• Nutrition Research and Practice
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• 제17권4호
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• pp.670-681
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• 2023

BACKGROUND/OBJECTIVES: Oxidative stress is caused by reactive oxygen species and free radicals that accelerate inflammatory responses and exacerbate fatigue. Tormentic acid (TA) has antioxidant and anti-inflammatory properties. Thus, the aim of present study is to determine the fatigue-regulatory effects of TA in H₂O₂-stimulated myoblast cell line, C2C12 cells and treadmill stress test (TST) and forced swimming test (FST) animal models. MATERIALS/METHODS: In the in vitro study, C2C12 cells were pretreated with TA before stimulation with H₂O₂. Then, malondialdehyde (MDA), lactate dehydrogenase (LDH), creatine kinase (CK) activity, tumor necrosis factor (TNF)-α, interleukin (IL)-6, superoxide dismutase (SOD), catalase (CAT), glycogen, and cell viability were analyzed. In the in vivo study, the ICR male mice were administered TA or distilled water orally daily for 28 days. FST and TST were then performed on the last day. In addition, biochemical analysis of the serum, muscle, and liver was performed. RESULTS: TA dose-dependently alleviated the levels of MDA, LDH, CK activity, TNF-α, and IL-6 in H₂O₂-stimulated C2C12 cells without affecting the cytotoxicity. TA increased the SOD and CAT activities and the glycogen levels in H₂O₂-stimulated C2C12 cells. In TST and FST animal models, TA decreased the FST immobility time significantly while increasing the TST exhaustion time without weight fluctuations. The in vivo studies showed that the levels of SOD, CAT, citrate synthase, glycogen, and free fatty acid were increased by TA administration, whereas TA significantly reduced the levels of glucose, MDA, LDH, lactate, CK, inflammatory cytokines, alanine transaminase, aspartate transaminase, blood urea nitrogen, and cortisol compared to the control group. CONCLUSIONS: TA improves fatigue by modulating oxidative stress and energy metabolism in C2C12 cells and animal models. Therefore, we suggest that TA can be a powerful substance in healthy functional foods and therapeutics to improve fatigue.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2023년도 임시총회 및 춘계학술대회
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• pp.17-17
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• 2023

Chrysanthemum zawadskii (C. zawadskii) is used in traditional East Asian medicine for the treatment of various diseases, including inflammatory disease. However, it has remained unclear whether extracts of C. zawadskii inhibit inflammasome activation in macrophages. The present study assessed the inhibitory effect of an ethanol extract of C. zawadskii (CZE) on the activation of the inflammasome in macrophages and the underlying mechanism. Bone marrow[-derived macrophages (BMDMs) were obtained from wild-type C57BL/6 mice. The release of IL-1β and lactate dehydrogenase in response to nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome activators, such as ATP, nigericin and monosodium urate (MSU) crystals, was significantly decreased by CZE in lipopolysaccharide(LPS)-primed BMDMs. Western blotting revealed that CZE inhibited ATP-induced caspase-1 cleavage and IL-1β maturation. To investigate whether CZE inhibits the priming step of the NLRP3 inflammasome, we confirmed the role of CZE at the gene level using RT-qPCR. CZE also downregulated the gene expression of NLRP3 and pro-IL-1β as well as NF-κB activation in BMDMs in response to LPS. Apoptosis associated speck-like protein containing a caspase-recruitment domain (CARD) oligomerization and speck formation by NLRP3 inflammasome activators were suppressed by CZE. By contrast, CZE did not affect NLR family CARD domain containing protein 4 (NLRC4) or absent in melanoma 2 (AIM2) inflammasome activation in response to Salmonella typhimurium and poly(dA:dT) in LPS-primed BMDMs, respectively. The results revealed that three key components of CZE, namely linarin, 3,5-dicaffeoylquinic acid and chlorogenic acid, decreased IL-1β secretion in response to ATP, nigericin and MSU. These findings suggest that CZE effectively inhibited activation of the NLRP3 inflammasome.

• Korean Journal of Radiology
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• 제22권6호
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• pp.994-1004
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• 2021

Objective: To extract pulmonary and cardiovascular metrics from chest CTs of patients with coronavirus disease 2019 (COVID-19) using a fully automated deep learning-based approach and assess their potential to predict patient management. Materials and Methods: All initial chest CTs of patients who tested positive for severe acute respiratory syndrome coronavirus 2 at our emergency department between March 25 and April 25, 2020, were identified (n = 120). Three patient management groups were defined: group 1 (outpatient), group 2 (general ward), and group 3 (intensive care unit [ICU]). Multiple pulmonary and cardiovascular metrics were extracted from the chest CT images using deep learning. Additionally, six laboratory findings indicating inflammation and cellular damage were considered. Differences in CT metrics, laboratory findings, and demographics between the patient management groups were assessed. The potential of these parameters to predict patients' needs for intensive care (yes/no) was analyzed using logistic regression and receiver operating characteristic curves. Internal and external validity were assessed using 109 independent chest CT scans. Results: While demographic parameters alone (sex and age) were not sufficient to predict ICU management status, both CT metrics alone (including both pulmonary and cardiovascular metrics; area under the curve [AUC] = 0.88; 95% confidence interval [CI] = 0.79-0.97) and laboratory findings alone (C-reactive protein, lactate dehydrogenase, white blood cell count, and albumin; AUC = 0.86; 95% CI = 0.77-0.94) were good classifiers. Excellent performance was achieved by a combination of demographic parameters, CT metrics, and laboratory findings (AUC = 0.91; 95% CI = 0.85-0.98). Application of a model that combined both pulmonary CT metrics and demographic parameters on a dataset from another hospital indicated its external validity (AUC = 0.77; 95% CI = 0.66-0.88). Conclusion: Chest CT of patients with COVID-19 contains valuable information that can be accessed using automated image analysis. These metrics are useful for the prediction of patient management.

• Korean Journal of Radiology
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• 제22권9호
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• pp.1514-1524
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• 2021

Objective: To develop a radiomics risk score based on dynamic contrast-enhanced (DCE) MRI for prognosis prediction in patients with glioblastoma. Materials and Methods: One hundred and fifty patients (92 male [61.3%]; mean age ± standard deviation, 60.5 ± 13.5 years) with glioblastoma who underwent preoperative MRI were enrolled in the study. Six hundred and forty-two radiomic features were extracted from volume transfer constant (K^trans), fractional volume of vascular plasma space (V_p), and fractional volume of extravascular extracellular space (V_e) maps of DCE MRI, wherein the regions of interest were based on both T1-weighted contrast-enhancing areas and non-enhancing T2 hyperintense areas. Using feature selection algorithms, salient radiomic features were selected from the 642 features. Next, a radiomics risk score was developed using a weighted combination of the selected features in the discovery set (n = 105); the risk score was validated in the validation set (n = 45) by investigating the difference in prognosis between the "radiomics risk score" groups. Finally, multivariable Cox regression analysis for progression-free survival was performed using the radiomics risk score and clinical variables as covariates. Results: 16 radiomic features obtained from non-enhancing T2 hyperintense areas were selected among the 642 features identified. The radiomics risk score was used to stratify high- and low-risk groups in both the discovery and validation sets (both p < 0.001 by the log-rank test). The radiomics risk score and presence of isocitrate dehydrogenase (IDH) mutation showed independent associations with progression-free survival in opposite directions (hazard ratio, 3.56; p = 0.004 and hazard ratio, 0.34; p = 0.022, respectively). Conclusion: We developed and validated the "radiomics risk score" from the features of DCE MRI based on non-enhancing T2 hyperintense areas for risk stratification of patients with glioblastoma. It was associated with progression-free survival independently of IDH mutation status.

• 한국식품저장유통학회지
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• 제30권3호
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• pp.514-525
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• 2023

본 연구는 매실식초 및 홍삼농축액 혼합 음료의 증진된 피로회복 효과를 확인하고자 유기산 함량과 고강도 운동 쥐모델에서 항피로 관련 인자를 측정하였다. 홍삼농축액 및 매실식초 혼합 음료 내 유기산 함량은 acetic acid가 1,654.17 ppm으로 가장 높은 함량을 보였고, malic acid와 citric acid가 각각 617.28, 600.12 ppm으로 확인되었다. 항피로 관련 인자 중 지구력을 측정한 결과, 홍삼매실식초 혼합음료(RPV)를 섭취한 군에서 138.83 min으로 가장 높은 지구력을 보였으며, 혈중 무기인산과 암모니아 및 젖산 함량은 0.67 mM, 24.28 mmol/L 및 1.75 mM으로 유의적으로 가장 낮은 수치를 보였다. 또한, 간 및 근육 내 글리코겐 함량에서 RPV는 각각 288.4, 22.84 ㎍/g으로 가장 높은 함량을 나타냈다. RPV의 혈청 및 근육조직 내 creatine kinase 함량은 465.42와 33.05 U/L로 유의적으로 가장 낮은 값으로 확인되었으며, 근육 내 lactate dehydrogenase 함량은 RPV에서 가장 높은 값인 140.13 U/L로 나타났다. 본 연구결과를 통해 풍부한 유기산을 가진 매실식초 및 홍삼농축액 혼합 음료의 섭취는 매실식초 또는 홍삼농축액의 단일 섭취에 비해 증진된 항피로 효과를 나타낸다는 것을 확인하였으며, 이는 피로회복 기능성식품 소재로 이용할 수 있을 것으로 기대한다.

• 대한임상검사과학회지
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• 제55권4호
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• pp.306-313
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• 2023

패혈증은 병원성 감염에 의해 여러 장기에 나타나는 전신성 염증 반응으로, 현재로서는 유망한 치료제가 없다. Signal transducer and activator of transcription 3 (STAT3)은 세포 신호전달 전사 인자로서 항염증 및 염증 반응과 관련된 다양한 세포의 생물학적 과정에서 중요한 역할을 한다. Niclosamide는 FDA에서 승인된 구충제로 STAT3 조절에 관여한다고 알려져 있다. C57BL/6 마우스에 복강 주사로 지질 다당체 (lipopolysaccharide, LPS)를 투여해 패혈증을 유발하였고, Niclosamide를 LPS 주사 2시간 후에 경구 투여하였다. 본 연구에서 Niclosamide가 LPS로 유발된 패혈증 모델의 생존률과 폐 손상을 완화시켰고, 혈청 내 interleukin (IL)-6, 종양괴사인자(tumor necrosis factor-α, TNF-α), IL-1β, AST, ALT, LDH 수치를 유의하게 감소시켰다. 또한 폐 조직 면역 블롯을 통해 PI3K, AKT, NF-κB, STAT3 신호 전달 경로가 Niclosamide에 의해 조절되는 것을 확인하였다. Niclosamide는 LPS를 자극한 RAW 264.7 세포주에서 IL-6, TNF-α, IL-1β와 같은 염증성 사이토카인의 발현을 감소시켰으며, 또한 STAT3의 인산화를 감소시켰다. 본 연구를 통해 Niclosamide에 의한 STAT3 조절이 염증 반응을 억제함으로써 패혈증 모델에 대한 새로운 치료 전략을 제시하였다.

• 한국식품저장유통학회지
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• 제31권2호
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• pp.298-306
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• 2024

본 연구에서는 식물 추출물 혼합 분말의 근육세포 분화 및 산화적 스트레스에 대한 세포 보호 효과를 확인하고자 하였다. 추출물을 최대 1,000 ㎍/mL 농도까지 세포에 처리한 결과, 세포 생존율이 감소하지 않음을 확인되었다. 식물 추출물 혼합분말이 근육세포 분화 인자에 미치는 영향을 확인하기 위해 myogenin과 MHC의 발현 여부를 확인한 결과, 무처리군에 비해 발현이 증가함을 확인하였다. H₂O₂에 의해 유도된 산화적 스트레스에 대한 세포 보호 효과를 확인한 결과, 식물 추출물 혼합 분말 처리에 의해 H₂O₂ 단독 처리군보다 세포 생존율이 증가하였으며, LDH와 creatine kinase의 활성이 감소하였다. 또한, Bax와 Bcl-2의 발현을 조절하여 caspase-9와 -3 활성화를 억제함을 확인하였다. 이를 통해 식물 추출물 혼합 분말의 근육세포 분화 효과 및 H₂O₂에 의해 유도된 산화적 스트레스에 대한 세포 보호 효과가 있음을 확인하였다. 따라서 식물 추출물 혼합 분말은 근감소증 개선을 위한 기능성 소재로써 활용이 가능할 것으로 판단되며, 향후 근감소증 개선을 위한 기능성 소재로서의 유효성 확보를 위해서 근감소증 세포 및 동물모델을 이용한 효능 및 기전 분석 연구가 더 필요할 것으로 사료된다.

• 한국식품저장유통학회지
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• 제31권2호
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• pp.276-286
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• 2024

본 연구에서는 후코이단/이고들빼기 혼합물이 HepG2 세포의 apoptosis에 미치는 영향을 확인하고 어떠한 경로를 통해 나타나는지를 조사하였다. 후코이단/이고들빼기 혼합물이 HepG2 세포의 증식을 억제하고 세포 독성을 나타냈다. 이러한 HepG2 세포의 증식 억제 및 세포 독성이 apoptosis에 의한 효과인지를 확인한 결과, DNA fragmentation과 mitochondria membrane potential의 저해를 일으키는 것을 확인하였다. 이러한 결과를 바탕으로 HepG2 세포에서 후코이단/이고들빼기 혼합물이 apoptosis를 유도하는 기전에 관여하는 단백질의 발현 양상을 확인한 결과, intrinsic apoptosis 경로인 p53을 증가시키고, Bcl-2 family인 Bcl-2의 억제 및 BAX의 증가를 통해서 cytochrome c를 증가시켜 caspase-9 활성화하였고, caspase-3를 활성화시켜 결과적으로 apoptosis를 유도하였다. 또한, 전반적으로 후코이단/이고들빼기 혼합물의 apoptosis 유도 효과는 후코이단만 처리한 것보다 더 높은 효과를 나타냈으며, 이는 이고들빼기 추출물과의 혼합물 제조를 통해서 후코이단의 apoptosis 유도 효과가 증대되는 것으로 판단된다. 이러한 결과는 후코이단/이고들빼기 혼합물이 HepG2 세포에서 apoptosis 관련 유전자의 발현 조절에 의해 항암 효과를 나타내며, 이는 후코이단/이고들빼기 혼합물의 항암 작용의 기전을 해석하였을 뿐만 아니라, 이러한 기전 연구를 바탕으로 실질적인 간암 치료제로서의 사용 가능성을 확인하기 위해서는 유용 물질 분석 및 in vivo에서 추가 실험 등이 다양하게 수행되어야 할 것으로 판단된다.

• Korean Journal of Radiology
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• 제24권8호
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• pp.772-783
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• 2023

Objective: Imaging-based survival stratification of patients with gliomas is important for their management, and the 2021 WHO classification system must be clinically tested. The aim of this study was to compare integrative imaging- and pathology-based methods for survival stratification of patients with diffuse glioma. Materials and Methods: This study included diffuse glioma cases from The Cancer Genome Atlas (training set: 141 patients) and Asan Medical Center (validation set: 131 patients). Two neuroradiologists analyzed presurgical CT and MRI to assign gliomas to five imaging-based risk subgroups (1 to 5) according to well-known imaging phenotypes (e.g., T2/FLAIR mismatch) and recategorized them into three imaging-based risk groups, according to the 2021 WHO classification: group 1 (corresponding to risk subgroup 1, indicating oligodendroglioma, isocitrate dehydrogenase [IDH]-mutant, and 1p19q-codeleted), group 2 (risk subgroups 2 and 3, indicating astrocytoma, IDH-mutant), and group 3 (risk subgroups 4 and 5, indicating glioblastoma, IDHwt). The progression-free survival (PFS) and overall survival (OS) were estimated for each imaging risk group, subgroup, and pathological diagnosis. Time-dependent area-under-the receiver operating characteristic analysis (AUC) was used to compare the performance between imaging-based and pathology-based survival model. Results: Both OS and PFS were stratified according to the five imaging-based risk subgroups (P < 0.001) and three imaging-based risk groups (P < 0.001). The three imaging-based groups showed high performance in predicting PFS at one-year (AUC, 0.787) and five-years (AUC, 0.823), which was similar to that of the pathology-based prediction of PFS (AUC of 0.785 and 0.837). Combined with clinical predictors, the performance of the imaging-based survival model for 1- and 3-year PFS (AUC 0.813 and 0.921) was similar to that of the pathology-based survival model (AUC 0.839 and 0.889). Conclusion: Imaging-based survival stratification according to the 2021 WHO classification demonstrated a performance similar to that of pathology-based survival stratification, especially in predicting PFS.

• IMMUNE NETWORK
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• 제20권5호
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• pp.40.1-40.15
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• 2020

The protein encoded by the Gene Associated with Retinoid-Interferon-Induced Mortality-19 (GRIM-19) is located in the mitochondrial inner membrane and is homologous to the NADH dehydrogenase 1-alpha subcomplex subunit 13 of the electron transport chain. Multiple sclerosis (MS) is a demyelinating disease that damages the brain and spinal cord. Although both the cause and mechanism of MS progression remain unclear, it is accepted that an immune disorder is involved. We explored whether GRIM-19 ameliorated MS by increasing the levels of inflammatory cytokines and immune cells; we used a mouse model of experimental autoimmune encephalomyelitis (EAE) to this end. Six-to-eight-week-old male C57BL/6, IFNγ-knockout (KO), and GRIM-19 transgenic mice were used; EAE was induced in all strains. A GRIM-19 overexpression vector (GRIM19 OVN) was electrophoretically injected intravenously. The levels of Th1 and Th17 cells were measured via flow cytometry, immunofluorescence, and immunohistochemical analysis. IL-17A and IFNγ expression levels were assessed via ELISA and quantitative PCR. IL-17A expression decreased and IFNγ expression increased in EAE mice that received injections of the GRIM-19 OVN. GRIM19 transgenic mice expressed more IFNγ than did wild-type mice; this inhibited EAE development. However, the effect of GRIM-19 overexpression on the EAE of IFNγ-KO mice did not differ from that of the empty vector. GRIM-19 expression was therapeutic for EAE mice, elevating the IFNγ level. GRIM-19 regulated the Th17/Treg cell balance.