• Title/Summary/Keyword: Disease models

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Emerging Genomics Technologies in Nutritional Sciences: Applications to obesity and hypertension research

  • Mouss, Naima-Moustaid;Sumithra Urs;Kim, Suyeon;Heo, Young-Ran
    • Proceedings of the Korean Nutrition Society Conference
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    • 2002.05a
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    • pp.29-41
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    • 2002
  • While the sequencing of several genomes was underway, several advanced techniques in genetics, molecular biology and protein chemistry emerged. Within the nutritional sciences, while the focus on nutrition education, epidemiology and public health aspects remains essential; it is crucial to incorporate the new advances in gene and protein discovery in nutritional studies. Nutrition is a discipline that has always integrated social, biochemical and physiological sciences from the studies at the molecule level to studies at the population level. For this reason, nutritionists are in a prime position to readily incorporate the current genomics approaches in nutrition research, All the available analytical techniques can and should be used in modern nutritional sciences. These include genetics, genomics, proteomics and metabolomics which also require integration and use of bioinformatics and computational methods for data analysis and management. These applications will be briefly reviewed with a primary focus on what the genomics and genetics approaches offer to nutritionists. We will use one of our research focus areas to illustrate uses of some of these applications in obesity-hypertension research. Our central hypothesis is that adipose tissue is an endocrine organ that plays a major role in obesity and related hypertension. We are primarily studying the renin angiotensin system (RAS). We provide evidence from our own studies and others for the paracrine as well as endocrine role of adipocyte-derived angiotensin II in adipocyte gene expression, adiposity and blood pressure regulation. Both cell culture studies as well as knockout and transgenic mice models are used to test our hypothesis. Genomics and proteomics technologies are currently developed to complement our physiological and molecular studies on the RAS and for a fine analysis of this system and its function in health and disease.

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Red Meat Intake and Risk of Non-Hodgkin Lymphoma: A Meta-Analysis

  • Fallahzadeh, Hosein;Cheraghi, Maria;Amoori, Neda;Alaf, Mehrangiz
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10421-10425
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    • 2015
  • Background: While the incidence of non-Hodgkins lymphoma (NHL) has been rising worldwide, the reasons remain undefined. Recent research has focused on effect of red andf processed meat intake as a risk factor, but with inconclusive results. We therefore conducted a meta-analysis of data published to date, to ascertain the overall association between intake and NHL. Materials and Methods: A published literature search was performed through Pubmed, Cochrane Library, Medline, and Science Citation Index Expanded databases for articles published in English. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated using random or fixed effects models. Heterogeneity was assessed using Chi-square and I2 statistics. Dissemination bias was evaluated by funnel plot analysis.We performed a formal meta-analysis using summary measures from these studies. Results: In total, 11 published studies were included in the final analysis. The combined analysis revealed that there was significant association between the red meat and NHL risk (OR=1.10, 95%CI: 1.02 to 1.19, p=0.01). Additionally, there was showed significance association between processed red meat and NHL risk (OR=1.17, 95%CI: 1.06 to 1.29, p=0.001). In subgroup analysis, a statistical significant association was noted between diffuse large B-cell lymphoma (DLBCL) (OR=1.20, 95%CI: 1.04 to 2.37, P=0.01) and red meat intake. Conclusions: In this meta-Analysis, there was evidence for association between consumption of red meat, or processed meat and risk of NHL, particularly with the DLBCL subtype in the red meat case.

18FDG Synthesis and Supply: a Journey from Existing Centralized to Future Decentralized Models

  • uz Zaman, Maseeh;Fatima, Nosheen;Sajjad, Zafar;Zaman, Unaiza;Tahseen, Rabia;Zaman, Areeba
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10057-10059
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    • 2015
  • Positron emission tomography (PET) as the functional component of current hybrid imaging (like PET/CT or PET/MRI) seems to dominate the horizon of medical imaging in coming decades. $^{18}$Flourodeoxyglucose ($^{18}FDG$) is the most commonly used probe in oncology and also in cardiology and neurology around the globe. However, the major capital cost and exorbitant running expenditure of low to medium energy cyclotrons (about 20 MeV) and radiochemistry units are the seminal reasons of low number of cyclotrons but mushroom growth pattern of PET scanners. This fact and longer half-life of $^{18}F$ (110 minutes) have paved the path of a centralized model in which $^{18}FDG$ is produced by commercial PET radiopharmacies and the finished product (multi-dose vial with tungsten shielding) is dispensed to customers having only PET scanners. This indeed reduced the cost but has limitations of dependence upon timely arrival of daily shipments as delay caused by any reason results in cancellation or rescheduling of the PET procedures. In recent years, industry and academia have taken a step forward by producing low energy, table top cyclotrons with compact and automated radiochemistry units (Lab-on-Chip). This decentralized strategy enables the users to produce on-demand doses of PET probe themselves at reasonably low cost using an automated and user-friendly technology. This technological development would indeed provide a real impetus to the availability of complete set up of PET based molecular imaging at an affordable cost to the developing countries.

Association of lnc-LAMC2-1:1 rs2147578 and CASC8 rs10505477 Polymorphisms with Risk of Childhood Acute Lymphoblastic Leukemia

  • Hashemi, Mohammad;Bahari, Gholamreza;Naderi, Majid;Bojd, Simin Sadeghi;Taheri, Mohsen
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.11
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    • pp.4985-4989
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    • 2016
  • Long non-coding RNAs (lncRNAs) are a novel class of non-protein coding RNAs that are involved in a wide variety of biological processes. There are limited data regarding the impact of lnc-LAMC2-1:1 rs2147578 as well as CASC8 rs10505477 T>C polymorphisms on cancer development. Here we examined for the first time whether rs2147578 and rs10505477 polymorphisms are associated with childhood acute lymphoblastic leukemia (ALL) in a total of 110 cases and 120 healthy controls. Genotyping was achieved by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The rs2147578 variant increased the risk of ALL in codominant (OR=4.33, 95%CI=2.00-9.37, p<0.0001, CG vs CC, and OR=5.81, 95%CI=2.30-14.69, p=0.0002, GG vs CC), dominant (OR=4.63, 95%CI=2.18-9.86, p<0.0001, CG+GG vs CC), overdominant (OR=1.74, 95%CI=1.02-2.97, p=0.0444, CG vs CC+GG) and allele (OR=1.91, 95%CI=1.32-2.77, p=0.0008, G vs C) inheritance models tested. No significant association was found between the CASC8 rs10505477 T>C variant and risk of childhood ALL. In conclusion, the present study revealed that the lnc-LAMC2-1:1 rs2147578 polymorphism may be a risk factor for developing childhood ALL. Further studies with larger sample sizes with different ethnicities are now required to confirm our findings.

Neuroprotective effect of lithium after pilocarpine-induced status epilepticus in mice

  • Hong, Namgue;Choi, Yun-Sik;Kim, Seong Yun;Kim, Hee Jung
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.1
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    • pp.125-131
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    • 2017
  • Status epilepticus is the most common serious neurological condition triggered by abnormal electrical activity, leading to severe and widespread cell loss in the brain. Lithium has been one of the main drugs used for the treatment of bipolar disorder for decades, and its anticonvulsant and neuroprotective properties have been described in several neurological disease models. However, the therapeutic mechanisms underlying lithium's actions remain poorly understood. The muscarinic receptor agonist pilocarpine is used to induce status epilepticus, which is followed by hippocampal damage. The present study was designed to investigate the effects of lithium post-treatment on seizure susceptibility and hippocampal neuropathological changes following pilocarpine-induced status epilepticus. Status epilepticus was induced by administration of pilocarpine hydrochloride (320 mg/kg, i.p.) in C57BL/6 mice at 8 weeks of age. Lithium (80 mg/kg, i.p.) was administered 15 minutes after the pilocarpine injection. After the lithium injection, status epilepticus onset time and mortality were recorded. Lithium significantly delayed the onset time of status epilepticus and reduced mortality compared to the vehicle-treated group. Moreover, lithium effectively blocked pilocarpine-induced neuronal death in the hippocampus as estimated by cresyl violet and Fluoro-Jade B staining. However, lithium did not reduce glial activation following pilocarpine-induced status epilepticus. These results suggest that lithium has a neuroprotective effect and would be useful in the treatment of neurological disorders, in particular status epilepticus.

Analysis of Ventricular Electromechanical Characteristics by Lesions in Sudden Myocardial Infraction: Computer Simulation Study (급성 심근경색 병변에 따른 심실의 전기 역학적 특성 분석: 컴퓨터 시뮬레이션 연구)

  • Baek, Dong Geun;Jeong, Da Un;Lim, Ki Moo
    • Journal of Biomedical Engineering Research
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    • v.38 no.6
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    • pp.313-320
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    • 2017
  • Myocardial infarction is a disease caused by stenosis of the coronary arteries. The high risk of sudden cardiac death due to myocardial infarction has triggered related researches that have been actively studied so far. However, these studies focused on the clinical results, which are mainly based on observations of symptoms due to infarction through electrocardiograms. Therefore, in this study, we tried to analyze the behavior of heart according to the position and volume of infarction lesion through the computer simulation study using three dimensional ventricular models. In order to implement infarction, commercial software was used to simulate cell necrosis due to blockage of a specific coronary. In addition, the conduction block due to infarction was mimicked by reducing the electrical conduction in the infarcted area, which was 100 times less than the electrical conduction of the whole ventricular lattice implemented by the finite element analysis method. Thus, this study classified the infarcted cases into the upper, middle, lower, and apex according to lattice data of eight different infraction areas. In other words, we assumed that myocardial infarction would have inherent electro-dynamic characteristics depending on the location and extent, and analyzed the ventricular electromechanical responses for infarction lesions using a three dimensional cardiac physiome model. The results showed that the volume of infarction did not directly affect the cardiac responses, but the location of the infarction lesions could influence the ventricular pumping efficiency. These suggest that the occlusion of specific coronary arteries may have a fatal effect on the decline in ventricular performance. In conclusion, although location of myocardial infarction lesions is considered to be an important variable to be considered clinically rather than lesion size, quantitative predictions should be made more in the future considering physiological factors such as lesion location and direction of myocardial fiber at that location.

Prevalence of Abdominal Obesity and Associated Factors among Korean Adults: The 2001 Korean National Health and Nutrition Examination Survey (한국 성인의 복부비만 빈도와 관련 인자: 2001 국민건강영양조사)

  • Chung, Hae-Rang
    • Journal of Nutrition and Health
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    • v.39 no.7
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    • pp.684-691
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    • 2006
  • Abdominal obesity (AO) is a strong risk factor for type 2 diabetes and cardiovascular disease, which has shown a remarkable increase in Korea. This study aimed to identify prevalence of AO and related risk factors in Korean adults. A total of 5,132 men and women aged 20-85 years old from the 2001 Korean National Health and Nutrition Examination Survey were included in the analyses. AO was defined as waist circumference >=90 cm in men and >=85 cm in women as proposed by Korean Society of Obesity. Multiple logistic regression was carried out to identify risk factors for AO. Three models were specified: (i) demographic and socioeconomic factors (model 1: age, education, poverty income ratio, employment), (ii) lifestyle factors and covariates (model 2: physical activity, cigarette smoking, alcohol consumption, dietary quality, type 2 diabetes, co-morbidity) and (iii) demographic, socioeconomic and lifestyle factors (model 3). The prevalence of AO was 24.1 % in men, 23.5% in women. High poverty income ratio in men and low education attainment in women were risk factors for AO in model. 1. There was a significant association of AO with alcohol consumption, physical inactivity and dietary quality in men, alcohol consumption and cigarette smoking in women. These factors except alcohol consumption in men became insignificant in model 3. This findings underscore the importance of developing AO prevention programs in Korea that target the at risk groups identified in this study. A program focusing on low income men or less educated women would be more efficient.

Egg consumption is associated with a lower risk of type 2 diabetes in middle-aged and older men

  • Lee, Jieul;Kim, Jihye
    • Nutrition Research and Practice
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    • v.12 no.5
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    • pp.396-405
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    • 2018
  • BACKGROUND/OBJECTIVES: This prospective study examined gender-specific associations between egg intake and the risk of developing type 2 diabetes using data from a large-scale cohort study. SUBJECTS/METHODS: A total of 7,002 Korean adults (40-69 years) without type 2 diabetes at baseline were analyzed. Dietary intake was evaluated by a food frequency questionnaire administered at baseline (2001-2002) and the second follow-up examination (2005-2006). Type 2 diabetes was diagnosed as a fasting glucose concentration ${\geq}126mg/dL$ or current use of glucose-lowering medications or insulin injection. Multivariate Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for incident type 2 diabetes according to egg consumption or cholesterol intake. RESULTS: During a 14-year follow up period, 857 subjects developed type 2 diabetes. In men, frequent egg intake (2- < 4 servings/week) was associated with a 40% lower risk of developing type 2 diabetes than infrequent egg intake (0- < 1 serving/week) (HR = 0.60, 95% CI: 0.37-0.97), whereas no association between egg intake and incidence of type 2 diabetes was observed in women (HR = 0.61, 95% CI: 0.27-1.37). There was no association between cholesterol intake and risk of incident type 2 diabetes in either men or women. CONCLUSIONS: Egg consumption was inversely related to the risk of incident type 2 diabetes in men, but not in women, suggesting gender differences in the relationship between diet and disease risk.

Emerging Genomics Technologies in Nutritional Sciences : Applications to Obesity and Hypertension Research

  • Moustaid-Moussa;Sumithra Urs;Kim, Suyeon;Heo, Young-Ran
    • Proceedings of the Korean Nutrition Society Conference
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    • 2002.06a
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    • pp.598-603
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    • 2002
  • While the sequencing of several genomes was underway, several advanced techniques in genetics, molecular biology and protein chemistry emerged. Within the notritional sciences, while the focus on nutrition education, epidemiology and public health aspects remains essential; it is crucial to incorporate the new advances in gene and protein discovery in nutritional studies. Nutrition is a discipline that has always integrated social, biochemical and physiological sciences from the studies at the molecule level to studies at the population level. for this reason, nutritionists are in a prime position to readily incorporate the current genomics approaches in nutrition research. All the available analytical techniques can and should be used in modem nutritional sciences. These include genetics, genomics, proteomics and metabolomics which also require integration and use of bioinformatics and computational methods for data analysis and management. These applications will be briefly reviewed with a primary focus on what the genomics and genetics approaches offer to nutritionists. We will use one of our research focus areas to illustrate uses of some of these applications in obesity-hypertension research. Our central hypothesis is that adipose tissue is an endocrine organ that plays a major role in obesity and related hypertension. We are primarily studying the renin angiotensin system (RAS). We provide evidence from our own studies and others for the paracrine as well as endocrine role of adipocyte-derived angiotensin II in adipocyte gene expression, adiposity and blood pressure regulation. Both cell culture studies as well as knockout and transgenic mice models are used to test our hypothesis. Genomics and proteomics technologies are currently developed to complement our physiological and molecular studies on the RAS and for a fine analysis of this system and its function in health and disease.

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Exploration of the Gene-Gene Interactions Using the Relative Risks in Distinct Genotypes (유전자형별 상대 위험도를 이용한 유전자-유전자간 상호작용 탐색)

  • Jung, Ji-Won;Yee, Jae-Yong;Lee, Suk-Hoon;Pa, Mi-Ra
    • The Korean Journal of Applied Statistics
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    • v.24 no.5
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    • pp.861-869
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    • 2011
  • One of the main objects of recent genetic studies is to understand genetic factors that induce complex diseases. If there are interactions between loci, it is difficult to find such associations through a single-locus analysis strategy. Thus we need to consider the gene-gene interactions and/or gene-environment interactions. The MDR(multifactor dimensionality reduction) method is being used frequently; however, it is not appropriate to detect interactions caused by a small fraction of the possible genotype pairs. In this study, we propose a relative risk interaction explorer that detects interactions through the calculation of the relative risks between the control and disease groups from each genetic combinations. For illustration, we apply this method to MDR open source data. We also compare the MDR and the proposed method using the simulated data eight genetic models.