• Biomedical Science Letters
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• v.29 no.4
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• pp.355-362
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• 2023

This study aimed to determine whether smoking affects the metabolic syndrome and its components through long-term follow-up. Of the 10,030 cohort subjects in the community-based Korean Genome and Epidemiology Study (KoGES) from 2001 to 2018, 2,848 people with metabolic syndrome and 4,854 people with insufficient data for analysis were excluded for this study. The study population comprised 2,328 individuals (1,123 men, 1,205 women) who were eligible for inclusion. The mean age of the participants was 49.2±7.5 years, and 21.9% were current smoker. In log rank test, current smoker had a significantly higher cumulative incidence of metabolic syndrome compared with non smoker (P<0.001). In the Cox proportional hazards model adjusted for key variables, metabolic syndrome (hazard ratio [HR] 1.57, P<0.001), high fasting glucose (HR 1.40, P<0.01), hypertriglyceridemia (HR 1.60, P<0.001), low HDL-cholesterol (HR, 1.30, P<0.01), and abdominal obesity (HR 1.32, P<0.01) in current smoker compared with non smoker were statistically significant, respectively, but not hypertension (HR 1.00, P>0.05). After adjustment for confounders, the time (P-time<0.001) and group (P-group<0.001) effects on metabolic syndrome score change were statistically significant. Furthermore, the interaction analysis of time and smoking group on the change in metabolic syndrome score was statistically significant (P-interaction<0.001). In long-term follow-up, smoking worsens metabolic syndrome.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2007.11a
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• pp.57-64
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• 2007

Metabolic interactions of the three major cannabinoids, ${\Delta}^9$-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) with steroid hormones were investigated. These cannabioids concentration-dependently inhibited $3{\beta}$-hydroxysteroid dehydrogenase and $17{\alpha}$-hydroxylase in rat adrenal and testis microsomes. CBD and CBN were the most potent inhibitors of $3{\beta}$-phydroxysteroid dehydrogenase and progesterone $17{\alpha}$-hydroxylase, respectively, in rat testis microsomes. Three cannabinoids highly attenuated hCG-stimulated testosterone production in rat testicular interstitial cells. These cannabinoids also decreased in levels of mRNA and protein of StAR in the rat testis cells. These results indicate that the cannabinoids could interact with steroid hormones, and exert their modulatory effects on endocrine and testicular functions. Metabolic interaction of a THC metabolite, $7{\beta}$-hydroxy-${\Delta}^8$-THC with steroids is also investigated. Monkey liver microsomes catalyzed the stereoselective oxidation of $7{\beta}$-hydroxy-${\Delta}^8$-THC to 7-oxo-${\Delta}^8$-THC, so-called microsomal alcohol oxygenase (MALCO). The reaction is catalyzed by CYP3A8 in the monkey liver microsomes, and required NADH as well as NADPH as an efficient cofactor, and its activity is stimulated by some steroids such as testosterone and progesterone. Kinetic analyses revealed that MALCO-catalyze reaction showed positive cooperativity. In order to explain the metabolic interaction between the cannabinoid metabolite and testosterone, we propose a novel kinetic model involving at least three binding sites for mechanism of the metabolic interactions.

• The Korean Journal of Pesticide Science
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• v.2 no.3
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• pp.1-20
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• 1998

Chlorsulfuron, one of sulfonylurea herbicides acts through inhibition of acetolactate syuthase (EC 4.1.3.18; ALS, also known as acetohydroxyacid synthase) in the branched-chain amino acid biosynthesis process. After chlorsulfuron-ALS interaction, many physiological and metabolic disruptions occur in plants. However, it is not clear how this chlorsulfuron-ALS interaction affects those physiological and metabolic processes and how this interaction leads subsequently to plant death. Several researchers suggested that the death of chlorsulfuron-treated plants might be due to a shortage of the branched-chain amino acids, an accumulation of toxic metabolites, and/or a depletion of photoassimilates. It remains as a mystery presently, however, if such changes result in the plant death. In this review, we discussed how the chlorsulfuran-ALS interaction leads to physiological and metabolic disruptions in plants.

• Bulletin of the Korean Chemical Society
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• v.34 no.1
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• pp.35-41
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• 2013

Metabolic analysis of CR6 interacting factor 1 (Crif1) deficient mouse embryonic fibroblasts with impaired oxidative phosphorylation has been carried out using LC-MS/MS and GC-MS methods. Metabolic profiles of the Crif1 deficient cells were comprehensively obtained for the first time. Loss of oxidative phosphorylation functions in mitochondria resulted in cancer-like metabolic reprogramming with consumption of majority of glucose carbon from up-regulated glycolysis to produce lactate, suppressed utilization of glucose carbon in the TCA cycle, increased amounts of amino acids. The changes in metabolic profile of the Crif1 deficient cells are most probably a consequence of metabolic reprogramming to meet the needs of energy balance and anabolic precursors in compensation for the loss of major oxidative phosphorylation functions.

• Biomolecules & Therapeutics
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• v.26 no.1
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• pp.69-80
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• 2018

Cancer cells reprogram cellular metabolism to support the malignant features of tumors, such as rapid growth and proliferation. The cancer promoting effects of metabolic reprogramming are found in many aspects: generating additional energy, providing more anabolic molecules for biosynthesis, and rebalancing cellular redox states in cancer cells. Metabolic pathways are considered the pipelines to supply metabolic cofactors of epigenetic modifiers. In this regard, cancer metabolism, whereby cellular metabolite levels are greatly altered compared to normal levels, is closely associated with cancer epigenetics, which is implicated in many stages of tumorigenesis. In this review, we provide an overview of cancer metabolism and its involvement in epigenetic modifications and suggest that the metabolic adaptation leading to epigenetic changes in cancer cells is an important non-genetic factor for tumor progression, which cooperates with genetic causes. Understanding the interaction of metabolic reprogramming with epigenetics in cancers may help to develop novel or highly improved therapeutic strategies that target cancer metabolism.

• Molecules and Cells
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• v.28 no.2
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• pp.75-80
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• 2009

The cyclic environmental conditions brought about by the 24 h rotation of the earth have allowed the evolution of endogenous circadian clocks that control the temporal alignment of behaviour and physiology, including the uptake and processing of nutrients. Both metabolic and circadian regulatory systems are built upon a complex feedback network connecting centres of the central nervous system and different peripheral tissues. Emerging evidence suggests that circadian clock function is closely linked to metabolic homeostasis and that rhythm disruption can contribute to the development of metabolic disease. At the same time, metabolic processes feed back into the circadian clock, affecting clock gene expression and timing of behaviour. In this review, we summarize the experimental evidence for this bimodal interaction, with a focus on the molecular mechanisms mediating this exchange, and outline the implications for clock-based and metabolic diseases.

• Journal of Industrial Convergence
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• v.20 no.11
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• pp.213-219
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• 2022

The purpose of this study was to examine the effect of balance training on metabolic syndrome indicators and functional fitness. For this purpose, a 12-week balance training was conducted for 16 elderly women who usually complain of back and shoulder pain. In addition, of the 16 subjects, 8 were classified into the exercise group and 8 into the control group, and the effectiveness of the training program was verified. As a result of examining the metabolic syndrome index and functional fitness before and after 12 weeks of balance training, the following results were obtained. First, a significant interaction was shown in the metabolic syndrome index before and after 12 weeks of balance training. Second, there was a significant interaction in functional fitness before and after 12 weeks of balance training. This confirmed that balance training had a positive effect on functional fitness along with positive changes in metabolic syndrome in elderly women. In the future, it is necessary to clarify the effect of balance training through the expansion of the training period and measurement variables.

• Archives of Obesity and Metabolism
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• v.2 no.2
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• pp.37-44
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• 2023

Weight gain is defined as the increase in body weight, increasing the prevalence of obesity, and results in metabolic diseases. Weight gain was reportedly caused by the interaction between the obesogenic environmental factors and individual metabolic factors. Sociodemographic and environmental factors (demographic factors, lifestyle/behavioral factors, food/nutritional factors, socioeconomic factors), drug-related secondary causes (some of the corticosteroids, antihyperglycemics, antihypertensives, antidepressants, etc.), and metabolic factors (aging and hormonal changes, menopause and decreased sex hormones, decreased adipocyte degradation, decreased fibroblast growth factor 21, central sympathetic nervous system hyperactivity, decreased sympathetic-adrenomedullary system activity) are significant factors related to weight gain. It is crucial to prevent weight gain and maintain an ideal weight, but studies on the risk factors of weight gain are insufficient. Therefore, this study evaluated the factors associated with weight gain to find strategies for preventing unnecessary weight gain.

• Molecules and Cells
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• v.44 no.1
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• pp.26-37
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• 2021

Human papillomaviruses (HPVs) cause cellular hyperproliferation-associated abnormalities including cervical cancer. The HPV genome encodes two major viral oncoproteins, E6 and E7, which recruit various host proteins by direct interaction for proteasomal degradation. Recently, we reported the structure of HPV18 E7 conserved region 3 (CR3) bound to the protein tyrosine phosphatase (PTP) domain of PTPN14, a well-defined tumor suppressor, and found that this intermolecular interaction plays a key role in E7-driven transformation and tumorigenesis. In this study, we carried out a molecular analysis of the interaction between CR3 of HPV18 E7 and the PTP domain of PTPN21, a PTP protein that shares high sequence homology with PTPN14 but is putatively oncogenic rather than tumor-suppressive. Through the combined use of biochemical tools, we verified that HPV18 E7 and PTPN21 form a 2:2 complex, with a dissociation constant of 5 nM and a nearly identical binding manner with the HPV18 E7 and PTPN14 complex. Nevertheless, despite the structural similarities, the biological consequences of the E7 interaction were found to differ between the two PTP proteins. Unlike PTPN14, PTPN21 did not appear to be subjected to proteasomal degradation in HPV18-positive HeLa cervical cancer cells. Moreover, knockdown of PTPN21 led to retardation of the migration/invasion of HeLa cells and HPV18 E7-expressing HaCaT keratinocytes, which reflects its protumor activity. In conclusion, the associations of the viral oncoprotein E7 with PTPN14 and PTPN21 are similar at the molecular level but play different physiological roles.

• Korean Journal of Radiology
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• v.23 no.10
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• pp.986-997
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• 2022

Objective: Whether metabolic redistribution occurs in patients with white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) is unknown. This study aimed 1) to propose a measure of the brain metabolic network for an individual patient and preliminarily apply it to identify impaired metabolic networks in patients with WMHs, and 2) to explore the clinical and imaging features of metabolic redistribution in patients with WMHs. Materials and Methods: This study included 50 patients with WMHs and 70 healthy controls (HCs) who underwent ¹⁸F-fluorodeoxyglucose-positron emission tomography/MRI. Various global property parameters according to graph theory and an individual parameter of brain metabolic network called "individual contribution index" were obtained. Parameter values were compared between the WMH and HC groups. The performance of the parameters in discriminating between the two groups was assessed using the area under the receiver operating characteristic curve (AUC). The correlation between the individual contribution index and Fazekas score was assessed, and the interaction between age and individual contribution index was determined. A generalized linear model was fitted with the individual contribution index as the dependent variable and the mean standardized uptake value (SUV_mean) of nodes in the whole-brain network or seven classic functional networks as independent variables to determine their association. Results: The means ± standard deviations of the individual contribution index were (0.697 ± 10.9) × 10^-3 and (0.0967 ± 0.0545) × 10^-3 in the WMH and HC groups, respectively (p < 0.001). The AUC of the individual contribution index was 0.864 (95% confidence interval, 0.785-0.943). A positive correlation was identified between the individual contribution index and the Fazekas scores in patients with WMHs (r = 0.57, p < 0.001). Age and individual contribution index demonstrated a significant interaction effect on the Fazekas score. A significant direct association was observed between the individual contribution index and the SUV_mean of the limbic network (p < 0.001). Conclusion: The individual contribution index may demonstrate the redistribution of the brain metabolic network in patients with WMHs.