• 인터넷정보학회논문지
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• 제23권3호
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• pp.35-45
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• 2022

현대에도 일부 소외된 지역에서는 의료 인력의 부족으로 인해 위·중증 환자에 대한 치료가 지연되는 경우가 많다. 의료 데이터에 대한 분석을 자동화하여 의료 서비스의 접근성 문제 및 의료 인력 부족을 해소하고자 하는 연구가 계속되고 있다. 컴퓨터 비전 기반의 진료 자동화는 훈련 목적에 대한 데이터 수집 및 라벨링 작업에서 많은 비용이 요구된다. 이러한 점은 희귀질환이나 시각적으로 뚜렷하게 정의하기 어려운 병리적 특징 및 기전을 구분하는 작업에서 두드러진다. 이상 탐지는 비지도 학습 전략을 채택함으로써 데이터 수집 비용을 크게 절감할 수 있는 방법으로 주목된다. 본 논문에서는 기존의 이상 탐지 기법들을 기반으로, 흉부 X-RAY 영상에 대해 이상 탐지를 수행하는 방법을 다음과 같이 제안한다. (1) 최적 해상도로 샘플링된 의료 영상의 색상 범위를 정규화한다. (2) 무병변 영상으로부터 패치 단위로 구분된 중간 수준 특징 집합을 추출하여 그 중 높은 표현력을 가진 일부 특징 벡터들을 선정한다. (3) 최근접 이웃 탐색 알고리즘을 기반으로 미리 선정된 무병변(정상) 특징 벡터들과의 차이를 측정한다. 본 논문에서는 PA 방식으로 촬영된 흉부 X-RAY 영상들에 대한 제안 시스템의 이상 탐지 성능을 세부 조건에 따라 상세히 측정하여 제시한다. PadChest 데이터세트로부터 추출한 서브세트에 대해 0.705 분류 AUROC를 보임으로써 의료 영상에 대한 이상 탐지 적용의 효과를 입증하였다. 제안 시스템은 의료 기관의 임상 진단 워크플로우를 개선하는 데에 유용하게 사용될 수 있으며, 의료 서비스 접근성이 낮은 지역에서의 조기 진단을 효율적으로 지원할 수 있다.

• Journal of Ginseng Research
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• 제46권6호
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• pp.759-770
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• 2022

Background: Aerobic cellular respiration provides chemical energy, adenosine triphosphate (ATP), to maintain multiple cellular functions. Sirtuin 1 (SIRT1) can deacetylate peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) to promote mitochondrial biosynthesis. Targeting energy metabolism is a potential strategy for the prevention and treatment of various diseases, such as cardiac and neurological disorders. Ginsenosides, one of the major bioactive constituents of Panax ginseng, have been extensively used due to their diverse beneficial effects on healthy subjects and patients with different diseases. However, the underlying molecular mechanisms of total ginsenosides (GS) on energy metabolism remain unclear. Methods: In this study, oxygen consumption rate, ATP production, mitochondrial biosynthesis, glucose metabolism, and SIRT1-PGC-1α pathways in untreated and GS-treated different cells, fly, and mouse models were investigated. Results: GS pretreatment enhanced mitochondrial respiration capacity and ATP production in aerobic respiration-dominated cardiomyocytes and neurons, and promoted tricarboxylic acid metabolism in cardiomyocytes. Moreover, GS clearly enhanced NAD⁺-dependent SIRT1 activation to increase mitochondrial biosynthesis in cardiomyocytes and neurons, which was completely abrogated by nicotinamide. Importantly, ginsenoside monomers, such as Rg1, Re, Rf, Rb1, Rc, Rh1, Rb2, and Rb3, were found to activate SIRT1 and promote energy metabolism. Conclusion: This study may provide new insights into the extensive application of ginseng for cardiac and neurological protection in healthy subjects and patients.

• Journal of Korean Neurosurgical Society
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• 제65권6호
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• pp.790-800
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• 2022

Objective : EID3 (EP300-interacting inhibitor of differentiation) was identified as a novel member of EID family and plays a pivotal role in colorectal cancer development. However, its role in glioma remained elusive. In current study, we identified EID3 as a novel oncogenic molecule in human glioma and is critical for glioma cell survival, proliferation and invasion. Methods : A total of five patients with glioma were recruited in present study and fresh glioma samples were removed from patients. Four weeks old male non-obese diabetic severe combined immune deficiency (NOD/SCID) mice were used as transplant recipient models. The subcutaneous tumor size was calculated and recorded every week with vernier caliper. EID3 and AMP-activated protein kinase α1 (AMPKα1) expression levels were confirmed by real-time polymerase chain reaction and Western blot assays. Colony formation assays were performed to evaluate cell proliferation. Methyl thiazolyl tetrazolium (MTT) assays were performed for cell viability assessment. Trypan blue staining approach was applied for cell death assessment. Cell Apoptosis DNA ELISA Detection Kit was used for apoptosis assessment. Results : EID3 was preferentially expressed in glioma tissues/cells, while undetectable in astrocytes, neuronal cells, or normal brain tissues. EID3 knocking down significantly hindered glioma cell proliferation and invasion, as well as induced reduction of cell viability, apoptosis and cell death. EID3 knocking down also greatly inhibited tumor growth in SCID mice. Knocking down of AMPKα1 could effectively rescue glioma cells from apoptosis and cell death caused by EID3 absence, indicating that AMPKα1 acted as a key downstream regulator of EID3 and mediated suppression effects caused by EID3 knocking down inhibition. These findings were confirmed in glioma cells generated patient-derived xenograft models. AMPKα1 protein levels were affected by MG132 treatment in glioma, which suggested EID3 might down regulate AMPKα1 through protein degradation. Conclusion : Collectively, our study demonstrated that EID3 promoted glioma cell proliferation and survival by inhibiting AMPKα1 expression. Targeting EID3 might represent a promising strategy for treating glioma.

• 대한한방내과학회지
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• 제43권4호
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• pp.625-642
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• 2022

목적: 본 연구는 위암 수술 후 장마비의 한의학적 치료 효과를 평가하기 위해 수행하였다. 방법: 2007년 1월 1일부터 2022년 5월 11일까지 출판된 연구들을 6개의 데이터베이스를 통해 수집하였다. 수술 후 한의학적 치료를 받은 위암 환자를 장마비 관련 지표들을 통해 관찰한 연구들을 선정하였다. 결과: 한약, 침, 뜸, 전기혈위자극, 이혈요법, 족삼리혈의 약물 주입을 수술 후 장마비 치료법으로 사용한 27편의 연구를 선정하였다. 한약, 한약과 침 병용요법, 침, 뜸, 전기혈위자극, 이혈요법, 족삼리혈의 네오스티그민 주입 치료군에서 수술 후 첫 가스 배출까지의 시간이 감소하였고 (p<0.00001), 수술 후 첫 배변까지의 시간이 한약. 한약과 침 병용요법, 침, 뜸, 전기혈위자극, 이혈요법, 족삼리혈의 네오스티그민 주입 치료군에서 유의미하게 감소하였다 (p<0.00001). 심각한 이상반응은 나타나지 않았다. 결론: 한의학적 치료는 위절제술 후 위암 환자에게 수술 후 장마비의 예방과 치료법으로 활용될 수 있으며 수술 후 장마비 치료의 임상적 효과를 명확히 하기 위해 후속 연구가 필요하다.

• Biomolecules & Therapeutics
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• 제30권6호
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• pp.529-539
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• 2022

Rheumatoid arthritis (RA) is a multifactorial immune-mediated disease, the pathogenesis of which involves different cell types. T-cell activation plays an important role in RA. Therefore, inhibiting T-cell activation is one of the current therapeutic strategies. Cytotoxic T-lymphocyte antigen 4-immunoglobulin (CTLA4-Ig), also known as abatacept, reduces cytokine secretion by inhibiting T-cell activation. To achieve a homeostatic therapeutic effect, CTLA4-Ig has to be administered repeatedly over several weeks, which limits its applicability in RA treatment. To overcome this limitation, we increased the number of sialic acid-capped antennas by genetically engineering the CTLA4 region to increase the therapeutic effect of CTLA4-Ig. N-acetylglucosaminyltransferase (GnT) and α2,6-sialyltransferase (α2,6-ST) were co-overexpressed in Chinese hamster ovary (CHO) cells to generate a highly sialylated CTLA4-Ig fusion protein, named ST6. The therapeutic and immunogenic effects of ST6 and CTLA4-Ig were compared. ST6 dose-dependently decreased paw edema in a mouse model of collagen-induced arthritis and reduced cytokine levels in a co-culture cell assay in a similar manner to CTLA4-Ig. ST6- and CTLA4-Ig-induced T cell-derived cytokines were examined in CD4 T cells isolated from peripheral blood mononuclear cells after cell killing through irradiation followed by flow- and magnetic-bead-assisted separation. Interestingly, compared to CTLA4-Ig, ST6 was substantially less immunogenic and more stable and durable. Our data suggest that ST6 can serve as a novel, less immunogenic therapeutic strategy for patients with RA.

• 대한조현병학회지
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• 제23권1호
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• pp.1-7
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• 2020

Objectives: This study aimed to identify factors affecting the duration of untreated psychosis (DUP) in patients with schizophrenia spectrum disorder. Methods: Six-hundred patients with schizophrenia spectrum disorder were recruited from mental health welfare centers in Gwangju Metropolitan City and Gyeonggi-do. Subjects were categorized into two groups according to median DUP. Demographic and clinical characteristics were compared between the two groups. Results: The mean DUP was 80.8 weeks, and the median DUP was 15.9 weeks. Patients with Medicaid, higher age, and longer duration of the schizophrenia prodrome were more likely to have a longer DUP. The DUP was shorter in patients who were consulted by family/relatives prior to treatment. Patients visiting university hospitals were more likely to have a shorter DUP compared with those visiting psychiatric clinics or small-sized mental hospitals, i.e., with less than 100 beds. A multivariate regression analysis showed that the duration of the prodrome was a factor that significantly affected DUP. Conclusion: The vulnerable group of patients with schizophrenia with a long DUP should be monitored closely. Moreover, it is necessary to develop a strategy to identify patients who have an insidious course of psychosis to reduce the DUP.

• Nutrition Research and Practice
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• 제16권5호
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• pp.589-603
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• 2022

BACKGROUND/OBJECTIVES: Previous studies have reported that protein supplementation contributes to the attenuation of inflammation. Serious trauma such as burn injury usually results in the excessive release of inflammatory factors and organs dysfunction. However, a few reports continued to focus on the function of protein ingestion in regulating burn-induced inflammation and organ dysfunction. MATERIALS/METHODS: This study established the rat model of 30% total body surface area burn injury, and evaluated the function of blended protein (mixture of whey and soybean proteins). Blood routine examination, inflammatory factors, blood biochemistry, and immunohistochemical assays were employed to analyze the samples from different treatment groups. RESULTS: Our results indicated a decrease in the numbers of white blood cells, monocytes, and neutrophils in the burn injury group administered with the blended protein nutritional support (Burn+BP), as compared to the burn injury group administered normal saline supplementation (Burn+S). Expressions of the pro-inflammatory factors (tumor necrosis factor-α and interleukin-6 [IL-6]) and chemokines (macrophage chemoattractant protein-1, regulated upon activation normal T cell expressed and secreted factor, and C-C motif chemokine 11) were dramatically decreased, whereas anti-inflammatory factors (IL-4, IL-10, and IL-13) were significantly increased in the Burn+BP group. Kidney function related markers blood urea nitrogen and serum creatinine, and the liver function related markers alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase were remarkably reduced, whereas albumin levels were elevated in the Burn+BP group as compared to levels obtained in the Burn+S group. Furthermore, inflammatory cells infiltration of the kidney and liver was also attenuated after burn injury administered with blended protein supplementation. CONCLUSIONS: In summary, nutritional support with blended proteins dramatically attenuates the burn-induced inflammatory reaction and protects organ functions. We believe this is a new insight into a potential therapeutic strategy for nutritional support of burn patients.

• 생명과학회지
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• 제33권3호
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• pp.295-303
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• 2023

면역 체계와 대사 체계는 항상성을 유지하는데 중요한 요소이다. 면역 반응과 대사 조절은 연관성이 높아, 정상적인 대사가 교란되면 대사 질환이 발생하며, 면역 반응에도 변화가 발생하였다. 마찬가지로, 비만은 면역 반응과 높은 관련이 있다. 에너지 대사의 불균형으로 발생하는 비만은 인슐린 저항성, 제2형 당뇨병, 지방간 질환, 동맥경화증, 고혈압 등의 대사 질환과 관련이 있다. 알려진 바로는, 비만은 낮은 수준의 염증이 만성화된 상태가 특징이다. 비만 환경에서, 면역세포의 미세 환경은 대식세포, 자연살해세포, T세포 같은 면역세포의 독특한 활성화 표현형에 의해 염증성이 되었다. 또한, 면역 세포는 세포 간의 기전, 사이토카인을 매개하는 기전을 통해 상호작용하여 비만으로 인한 염증 반응을 강화한다. 이러한 현상은 기존의 췌장 리파아제나 알파-아밀라아제 같은 체내 효소의 억제나 지방전구세포의 분화를 억제를 표적으로 하는 일반적인 비만의 약리학적 치료 외에 면역세포 활성화 조절을 표적으로 하는 비만의 약리학적 치료 전략을 시사한다. 본 논문에서는 대식세포, 자연살해세포, T세포의 활성화 표현형과 비만 환경 내이들의 양상에 대해 정리하였다. 또한, 본 논문에서는 현재까지 확인된 면역세포의 활성화 조절을 통한 비만을 완화하는 약리학적 물질에 대해서 정리하였다.

• BMB Reports
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• 제56권3호
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• pp.196-201
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• 2023

Renal fibrosis is the final manifestation of chronic kidney disease (CKD) regardless of etiology. Hypoxia-inducible factor-2 alpha (HIF-2α) is an important regulator of chronic hypoxia, and the late-stage renal tubular HIF-2α activation exerts protective effects against renal fibrosis. However, its specific role in progressive renal fibrosis remains unclear. Here, we investigated the effects of the long-term tubular activation of HIF-2α on renal function and fibrosis, using in vivo and in vitro models of renal fibrosis. Progressive renal fibrosis was induced in renal tubular epithelial cells (TECs) of tetracycline-controlled HIF-2α transgenic (Tg) mice and wild-type (WT) controls through a 6-week adenine diet. Tg mice were maintained on doxycycline (DOX) for the diet period to induce Tg HIF-2α expression. Primary TECs isolated from Tg mice were treated with DOX (5 ㎍/ml), transforming growth factor-β1 (TGF-β1) (10 ng/ml), and a combination of both for 24, 48, and 72 hr. Blood was collected to analyze creatinine (Cr) and blood urea nitrogen (BUN) levels. Pathological changes in the kidney tissues were observed using hematoxylin and eosin, Masson's trichrome, and Sirius Red staining. Meanwhile, the expression of fibronectin, E-cadherin and α-smooth muscle actin (α-SMA) and the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was observed using western blotting. Our data showed that serum Cr and BUN levels were significantly lower in Tg mice than in WT mice following the adenine diet. Moreover, the protein levels of fibronectin and E-cadherin and the phosphorylation of p38 MAPK were markedly reduced in the kidneys of adenine-fed Tg mice. These results were accompanied by attenuated fibrosis in Tg mice following adenine administration. Consistent with these findings, HIF-2α overexpression significantly decreased the expression of fibronectin in TECs, whereas an increase in α-SMA protein levels was observed after TGF-β1 stimulation for 72 hr. Taken together, these results indicate that long-term HIF-2α activation in CKD may inhibit the progression of renal fibrosis and improve renal function, suggesting that long-term renal HIF-2α activation may be used as a novel therapeutic strategy for the treatment of CKD.

• Journal of Ginseng Research
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• 제47권2호
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• pp.199-209
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• 2023

Background: Due to the interrupted blood supply in cerebral ischemic stroke (CIS), ischemic and hypoxia results in neuronal depolarization, insufficient NAD+, excessive levels of ROS, mitochondrial damages, and energy metabolism disorders, which triggers the ischemic cascades. Currently, improvement of mitochondrial functions and energy metabolism is as a vital therapeutic target and clinical strategy. Hence, it is greatly crucial to look for neuroprotective natural agents with mitochondria protection actions and explore the mediated targets for treating CIS. In the previous study, notoginseng leaf triterpenes (PNGL) from Panax notoginseng stems and leaves was demonstrated to have neuroprotective effects against cerebral ischemia/reperfusion injury. However, the potential mechanisms have been not completely elaborate. Methods: The model of middle cerebral artery occlusion and reperfusion (MCAO/R) was adopted to verify the neuroprotective effects and potential pharmacology mechanisms of PNGL in vivo. Antioxidant markers were evaluated by kit detection. Mitochondrial function was evaluated by ATP content measurement, ATPase, NAD and NADH kits. And the transmission electron microscopy (TEM) and pathological staining (H&E and Nissl) were used to detect cerebral morphological changes and mitochondrial structural damages. Western blotting, ELISA and immunofluorescence assay were utilized to explore the mitochondrial protection effects and its related mechanisms in vivo. Results: In vivo, treatment with PNGL markedly reduced excessive oxidative stress, inhibited mitochondrial injury, alleviated energy metabolism dysfunction, decreased neuronal loss and apoptosis, and thus notedly raised neuronal survival under ischemia and hypoxia. Meanwhile, PNGL significantly increased the expression of nicotinamide phosphoribosyltransferase (NAMPT) in the ischemic regions, and regulated its related downstream SIRT1/2/3-MnSOD/PGC-1α pathways. Conclusion: The study finds that the mitochondrial protective effects of PNGL are associated with the NAMPT-SIRT1/2/3-MnSOD/PGC-1α signal pathways. PNGL, as a novel candidate drug, has great application prospects for preventing and treating ischemic stroke.