• Title/Summary/Keyword: Cancer Metabolism

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Role of Sirtuin 1 in Depression and Associated Mechanisms (우울증에 관한 Sirtuin 1의 역할과 관련된 기전)

  • Seog, Dae-Hyun;Park, Sung Woo
    • Journal of Life Science
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    • v.31 no.12
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    • pp.1120-1127
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    • 2021
  • Depression has a negative impact on social functioning due to its high prevalence and increased suicide rate, and is a disease with a high economic burden. Depression is related to diverse brain-related phenomena, such as neuroinflammation, synaptic dysfunction, and cognitive deficit. As antidepressant drugs used in clinical trials have shown poor therapeutic effects, antidepressant drugs that show rapid efficacy urgently need to be developed. Although studies on various genes, proteins, and signaling pathways related to depression have been conducted, the pathogenesis of depression has not been clearly elucidated. Sirtuin 1 is a nicotinamide-adenine dinucleotide- (NAD+-) dependent histone deacetylase and is involved in cell differentiation, apoptosis, autophagy, and cancer metabolism. Recent genetic studies found that sirtuin 1 is a potential target gene for depression. In addition, preclinical studies reported that sirtuin 1 signaling affects depression-like behavior. In this review, we attempt to present up-to-date knowledge of depression and sirtuin 1. We describe the various roles of sirtuin 1 in the regulation of glial activation, circadian rhythm, neurogenesis, and cognitive function and the effects of its expression on depression. Further, we discuss the effect of sirtuin 1 on the impairment of neural plasticity, one of the key mechanisms of depression, and the associated mechanisms of sirtuin 1.

Four Times of Relapse of Plasmodium vivax Malaria Despite Primaquine Treatment in a Patient with Impaired Cytochrome P450 2D6 Function

  • Choi, Sungim;Choi, Heun;Park, Seong Yeon;Kwak, Yee Gyung;Song, Je Eun;Shin, So Youn;Baek, Ji Hyeon;Shin, Hyun-IL;Oh, Hong Sang;Kim, Yong Chan;Yeom, Joon-Sup;Han, Jin-Hee;Kim, Min Jae
    • Parasites, Hosts and Diseases
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    • v.60 no.1
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    • pp.39-43
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    • 2022
  • Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.

Analysis of Potential Active Ingredients and Treatment Mechanism of Ponciri Fructus Immaturus for Dermatitis Accompanied by Pruritus Using Network Pharmacology (네트워크 약리학을 이용한 소양증을 동반한 피부 염증에 대한 지실(枳實)의 잠재적 치료기전 탐색)

  • Seo, GwangYeel;Kim, Jundong;Kim, Byunghyun;Kim, Kyu-Seok;Nam, Hae-jeong;Kim, Yoon-Bum
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.35 no.4
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    • pp.75-94
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    • 2022
  • Objectives : To identify the active ingredient of Poncirus Trifoliata Immaturus and to explore the mechanism expected to potentially act on dermatitis accompanied by pruritus. Methods : We conducted the network pharmacological analysis. We selected effective ingredients among the active compounds of Poinciri Fructus Immaturus. We found the target protein of the selected active ingredient, disease(dermatitis accompanied by pruritus) and fexofenadine. Then we established the network between the proteins which Poinciri Fructus Immaturus and fexofenadine intersected with disease respectively, and the coregene was also extracted. After that, the active pathways in the human body involving the groups and coregenes were searched. Results : Total of 7 active ingredients were selected, and 202 target proteins were collected. There were 756 proteins related to inflammatory skin disease accompanied by pruritus, and 75 proteins were related to fexofenadine. 42 proteins crossed by Poinciri Fructus Immaturus with a disease, and 31 proteins crossed by fexofenadine with a disease. 12 proteins were found as a coregene from the proteins that cross Poinciri Fructus Immaturus and disease. Coregenes are involved in 'Nitric-oxide synthase regulator activity', 'Epidermal growth factor receptor signaling pathway'. 2 groups that extracted are invloved in 'Fc receptor signaling pathway', 'Central carbon metabolism in cancer', 'Phosphatidylinositol 3-kinase complex, class IB', and 'omega-hydroxylase P450 pathway'. Conclusion : It is expected that Poinciri Fructus Immaturus will be able to show direct or indirect anti-pruritus and anti-inflammatory effects on skin inflammation accompanied by pruritus in the future. And it is also expected to have a synergy effect with fexofenadine on skin disease.

Optimization of Automated Solid Phase Extraction-based Synthesis of [18F]Fluorocholine (고체상 추출법을 기반으로 한 [18F]Fluorocholine 합성법의 최적화 연구)

  • Jun Young PARK;Jeongmin SON;Won Jun KANG
    • Korean Journal of Clinical Laboratory Science
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    • v.55 no.4
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    • pp.261-268
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    • 2023
  • [18F]Fluorocholine is a radiopharmaceutical used non-invasively in positron emission tomography to diagnose parathyroid adenoma, prostate cancer, and hepatocellular carcinoma by evaluating the choline metabolism. In this study, a radiolabeling method for [18F]fluorocholine was optimized using a solid phase extraction (SPE) cartridge. [18F]Fluorocholine was labeled in two steps using an automated synthesizer. In the first step, dibromomethane was reacted with [18F]KF/K2.2.2/K2CO3 to obtain the intermediate [18F]fluorobromomethane. In the second step, [18F]fluorobromomethane was passed through a Sep-Pak Silica SPE cartridge to remove the impurities and then reacted with N,N-dimethylaminoethanol (DMAE) in a Sep-Pak C18 SPE cartridge to label [18F]fluorocholine. The reaction conditions of [18F]fluorocholine were optimized. The synthesis yield was confirmed according to the number of silica cartridges and DMAE concentration. No statistically significant difference in the synthesis yield of [18F]fluorocholine was observed when using four or three silica cartridges (P>0.05). The labeling yield was 11.5±0.5% (N=4) when DMAE was used as its original solution. On the other hand, when diluted to 10% with dimethyl sulfoxide, the radiochemical yield increased significantly to 30.1±5.2% (N=20). In conclusion, [18F]Fluorocholine for clinical use can be synthesized stably in high yield by applying an optimized synthesis method.

Anti-inflammatory effect of Althaea rosea L. Callus extract by applying biorenovation (생물전환 기법을 적용한 접시꽃 callus 추출물의 항염증 활성)

  • Yeon-Su Koo;Tae-Jin Park;Jung-Hwan Kim;Seung-Young Kim
    • Journal of Applied Biological Chemistry
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    • v.66
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    • pp.39-45
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    • 2023
  • Biorenovation is a biotransformation method that converts the structure of chemical compounds and natural product through biocatalytic metabolism of microorganism and could enhance biological effectiveness and mitigate cytotoxicity compared to its substrates. Althaea rosea L. has been used as oriental medicine and is known for physiological efficacies such as antiurolithiatic, anti-inflammatory, and anti-cancer activities. A. rosea L. callus, the plant tissue grown to protect its wound, has been reported to have antioxidant and whitening effects. However, mechanisms of its other activity such as inflammation have not yet been investigated. In this study, we extracted A. rosea L. callus (AR) and produced biorenovated AR (ARBR), and then analyzed anti-inflammatory effect in Lipopolysaccharide-induced RAW 264.7 macrophage at 50, 100, 200 ㎍/mL of ARBR. As a result of inhibition test of nitric oxide production, it was found that ARBR was superior to AR without apparent toxicity. Furthermore, ARBR significantly inhibited production of prostaglandin E2, inducible nitric oxide synthase, cyclooxygenase-2 and pro-inflammatory cytokines including Tumor necrosis factor-α, Interleukin-6, Interleukin-1β in a concentration-dependent manner. In conclusion, we suggest that ARBR could regulate the excessive inflammatory response to an appropriate level and be a promising material for functional cosmetics and pharmaceuticals.

A Study of the Changes of Breast Uptake in Menstrual Cycle on 18F-FDG PET/CT (월경 주기에 따른 18F-FDG PET/CT에서 유방 섭취 변화에 관한 고찰)

  • Tak, Yeojin;Park, Min Soo;Lee, Juyoung;Park, Hoon-Hee
    • Journal of radiological science and technology
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    • v.38 no.1
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    • pp.31-38
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    • 2015
  • $^{18}F-FDG$ PET/CT has been known a useful modality to diagnose high-glucose-using cells such as cancer cells by glucose metabolism of FDG. Mainly, FDG takes on cancer and inflammatory cells; however, there have been FDG uptakes on normal tissues by individual physiological characteristics, occasionally. Especially, in fertile females, unusual FDG uptake of breast changes as the menstrual cycle, and disturb diagnosis. Therefore, the study aimed to evaluate the change of breast FDG uptake in menstrual cycle on $^{18}F-FDG$ PET/CT. 160 females ($34{\pm}3.5$ years old) who do not undergo a gynecologic anamnesis and have regular menstrual cycle over the previous 6 months were examined. They were divided 4 groups (each 40 patients) as flow phase, proliferative phase, ovulatory phase and secretory phase using Pregnancy Calculator 0.14. and history taking. Discovery Ste (GE Healthcare, Milwaukee, Mi, USA) was used a s PET/CT. We analyzed SUVs on accumulated region on breast, and 3 nuclear medicine specialists did the Blind test. SUVs on the Breast were flow phase ($1.64{\pm}0.25$), proliferative phase ($0.93{\pm}0.28$), ovulatory phase ($1.66{\pm}0.26$) and secretory phase ($1.77{\pm}0.28$). It showed high uptake value in secretory, flow phase and ovulatory phase (p<0.05). In gross analysis, the accumulation of breast was divided into 3 grades as comparing with lung and liver. The breast's uptake was equal to lung (Grade I); between lung and liver (Grade II); equal to or greater than liver (Grade III). The results showed high uptake value in secretory, flow phase and ovulatory phase (p<0.05). In fertile females, FDG uptake of breast changed as menstrual cycle, and it available to diagnose breast disease. Therefore, we consider reducing false-negative finding of breast disease, by doing examination on appropriate period through history taking about individual menstrual cycle.

A Study of the Change of Breast Uptake in Menstrual Cycle on $^{18}F$-FDG PET/CT (월경 주기에 따른 $^{18}F$-FDG PET/CT에서의 유방 섭취 변화에 관한 고찰)

  • Park, Min-Soo;Park, Hoon-Hee;Kim, Jung-Yul;Lim, Han-Sang;Kim, Jae-Sam;Lee, Chang-Ho
    • The Korean Journal of Nuclear Medicine Technology
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    • v.15 no.1
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    • pp.39-44
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    • 2011
  • Purpose: $^{18}F$-FDG PET/CT has been known a useful modality to diagnose high-glucose-using cells such as cancer cells by glucose metabolism of FDG. Mainly, FDG takes on cancer and inflammatory cells; However, There have been FDG uptakes on normal tissues by individual physiological characteristics, occasionally. Especially, in fertile females, unusual FDG uptake of breast changes as the menstrual cycle, and disturb diagnosis. Therefore, the study aimed to evaluate the change of breast FDG uptake in menstrual cycle on $^{18}F$-FDG PET/CT. Materials and Methods: 160 females ($34{\pm}3.5$ years old) who do not undergo a gynecologic anamnesis and have regular menstrual cycle over the previous 6 months were examined, from March 2009 to February 2010. They were divided 4 groups (each 40 patients) as flow phase, proliferative phase, ovulatory phase and secretory phase using Pregnancy Calculator 0.14. and history taking. Discovery Ste (GE Healthcare, Milwaukee, Mi, USA) was used as PET/CT. We analyzed SUVs on accumulated region on breast, and 3 nuclear medicine specialists did the Blind test. Results: SUVs on the Breast were flow phase ($1.64{\pm}0.25$), proliferative phase ($0.93{\pm}0.28$), ovulatory phase ($1.66{\pm}0.26$) and secretory phase ($1.77{\pm}0.28$). It showed high uptake value in secretory, flow phase and ovulatory phase (p<0.05). In gross analysis, the accumulation of breast was divided into 3 grades as comparing with lung and liver. The breast's uptake was equal to lung (Grade I); between lung and liver (Grade II); equal to or greater than liver (Grade III). The results showed high uptake value in secretory, flow phase and ovulatory phase (p<0.05). Conclusion: In fertile females, FDG uptake of breast changed as menstrual cycle, and it available to diagnose breast disease. Therefore, we consider reducing false-negative finding of breast disease, by doing examination on appropriate period through history taking about individual menstrual cycle.

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Literature review and future tasks necessary to establish of Korean Dietary Reference Intake for choline (콜린의 한국인 영양소 섭취기준 제정 검토를 위한 문헌 고찰 및 향후 과제)

  • Shim, Eugene;Park, Jae-Hee;Lee, Yunjung;Park, Eunju
    • Journal of Nutrition and Health
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    • v.55 no.2
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    • pp.211-226
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    • 2022
  • Choline, an essential nutrient for humans, is required for the structural integrity of the cell membranes, methyl-group metabolism, synthesis of the neurotransmitter acetylcholine, synthesis of the membrane phospholipid components of the cell membranes, and the transport of lipids and cholesterol. Choline can be synthesized in the body, but it is insufficient to meet the daily requirements and hence it must be obtained through the diet. In the United States/Canada, Australia/New Zealand, Europe, China, and Taiwan, the adequate intake (AI) and tolerable upper intake level (UL) of choline have been established, while the establishment of the 2020 Dietary Reference Intakes for Koreans (KDRI) for choline was postponed due to the lack of a choline database for Korean foods and studies on the choline intake of Koreans. However, as part of the preparation work for the 2020 DRI revision and finalization, choline intake and the possibility of disease occurrence were verified through analysis of published data. The groundwork for the subsequent establishment of a choline DRI was laid through a literature search, evaluation, and review of the literature reported from 1949 up to 2019. This can be regarded as the culmination of this project. According to the results of randomized controlled trials (RCTs), cohort studies, case-control studies, and cross-sectional observational studies in humans, approximately 400-500 mg/day of choline intake was effective in preventing liver function damage (fatty liver), neural tube damage, cardiovascular disease, breast cancer, and cognitive function improvement. The same amount of choline intake, however, also correlated with the risk of prostate and colorectal cancer. At present, there is limited information available on choline intake and health outcomes, particularly for the Korean population. More human studies, including clinical trials on the requirements and the physiological benefits associated with dietary intake, are needed to establish the KDRI for choline.

Human Surfactant Protein-A(SP-A) Gene Locus Associated with Mycoplasma pneumoniae Pneumonia in Korean Children (Mycoplasma pneumoniae 폐렴과 관련된 폐 표면 활성제 단백-A(Human Surfactant Protein-A) 유전자 대립 형질)

  • Kim, Seung Soo;Lee, In Kyu;Ko, Jung Ho;Oh, Myung Ho;Bae, Chong Woo
    • Clinical and Experimental Pediatrics
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    • v.48 no.4
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    • pp.376-379
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    • 2005
  • Purpose : Mycoplasama pneumoniae is a leading cause of pneumonia and exacerbates other respiratory conditions such as asthma. Surfactant protein A(SP-A) is involved in surfactant physiology and surfactant structure, and plays a major role in innate host defense and inflammatory processes in the lung. In this study, SP-A mediated mycoplasma cidal activity. The candidate-gene approach was used to study the association between the SP-A gene locus and Mycoplasama pneumoniae pneumonia in the genetically homogeneous Korean population. Methods : PCR-cRFLP-based methodology was used to detect SP-A genotype. The forty nine children with Mycoplasama pneumoniae pneumonia were matched to 50 nomal neonates. Results : The specific frequencies for the alleles of the SP-A1 and SP-A2 gene in the study population were : $6A^2=21$ percent, $6A^3=45$ percent, $6A^4=11$ percent, $6A^8=9$ percent, $6A^{14}=8$ percent, 1A=11.3 percent, $1A^0=38$ percent, $1A^1=12.7$ percent, $1A^2=9.2$ percent, $1A^5=15.5$ percent, $1A^7=2.9$ percent, $1A^8=4.9$ percent, $1A^9=2.2$ percent, others=3.3 percent. The frequencies of specific genotypes such as $1A^2$ was higher than control group, significantly. Conclusion : $1A^2$ are susceptible factors for Mycoplasama pneumoniae pneumonia. We conclude that the SP-A gene locus($1A^2$) is an important determinant for predisposition to Mycoplasama pneumoniae pneumonia in children.

Anti-Obesity Effects of Jeju Hallabong Tangor (Citrus kiyomi${\times}$ponkan) Peel Extracts in 3T3-L1 Adipocytes (제주산 한라봉 과피 추출물의 지방세포에서의 항비만 효과)

  • Lim, Heejin;Seo, Jieun;Chang, Yun-Hee;Han, Bok-Kyung;Jeong, Jung-Ky;Park, Su-Beom;Choi, Hyuk-Joon;Hwang, Jinah
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.11
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    • pp.1688-1694
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    • 2014
  • Jeju Hallabong Tangor (Citrus kiyomi${\times}$ponkan) is a Citrus species with a variety of physiological properties such as anti-oxidant, anti-inflammation, anti-cancer, and anti-obesity. We investigated the anti-obesity effects of Hallabong Tangor peel extracts before (HLB) and after (HLB-C) bioconversion with cytolase based on modulation of adipocyte differentiation and lipid metabolism in 3T3-L1 adipocytes. Treatment with cytolase decreased flavanone rutinoside forms (narirutin and hesperidin) and increased flavanone aglycone forms (naringenin and hesperetin). During adipocyte differentiation, 3T3-L1 cells were treated with 0.5 mg/mL of Sinetrol (a positive control), HLB or HLB-C. Adipocyte differentiation was inhibited in both citrus groups, but not in control and Sinetriol groups. HLB and HLB-C tended to reduce insulin-induced mRNA levels of CCAAT/enhancer-binding protein ${\alpha}$ ($C/EBP{\alpha}$) and sterol regulatory element-binding protein 1c (SREBP1c). Compared to the control and Sinetrol groups, HLB and HLB-C markedly suppressed insulin-induced protein expression of $C/EBP{\alpha}$ and peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$). The HLB and Sinetrol groups, but not HLB-C group, significantly increased adipolytic activity with higher release of free glycerol compared to the control group in differentiated 3T3-L1 adipocytes. These results suggest that bio-conversion of Hallabong Tangor peel extracts with cytolase increases aglycone flavonoids. Irrespective of bioconversion, both Hallabong Tangor peel extracts exert anti-obesity effects that may contribute to prevention of obesity through inhibition of adipocyte differentiation or induction of adipolytic activity.