• Molecules and Cells
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• v.45 no.10
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• pp.718-728
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• 2022

Splicing factor B subunit 4 (SF3B4), a component of the U2-pre-mRNA spliceosomal complex, contributes to tumorigenesis in several types of tumors. However, the oncogenic potential of SF3B4 in lung cancer has not yet been determined. The in vivo expression profiles of SF3B4 in non-small cell lung cancer (NSCLC) from publicly available data revealed a significant increase in SF3B4 expression in tumor tissues compared to that in normal tissues. The impact of SF3B4 deletion on the growth of NSCLC cells was determined using a siRNA strategy in A549 lung adenocarcinoma cells. SF3B4 silencing resulted in marked retardation of the A549 cell proliferation, accompanied by the accumulation of cells at the G0/G1 phase and increased expression of p27, p21, and p53. Double knockdown of SF3B4 and p53 resulted in the restoration of p21 expression and partial recovery of cell proliferation, indicating that the p53/p21 axis is involved, at least in part, in the SF3B4-mediated regulation of A549 cell proliferation. We also provided ubiquitination factor E4B (UBE4B) is essential for p53 accumulation after SF3B4 depletion based on followings. First, co-immunoprecipitation showed that SF3B4 interacts with UBE4B. Furthermore, UBE4B levels were decreased by SF3B4 depletion. UBE4B depletion, in turn, reproduced the outcome of SF3B4 depletion, including reduction of polyubiquitinated p53 levels, subsequent induction of p53/p21 and p27, and proliferation retardation. Collectively, our findings indicate the important role of SF3B4 in the regulation of A549 cell proliferation through the UBE4B/p53/p21 axis and p27, implicating the therapeutic strategies for NSCLC targeting SF3B4 and UBE4B.

• IMMUNE NETWORK
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• v.14 no.5
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• pp.227-236
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• 2014

Understanding germinal center reactions is crucial not only for the design of effective vaccines against infectious agents and malignant cells but also for the development of therapeutic intervention for the treatment of antibody-mediated immune disorders. Recent advances in this field have revealed specialized subsets of T cells necessary for the control of B cell responses in the follicle. These cells include follicular regulatory T cells and Qa-1-restricted cluster of differentiation $(CD)8^+$ regulatory T cells. In this review, we discuss the current knowledge related to the role of regulatory T cells in the B cell follicle.

• Natural Product Sciences
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• v.4 no.3
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• pp.136-142
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• 1998

Atratoxin $B_1$ which was found to inhibit the growth of Candida albicans caused structural and morphological alteration of the cells. Increased accumulation of vesicles and membranous bodies in the cytoplasm, and alterations of the cell membrane and cell wall were most obvious. Sequential lytic events of the cells eventually resulted in complete disintegration of the cytoplasmic structures. These results suggested that atratoxin $B_1$ functioned by either blocking the biosynthetic step during cell wall synthesis, altering cell wall metabolism or dissolution of the cell organelles. These changes caused a progressive destruction of the cell wall leading to cell lysis.

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.115.1-115.1
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• 2000

• Korean Journal of Clinical Laboratory Science
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• v.52 no.3
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• pp.245-252
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• 2020

Macrophage cell death contributes to the formation of plaque, leading to the development of atherosclerosis. The accumulation of triglyceride (TG) is also associated with the pathogenesis of atherosclerosis. A previous study reported that TG induces the cell death of macrophages. This study examined whether the cytoplasmic release of cathepsin B from lysosome is associated with the TG-induced cell death of macrophage. The release of cathepsin B was increased in the TG-treated THP-1 macrophages, but the TG treatment did not affect cathepsin B expression. Furthermore, the inhibition of cathepsin B by its inhibitor, CA-074 Me, partially inhibited the TG-induced cell death of macrophage. TG-triggered macrophage cell death is mediated by the activation of caspase-1, -2, and apoptotic caspases. Therefore, this study investigated whether cathepsin B is implicated in the activation of these caspases. The inhibition of cathepsin B blocked the activation of caspase-7, -8, and -1 but did not affect the activity of caspase-3, -9, and -2. Overall, these results suggest that TG-induced cytoplasmic cathepsin B causes THP-1 macrophage cell death by activating caspase-1, leading to subsequent activation of the extrinsic apoptotic pathway.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.3
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• pp.428-436
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• 2003

Epidemiological studies have observed a negative association between increased consumption of green and yellow vegetables and cancer incidence. These vegetables contain carotenoids, which are reported to exhibit anticarcinogenic effects. Overexpression of ErbB2 and ErbB3 genes is a frequent event in several human cancers. The present study was performed to determine whether $\alpha$-carotene, $\beta$-carotene, lutein, or lycopene inhibits cell growth and to assess such an effect is related to changes in the levels of the ErbB receptor family and tile ErbB3 receptor signaling pathway in HT-29 cells. HT-29 cells were cultured in serum-free medium in the presence of various concentrations (0~100 $\mu$M) of the individual carotenoids. $\alpha$ -Carotene and lycopene significantly inhibited cell growth in a dose-dependent manner, whereas lutein slightly inhibited cell growth and $\beta$-carotene increased cell growth. Lycopene is more potent than $\alpha$ -carotene in inhibiting HT-29 cell growth. Lycopene inhibited DNA synthesis and induced apoptosis of HT-29 cells. The ErbB3 ligand heregulin (HRG) increased cell growth but did not prevent the lycopene-induced inhibition of cell growth. Lycopene decreased ErbB2 protein levels in a dose-dependent manner. Immunoprecipitation/Western blot studies revealed that lycopene inhibited HRG-induced phosphorylation of ErbB3, recruitment of the 985 regulatory subunit of phosphatidylinositol 3-kinase (PI3K) to the ErbB3 receptor, and phosphorylation of Akt. These results indicate that downregulation of ErbB2/ErbB3/PI3K/Akt signaling may be one of the mechanisms by which lycopene inhibits HT-29 cell pro-liferation and induces apoptosis.

• Journal of Periodontal and Implant Science
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• v.37 no.sup2
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• pp.371-384
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• 2007

연구 목적 : 면역 반응에서 B-1 세포의 정확한 역할은 아직 명확히 규명되지 않았으나 최근 B-1 세포가 면역의 내성을 야기하고 유지하는데 필요한 특성들을 가지고 있음이 밝혀지고 있다. 이에 본 연구에서는 B-1 세포 유래 단클론 항체의 특성과 항원 자극에 대한 B 세포의 동시자극자 (MHC Class, B7-2, 7-2) 발현을 평가하여 B 세포의 면역조절 기능을 알아보고자 한다. 연구 대상 및 방법 : B-1 세포 유래 단클론 항체를 형성하는 잡종세포주를 이용하여 다양한 내, 외인성 항원에 대한 단클론 항체의 반응 양상을 평가하였다. 여러 내, 외인성 항원으로 면역한 쥐의 복강과 비장 B 세포의 동시자극자의 발현을 Fluorescence Activated Cell Sorting (FACS)을 이용하여 평가하였다. 결과 : 최종적으로 단클론을 형성하는 2개의 클론을 형성하였고, 이 B-1 세포 유래 단클론 항체는 dose-saturable pattern을 띄는 다중 반응성을 나타내었다. FACS를 이용한 동시자극자의 발현 검사에서는 MHC 발현은 복강과 비장의 B 세포가 유사하였으나, B7-1과 7-2는 복강의 B 세포에서 더 뚜렷한 발현을 보여주었다. 결론 : B-1 세포 유래 단클론 항체는 다양한 내, 외인성 항원 자극에 대해 dose-saturable한 다중반응성을 나타낸다. 복강과 비장의 B세포는 내, 외인성 항원의 면역에 있어서 동시자극자 발현이 명확히 다른 양상을 나타냄을 확인할 수 있었다.

• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.170-178
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• 2022

The airway epithelium is equipped with the ability to resist respiratory disease development and airway damage, including the migration of airway epithelial cells and the activation of TLR3, which recognizes double-stranded (ds) RNA. Primary cilia on airway epithelial cells are involved in the cell cycle and cell differentiation and repair. In this study, we used Beas-2B human bronchial epithelial cells to investigate the effects of the TLR3 agonist polyinosinic:polycytidylic acid [Poly(I:C)] on airway cell migration and primary cilia (PC) formation. PC formation increased in cells incubated under serum deprivation. Migration was faster in Beas-2B cells pretreated with Poly(I:C) than in control cells, as judged by a wound healing assay, single-cell path tracking, and a Transwell migration assay. No changes in cell migration were observed when the cells were incubated in conditioned medium from Poly(I:C)-treated cells. PC formation was enhanced by Poly(I:C) treatment, but was reduced when the cells were exposed to the ciliogenesis inhibitor ciliobrevin A (CilioA). The inhibition of Beas-2B cell migration by CilioA was also assessed and a slight decrease in ciliogenesis was detected in SARS-CoV-2 spike protein (SP)-treated Beas-2B cells overexpressing ACE2 compared to control cells. Cell migration was decreased by SP but restored by Poly(I:C) treatment. Taken together, our results demonstrate that impaired migration by SP-treated cells can be attenuated by Poly(I:C) treatment, thus increasing airway cell migration through the regulation of ciliogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.491-495
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• 2016

Background: Small B-cell non-Hodgkins lymphoma (NHL) is difficult to be distinguished from non-neoplastic reactive processes using conventional haematoxylin-eosin (HE) staining due to different interpretations among pathologists with diagnosis based on morphologic features. Ancillary examinations such as immunohistochemical (IHC) staining are essential. However, negative or doubtful results are still sometimes obtained due to unsatisfactory tissue processing or IHC technique. The polymerase chain reaction (PCR) as a molecular diagnostic technique is very sensitive and specific. Clonality detection of heavy chain immunoglobulin (IgH) gene rearrangement has been widely used to establish diagnosis of B-cell NHL. Aims: To elaborate interobserver variation in small B-cell NHL diagnosis based on morphologic features only and to confirm sensitivity and specificity of the PCR technique as an ancillary method. Materials and Methods: A toptal of 28 samples of small B cell NHL and suspicious lymphoma were interpreted by 3 pathologists in Sardjito General Hospital based on their morphology only. The reliability of assessment and the coefficient of interobserver agreement were calculated by Fleiss kappa statistics. Interpretation results were confirmed with IHC staining (CD20, CD3, Bcl2). PCR was performed to analyze the clonality of IgH gene rearrangement. Results: Interobserver agreement in morphologic evalution of small B cell NHL and chronic lymphadenitis revealed kappa coefficient 0.69 included in the substantial agreement category. The cases were divided into 3 groups based on morphology and IHC results; lymphoma, reactive process and undetermined group. PCR analysis showed 90% sensitivity and 60% specificity. Conclusions: The present study revealed a substantial agreement among pathologists in small B-cell NHL diagnosis. For difficult cases, PCR is useful as complementary method to morphologic and IHC examinations to establish definitive diagnosis.

• Korean Journal of Microbiology
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• v.35 no.2
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• pp.164-168
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• 1999

TGF-$\beta$3 is among five TGF-$\beta$ isolorms and shows 80% sequence identity to TGF-$\beta$I, a prototype of TGF--$\beta$. It has been reported that TGF-$\beta$I, particularly in the presence of IL-2 or L-5, increases the pmduction of IgA and IgG2b isoiypes by LPS-actwated murine B cells. We examined the effect of TGF-P3 on Ig synlhesis by B cells from different lymphoid origins. IgA induction by TGP-$\beta$3 was mardnal in LPS-activated spleen B cell culture, while 1gA production was markedly enhanced in the culture shulated with TGF-$\beta$P3 and L-5. In addition, number of IgA secreting cells was increased by TGF-$\beta$P3. Under the same conditions, TGP-$\beta$3 alone was enough to increase IgG2b production but IgM and 1gGl. Sirmlar patiem of IgA and IgGZb enbancement by TGF-$\beta$3 and L-5 was observed in the cullures of mesenteric lymph node B cells. Thus, overall effect of TGF-$\beta$3 on Ig synthesis was quite similar to that of TGF-$\beta$I. Nonetheless, it remains to be underslood whether TGF-$\beta$3 is an important modulator in B cell differentiation since regulation of TGF-$\beta$3 expression is considered to differ from that of TGF-$\beta$I