• Korean Journal of Radiology
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• 제22권2호
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• pp.213-224
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• 2021

Objective: Clinical outcomes of patients who undergo transarterial chemoembolization (TACE) for single small hepatocellular carcinoma (HCC) are not consistent, and may differ based on certain imaging findings. This retrospective study was aimed at determining the efficacy of pre-TACE CT or MR imaging findings in predicting survival outcomes in patients with small HCC upon being treated with TACE. Besides, the study proposed to build a risk prediction model for these patients. Materials and Methods: Altogether, 750 patients with functionally good hepatic reserve who received TACE as the first-line treatment for single small HCC between 2004 and 2014 were included in the study. These patients were randomly assigned into training (n = 525) and validation (n = 225) sets. Results: According to the results of a multivariable Cox analysis, three pre-TACE imaging findings (tumor margin, tumor location, enhancement pattern) and two clinical factors (age, serum albumin level) were selected and scored to create predictive models for overall, local tumor progression (LTP)-free, and progression-free survival in the training set. The median overall survival time in the validation set were 137.5 months, 76.1 months, and 44.0 months for low-, intermediate-, and high-risk groups, respectively (p < 0.001). Time-dependent receiver operating characteristic curves of the predictive models for overall, LTP-free, and progression-free survival applied to the validation cohort showed acceptable areas under the curve values (0.734, 0.802, and 0.775 for overall survival; 0.738, 0.789, and 0.791 for LTP-free survival; and 0.671, 0.733, and 0.694 for progression-free survival at 3, 5, and 10 years, respectively). Conclusion: Pre-TACE CT or MR imaging findings could predict survival outcomes in patients with small HCC upon treatment with TACE. Our predictive models including three imaging predictors could be helpful in prognostication, identification, and selection of suitable candidates for TACE in patients with single small HCC.

• 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.

• 한국산업보건학회지
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• 제34권1호
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• pp.57-66
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• 2024

Objective: Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects. This study aimed to investigate the association between low peripheral oxygen saturation levels (SpO₂), and composite indices predicting death in male patients with (COPD). Method: A total of 140 participants with post-bronchodilator FEV₁/FVC ratio less than 0.7 were included. Three composite indices (ADO, DOSE, BODEx) were calculated using six variables such as age (A), airflow obstruction (O), body mass index (B), dyspnea (D), exacerbation history (E or Ex), and smoking status (S). Severity of airflow limitation was classified according to Global Initiative for Obstructive Lung Disease (GOLD) guidelines. SpO₂ was measured by pulse oximetry, and anemia and iron deficiency were assessed based on blood hemoglobin levels and serum markers such as ferritin, transferrin saturation, or soluble transferrin receptor. Results: Participants with low SpO₂ (<95%) showed significantly lower levels of %FEV₁ predicted (p=0.020) and %FEV₁/FVC ratio (p=0.002) compared to those with normal SpO₂ levels. The mMRC dyspnea scale (p<0.001) and GOLD grade (p=0.002) showed a significant increase in the low SpO₂ group. Receiver Operating Characteristic analysis revealed higher area under the curve for %FEV₁ (p=0.020), %FEV₁/FVC(p=0.002), mMRC dyspnea scale (p=0.001), GOLD grade (p=0.010), ADO (p=0.004), DOSE (p=0.002), and BODEx (p=0.011) in the low SpO₂ group. Conclusion: These results suggest that low SpO₂ levels are related to increased airflow limitation and the composite indices of COPD.

• Korean Journal of Radiology
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• 제21권11호
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• pp.1230-1238
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• 2020

Objective: We aimed to assess the effects of remote ischemic pre-conditioning (RIPC) on the incidence of contrast-induced nephropathy (CIN) after an intravenous (IV) or intra-arterial injection of contrast medium (CM) in patient and control groups. Materials and Methods: This prospective, randomized, single-blinded, controlled trial included 26 patients who were hospitalized for the evaluation of the feasibility of transcatheter aortic valve implantation and underwent investigations including contrast-enhanced computed tomography (CT), with Mehran risk scores greater than or equal to six. All the patients underwent four cycles of five minute-blood pressure cuff inflation followed by five minutes of total deflation. In the RIPC group (n = 13), the cuff was inflated to 50 mm Hg above the patient's systolic blood pressure (SBP); in the control group (n = 13), it was inflated to 10 mm Hg below the patient's SBP. The primary endpoint was the occurrence of CIN. Additionally, variation in the serum levels of cystatin C was assessed. Results: One case of CIN was observed in the control group, whereas no cases were detected in the RIPC group (p = 0.48, analysis of 25 patients). Mean creatinine values at the baseline, 24 hours after injection of CM, and 48 hours after injection of CM were 88 ± 32 μmol/L, 91 ± 28 μmol/L and 82 ± 29 μmol/L, respectively (p = 0.73) in the RIPC group, whereas in the control group, they were 100 ± 36 μmol/L, 110 ± 36 μmol/L, and 105 ± 34 μmol/L, respectively (p = 0.78). Cystatin C values (median [Q1, Q3]) at the baseline, 24 hours after injection of CM, and 48 hours after injection of CM were 1.10 [1.08, 1.18] mg/L, 1.17 [0.97, 1.35] mg/L, and 1.12 [0.99, 1.24] mg/L, respectively (p = 0.88) in the RIPC group, whereas they were 1.11 [0.97, 1.28] mg/L, 1.13 [1.08, 1.25] mg/L, and 1.16 [1.03, 1.31] mg/L, respectively (p = 0.93), in the control group. Conclusion: The risk of CIN after an IV injection of CM is very low in patients with Mehran risk score greater than or equal to six and even in the patients who are unable to receive preventive hyperhydration. Hence, the Mehran risk score may not be an appropriate method for the estimation of the risk of CIN after IV CM injection.

• 한국간담췌외과학회지
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• 제26권1호
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• pp.40-46
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• 2022

Backgrounds/Aims: The role of inflammation in malignant cell proliferation has been well described. High values of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) as markers of systemic inflammation have shown associations with unfavorable long-term outcomes. The purpose of this study was to determine values of NLR and PLR evaluated prior to and after surgery and their associations with mortality and recurrence rates of liver transplant patients with hepatocellular carcinoma (HCC). Methods: A total of 105 patients with HCC who underwent orthotopic liver transplantation (OLT) were retrospectively reviewed. NLR and PLR values were obtained from complete blood counts prior to and after surgery. Overall survival (OS) and recurrence-free survival (RFS) in relation with delta NLR and PLR were estimated. Results: Serum alpha-fetoprotein levels > 100 ng/mL (p = 0.014) and lymphovascular emboli in the specimen (p = 0.048) were identified to be significant predictors of RFS. Child-Pugh score (p = 0.016) was found to be an independent factor associated with poorer OS. An increasing delta PLR was associated with worse RFS, although it showed no significant association with OS. Conclusions: The analysis of PLR as a continuous variable may predict recurrence outcomes in patients undergoing OLT for HCC. It is more representative than isolated values.

• 한국간담췌외과학회지
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• 제26권3호
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• pp.257-262
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• 2022

Backgrounds/Aims: Middle hepatic vein (MHV) is usually preserved as a part of the right or left hepatectomy in order preserve the venous outflow of remnant liver. The aim of this study was to evaluate if resection of MHV could influence post-resection outcomes of standard right or left hepatectomy. Methods: Patients who underwent standard right or left hepatectomy between January 2015 and December 2019 were included. Anatomical remnant liver volumes were measured retrospectively using the Hermes workstation (Hermes Medical Solutions AB, Stockholm, Sweden). Uni- and multi-variate analyses were performed to assess the difference in outcomes of those with preservation of MHV and those without preservation. Results: A total of 144 patients were included. Right hepatectomy was performed for 114 (79.2%) and left hepatectomy was performed for 30 (20.8%) patients. MHV was resected for 13 (9.0%) in addition to the standard right or left hepatectomy. Median remnant liver volume was significantly higher in the MHV resected group (p < 0.01). There was no significant difference in serum level of bilirubin, international normalized ratio, alanine aminotransferase, creatinine on postoperative day 1, 3, 5, or 10, ≥ grade IIIa complications (p = 0.44), or 90-day mortality (p = 0.41). On multivariable analysis, resection of the MHV did not influence the incidence of post hepatectomy liver failure (p = 0.52). Conclusions: Resection of the MHV at standard right or left hepatectomy did not have a negative impact on postoperative outcomes of patients with adequate remnant liver volume.

• Molecules and Cells
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• 제26권5호
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• pp.443-453
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• 2008

The Bric-a-brac, Tramtrack, Broad-complex (BTB) domain is a protein-protein interaction domain that is found in many zinc finger transcription factors. BTB containing proteins play important roles in a variety of cellular functions including regulation of transcription, regulation of the cytoskeleton, protein ubiquitination, angiogenesis, and apoptosis. Here, we report the cloning and characterization of a novel human gene, KLHL31, from a human embryonic heart cDNA library. The cDNA of KLHL31 is 5743 bp long, encoding a protein product of 634 amino acids containing a BTB domain. The protein is highly conserved across different species. Western blot analysis indicates that the KLHL31 protein is abundantly expressed in both embryonic skeletal and heart tissue. In COS-7 cells, KLHL31 proteins are localized to both the nucleus and the cytoplasm. In primary cultures of nascent mouse cardiomyocytes, the majority of endogenous KLHL31 proteins are localized to the cytoplasm. KLHL31 acts as a transcription repressor when fused to GAL4 DNA-binding domain and deletion analysis indicates that the BTB domain is the main region responsible for this repression. Overexpression of KLHL31 in COS-7 cells inhibits the transcriptional activities of both the TPA-response element (TRE) and serum response element (SRE). KLHL31 also significantly reduces JNK activation leading to decreased phosphorylation and protein levels of the JNK target c-Jun in both COS-7 and Hela cells. These results suggest that KLHL31 protein may act as a new transcriptional repressor in MAPK/JNK signaling pathway to regulate cellular functions.

• Journal of Animal Science and Technology
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• 제54권2호
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• pp.103-109
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• 2012

본 연구는 기존 단독배양 위주로 이루어져온 세포배양 연구의 방법학적 한계의 극복과 대안을 제시하고자 지방과 근육세포주의 단독 및 공동배양에서 배양기법에 따른 지방 및 근육세포의 분화에 미치는 영향을 비교 조사하고자 실시하였다. 3T3-L1 (지방세포) 및 L6 (근육세포) 세포주는 성장배지인 10% FBS/DMEM (1% Pen-Strep solution 및 0.1% Fungizone 첨가) 하에서 48h 동안 단독배양 후 5% FBS/DMEM에서 배양하였다. 분화를 위한 단독 및 공동배양에서는 지방 및 근육세포 모두 분화유도물질 없이 2% FBS/DMEM으로 배양하였고, 공동배양에서는 $0.4{\mu}m$ insert membrane을 사용하여 6 well plate 하단에 L6 cell을, 상단에는 3T3-L1 cell을 공생시켰다. 지방 및 근육세포 분화정도 측정은 세포별 형태학적 측정과 glycerol-3-phosphate dehydrogenase (GPDH) 및 creatine kinase (CK) 분석을 통해 조사되었다. 형태학적으로 볼때 3T3-L1 세포주는 공동배양보다 단독배양 시 분화가 더욱 잘 일어났고 L6 세포주의 경우 역으로 같았다. 세포물질 분석에서는 분화배지 처리일(day 0)과 비교해 단독 및 공동배양 모두 지방세포 내 GPDH의 활성도가 유의적으로(P<0.05) 증가했음을 확인할 수 있었고 단독배양이 공동배양보다 유의적으로(P<0.05) 높은 수준의 GPDH 활성도를 보였다. L6 역시 마찬가지로 분화배지 처리일에 비하여 단독 및 공동배양 모두 CK 활성도가 유의적으로(P<0.05) 높았고, CK 활성도가 공동배양에서 유의적으로(P<0.05) 높게 나타남을 확인할 수 있었다. 이러한 결과는 기존 연구에서 이용된 단독 배양을 통한 세포 분화 결과 등은 생체와 비교 시 방법학적 한계로 인해 실제 생체 내에서는 그 분화정도가 매우 다를 것으로 생각되며, 이것은 앞으로 정확한 세포배양 결과 확보를 위해서는 단독배양보다는 공동배양기법을 사용해야 함을 의미한다. 향후 다양한 조건과 분화조절 물질들의 첨가를 통한 추가적인 공동배양실험이나 지방분화관련 분자생물학적 물질분석 등 다양한 실험 수행 시 보다 현실적이고 대량의 기초자료 확보가 가능할 것으로 판단된다.

• 대한약리학회지
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• 제26권2호
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• pp.193-207
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• 1990

Transforming growth factor ${\beta}(TGF-{\beta})$는 많은 세포의 증식, 분화 및 여러가지 세포기능에 대해 다양한 조절기능을 갖고 있는 multifunctional polypeptide로 알려져 있다. $TGF-{\beta}$는 골기질에 상당량 존재하며 골조직 대사에 대해 광범위한 영향을 나타낸다. 여러가지 연구결과에 의해 기질과 연관된 $TGF-{\beta}$는 골세포 자체의 산물로 여겨지고 있으나 골조직세포군중 어느종류의 세포가 $TGF-{\beta}$를 형성하는지에 대해서는 논란이 되고 있다. 본 연구는 $TGF-{\beta}$를 형성하는 골조직세포를 규명하고 $TGF-{\beta}$가 서로 다른 세포들에 미치는 영향을 관찰하고자 하였다. 본 실험에 필요한 특정골조직세포군을 얻기 위하여 백서태자두개관을 연속효소처리하여 수집한 골조직세포군의 생화학적 특성규명을 시행하였다. 효소 처리후 초기에 유리되는 세포는 섬유아세포의 특성을 보이며 후기에 유리되는 세포는 acid 및 alkaline phosphatase 활성과 부갑상선호르몬, calcitonin, prostaglandin $E_{2}$에 대한 c-AMP의 반응 및 교원 단백질합성등을 통해 볼때 조골세포유사세포로 보여진다. 골조직과 두개관세포 추출물의 Polyacrylamlde gel과 immunoblot analysis에 의해 골조직내에 $TGF-{\beta}$의 존재와 골세포에 의한 $TGF-{\beta}$의 생성을 확인하였다. 두개관 세포 추출물의 분석에서 모든 세포군에서 $TGF-{\beta}$가 합성되는 것을 관찰하였다. 외부에서 $TGF-{\beta}$를 가한 경우 무혈청 배지에서 골조직 증식에 대해 두가지 양상의 반응을 보였다. 조골세포 유사세포에서는 촉진하는 반응을 보였으나 섬유아세포군에서는 억제반응을 나타냈다. 반면에 교원 및 비교원 단백질 합성에 있어서는 모든 두개관세포군이 촉진반응을 보였다. 단백질 합성증가는 교원단백에 특이성이라기 보다는 일반적인 증가로 보여진다. 또한 단백질합성증가에 대한 $TGF-{\beta}$의 영향은 세포증식과의 관련성이 없는 것으로 사료된다. 결국 골세포에 의한 $TGF-{\beta}$의 생성과 여러 세포군에 대한 서로 다른 작용으로 보아 $TGF-{\beta}$는 autocrine과 paracrine 양상으로 세포기능을 조절함으로써 골조직 대사를 조절하는 중요한 기능을 발휘하는 것으로 사료된다.

• 한국식품위생안전성학회지
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• 제26권1호
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• pp.49-56
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• 2011

전통적으로 사용되어온 ${\beta}$-glucan에 대한 기초적 연구로서 본 실험은 ${\beta}$-glucan의 영양학적 성분을 분석하고 이를 투여했을 때 흰쥐의 발육에 미치는 영향에 대하여 고찰하였다. SD종 5주령의 어린 쥐를 각각 5마리씩 배치하였고, ${\beta}$-glucan을 급여하지않은 대조군, ${\beta}$-glucan을 D.W-(distilled water)에 용해시켜 저용량 (하루 사료섭취량의 0.2%의 ${\beta}$-glucan), 중간용량 (하루 사료섭취량의 1%의 ${\beta}$-glucan), 고용량 (하루 사료섭취량의 5%의 ${\beta}$-glucan) 으로 구분하여 6주간 사육하였으며, 실험쥐의 체중, 식이섭취량, 식이효율, 장기발육 및 혈액 형상에 대하여 조사하였다. 실험군 모두에서 실험쥐의 시험 종료시 평균체중과 식이섭취량의 통계적 유의차는 발견되지않았다. 그리고 간, 심장, 선장, 및 위장 등의 장기무게와 백혈구, 적혈구, 혈색소, 헤마토크릿 및 혈소판 등의 혈액학적 지수에 있어서도 통계적 유의차가 발견되지 않았다. 즉 ${\beta}$-glucan식이로 이상적으로 장기가 비대해지거나 억제됨 없이 정상적 발육이 이루어졌으며, 이상현상없이 정상적 혈액학적 지수를 나타내었다. 따라서 본 연구의 결과는 ${\beta}$-glucan이 생리대사에 무해하고 안전하며, 면역력증진 효능에 대한 세부적 및 과학적 규명과 함께 면역력증강 사료첨가제로 개발 필요성 및 가능성을 시사한다.