• 농업과학연구
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• 제49권1호
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• pp.11-18
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• 2022

A disrupted immune system during pregnancy is involved in pregnancy complications, such as spontaneous abortion, preeclampsia, and recurrent pregnancy loss. This study examined the role of toll-like receptor (TLR) 4 and ASC (apoptosis-associated speck-like protein containing a CARD [c-terminal caspase recruitment domain]) in pregnancy complications using a lipopolysaccharide (LPS)-induced miscarriage mice model. Incidences of miscarriage and embryonic resorption were examined at 9.5 days of pregnancy in wild-type (WT), ASC knockout (KO), and TLR4 KO mice after injecting them with LPS. The fetuses and placenta were obtained after sacrifice at 15.5 days of pregnancy. A significantly lower frequency of fetus absorption was found in TLR4 KO mice, whereas corresponding absorption outcomes were strongly induced in the WT and ASC KO mice upon an LPS injection. As expected, TLR4 KO mice were resistant to LPS-induced abortion. A histological analysis of the miscarried placenta showed increasing levels of the eosin staining of spongiotrophoblast cells without any obvious difference between WT and ASC KO mice. These results suggest that TLR4 KO mice are resistant to LPS, which affects pregnancy persistence, whereas WT and ASC KO mice show high miscarriage rates due to LPS. Moreover, the ASC adaptor is not directly involved in LPS-induced miscarriages, and the NLRP3 inflammasome can be activated by other proteins in the absence of ASC.

• 한국축산식품학회지
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• 제43권4호
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• pp.659-673
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• 2023

Compared to infant formula, breast milk is the best source of nutrition for infants; it not only improves the neonatal intestinal function, but also regulates the immune system and gut microbiota composition. However, probiotic-fortified infant formula may further enhance the infant gut environment by overcoming the limitations of traditional infant formula. We investigated the probiotic formula administration for one month by comparing 118 Korean infants into the following three groups: infants in each group fed with breast milk (50), probiotic formula (35), or placebo formula-fed group (33). Probiotic formula improved stool consistency and defecation frequency compared to placebo formula-fed group. The probiotic formula helped maintaining the level of secretory immunoglobulin A (sIgA), which had remarkably decreased over time in placebo formula-fed infants (compared to weeks 0 and 4). Moreover, probiotic formula decreased the acidity of stool and considerably increased the butyrate concentration. Furthermore, the fecal microbiota of each group was evaluated at weeks 0 and 4. The microbial composition was distinct between each groups, and the abundance of health-promoting bacteria increased in the probiotic formula compared to the placebo formula-fed group. In summary, supplementation of probiotic infant formula can help optimize the infant gut environment, microbial composition, and metabolic activity of the microbiota, mimicking those of breast milk.

• Genomics & Informatics
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• 제21권2호
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• pp.22.1-22.15
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• 2023

Kidney renal clear cell carcinoma (KIRC) is one of the most aggressive cancer type of the urinary system. Metastatic KIRC patients have poor prognosis and limited therapeutic options. Ankyrin 3 (ANK3) is a scaffold protein that plays important roles in maintaining physiological function of the kidney and its alteration is implicated in many cancers. In this study, we investigated differential expression of ANK3 in KIRC using GEPIA2, UALCAN, and HPA databases. Survival analysis was performed by GEPIA2, Kaplan-Meier plotter, and OS-kirc databases. Genetic alterations of ANK3 in KIRC were assessed using cBioPortal database. Interaction network and functional enrichment analyses of ANK3-correlated genes in KIRC were performed using GeneMANIA and Shiny GO, respectively. Finally, the TIMER2.0 database was used to assess correlation between ANK3 expression and immune infiltration in KIRC. We found that ANK3 expression was significantly decreased in KIRC compared to normal tissues. The KIRC patients with low ANK3 expression had poorer survival outcomes than those with high ANK3 expression. ANK3 mutations were found in 2.4% of KIRC patients and were frequently co-mutated with several genes with a prognostic significance. ANK3-correlated genes were significantly enriched in various biological processes, mainly involved in peroxisome proliferator-activated receptor (PPAR) signaling pathway, in which positive correlations of ANK3 with PPARA and PPARG expressions were confirmed. Expression of ANK3 in KIRC was significantly correlated with infiltration level of B cell, CD8+ T cell, macrophage, and neutrophil. These findings suggested that ANK3 could serve as a prognostic biomarker and promising therapeutic target for KIRC.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제26권4호
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• pp.201-212
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• 2023

Purpose: The gastrointestinal system is the most commonly affected organ, followed by the lungs, in patients with primary immunodeficiency disease (PID). Hence, it is common for children with PIDs to present with gastrointestinal symptoms. We aimed to analyze the clinical and histopathological findings of patients who were initially admitted to pediatric gastroenterology/hepatology clinics and subsequently diagnosed with PIDs to identify the clinical clues for PIDs. Methods: The demographic, laboratory, and histopathological findings, treatment modality, and outcomes of patients initially admitted to the pediatric gastroenterology/hepatology unit and subsequently diagnosed with PIDs were recorded. Results: The study included 24 patients (58.3% male; median age [range]: 29 [0.5-204] months). Common clinical presentations included chronic diarrhea (n=8), colitis (n=6), acute hepatitis (n=4), and acute liver failure (n=2). The association of autoimmune diseases, development of malignant diseases, and severe progression of viral diseases was observed in 20.8%, 8.3%, and 16.6% of the patients, respectively. Antibody deficiency was predominantly diagnosed in 29.2% of patients, combined immunodeficiency in 20.8%, immune dysregulation in 12.5%, defects in intrinsic and innate immunity in 4.2%, autoinflammatory disorders in 8.3%, and congenital defects of phagocytes in 4.2%. Five patients remained unclassified (20.8%). Conclusion: Patients with PIDs may initially experience gastrointestinal or liver problems. It is recommended that the association of autoimmune or malignant diseases or severe progression of viral diseases provide pediatric gastroenterologists some suspicion of PIDs. After screening using basic laboratory tests, genetic analysis is mandatory for a definitive diagnosis.

• 운동영양학회지
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• 제23권1호
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• pp.13-20
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• 2019

[Purpose] The OPG/RANK/RANKL signaling is a new family of bone metabolism biomarkers belonging to the immune system. However, the bone metabolism response to long-term exercise in the RANKL/RANK/OPG signaling is less evident. The purpose of this study was to examine these biomarkers in healthy college females after 12-weeks combined exercise intervention. [Methods] Participants (N=22, 22.4±1.3yrs) were randomly divided in two different group: 12 in the control group and 10 in the exercise group performing combined exercise program that interventions was conducted 3 times per week for 12 weeks. The outcome measures included serum concentrations of RANKL, OPG and bone metabolic cytokines such as TNF-α and IL-6, and mRNA expressions of same variables from PBMC. VO_2max and bone mineral density (BMD) were measured at before and after exercise intervention. [Results] There were no significant differences in the serum RANKL, OPG concentrations and all RANKL/RANK/OPG signaling mRNA expression on interaction effect between group and time (NS). Also no significant differences were found in the serum TNF-α and IL-6 concentrations and mRNA expression (NS). The IL-6 mRNA expression only showed significant difference in the main effect of groups (p<.05). There were also no significant differences in the VO_2max and BMD on interaction effect between group and time (NS). [Conclusion] These results suggested that there were no effects on bone mineral density and RANKL/RANK/OPG signaling without the effect of 8-weeks combined exercise on cardiovascular endurance fitness.

• 한국작물학회:학술대회논문집
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• 한국작물학회 2022년도 추계학술대회
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• pp.330-330
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• 2022

In recent studies, cold plasma has been used to induce exudation of polyphenols and flavonoids from food materials, leading to enhancement of functional properties. And it is known that polyphenols interact with inflammation related metabolism. The objectives of this study were to investigate the effects of cold plasma treatments on the increase of total phenolic content (TPC), total flavonoid content (TFC), and anti-inflammatory activities of 'Sinpalkwang' peanut (Arachis hypogaea L.) hull. Plasma treatments were carried out using a dielectric barrier discharge gas exchange system at different radicals and temperatures (O₃-25℃, O₃-150℃, NO_x-150℃). Significant differences in TPC, TFC, and inflammatory mediator such as nitric oxide (NO) and tumor necrosis factor a (TNF-α) in lipopolysaccharide stimulated Raw 264.7 macrophages were observed between treated and non-treated peanut hull samples (p < 0.001). Cold plasma treated samples showed higher content (TPC: 2.87-2.93 mg/g sample, TFC: 0.96-0.98 mg/g sample) than non-treated sample (TPC: 2.47 mg/g sample, TFC: 0.78 mg/g sample). Cold plasma treated samples showed lower content of NO (3.3-5.0 uM) and TNF-α (141.4-162.2 ng/mL) than non-treated sample (NO: 11.1 uM, TNF-α: 210.2 ng/mL). This study suggests that cold plasma has potential to improve functionalities of food materials and that cold plasma treated peanut hull can be used as immune enhancing materials.

• 한국동물생명공학회지
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• 제38권3호
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• pp.89-98
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• 2023

Background: The regulation of maternal immunity is critical for the establishment and maintenance of successful pregnancy. Among many cell types regulating the immune system, innate lymphoid cells (ILCs) are known to play an important role in innate immunity. Although some reports show that ILCs are present at the maternalconceptus interface in humans and mice, the expression and function of ILCs in the endometrium have not been studied in pigs. Methods: Thus, we determined the expression, localization, and regulation of ILC markers, CD127 (a common marker for ILCs), BCL11B (a ILC2 marker), and RORC (a ILC3 marker) at the maternal-conceptus interface in pigs. Results: The expression of BCL11B and RORC, but not CD127, in the endometrium changed during pregnancy in a stage-specific manner and the expression of CD127, BCL11B, and RORC was greatest on Day 15 during pregnancy. CD127, BCL11B, and RORC were also expressed in conceptus tissues during early pregnancy and in chorioallantoic tissues during the later stage of pregnancy. BCL11B and RORC proteins were localized to specific cells in endometrial stroma. The expression of CD127 and BCL11B, but not RORC, was increased by the increasing doses of interferon-γ (IFNG) in endometrial explants. Conclusions: These results suggest that ILCs present at the maternal-conceptus interface may play a role in the establishment and maintenance of pregnancy by regulating the innate immunity in pigs.

• BMB Reports
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• 제57권5호
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• pp.256-261
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• 2024

In the context of aging, the susceptibility to infectious diseases increases, leading to heightened morbidity and mortality. This phenomenon, termed immunosenescence, is characterized by dysregulation in the aging immune system, including abnormal alterations in lymphocyte composition, elevated basal inflammation, and the accumulation of senescent T cells. Such changes contribute to increased autoimmune diseases, enhanced infection severity, and reduced responsiveness to vaccines. Utilizing aging animal models becomes imperative for a comprehensive understanding of immunosenescence, given the complexity of aging as a physiological process in living organisms. Our investigation focuses on Cisd2, a causative gene for Wolfram syndrome, to elucidate on immunosenescence. Cisd2 knockout (KO) mice, serving as a model for premature aging, exhibit a shortened lifespan with early onset of aging-related features, such as decreased bone density, hair loss, depigmentation, and optic nerve degeneration. Intriguingly, we found that the Cisd2 KO mice present a higher number of neutrophils in the blood; however, isolated neutrophils from these mice display functional defects. Through mass spectrometry analysis, we identified an interaction between Cisd2 and Calnexin, a protein known for its role in protein quality control. Beyond this function, Calnexin also regulates calcium homeostasis through interaction with sarcoendoplasmic reticulum calcium transport ATPase (SERCA). Our study proposes that Cisd2 modulates calcium homeostasis via its interaction with Calnexin and SERCA, consequently influencing neutrophil functions.

• BMB Reports
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• 제57권5호
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• pp.207-215
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• 2024

The gut microbiota, an intricate community of bacteria residing in the gastrointestinal system, assumes a pivotal role in various physiological processes. Beyond its function in food breakdown and nutrient absorption, gut microbiota exerts a profound influence on immune and metabolic modulation by producing diverse gut microbiota-generated metabolites (GMGMs). These small molecules hold potential to impact host health via multiple pathways, which exhibit remarkable diversity, and have gained increasing attention in recent studies. Here, we elucidate the intricate implications and significant impacts of four specific metabolites, Urolithin A (UA), equol, Trimethylamine N-oxide (TMAO), and imidazole propionate, in shaping human health. Meanwhile, we also look into the advanced research on GMGMs, which demonstrate promising curative effects and hold great potential for further clinical therapies. Notably, the emergence of positive outcomes from clinical trials involving GMGMs, typified by UA, emphasizes their promising prospects in the pursuit of improved health and longevity. Collectively, the multifaceted impacts of GMGMs present intriguing avenues for future research and therapeutic interventions.

• IMMUNE NETWORK
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• 제23권2호
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• pp.18.1-18.15
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• 2023

It has been reported that some exercise could enhance the anti-viral antibody titers after vaccination including influenza and coronavirus disease 2019 vaccines. We developed SAT-008, a novel digital device, consists of physical activities and activities related to the autonomic nervous system. We assessed the feasibility of SAT-008 to boost host immunity after an influenza vaccination by a randomized, open-label, and controlled study on adults administered influenza vaccines in the previous year. Among 32 participants, the SAT-008 showed a significant increase in the anti-influenza antibody titers assessed by hemagglutination-inhibition test against antigen subtype B Yamagata lineage after 4 wk of vaccination and subtype B Victoria lineage after 12 wk (p<0.05). There was no difference in the antibody titers against subtype "A." The SAT-008 also showed significant increase in the plasma cytokine levels of IL-10, IL-1β, and IL-6 at weeks 4 and 12 after the vaccination (p<0.05). A new approach using the digital device may boost host immunity against virus via vaccine adjuvant-like effects.