulating TGs metabolism because it inhibits lipoprotein lipase (LPL) and hepatic lipase activity but also hepatic uptake of TGs-rich particles. Evinacumab is a monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3) and it seems that it can substantially lower elevated TGs levels because ANGPTL3 also regulates TGs metabolism. Pemafibrate is a selective peroxisome proliferator-activated receptor alpha modulator which also decreases TGs, and improves other lipid parameters. It seems that it also has some other possible antiatherogenic effects. Alipogene tiparvovec is a nonreplicating adeno-associated viral vector that delivers copies of the LPL gene to muscle tissue which accelerates the clearance of TG-rich lipoproteins thus decreasing extremely high TGs levels. Pradigastat is a novel diacylglycerol acyltransferase 1 inhibitor which substantially reduces extremely high TGs levels and appears to be promising in treatment of the rare familial chylomicronemia syndrome.

• BMB Reports
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• 제53권12호
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• pp.646-651
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• 2020

Bone resorption is linked to bone formation via temporal and spatial coupling within the remodeling cycle. Several lines of evidence point to the critical role of coupling factors derived from pre-osteoclasts (POCs) during the regulation of bone marrow-derived mesenchymal stem cells (BMMSCs). However, the role of glial cell-derived neurotrophic factor (GDNF) in BMMSCs is not completely understood. Herein, we demonstrate the role of POC-derived GDNF in regulating the migration and osteogenic differentiation of BMMSCs. RNA sequencing revealed GDNF upregulation in POCs compared with monocytes/macrophages. Specifically, BMMSC migration was inhibited by a neutralizing antibody against GDNF in pre-osteoclast-conditioned medium (POC-CM), whereas treatment with a recombinant GDNF enhanced migration and osteogenic differentiation. In addition, POC-CM derived from GDNF knock-downed bone marrow macrophages suppressed BMMSC migration and osteogenic differentiation. SPP86, a small molecule inhibitor, inhibits BMMSC migration and osteogenic differentiation by targeting the receptor tyrosine kinase RET, which is recruited by GDNF into the GFRα1 complex. Overall, this study highlights the role of POC-derived GDNF in BMMSC migration and osteogenic differentiation, suggesting that GDNF regulates bone metabolism.

• Nuclear Engineering and Technology
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• 제55권4호
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• pp.1265-1268
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• 2023

One important issue in using radiopharmaceuticals as therapeutic and imaging agents is predicting different organ absorbed dose following their injection. The present study aims at extrapolating dosimetry estimates to a female phantom from the animal data of ⁸⁹Zr radionuclide accumulation using the Sparks-Idogan relationship. The absorbed dose of ⁸⁹Zr radionuclide in different organs of the human body was calculated based on its distribution data in mice using both MIRD method and the MCNP simulation code. In this study, breasts, liver, heart wall, stomach, kidneys, lungs and spleen were considered as source and target organs. The highest and the lowest absorbed doses were respectively delivered to the liver (4.00E-02 and 3.43E-02 mGy/MBq) and the stomach (1.83E-03 and 1.66E-03 mGy/MBq). Moreover, there was a good agreement between the results obtained from both MIRD and MCNP methods. Therefore, according to the dosimetry results, [⁸⁹Zr] DFO-CR011-PET/CT seems to be a suitable for diagnostic imaging of the breast anomalies for CDX-011 targeting gpNMB in patients with TNBC in the future.