• Animal Bioscience
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• 제36권3호
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• pp.441-450
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• 2023

Objective: Serum amyloid A3 (SAA3), an acute phase response protein, plays important roles in opsonization, antimicrobial activity, chemotactic activity, and immunomodulation, but its expression, regulation, and function at the maternal-conceptus interface in pigs are not fully understood. Therefore, we determined the expression of SAA3 in the endometrium throughout the estrous cycle and at the maternal-conceptus interface during pregnancy. Methods: Endometrial tissues from pigs at various stages of the estrous cycle and pregnancy and with conceptuses derived from somatic cell nuclear transfer (SCNT), conceptus tissues during early pregnancy, and chorioallantoic tissues during mid- to late pregnancy were obtained and the expression of SAA3 was analyzed. The effects of the steroid hormones, interleukin-1β (IL1B), and interferon-γ (IFNG) on the expression of SAA3 were determined in endometrial explant cultures. Results: SAA3 was expressed in the endometrium during the estrous cycle and pregnancy, with the highest level on day 12 of pregnancy. The expression of SAA3 in the endometrium was significantly higher on day 12 of pregnancy than during the estrous cycle. Early-stage conceptuses and chorioallantoic tissues during mid to late pregnancy also expressed SAA3. The expression of SAA3 was primarily localized to luminal epithelial cells in the endometrium. In endometrial explant cultures, the expression of SAA3 was induced by increasing doses of IL1B and IFNG. Furthermore, the expression of SAA3 decreased significantly in the endometria of pigs carrying conceptuses derived from SCNT on day 12 of pregnancy. Conclusion: These results suggest that the expression of SAA3 in the endometrium during the implantation period increases in response to conceptus-derived IL1B and IFNG. The failure of those appropriate interactions between the implanting conceptus and the endometrium leads to dysregulation of endometrial SAA3 expression, which could result in pregnancy failure. In addition, SAA3 could be a specific endometrial epithelial marker for conceptus implantation in pigs.

• Microbiology and Biotechnology Letters
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• 제51권1호
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• pp.109-123
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• 2023

Preterm birth (PTB) is defined as giving birth prior to the 37th week of pregnancy and is a major cause of infant mortality. Studies have indicated that the vaginal microbiota's composition and its dysbiosis, particularly during pregnancy, may play a major role in PTB. While previous research work concentrated on well-studied microorganisms such as Lactobacillus, Prevotella, Gardnerella, various other microbes, and their significance in the vaginal microbiota's stability remain unknown. Moreover, current studies have focused primarily on the relative abundances of the microbes found, without considering their interactions with other members of the vaginal microbiota. In this work, we developed a novel computational approach and performed taxonomic classification of vaginal microbiota samples stratified longitudinally (Term/PTB) to observe compositional disparities and find underexamined microbes that may be contributing to PTB. Furthermore, we carried out a correlational analysis to build a microbial co-interaction network and investigated the functional implications of the genes present in both Term and PTB samples. The co-occurrence network revealed that Lactobacillus acts in solidarity to maintain the stability of the vaginal microbiota and did not have strong co-interactions with any of the other microbes. Similarly, microbes with strong interactions with Atopobium, a well-known marker microbe of PTB, were also observed. Additionally, several genes such as PTXA, FANCM, GPX, and DUSP were found to be playing an important role in the occurrence of PTB. This study provides a novel conceptual framework revealing distinct vaginal microbiota signatures that could be potential therapeutic targets for the prevention of PTB.

• Journal of Pharmacopuncture
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• 제25권4호
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• pp.390-395
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• 2022

Objectives: Sweet bee venom (sBV) is purified from Apis mellifera, containing a high level of melittin-its main component. It has been used as a therapeutic agent for pain relief and anti-inflammation, as well as for treating neuronal abnormalities. Recently, there have been studies on the therapeutic application of sBV for anticancer treatment. In the present study, we investigated the pharmacological effect of sBV treatment in A549 human lung cancer cells. Methods: We used microscopic analysis to observe the morphological changes in A549 cells after sBV treatment. The MTT assay was used to examine the cytotoxic effect after dose-dependent sBV treatment. Molecular changes in sBV were evaluated by the expression of apoptosis marker proteins using western blot analysis. Results: Microscopic analysis suggested that the growth inhibitory effect occurred in a dose-dependent manner; however, cell lysis occurred at a concentration over 20 ㎍/mL of sBV. The MTT assay indicated that sBV treatment exhibited a growth inhibitory effect at a concentration over 5 ㎍/mL. On fluorescence activated cell sorting analysis, G0 dead cells were observed after G1 arrest at treatment concentrations up to 10 ㎍/mL. However, rapid cell rupture was observed at a concentration of 20 ㎍/mL. Western blot analysis demonstrated that sBV treatment modulated the expression of multiple cell death-related proteins, including cleaved-PARP, cleaved-caspase 9, p53, Bcl2, and Bax. Conclusion: sBV induced cell death in A549 human lung cancer cells at a pharmacological concentration, albeit causing hemolytic cell death at a high concentration.

• Journal of Ginseng Research
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• 제47권3호
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• pp.440-447
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• 2023

Background: The human hair follicle undergoes cyclic phases-anagen, catagen, and telogen-throughout its lifetime. This cyclic transition has been studied as a target for treating hair loss. Recently, correlation between the inhibition of autophagy and acceleration of the catagen phase in human hair follicles was investigated. However, the role of autophagy in human dermal papilla cells (hDPCs), which is involved in the development and growth of hair follicles, is not known. We hypothesized that acceleration of hair catagen phase upon inhibition of autophagy is due to the downregulation of Wnt/β-catenin signaling in hDPCs, and that components of Panax ginseng extract can increase the autophagic flux in hDPCs. Methods: We generated an autophagy-inhibited condition using 3-methyladenine (3-MA), a specific autophagy inhibitor, and investigated the regulation of Wnt/β-catenin signaling using the luciferase reporter assay, qRT-PCR, and western blot analysis. In addition, cells were cotreated with ginsenoside Re and 3-MA and their roles in inhibiting autophagosome formation were investigated. Results: We found that the unstimulated anagen phase dermal papilla region expressed the autophagy marker, LC3. Transcription of Wnt-related genes and nuclear translocation of β-catenin were reduced after treatment of hDPCs with 3-MA. In addition, treatment with the combination of ginsenoside Re and 3-MA changed the Wnt activity and hair cycle by restoring autophagy. Conclusions: Our results suggest that autophagy inhibition in hDPCs accelerates the catagen phase by downregulating Wnt/β-catenin signaling. Furthermore, ginsenoside Re, which increased autophagy in hDPCs, could be useful for reducing hair loss caused by abnormal inhibition of autophagy.

• Molecules and Cells
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• 제46권6호
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• pp.387-398
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• 2023

Microtubule acetylation has been proposed as a marker of highly heterogeneous and aggressive triple-negative breast cancer (TNBC). The novel microtubule acetylation inhibitors GM-90257 and GM-90631 (GM compounds) cause TNBC cancer cell death but the underlying mechanisms are currently unknown. In this study, we demonstrated that GM compounds function as anti-TNBC agents through activation of the JNK/AP-1 pathway. RNA-seq and biochemical analyses of GM compound-treated cells revealed that c-Jun N-terminal kinase (JNK) and members of its downstream signaling pathway are potential targets for GM compounds. Mechanistically, JNK activation by GM compounds induced an increase in c-Jun phosphorylation and c-Fos protein levels, thereby activating the activator protein-1 (AP-1) transcription factor. Notably, direct suppression of JNK with a pharmacological inhibitor alleviated Bcl2 reduction and cell death caused by GM compounds. TNBC cell death and mitotic arrest were induced by GM compounds through AP-1 activation in vitro. These results were reproduced in vivo, validating the significance of microtubule acetylation/JNK/AP-1 axis activation in the anti-cancer activity of GM compounds. Moreover, GM compounds significantly attenuated tumor growth, metastasis, and cancer-related death in mice, demonstrating strong potential as therapeutic agents for TNBC.

• The Korean Journal of Physiology and Pharmacology
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• 제27권2호
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• pp.157-165
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• 2023

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and current therapeutic strategies are limited in their effectiveness. The expressions of Rab5 and the M2 tumor-associated macrophage marker CD163 in tissues were detected by Western blot. The migration and invasion of cells were determined using a Transwell assay. The expressions of the exosome markers were evaluated by Western blot. The polarization of human macrophages (THP-1) was determined by incubation of THP-1 cells with conditioned medium or exosomes collected from MDA-MB-231 cells with indicated transfections or by a coculture system of THP-1 and MDA-MB-231 cells. The M1 and M2 macrophage markers were evaluated by qRT-PCR. The expression of Rab5 in TNBC was significantly higher than that in normal breast tissue. Rab5 expressions in triple-negative and luminal A breast cancer were higher than those in other molecular subtypes. Higher CD163 expression was observed in triple-negative breast cancer and in triple-negative and luminal B subtypes. Rab5 knockdown suppressed but Rab5 overexpression promoted the migration and invasion capacity of MDA-MB-231 cells. The levels of CD63 and CD9 in the medium of Rab5 knockdown cells were lower than those in control cells, whereas higher levels of CD63 and CD9 were observed in Rab5 overexpression cells. Rab5 knockdown decreased the excretion but did not alter the diameter of the exosomes. Knockdown of Rab5 facilitated the anti-tumor polarization of macrophages, which was partially reversed by Rab5 overexpression. Therefore, Rab5 is expected to be a potential therapeutic target for triple-negative breast cancer.

• Journal of Chest Surgery
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• 제56권2호
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• pp.99-107
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• 2023

Background: The neutrophil-to-lymphocyte ratio (NLR) has been suggested as a novel predictive marker of cardiovascular disease. However, its prognostic role in patients under-going coronary artery bypass grafting (CABG) is unclear. This study aimed to determine the association between the preoperative NLR and early mortality in patients undergoing CABG. Methods: Cardiac surgery was performed in 2,504 patients at Seoul St. Mary's Hospital from January 2010 to December 2021. This study retrospectively reviewed 920 patients who underwent isolated CABG, excluding those for whom the preoperative NLR was unavailable. The primary endpoints were the 30- and 90-day mortality after isolated CABG. Risk factor analysis was performed using logistic regression analysis. Based on the optimal cut-off value of preoperative NLR on the receiver operating characteristic curve, high and low NLR groups were compared. Results: The 30- and 90-day mortality rates were 3.8% (n=35) and 7.0% (n=64), respectively. In the multivariable analysis, preoperative NLR was significantly associated with 30-day mortality (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.17-1.39; p<0.001) and 90-day mortality (OR, 1.17; 95% CI, 1.07-1.28; p<0.001). The optimal cut-off value of the preoperative NLR was 3.4. Compared to the low NLR group (<3.4), the high NLR group (≥3.4) showed higher 30- and 90-day mortality rates (1.4% vs. 12.1%, p<0.001; 2.8% vs. 21.3%, p<0.001, respectively). Conclusion: Preoperative NLR was strongly associated with early mortality after isolated CABG, especially in patients with a high preoperative NLR (≥3.4). Further studies with larger cohorts are necessary to validate these results.

• 중국학논총
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• 제53호
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• pp.1-16
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• 2017

The grammatical meaning of "了", a marker of aspects in Mandarin has been described differently among researchers, three of which are to express the end, a certain phase of event and the start of an event or a state. This paper consists of four parts. Set out below is a summary of main points of each part. The first chapter elaborates on the results of previous related studies, points out the purpose and meaning of the current study. Chapter two introduces marked "了" including concepts of the meaning and "Done", "complete whole", "realization" Corresponds to the case study. And explains syntactic and semantic features of the "了", highlights the look "of the了" problems of syntax and semantics, "了2" made three domains Limit 3 Including of the knowledge. This chapter holds that its grammartical meaning can be described as follows an event has taken place or a state has formed prior to a certain reference time, and that the grammartical meanings mentioned above can be considered sub - grammartical meanings of "了",which result from different prominence of the phases of an event. Chapter three explains tag component of the "了1", "了2". It discusses limited constraints, first place for "了" syntactic meaning, "The End" and "extension" of the opposition for "了" is looming around the root system, "了" and "着" sentence structure and semantic and syntactic forms. Chapter four discusses bounded features of the 了. It mainly focuses on "了"of bounded / unbounded function. It analyses the functions of components and explains a bounded function of "了1" and a bounded function of "了2". Chapter five is the conclusion. It consolidates and summarises the previous contents of the paper and points out the conclusion.

• Journal of English Language & Literature
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• 제56권2호
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• pp.187-217
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• 2010

By reading the main character, Rene Gallimard, in M. Butterfly as a spatial metaphor of America, this article examines how homogeneous American national identity of heterosexuality and white masculinity has been reinforced since the cold war and has constituted a crisis of hegemony with the decline of imperialism and how its pathological symptom is shown through the melancholic suicide of Gallimard. This article also argues how the feminine attributes implied in race, gender and sexuality in M. Butterfly are designated and allegorized as an impure, contaminated and ahistorical marker of national integrity in pthe social and material status of the heterosexual American white male. To develop my argument, I read M. Butterfly from a psychoanalytic point of view. Therefore I depend on Freud, Lacan, and Bhabha's psychoanalysis as the theoretical basis. In this paper, I also argue that the homogenized and fixed national identity is splitted and collapsed from within as shown in the Gallimard's melancholy and in the process of splitting the "Third Space" of hybrid subjects for the marginal and the emergent like Song Liling, a homosexual Asian man, can be built "from a space in-between." Therefore Hwang calls into questions conventions of fixed, essentialist identities through the shifting gender identities between Song and Gallimard in M. Butterfly and how identities in the plural are constructed variously in throughly historicized, politicized situations, and these constructions can be complicated by relations of power.

• Parasites, Hosts and Diseases
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• 제61권4호
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• pp.455-462
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• 2023

Since 2015, countries in the Sahel region have implemented large-scale seasonal malaria chemoprevention (SMC). However, the mass use of sulfadoxine-pyrimethamine (SP) plus amodiaquine impacts the genetic diversity of malaria parasites and their sensitivity to antimalarials. This study aimed to describe and compare the genetic diversity and SP resistance of Plasmodium falciparum strains in Mali and Niger. We collected 400 blood samples in Mali and Niger from children aged 3-59 months suspected of malaria. Of them, 201 tested positive (Niger, 111, 55.2%; Mali, 90, 44.8%). Polymorphism of merozoite surface protein 1 (msp1) genetic marker showed 201 allotypes. The frequency of the RO33 allotype was significantly higher in Niger (63.6%) than in Mali (39.3%). There was no significant difference in the frequency of the K1 and MAD20 allotypes between the 2 countries. The multiplicity of infection was 2 allotypes per patient in Mali and one allotype per patient in Niger. The prevalence of strains with the triple mutants Pfdhfr51I/Pfdhfr59R/Pfdhps436A/F/H and Pfdhfr51I/Pfdhfr59R/Pfdhps437G was 18.1% and 30.2%, respectively, and 7.7% carried the quadruple mutant Pfdhfr51I/Pfdhfr59R/Pfdhps436A/F/H/Pfdhps437G. Despite the significant genetic diversity of parasite populations, the level of SP resistance was comparable between Mali and Niger. The frequency of mutations conferring resistance to SP still allows its effective use in intermittent preventive treatment in pregnant women and in SMC.