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Evaluation of Near-infrared Fluorescence-conjugated Peptides for Visualization of Human Epidermal Receptor 2-overexpressed Gastric Cancer

  • Jeong, Kyoungyun;Kong, Seong-Ho;Bae, Seong-Woo;Park, Cho Rong;Berlth, Felix;Shin, Jae Hwan;Lee, Yun-Sang;Youn, Hyewon;Koo, Eunhee;Suh, Yun-Suhk;Park, Do Joong;Lee, Hyuk-Joon;Yang, Han-Kwang
    • Journal of Gastric Cancer
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    • v.21 no.2
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    • pp.191-202
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    • 2021
  • Purpose: A near-infrared (NIR) fluorescence imaging is a promising tool for cancer-specific image guided surgery. Human epidermal receptor 2 (HER2) is one of the candidate markers for gastric cancer. In this study, we aimed to synthesize HER2-specific NIR fluorescence probes and evaluate their applicability in cancer-specific image-guided surgeries using an animal model. Materials and Methods: An NIR dye emitting light at 800 nm (IRDye800CW; Li-COR) was conjugated to trastuzumab and an HER2-specific affibody using a click mechanism. HER2 affinity was assessed using surface plasmon resonance. Gastric cancer cell lines (NCI-N87 and SNU-601) were subcutaneously implanted into female BALB/c nu (6-8 weeks old) mice. After intravenous injection of the probes, biodistribution and fluorescence signal intensity were measured using Lumina II (Perkin Elmer) and a laparoscopic NIR camera (InTheSmart). Results: Trastuzumab-IRDye800CW exhibited high affinity for HER2 (KD=2.093(3) pM). Fluorescence signals in the liver and spleen were the highest at 24 hours post injection, while the signal in HER2-positive tumor cells increased until 72 hours, as assessed using the Lumina II system. The signal corresponding to the tumor was visually identified and clearly differentiated from the liver after 72 hours using a laparoscopic NIR camera. Affibody-IRDye800CW also exhibited high affinity for HER2 (KD=4.71 nM); however, the signal was not identified in the tumor, probably owing to rapid renal clearance. Conclusions: Trastuzumab-IRDye800CW may be used as a potential NIR probe that can be injected 2-3 days before surgery to obtain high HER2-specific signal and contrast. Affibody-based NIR probes may require modifications to enhance mobilization to the tumor site.

Dielectric Properties of (Ba0.7Sr0.3-3x/2Lax)(Ti0.9Zr0.1)O3 Ceramics with La3+ Substitution for Sr2+-Site ((Ba0.7Sr0.3-3x/2Lax)(Ti0.9Zr0.1)O3 세라믹의 Sr2+-자리에 대한 La3+ 치환에 따른 유전 특성)

  • Si Hyun Kim;Ju Hye Kim;Eung Soo Kim
    • Korean Journal of Materials Research
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    • v.33 no.11
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    • pp.465-474
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    • 2023
  • The effects of La3+ substitution for Sr2+-site on the crystal structure and the dielectric properties of (Ba0.7Sr0.3-3x/2Lax) (Ti0.9Zr0.1)O3 (BSLTZ) (0.005 ≤ x ≤ 0.02) ceramics were investigated. The structural characteristics of the BSLTZ ceramics were quantitatively evaluated using the Rietveld refinement method from X-ray diffraction (XRD) data. For the specimens sintered at 1,550 ℃ for 6 h, a single phase with a perovskite structure and homogeneous microstructure were observed for the entire range of compositions. With increasing La3+ substitution (x), the unit cell volume decreased because the ionic size of La3+ (1.36 Å) ions is smaller than that of Sr2+ (1.44 Å) ions. With increasing La3+ substitution (x), the tetragonal phase fraction increased due to the A-site cation size mismatch effect. Dielectric constant (εr) increased with the La3+ substitution (x) due to the increase in tetragonality (c/a) and the average B-site bond valence of the ABO3 perovskite. The BSLTZ ceramics showed a higher dielectric loss due to the smaller grain size than that of (Ba0.7Sr0.3)(Ti0.9Zr0.1)O3 ceramics. BSLTZ (x = 0.02) ceramics met the X7R specification proposed by the Electronic Industries Association (EIA).

Prediction of Patient Management in COVID-19 Using Deep Learning-Based Fully Automated Extraction of Cardiothoracic CT Metrics and Laboratory Findings

  • Thomas Weikert;Saikiran Rapaka;Sasa Grbic;Thomas Re;Shikha Chaganti;David J. Winkel;Constantin Anastasopoulos;Tilo Niemann;Benedikt J. Wiggli;Jens Bremerich;Raphael Twerenbold;Gregor Sommer;Dorin Comaniciu;Alexander W. Sauter
    • Korean Journal of Radiology
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    • v.22 no.6
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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.

Inhibitory Effects of Ssanghwa-tang on Lung Injury and Muscle Loss in a Cigarette Smoke Extract and Lipopolysaccharide-induced Chronic Obstructive Pulmonary Disease Mouse Model (표준담배추출물과 Lipopolysaccharide로 유발한 만성폐쇄성폐질환 동물모델에서 쌍화탕의 폐손상 및 근감소 억제 효과)

  • Jin-kwan Choi;Won-kyung Yang;Su-won Lee;Seong-cheon Woo;Seung-hyung Kim;Yang-chun Park
    • The Journal of Internal Korean Medicine
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    • v.45 no.1
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    • pp.11-30
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    • 2024
  • Objectives: This study evaluated the effects of Ssanghwa-tang (SHT) on lung injury and muscle loss in a COPD mouse model. Methods: C57BL/6 mice were challenged with cigarette smoke extract and lipopolysaccharide, and then treated with two concentrations of SHT (250 and 500 mg/kg). After sacrifice, the bronchoalveolar lavage fluid (BALF) or lung tissue was analyzed by cytospin, ELISA, real-time PCR, flow cytometry analysis, and H&E and Masson's trichrome staining. The grip strength of COPD mice was measured using a grip strength meter. The running time of COPD mice was measured by a treadmill test. Muscle tissue of the quadriceps was stained with H&E and Masson's trichrome staining. Results: SHT significantly inhibited the increase in neutrophil numbers in BALF and significantly decreased immune cell activity in BALF and lung tissue. It also significantly inhibited the increase in TNF-α, IL-17, and MIP2 in BALF. Real-time PCR analysis revealed that the mRNA expression of TNF-α, IL-17, MIP2, and TRPV1 in lung tissue showed a significant decrease compared with the control group. Lung tissue damage was significantly reduced in the histological analysis. The grip strength and running time of the COPD mice showed a significant decrease compared with the control group. In histological staining, SHT was found to reduce the damage to muscle tissue. Conclusions: This study indicates that SHT can be used as a therapeutic agent for COPD patients by inhibiting lung injury and muscle loss.

GRIM-19 Ameliorates Multiple Sclerosis in a Mouse Model of Experimental Autoimmune Encephalomyelitis with Reciprocal Regulation of IFNγ/Th1 and IL-17A/Th17 Cells

  • Jeonghyeon Moon;Seung Hoon Lee;Seon-yeong Lee;Jaeyoon Ryu;Jooyeon Jhun;JeongWon Choi;Gyoung Nyun Kim;Sangho Roh;Sung-Hwan Park;Mi-La Cho
    • IMMUNE NETWORK
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    • v.20 no.5
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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.

Effects of Estrogen on the Transcriptional Activities of Catecholamine Biosynthesizing Enzymes in the Brain and Adrenal Gland of Ovariectomized Rats (난소 절제 흰쥐의 뇌와 부신에서의 Catecholamine Biosynthesizing Enzyme들의 전사에 미치는 Estrogen의 효과)

  • 유경신;이종화;최돈찬;이성호
    • Development and Reproduction
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    • v.6 no.2
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    • pp.117-122
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    • 2002
  • Dopamine(DA), norepinephrine(NE), and epinephrine(E) belong to a class of neurotransmitters known as catecholamine (CA) which are synthesized and secreted by mammalian brain and adrenal medulla. CA regulate several behavior patterns connected with breeding, and regulate GnRH-gonadotropin hormone axis' vitality between hypothalamus-pituitary gland linking with reproduction freeze. The present study examined effects of sex steroid hormone on the transcriptional activities of CA biosynthesis enzymes, tyrosine hydroxylase(TH), dopamine $\beta$ -hydroxylase(DBH), and phenylethaolamine-N-methyl transferase(PNMT). Mature female rats were ovariectomized(OVX) and implanted with 17 $\beta$-estradiol(E$_2$: 500 $\mu\textrm{g}$/ml) or sesame oil. Forty-eight hours after implantation all the animals were sacrificed. Total RNAs were extracted immediately and were applied to semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR). The expression level of TH was appeared by hypothalamus > SNc> adrenal medulla orders in OVX+Oil group, and by SNc > hypothalamus) adrenal medulla orders in OVX+E$_2$ group. Treatment with E$_2$ significantly increased TH expression in SNc and adrenal medulla but in hypothalamus, the reduced TH expression was observed. The expression level of DBH was appeared by adrenal medulla > SNc > hypothalamus orders in OVX+Oil group and in OVX+E$_2$ group. Administration of E$_2$ significantly reduced DBH expression in SNc, and increased in adrenal medulla. Two cDNA products, large(PNMT1) and small(PMNTs) species of 110bp difference, were amplified in SNc and hypothalamus, but only PNMTs was observed in adenal medulla. The PNMTs expression level was in the order of adrenal medulla > hypothalamus > SNc in both OVX+Oil and OVX+E$_2$ group. The PNMTs expression in SNc and adrenal medulla was significantly increased byE$_2$. The present report demonstrated that estrogen effects on transcriptional activities for CA biosynthethic enzymes were tissue specific in adrenal medulla as well as different region of brain. These results suggest that it might be crucial relationship between the type of estrogen receptor and CA enzyme gene expression.

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Effects of Gamma Irradiation on Shelf-Life and Sensory Scores of Squid Sundae under Accelerated Storage Conditions (감마선 조사 처리가 가속저장 오징어순대의 저장성 및 기호성에 미치는 영향)

  • Kim, Hyun-Jee;Kim, Koth-Bong-Woo-Ri;Kim, Dong-Hyun;SunWoo, Chan;Jung, Seul-A;Jeong, Da-Hyun;Jung, Hee-Ye;Kim, Jae-Hun;Lee, Ju-Woon;Do, Sang-Ryong;Byun, Myoung-Woo;Ahn, Dong-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.10
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    • pp.1441-1447
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    • 2012
  • This study was conducted to examine the effects of gamma irradiation on the shelf-life and sensory scores of squid Sundae under accelerated storage conditions. Squid Sundae was stored at $37^{\circ}C$ for 35 days following gamma irradiation at doses of 0, 10, and 20 kGy. For total viable cell counts, control and gamma-irradiated (GI) (10 kGy) squid Sundae were already spoiled in 4 days, whereas GI (20 kGy) squid Sundae showed complete suppression of bacterial growth during storage. There were no significant changes in pH values compared to the control. The VBN and TBARS (thiobarbituric acid reactive substance) values of GI (20 kGy) squid Sundae were significantly lower than those of the control. In addition, the induction period of GI (20 kGy) squid Sundae as measured by a Rancimat showed a higher level compared to that of the control. In the sensory evaluation, there were no significant changes between the control and GI samples. These results suggest that a dose of 20 kGy is the optimum and effective dose for preservation of squid Sundae.

Study on the Utilization of Sawdust Bedding Barn for Dairy Cows (착유우의 톱밥발효우사 이용연구 제 1 보 : 낙농가의 톱밥발효우사 형태별 이용효과 비교)

  • Kweon, Du-Jung;Kweon, Ung-Gi;Ki, Wang-Seok;Lee, Kee-Jong;Han, Jeong-Dae;Jung, Suk-Chan;Kang, Seung-Won;Kang, Sang-Lyol;Jung, Hyoung-Sup;Chang, Hak-Joo
    • Journal of Animal Environmental Science
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    • v.1 no.1
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    • pp.9-19
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    • 1995
  • This study was carried out to investigate the effect of sawdust bedding barn on manure handing, management labour and physiological aspect of dairy cows, and then to establish the criteria on the optimum utilization method of sawdust bedding barn. 46 tie stall barns and 49 sawdust bedding barns were surveyed to cmopare the milk productivity between two different barns, and also 5 tie stall barns, 15 sawdust bedding barns and 1 rice hull bedding barn were selected to study the utilization situation of sawdust barn in Kyung-Ki province area. The major results obtained were as follows; 1. The roof material of sawdust barn were consisted of 66% vinyl house, 23% PVC light and 11% slate and galvanum coated tin. Most of the floor structure was earth ground with the rate of the approximately 82%. 2. The average occupied area of sawdust bed per cow was 15.2 $m^2$, depth that 30 cm and the utilization period was 12 months. 3. Milk Yield was significantly higher at sawdust barn than at tie stall barn(P<0.01). Bacterial and somatic cell count in raw milk were less at the sawdust barn than in tie stall barn. However, there was not significance difference between two barns. 4. The labour hour needed to cow management in the sawdust barn was approximately 48% of that of tie stall barn. 5. The temperature and moisture content measured in sawdust bed were closely affected by seasonal ambient temperature. The skin and hair of cow were much cleaner at the PVC light roofed sawdust barn than any other roof materials. 6. The additives used for improving of fermentation did not show any effect on temperature and moisture content in sawdust bed. When the ambient temperature was $30.4^{\circ}C$, the surface temperature of measured 1 cm above the sawdust bed was $12.2^{\circ}C$ lower and the temperature of 100 cm above the sawdust bed was $2.4^{\circ}C lower under shading net facility than that of vinyl roofed one.7. The hoof length of miking cow was 7.95 cm in tie stall and 9.19 cm in sawdust barn with high significance (P<0.01). And disease occurence such as mastitis and foot-rot tended to decrease in the sawdust barn. 8. The number of total bacteria and coliform bacteria were less in the sawdust bed compared with earth ground resting area. And a parasite strongyloides papillosus was detected but without any infected cow. 9. The nitrate($NO_3N$) content in non-roofed earth ground resting area and earth ground under the sawdust bed was likely to pollute the ground water. 10. In economic point of view, rice hull bedding barn was the cheapest among different systems. And in the sawdust bedding barn PVC light + slate roofed barn was most desirable, and vinyl roofed one the least.

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Physiological Activities of Commercial Instant Curry Powders and Individual Spices (시판 instant curry 및 curry 사용원료의 생리활성)

  • Chung, Myong-Soo;Jung, Seung-Hyeon;Lee, Jin-Sun;Park, Ki-Moon
    • Korean Journal of Food Science and Technology
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    • v.35 no.1
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    • pp.125-131
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    • 2003
  • Physiological activities of hot water extracts of 10 commercial instant curry powders and 6 spices, were investigated. All spice extracts except ginger showed significant antioxidant activities on the autoxidation of linoleic curry acid (p<0.01). Antioxidant activities of clove and fennel were significantly higher than ${\alpha}-tocopherol$, instant curry powders, and other spices, Red pepper $(52.8{\pm}2.13%)$, clove, and coriander showed significant inhibitory activities against angiotensin-I-converting enzyme (p<0.001). Cytotoxic effects of instant curry powder and spices against human cancer cell lines were examined through MTT assay. Black pepper $(29.31{\pm}2.21%\;cytotoxic\;rate)$ and cardamon $(19.41{\pm}3.92%)$ were effective against MCF-7 (p<0.01), Clove $(42.92{\pm}5.57%)$ against HeLa (p<0.01). Ginger $(34.21{\pm}1.11%)$, cardamon, and black pepper against A172 (p<0.001), garlic $(82.88{\pm}0.53%)$ against SN12C (p<0.001), garlic $(71.63{\pm}0.38%)$, red pepper, ginger, fenugreek, SPC, cumin, and MPC against SNU-638 (p<0.001), and cassia $(82.84{\pm}16.92%)$ against A549 (p<0.001).

The Effects of Various Factors on Milk Yield and Variation in Milk Yield Between Milking, Milk Components, Milking Duration, and Milking Flow Rate in Holstein Dairy Cattle (착유우의 연속유량, 유량변이, 유성분, 체세포수, 비유지속시간, 비유속도에 대한 산차, 착유시간, 유기 및 착유간격의 효과)

  • Ahn, B.S.;Jeon, B.S.;Baek, K.S.;Park, S.J.;Lee, H.J.;Lee, W.S.;Kim, S.B.;Park, S.B.;Kim, H.S.;Ju, J.C.;Khan, M. A.
    • Journal of Animal Science and Technology
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    • v.47 no.6
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    • pp.919-924
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    • 2005
  • This study was carried out to estimate the effects of parity, milking time, milking interval and days in milk(DIM) on variation in milk yield between consecutive milkings(am to pm to am), morning and evening milk yield and its components, somatic cell counts(SCS), milking duration, milk flow rate and peak milk flow in Holstein dairy cattle. Records from one hundred and twenty two heads of Holstein cattle at National Livestock Research Institute, Korea were used for this study from July 1 to August 8, 2005. The experimental herd had average 1.6$\pm$0.9 parities, 199.8$\pm$109.1 DIM and 12.26$\pm$4.06kg milk yields at each milking. Milking yield, percent milk fat and SNF, milking duration and average milk flow were significantly varied by parity, milking time and DIM. Percent milk protein and lactose were varied by parity and DIM, however SCS and average milk flow were affected by parity and milking time. Milking interval significantly affected the consecutive, morning and evening milk yield and average milk flow. However, MUN was not affected by parity, milking time, DIM and milking interval. Milk yield was decreased with increasing parity. Milk yield in the morning was higher than that of in the evening. Milk yield between consecutive milking was not affected by parity, however, affected by milking time. Percent milk Fat, SNF and SCS were higher at in evening milk than those of in morning milk. Milk protein, lactose, SNF, SCS, milking duration and peak milk flow rate were influenced by parity. This study suggested that milk yield variation between consecutive milking, milking flow rate, and milking duration could be important traits for enhancing Holstein cattle productivity however, and more study is needed to estimate genetic parameters for such traits.