• BMB Reports
• /
• 제54권9호
• /
• pp.464-469
• /
• 2021

Cardiomyocyte differentiation occurs through complex and finely regulated processes including cardiac lineage commitment and maturation from pluripotent stem cells (PSCs). To gain some insight into the genome-wide characteristics of cardiac lineage commitment, we performed transcriptome analysis on both mouse embryonic stem cells (mESCs) and human induced PSCs (hiPSCs) at specific stages of cardiomyocyte differentiation. Specifically, the gene expression profiles and the protein-protein interaction networks of the mESC-derived platelet-derived growth factor receptor-alpha (PDGFRα)⁺ cardiac lineage-committed cells (CLCs) and hiPSC-derived kinase insert domain receptor (KDR)⁺ and PDGFRα⁺ cardiac progenitor cells (CPCs) at cardiac lineage commitment were compared with those of mesodermal cells and differentiated cardiomyocytes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the genes significantly upregulated at cardiac lineage commitment were associated with responses to organic substances and external stimuli, extracellular and myocardial contractile components, receptor binding, gated channel activity, PI3K-AKT signaling, and cardiac hypertrophy and dilation pathways. Protein-protein interaction network analysis revealed that the expression levels of genes that regulate cardiac maturation, heart contraction, and calcium handling showed a consistent increase during cardiac differentiation; however, the expression levels of genes that regulate cell differentiation and multicellular organism development decreased at the cardiac maturation stage following lineage commitment. Additionally, we identified for the first time the protein-protein interaction network connecting cardiac development, the immune system, and metabolism during cardiac lineage commitment in both mESC-derived PDGFRα⁺ CLCs and hiPSC-derived KDR⁺PDGFRα⁺ CPCs. These findings shed light on the regulation of cardiac lineage commitment and the pathogenesis of cardiometabolic diseases.

• Genomics & Informatics
• /
• 제1권1호
• /
• pp.1-6
• /
• 2003

In conclusion, the seemingly fuzzy and disorganized data of biology with thousands of different layers ranging from molecule to the Internet have refused so far to be mapped precisely and predicted successfully by mathematicians, physicists or computer scientists. Genomics and bioinformatics are the fields that process such complex data. The insights on the nature of biological entities as complex interaction networks are opening a door toward a generalization of the representation of biological entities. The main challenge of genomics and bioinformatics now lies in 1) how to data mine the networks of the domains of bioinformatics, namely, the literature, metabolic pathways, and proteome and structures, in terms of interaction; and 2) how to generalize the networks in order to integrate the information into computable genomic data for computers regardless of the levels of layer. Once bioinformatists succeed to find a general principle on the way components interact each other to form any organic interaction network at genomic scale, true simulation and prediction of life in silico will be possible.

• Biomolecules & Therapeutics
• /
• 제26권1호
• /
• pp.10-18
• /
• 2018

Tumors are dynamic metabolic systems which highly augmented metabolic fluxes and nutrient needs to support cellular proliferation and physiological function. For many years, a central hallmark of tumor metabolism has emphasized a uniformly elevated aerobic glycolysis as a critical feature of tumorigenecity. This led to extensive efforts of targeting glycolysis in human cancers. However, clinical attempts to target glycolysis and glucose metabolism have proven to be challenging. Recent advancements revealing a high degree of metabolic heterogeneity and plasticity embedded among various human cancers may paint a new picture of metabolic targeting for cancer therapies with a renewed interest in glucose metabolism. In this review, we will discuss diverse oncogenic and molecular alterations that drive distinct and heterogeneous glucose metabolism in cancers. We will also discuss a new perspective on how aberrantly altered glycolysis in response to oncogenic signaling is further influenced and remodeled by dynamic metabolic interaction with surrounding tumor-associated stromal cells.

• 디지털융복합연구
• /
• 제11권11호
• /
• pp.553-560
• /
• 2013

본 연구는 u-health system을 활용하여 대사증후군을 관리하고 위험인자, 신체구성, 체력의 변화를 검증하는데 그 목적이 있다. 남녀 노인 46명(남 24명; 여 22명)을 대상으로, 재택 개별 운동군과 u-health system 활용군으로 분류하였으며, 실험군과 대조군은 대사증후군 위험인자, 신체구성, 체력 검사를 실시한 후, 각각의 중재방법을 실시하고 12주 후에 같은 검사를 실시하였다. 대사증후군 지표는 남성과 여성 모두 혈당과 허리둘레에서 유의한 상호작용이 나타났다. 신체구성은 남성에서는 체중, 근육량, 체지방량, 체지방율, BMI에서 유의한 상호작용이 나타났으며, 여성의 경우 남성과 달리 근육량에서만 상호작용이 나타났다. 체력에서는 남성의 경우, 3m 왕복걷기, 기능적 팔뻗기, 보행속도에서 상호작용효과가 나타났으며, 여성의 경우 앉았다 일어나기, 6분 걷기, 악력에서 유의한 차이가 나타나 남성 그룹과는 차이를 보였다. 결론적으로 u-health system 통한 혈압, 혈당, 운동량의 수시 체크와 피드백은 대사증후군을 보다 지속적으로 관리하는데 효과가 있는 것으로 보인다. 그러나 운동 시 정확한 동작이나 방법에 대한 피드백을 제공하는 것은 아직도 부족한 부분이 많은 것으로 생각되어 이에 대한 정확한 정보를 제공할 수 있도록 개선이 필요하다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권22호
• /
• pp.10027-10031
• /
• 2014

Background: We investigated the risk of cancer mortality according to obesity status and metabolic health status using sampled cohort data from the National Health Insurance system. Materials and Methods: Data on body mass index and fasting blood glucose in the sampled cohort database (n=363,881) were used to estimate risk of cancer mortality. Data were analyzed using a Cox proportional hazard model (Model 1 was adjusted for age, sex, systolic blood pressure, diastolic blood pressure, total cholesterol level and urinary protein; Model 2 was adjusted for Model 1 plus smoking status, alcohol intake and physical activity). Results: According to the obesity status, the mean hazard ratios were 0.82 [95% confidence interval (CI), 0.75-0.89] and 0.79 (95% CI, 0.72-0.85) for the overweight and obese groups, respectively, compared with the normal weight group. According to the metabolic health status, the mean hazard ratio was 1.26 (95% CI, 1.14-1.40) for the metabolically unhealthy group compared with the metabolically healthy group. The interaction between obesity status and metabolic health status on the risk of cancer mortality was not statistically significant (p=0.31). Conclusions: We found that the risk of cancer mortality decreased according to the obesity status and increased according to the metabolic health status. Given the rise in the rate of metabolic dysfunction, the mortality from cancer is also likely to rise. Treatment strategies targeting metabolic dysfunction may lead to reductions in the risk of death from cancer.

• Molecules and Cells
• /
• 제42권4호
• /
• pp.292-300
• /
• 2019

Immunometabolism, defined as the interaction of metabolic pathways with the immune system, influences the pathogenesis of metabolic diseases. Metformin and carbon monoxide (CO) are two pharmacological agents known to ameliorate metabolic disorders. There are notable similarities and differences in the reported effects of metformin and CO on immunometabolism. Metformin, an anti-diabetes drug, has positive effects on metabolism and can exert anti-inflammatory and anti-cancer effects via adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms. CO, an endogenous product of heme oxygenase-1 (HO-1), can exert anti-inflammatory and antioxidant effects at low concentration. CO can confer cytoprotection in metabolic disorders and cancer via selective activation of the protein kinase R-like endoplasmic reticulum (ER) kinase (PERK) pathway. Both metformin and CO can induce mitochondrial stress to produce a mild elevation of mitochondrial ROS (mtROS) by distinct mechanisms. Metformin inhibits complex I of the mitochondrial electron transport chain (ETC), while CO inhibits ETC complex IV. Both metformin and CO can differentially induce several protein factors, including fibroblast growth factor 21 (FGF21) and sestrin2 (SESN2), which maintain metabolic homeostasis; nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the antioxidant response; and REDD1, which exhibits an anticancer effect. However, metformin and CO regulate these effects via different pathways. Metformin stimulates p53- and AMPK-dependent pathways whereas CO can selectively trigger the PERK-dependent signaling pathway. Although further studies are needed to identify the mechanistic differences between metformin and CO, pharmacological application of these agents may represent useful strategies to ameliorate metabolic diseases associated with altered immunometabolism.

• 셀메드
• /
• 제4권3호
• /
• pp.17.1-17.8
• /
• 2014

Herbal remedies are commonly used by patients worldwide. Because these herbal preparations share the same metabolic and transport proteins with prescribed medicines, the potential for a drug-herb interaction is substantial and is an issue of significant concern. This review paper summarizes drug-herb interactions involving inhibition or induction of cytochrome P450 enzymes, drug transporters as well as modulation of drug pharmacodynamics. An increasing number of in vitro and animal studies, case reports and clinical trials evaluating such interactions have been reported, and implications of these studies are discussed in this review. The most commonly implicated drugs in the interaction include anticoagulants, antiplatelets, immunosuppressants, anti-neoplastics, protease inhibitors, and some antidepressants. Pharmacokinetic and/or pharmacodynamic interactions of five commonly used herbal remedies (danshen, garlic, Ginkgo biloba, ginseng, and St John's wort) with these drugs are presented, with focus of discussion being the potentials for interaction, their mechanisms and clinical implications. There is a necessity for adequate pharmacovigilance to be carried out in minimizing unanticipated but often preventable drug-herb interactions.

• 한국보건간호학회지
• /
• 제30권1호
• /
• pp.149-163
• /
• 2016

Purpose: The aim of this study was to assess the readability and suitability of printed educational materials related to metabolic syndrome in South Korea. Methods: Data were collected on 15 educational materials on metabolic syndrome from public health centers in Seoul. The 9 Graded Korean Vocabulary Classification and Korean version of SAM (Suitability Assessment of Materials) were used for the readability evaluation and the suitability evaluation respectively. Results: Overall average of the readability was 3.0th grade level. The percentage of 1st to 4th grade words was 79.4%. The printed educational materials on metabolic syndrome were written according to recommended reading levels. In suitability assessment, 2 out of 15 materials(13.3%) were scored as superior, 12 materials(80.0%) were scored as adequate and only 1 (6.7%) was scored as inadequate. The total average score of suitability was adequate. However, there are limitations in "summary and review" and "context is given first" due to limited writing pages. Conclusion: Readability and suitability of educational materials for metabolic syndrome were evaluated as adequate level. However, future health educational materials should be evaluated for readability via different factors including length of sentences, numbers of sentences, and structure of sentences. In addition, for easier understanding and motivation of readers, materials should use summary & review, context and proper interaction.

• The Korean Journal of Physiology and Pharmacology
• /
• 제12권4호
• /
• pp.199-204
• /
• 2008

KIF1B${\beta}$ is a member of the Kinesin superfamily proteins (KIFs), which are microtubule-dependent molecular motors that are involved in various intracellular organellar transport processes. KIF1B${\beta}$ is not restricted to neuronal systems, however, is widely expressed in other tissues, even though the function of KIF1B${\beta}$ is still unclear. To elucidate the KIF1B${\beta}$-binding proteins in non-neuronal cells, we used the yeast two-hybrid system, and found a specific interaction of KIF1B${\beta}$ and the sorting nexin (SNX) 17. The C-terminal region of SNX17 is required for the binding with KIF1B${\beta}$. SNX17 protein bound to the specific region of KIF1Bf3 (813-916. aa), but not to other kinesin family members. In addition, this specific interaction was also observed in the Glutathione S-transferase pull-down assay. An antibody to SNX17 specifically co-immunoprecipitated KIF1B${\beta}$ associated with SNX17 from mouse brain extracts. These results suggest that SNX17 might be involved in the KIF1B${\beta}$-mediated transport as a KIF1B${\beta}$ adaptor protein.

• Nutrition Research and Practice
• /
• 제6권1호
• /
• pp.78-85
• /
• 2012

Whether the $FTO$ polymorphisms interact with environmental factors has not yet been evaluated in associations with metabolic syndrome (MS) risk. The present study investigated the association of the $FTO$ rs9939609 genotypes, body mass index (BMI), and lifestyle-related factors including smoking, alcohol drinking, physical activity, and diet with MS incidence. A population-based prospective cohort study comprised 3,504 male and female Koreans aged 40 to 69 years. At the beginning of the study, all individuals were free of MS and known cardiovascular disease. Incident cases of MS were identified by biennial health examinations during a follow-up period from April 17, 2003 to April 15, 2009. Pooled logistic regression analysis was applied to obtain relative odds (RO) of MS with its 95% confidence interval (CI). After controlling for potential MS risk factors, we observed no association between the rs9939609 genotypes and MS incidence. In analysis stratified by BMI, however, carriers with the $FTO$ risk allele whose BMI is $29kg/m^2$ or greater showed an approximately 6-fold higher RO (95% CI: 3.82 to 9.30) compared with non-carriers with BMI less than $25kg/m^2$. In particular, the association between the rs9939609 variants and MS risk was significantly modified by high BMI (P-value for interaction < 0.05). Such significant interaction appeared in associations with central obesity and high blood pressure among the MS components. Because carriers of the $FTO$ risk alleles who had BMI of $29kg/m^2$ or greater are considered a high risk population, we suggest that they may need intensive weight loss regimens to prevent MS development.