• Tuberculosis and Respiratory Diseases
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• 제82권2호
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• pp.143-150
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• 2019

Background: The purpose of this study was to analyze the relationship between the gene mutation patterns by the GenoType MTBDRplus (MTBDRplus) assay and the phenotypic drug susceptibility test (pDST) results of isoniazid (INH) and prothionamide (Pto). Methods: A total of 206 patients whose MTBDRplus assay results revealed katG or inhA mutations were enrolled in the study. The pDST results were compared to mutation patterns on the MTBDRplus assay. Results: The katG and inhA mutations were identified in 68.0% and 35.0% of patients, respectively. Among the 134 isolated katG mutations, three (2.2%), 127 (94.8%) and 11 (8.2%) were phenotypically resistant to low-level INH, high-level INH, and Pto, respectively. Among the 66 isolated inhA mutations, 34 (51.5%), 18 (27.3%) and 21 (31.8%) were phenotypically resistant to low-level INH, high-level INH, and Pto, respectively. Of the 34 phenotypic Pto resistant isolates, 21 (61.8%), 11 (32.4%), and two (5.9%) had inhA, katG, and both gene mutations. Conclusion: It is noted that Pto may still be selected as one of the appropriate multidrug-resistant tuberculosis regimen, although inhA mutation is detected by the MTBDRplus assay until pDST confirms a Pto resistance. The reporting of detailed mutation patterns of the MTBDRplus assay may be important for clinical practice, rather than simply presenting resistance or susceptibility test results.

• IMMUNE NETWORK
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• 제20권1호
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• pp.10.1-10.14
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• 2020

Immune checkpoint inhibitors (ICIs) have shown remarkable benefit in the treatment of patients with non-small-cell lung cancer (NSCLC) and have emerged as an effective treatment option even in the first-line setting. ICIs can block inhibitory pathways that restrain the immune response against cancer, restoring and sustaining antitumor immunity. Currently, there are 4 PD-1/PD-L1 blocking agents available in clinics, and immunotherapy-based regimen alone or in combination with chemotherapy is now preferred option. Combination trials assessing combination of ICIs with chemotherapy, targeted therapy and other immunotherapy are ongoing. Controversies remain regarding the use of ICIs in targetable oncogene-addicted subpopulations, but their initial treatment recommendations remained unchanged, with specific tyrosine kinase inhibitors as the choice. For the majority of patients without targetable driver oncogenes, deciding between therapeutic options can be difficult due to lack of direct cross-comparison studies. There are continuous efforts to find predictive biomarkers to find those who respond better to ICIs. PD-L1 protein expressions by immunohistochemistry and tumor mutational burden have emerged as most well-validated biomarkers in multiple clinical trials. However, there still is a need to improve patient selection, and to establish the most effective concurrent or sequential combination therapies in different NSCLC clinical settings. In this review, we will introduce currently used ICIs in NSCLC and analyze most recent trials, and finally discuss how, when and for whom ICIs can be used to provide promising avenues for lung cancer treatment.

• Asian-Australasian Journal of Animal Sciences
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• 제16권10호
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• pp.1518-1523
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• 2003

This experiment was conducted to investigate the effect of various feeding regimens on growth performance, nutrient digestibilities, nitrogen retention, blood urea nitrogen (BUN) concentration and feed cost in young pigs weaned at 21 days of age. One hundred twenty crossbred pigs (Landrace${\times}$Large White${\times}$Duroc, average 6.8 kg BW), weaned at 21 days of age, were allotted to 5 treatments in a 5 replicates by a randomized completely block (RCB) design. Treatments were as follow: 1) 1P (1-4 weeks: CP 23% and lysine 1.60%), 2) 2P-I (1 week: CP 23% and lysine 1.60%, 2-4 weeks: CP 21% and lysine 1.45%), 3) 2P-II (1-2 weeks: CP 23% and lysine 1.60%, 3-4 weeks: CP 21% and lysine 1.45%), 4) 2P-III (1-3 weeks: CP 23% and lysine 1.60%, 4 week: CP 21% and lysine 1.45%), 5) 3P (1 week: CP 23% and lysine 1.60%, 2-3 weeks: CP 21% and lysine 1.45%, 4 week: CP 19% and lysine 1.30%). Three different diets were formulated and supplied according to phase feeding programs. Diet 1 contains 23% crude protein and 1.60% lysine, diet 2 contains 21% crude protein and 1.45% lysine and diet 3 contains 19% crude protein and 1.30 lysine, respectively. Although there was no significant difference in growth performances, there was a beneficial effect of 3 phase feeding. The ADG was higher in 3P treatment than other treatments and it was observed clearly in late period (3-4 weeks) than in early period. Also, with increase in age, growth rate of pigs in 3P treatment was higher than that in 1P treatment approximately 37% (p=0.1379). There were no significant differences among all treatments in nutrient digestibility. The concentration of BUN was higher in pigs were fed diet containing 21% crude protein and 1.45% lysine (eg, 2P-1 and 3P) than those supplied diet containing high nutrient value at 2 week. The lowest feed cost/kg weight gain of pigs showed in 3P among treatments (p<0.05) whereas, high feed cost/kg weight gain of pigs was calculated in 1P and 2P-II treatments compared with 2P-I and 2 P-II (p<0.05), because of high milk products were used in those diet.

• Animal Bioscience
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• 제35권5호
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• pp.690-697
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• 2022

Objective: This study aimed to evaluate the effect of the ad libitum and restricted feeding regimen on fasting heat production (FHP) and body composition. Methods: Twelve Hubbard broilers breeders were selected with the same body weight and submitted in two feeding regimes: Restricted (T1) with feed intake of 150 g/bird/d and ad libitum (T2). The birds were randomly distributed on the treatments in two runs with three replications per treatment (per run). The birds were adapted to the feed regimens for ten days. After that, they were allocated in the open-circuit chambers and kept for three days for adaptation. On the last day, oxygen consumption (VO₂) and carbon dioxide production (VCO₂) were measured by 30 h under fasting. The respiratory quotient (RQ) was calculated as the VCO₂/VO₂ ratio, and the heat production (HP) was obtained using the Brower equation (1985). The FHP was estimated throughout the plateau of HP 12 hours after the feed deprivation. The body composition was analyzed by dual-energy X-ray absorptiometry scanning at the end of each period. Data were analyzed for one-way analysis of variance using the Minitab software. Results: The daily feed intake was 30 g higher to T2 (p<0.01) than the T1. Also, the birds of the T2 had significatively (p<0.05) more oxygen consumption (+3.1 L/kg^0.75/d) and CO₂ production (+2.2 L/kg^0.75/d). That resulted in a higher FHP 359±14 kJ/kg^0.75/d for T2 than T1 296±17.23 kJ/kg^0.75/d. In contrast, the RQ was not different between treatments, with an average of 0.77 for the fasting condition. In addition, protein and fat composition were not affected by the treatment, while a tendency (p<0.1) was shown to higher bone mineral content on the T1. Conclusion: The birds under ad libitum feeding had a higher maintenance energy requirement but their body composition was not affected compared to restricted feeding.

• 생명과학회지
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• 제26권4호
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• pp.431-438
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• 2016

TRAIL은 정상세포에서는 세포독성을 나타내지 않는 반면, 암세포에서는 사멸을 유도하므로 항암제로 각광받고 있지만 많은 암세포에서 TRAIL에 저항성을 가지고 있는 것으로 알려져 있으므로 이를 극복해야하는 큰 어려움이 남아있다. 본 연구에서는 TRAIL에 저항성을 가지는 인간 방광암 세포주인 5637 세포를 이용하여 histone deacetylase 억제제인 sodium butyrate (SB)와 TRAIL을 혼합처리하였을 경우 유발되는 세포사멸 효과와 이와 관련된 분자생물학적 메카니즘을 연구하였다. 세포독성이 없는 조건의 TRAIL과 SB를 혼합처리 하였을 경우 SB 단독처리군 보다 세포사멸이 현저하게 증가하는 것으로 확인되었다. TRAIL과 SB의 혼합처리는 caspases (caspase-3, -8 and -9)의 활성화 및 PARP의 단편화를 유발하였다. 하지만 caspase 억제제에 의하여 TRAIL과 SB의 혼합처리에 의하여 유발되는 apoptosis가 현저하게 억제되는 것으로 나타났다. 또한 TRAIL과 SB의 혼합처리는 세포표면에 존재하는 DR5의 발현 증가 및 c-FLIP의 발현 감소를 유발하였으며, pro-apoptotic protein인 Bax와 세포질 cytochrome c의 발현 증가 및 anti- apoptotic protein인 Bcl-xL의 발현감소와 함께 tBid의 형성을 유발하였다. 이는 SB와 TRAIL의 혼합처리가 안전하고 선택적으로 TRAIL에 저항성을 가지는 방광암 세포에서 치료하는데 효과적인 전략임을 제시하는 결과이다.

• Journal of Nutrition and Health
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• 제15권3호
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• pp.212-222
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• 1982

본(本) 연구자(硏究者)는 21세(歲)부터 25세(歲)까지의 건강(健康)한 여대생(女大生) 8명(名)을 대상(對象)으로 식이중(食餌中)의 단백질(蛋白質) 급원(給源)((동물성)(動物性)과 식물성(植物性) 단백질(蛋白質))을 달리했을 때 혈청중(血淸中)의 cholesterol 농도(濃度)와 triglyceride 농도(濃度) 및 24시간(時間) 뇨중(尿中)의 creatinine 농도(濃度)와 3-methylhistidine의 농도(濃度)에 미치는 영향(影響)을 살펴보았다. 조사대상자(調査對象者)들은 control diet와 meat diet와 textured soy protein (TSP) diet를 각(各) 3일씩 섭취(攝取)하였으며, 각(各) 식이(食餌)의 3일째 되는 날에는 24시간(時間) 뇨(尿)를 채취(採取)하였고, 4일째 되는 날 아침 식사(食事) 전에 채혈(採血)하여 분석(分析)한 결과(結果)는 다음과 같다. 1) 혈청(血淸) cholesterol 농도(濃度)는 meat diet 시에 control diet보다 현저(顯著)하게 증가(增加)하였으며 (P<0.05), TSP diet시에는 control diet 보다 현저(顯著)하게 감소(減少)하였고 (P<0.01) meat diet와 비교(比較)시에도 현저(顯著)하게 감소(減少)되었다(P<0.01). 2) 혈청(血淸) triglyceride 농도(濃度)는 meat diet 시에 control diet 보다 감소(減少) 되었으나, 유의적(有意的)인 차이(差異)는 없었고 meat diet와 비교(比較)시에는 현저(顯著)하게 감소(減少)되었다(P<0.01). 3) 뇨중(尿中)의 creatinine 농도(濃度)는 meat diet 시에 control diet보다 약간 증가(增加)했으나 유의적(有意的)인 차이(差異)는 없었다. TSP diet 시에는 control diet보다 약간 감소(減少)하였으나 유의적(有意的)인 차이(差異)는 없었고 meat diet와 비교(比較)시에는 현저(顯著)하게 감소(減少)되었다(P<0.05). 4) 뇨중(尿中)의 3-methylhistidine 농도(濃度)는 meat diet 시에 control diet보다 약간 증가(增加)했으나, 유의적(有意的)인 차이(差異)는 없었다. TSP diet 시에는 control diet보다 약간 감소(減少)하였으나 유의적(有意的)인 차이(差異)는 없었고 meat diet와 비교(比較)시에는 현저(顯著)하게 감소(減少)되었다 (P<0.05). 5) 3-methylhistidine가 creatinine의 비(比)는 control diet 보다 meat diet와 TSP diet 시에 약간 증가(增加)하였으나, 유의적(有意的)인 차이(差異)는 없었다.

• Clinical and Experimental Pediatrics
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• 제61권2호
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• pp.53-58
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• 2018

Purpose: Although the prognosis is generally good in patients with intermediate-risk neuroblastoma, no consensus has been reached on the ideal treatment regimen. This study analyzed treatment outcomes and toxicities in patients younger than 18 months with stage 4 MYCN nonamplified neuroblastoma. Methods: We retrospectively analyzed 20 patients younger than 18 months newly diagnosed with stage 4 MYCN nonamplified neuroblastoma between January 2009 and December 2015. Patients received 9 cycles of chemotherapy and surgery, with or without local radiotherapy, followed by 12 cycles of differentiation therapy with 13-cis-retinoic acid. Chemotherapy consisted of alternating cycles of cisplatin, etoposide, doxorubicin, and cyclophosphamide (CEDC) and ifosfamide, carboplatin, and etoposide (ICE) regimens. Results: The most common primary tumor site was the abdomen (85%), and the most common metastatic sites were the lymph nodes (65%), followed by the bones (60%), liver (55%), skin (45%), and bone marrow (25%). At the end of induction therapy, 14 patients (70%) achieved complete response, with 1 achieving very good partial response, 4 achieving partial response, and 1 showing mixed response. Nine patients (45%) received local radiotherapy. At a median follow-up of 47 months (range, 17-91 months), none of these patients experienced relapse, progression, or secondary malignancy, or died. Three years after chemotherapy completion, none of the patients had experienced grade ${\geq}3$ late adverse effects. Conclusion: Patients younger than 18 months with stage 4 MYCN nonamplified neuroblastoma showed excellent outcomes, without significant late adverse effects, when treated with alternating cycles of CEDC and ICE, followed by surgery and differentiation therapy.

• Clinical and Experimental Pediatrics
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• 제60권4호
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• pp.118-123
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• 2017

Purpose: Tuberculosis (TB) remains a problem in the community. TB patients usually experience malnutrition, which is characterized by both decreased body weight (BW) and body fat percentage (BFP). Leptin, an important regulator of BW, also plays an important role in cellular immunity, which is integral to defense against Mycobacterium tuberculosis infection. We analyzed the effect of an anti-TB treatment regimen on the leptin level, BW, and BFP of children with TB. Methods: The design of this study was a group interrupted time series. The subjects were children with probable TB according to clinical criteria based on an Indonesian scoring system adopted from the Consensus of Expert Panel. BW; BFP; energy intake; fat and protein intake; and leptin levels before, 2 months after (intensive phase), and 6 months after (continuation phase) anti-TB treatment, were measured. About 40 children, aged 5-14 years, participated in this study. Results: The BW, BFP and leptin level increased from before treatment to after completion of the intensive phase and still showed an increased during the continuation phase: BW 18.65 kg, 19.75 kg, and 20.85 kg; BFP 18.3%, 19.5%, and 20.2%; and leptin level 1.9 mg/dL, 3.07 mg/dL, and 3.4 mg/dL, respectively (P<0.01). Conclusion: Leptin level, BW, and BFP increased throughout the course of anti-TB treatment, compared with pretreatment values. Further research is needed to compare the results with data for healthy children.

• IMMUNE NETWORK
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• 제13권6호
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• pp.275-282
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• 2013

Influenza virus is one of the major sources of respiratory tract infection. Due to antigenic drift in surface glycoproteins the virus causes annual epidemics with severe morbidity and mortality. Although hemagglutinin (HA) is one of the highly variable surface glycoproteins of the influenza virus, it remains the most attractive target for vaccine development against seasonal influenza infection because antibodies generated against HA provide virus neutralization and subsequent protection against the virus infection. Combination of recombinant adenovirus (rAd) vector-based vaccine and mucosal administration is a promising regimen for safe and effective vaccination against influenza. In this study, we constructed rAd encoding the globular head region of HA from A/Puerto Rico/8/34 virus as vaccine candidate. The rAd vaccine was engineered to express high level of the protein in secreted form. Intranasal or sublingual immunization of mice with the rAd-based vaccine candidates induced significant levels of sustained HA-specific mucosal IgA and IgG. When challenged with lethal dose of homologous virus, the vaccinated mice were completely protected from the infection. The results demonstrate that intranasal or sublingual vaccination with HA-encoding rAd elicits protective immunity against infection with homologous influenza virus. This finding underlines the potential of our recombinant adenovirus-based influenza vaccine candidate for both efficacy and rapid production.

• Nutrition Research and Practice
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• 제13권4호
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• pp.286-294
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• 2019

BACKGROUND/OBJECTIVES: Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LCPUFA), is acquired by dietary intake or the in vivo conversion of ${\alpha}$-linolenic acid. Many enzymes participating in LCPUFA synthesis are regulated by peroxisome proliferator-activated receptor alpha ($PPAR{\alpha}$). Therefore, it was hypothesized that the tissue accretion of endogenously synthesized DHA could be modified by $PPAR{\alpha}$. MATERIALS/METHODS: The tissue DHA concentrations and mRNA levels of genes participating in DHA biosynthesis were compared among $PPAR{\alpha}$ homozygous (KO), heterozygous (HZ), and wild type (WT) mice (Exp I), and between WT mice treated with clofibrate ($PPAR{\alpha}$ agonist) or those not treated (Exp II). In ExpII, the expression levels of the proteins associated with DHA function in the brain cortex and retina were also measured. An n3-PUFA depleted/replenished regimen was applied to mitigate the confounding effects of maternal DHA. RESULTS: $PPAR{\alpha}$ ablation reduced the hepatic Acox, Fads1, and Fads2 mRNA levels, as well as the DHA concentration in the liver, but not in the brain cortex. In contrast, $PPAR{\alpha}$ activation increased hepatic Acox, Fads1, Fads2, and Elovl5 mRNA levels, but reduced the DHA concentrations in the liver, retina, and phospholipid of brain cortex, and decreased mRNA and protein levels of the brain-derived neurotrophic factor in brain cortex. CONCLUSIONS: LCPUFA enzyme expression was altered by $PPAR{\alpha}$. Either $PPAR{\alpha}$ deficiency or activation-decreased tissue DHA concentration is a stimulus for further studies to determine the functional significance.