• Archives of Obesity and Metabolism
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• v.2 no.1
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• pp.29-35
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• 2023

Familial hypercholesterolemia (FH) is a genetic disease that is not well known or diagnosed in Korea. This disease is associated with persistently high levels of low-density lipoprotein cholesterol (LDL-C), which increase the risk of coronary artery disease at a young age. Therefore, early diagnosis and treatment are important; however, there are no global consensus diagnostic criteria. In Korea, the Dutch Lipid Clinic Network diagnostic criteria, and the Simon Broome diagnostic criteria were used for diagnosis of FH according to the agreement announced at the Korean Society of Lipid and Atherosclerosis (KSoLA) in 2022. Recently, the absence of coronary artery calcification has been considered a good prognostic factor, even among patients with very high LDL-C levels who are considered to be at high risk for atherosclerotic cardiovascular disease. We describe throughout this paper the diagnosis and treatment of FH in a young male without coronary artery calcification.

• IMMUNE NETWORK
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• v.21 no.3
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• pp.20.1-20.18
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• 2021

The gut is an important organ with digestive and immune regulatory function which consistently harbors microbiome ecosystem. The gut microbiome cooperates with the host to regulate the development and function of the immune, metabolic, and nervous systems. It can influence disease processes in the gut as well as extra-intestinal organs, including the brain. The gut closely connects with the central nervous system through dynamic bidirectional communication along the gut-brain axis. The connection between gut environment and brain may affect host mood and behaviors. Disruptions in microbial communities have been implicated in several neurological disorders. A link between the gut microbiota and the brain has long been described, but recent studies have started to reveal the underlying mechanism of the impact of the gut microbiota and gut barrier integrity on the brain and behavior. Here, we summarized the gut barrier environment and the 4 main gut-brain axis pathways. We focused on the important function of gut barrier on neurological diseases such as stress responses and ischemic stroke. Finally, we described the impact of representative environmental sensors generated by gut bacteria on acute neurological disease via the gut-brain axis.

• IMMUNE NETWORK
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• v.16 no.2
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• pp.85-98
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• 2016

The mitogen-activated protein kinases (MAPKs) are key regulators of cell growth and survival in physiological and pathological processes. Aberrant MAPK signaling plays a critical role in the development and progression of human cancer, as well as in determining responses to cancer treatment. The MAPK phosphatases (MKPs), also known as dual-specificity phosphatases (DUSPs), are a family of proteins that function as major negative regulators of MAPK activities in mammalian cells. Studies using mice deficient in specific MKPs including MKP1/DUSP1, PAC-1/DUSP2, MKP2/DUSP4, MKP5/DUSP10 and MKP7/DUSP16 demonstrated that these molecules are important not only for both innate and adaptive immune responses, but also for metabolic homeostasis. In addition, the consequences of the gain or loss of function of the MKPs in normal and malignant tissues have highlighted the importance of these phosphatases in the pathogenesis of cancers. The involvement of the MKPs in resistance to cancer therapy has also gained prominence, making the MKPs a potential target for anti-cancer therapy. This review will summarize the current knowledge of the MKPs in cancer development, progression and treatment outcomes.

• IMMUNE NETWORK
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• v.23 no.1
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• pp.6.1-6.24
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• 2023

Intestinal microorganisms interact with various immune cells and are involved in gut homeostasis and immune regulation. Although many studies have discussed the roles of the microorganisms themselves, interest in the effector function of their metabolites is increasing. The metabolic processes of these molecules provide important clues to the existence and function of gut microbes. The interrelationship between metabolites and T lymphocytes in particular plays a significant role in adaptive immune functions. Our current review focuses on 3 groups of metabolites: short-chain fatty acids, bile acids metabolites, and polyamines. We collated the findings of several studies on the transformation and production of these metabolites by gut microbes and explained their immunological roles. Specifically, we summarized the reports on changes in mucosal immune homeostasis represented by the Tregs and Th17 cells balance. The relationship between specific metabolites and diseases was also analyzed through latest studies. Thus, this review highlights microbial metabolites as the hidden treasure having potential diagnostic markers and therapeutic targets through a comprehensive understanding of the gut-immune interaction.

• IMMUNE NETWORK
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• v.23 no.1
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• pp.7.1-7.27
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• 2023

The mammalian intestines harbor trillions of commensal microorganisms composed of thousands of species that are collectively called gut microbiota. Among the microbiota, bacteria are the predominant microorganism, with viruses, protozoa, and fungi (mycobiota) making up a relatively smaller population. The microbial communities play fundamental roles in the maturation and orchestration of the immune landscape in health and disease. Primarily, the gut microbiota modulates the immune system to maintain homeostasis and plays a crucial role in regulating the pathogenesis and pathophysiology of inflammatory, neuronal, and metabolic disorders. The microbiota modulates the host immune system through direct interactions with immune cells or indirect mechanisms such as producing short-chain acids and diverse metabolites. Numerous researchers have put extensive efforts into investigating the role of microbes in immune regulation, discovering novel immunomodulatory microbial species, identifying key effector molecules, and demonstrating how microbes and their key effector molecules mechanistically impact the host immune system. Consequently, recent studies suggest that several microbial species and their immunomodulatory molecules have therapeutic applicability in preclinical settings of multiple disorders. Nonetheless, it is still unclear why and how a handful of microorganisms and their key molecules affect the host immunity in diverse diseases. This review mainly discusses the role of microbes and their metabolites in T helper cell differentiation, immunomodulatory function, and their modes of action.

• The Korean Journal of Nuclear Medicine
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• v.38 no.3
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• pp.233-240
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• 2004

Purpose: We developed a computer-aided classifier using artificial neural network (ANN) to discriminate the cerebral metabolic pattern of medial and lateral temporal lobe epilepsy (TLE). Materials and Methods: We studied brain F-18-FDG PET images of 113 epilepsy patients sugically and pathologically proven as medial TLE (left 41, right 42) or lateral TLE (left 14, right 16). PET images were spatially transformed onto a standard template and normalized to the mean counts of cortical regions. Asymmetry indices for predefined 17 mirrored regions to hemispheric midline and those for medial and lateral temporal lobes were used as input features for ANN. ANN classifier was composed of 3 independent multi-layered perceptrons (1 for left/right lateralization and 2 for medial/lateral discrimination) and trained to interpret metabolic patterns and produce one of 4 diagnoses (L/R medial TLE or L/R lateral TLE). Randomly selected 8 images from each group were used to train the ANN classifier and remaining 51 images were used as test sets. The accuracy of the diagnosis with ANN was estimated by averaging the agreement rates of independent 50 trials and compared to that of nuclear medicine experts. Results: The accuracy in lateralization was 89% by the human experts and 90% by the ANN classifier Overall accuracy in localization of epileptogenic zones by the ANN classifier was 69%, which was comparable to that by the human experts (72%). Conclusion: We conclude that ANN classifier performed as well as human experts and could be potentially useful supporting tool for the differential diagnosis of TLE.

• Science of Emotion and Sensibility
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• v.13 no.1
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• pp.235-242
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• 2010

Emotion science is one of the rapidly expanding engineering/scientific disciplines which has a major impact on human society. Such growing interests in emotion science and engineering owe the recent trend that various academic fields are being merged. In this paper we review the recent techniques in the measuring the emotion related elements and applications which include animal model system to investigate the neural network and behaviour, artificial nose/neuronal chip for in-depth understanding of sensing the outer stimuli, metabolic controlling using emotional stimulant such as sounds. In particular, microfabrication techniques made it possible to construct nano/micron scale sensing parts/chips to accommodate the olfactory cells and neuron cells and gave us a new opportunities to investigate the emotion precisely. Recent developments in the measurement techniques will be able to help combine the social sciences and natural sciences, and consequently expand the scope of studies.

• IMMUNE NETWORK
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• v.11 no.2
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• pp.107-113
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• 2011

Background: Metabolic disorders, including type II diabetes and obesity, present major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has become the focus of a great deal of attention as a novel therapeutic target for the treatment of metabolic syndromes. In this study, we evaluated whether dietary aloe could reduce obesity-induced inflammation and adipogenesis. Methods: Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Results: Aloe QDM complex downregulated fat size through suppressed expression of scavenger receptors on adipose tissue macrophages (ATMs) compared with HFD. Both white adipose tissue (WATs) and muscle exhibited increased AMPK activation through aloe supplementation, and in particular, the Aloe QDM complex. Obesity-induced inflammatory cytokines (IL-$1{\beta}$ and -6) and $HIF1{\alpha}$ mRNA and protein were decreased markedly, as was macrophage infiltration by the Aloe QDM complex. Further, the Aloe QDM complex decreased the translocation of NF-${\kappa}B$ p65 from the cytosol in the WAT. Conclusion: Dietary aloe formula reduced obesity-induced inflammatory responses by activation of AMPK in muscle and suppression of proinflammatory cytokines in the WAT. Additionally, the expression of scavenger receptors in the ATM and activation of AMPK in WAT led to reduction in the percent of body fat. Thus, we suggest that the effect of the Aloe QDM complex in the WAT and muscle are related to activation of AMPK and its use as a nutritional intervention against T2D and obesity-related inflammation.

• IMMUNE NETWORK
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• v.12 no.5
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• pp.196-206
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• 2012

Besides their role as building blocks of protein, there are growing evidences that some amino acids have roles in regulating key metabolic pathways that are necessary for maintenance, growth, reproduction, and immunity. Here, we evaluated the modulatory functions of several amino acids in protective immunity against mucosal infection of herpes simplex virus type 1 (HSV-1). We found that glutamine (Gln) and leucine (Leu) showed enhanced protective immunity to HSV-1 mucosal infection when two administration of Gln and single administration of Leu per day, but not when administered in combinations. Ameliorated clinical signs of HSV-1 challenged mice by the intraperitoneal administration of Gln and Leu were closely associated with viral burden and IFN-${\gamma}$ production in the vaginal tract at 2 and 4 days post-infection. In addition, the enhanced production of vaginal IFN-${\gamma}$ appeared to be caused by NK and HSV-1 antigen-specific Th1-type CD4+ T cells recruited into vaginal tract of mice treated with Gln and Leu, which indicates that IFN-${\gamma}$, produced by NK and Th1-type CD4+ T cells, may be critical to control the outcome of diseases caused by HSV-1 mucosal infection. Collectively, our results indicate that intraperitoneal administration of Gln and Leu following HSV-1 mucosal infection could provide beneficial effects for the modulation of protective immunity, but dosage and frequency of administration should be carefully considered, because higher frequency and overdose of Gln and Leu, or their combined treatment, showed detrimental effects to protective immunity.

• Journal of Microbiology and Biotechnology
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• v.18 no.8
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• pp.1368-1376
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• 2008

In our previous study, the expression of active H-ferritins in Saccharomyces cerevisiae was found to reduce cell growth and reactive oxygen species (ROS) generation upon exposure to oxidative stress; such expression enhanced that of high-affinity iron transport genes (FET3 and FTR1). The results suggested that the recombinant cells expressing H-ferritins induced cytosolic iron depletion. The present study analyzes metabolic changes under these circumstances via proteomic methods. The YGH2 yeast strain expressing A-ferritin, the YGH2-KG (E62K and H65G) mutant strain, and the YGT control strain were used. Comparative proteomic analysis showed that the synthesis of 34 proteins was at least stimulated in YGH2, whereas the other 37 proteins were repressed. Among these, the 31 major protein spots were analyzed via nano-LC/MS/MS. The increased proteins included major heat-shock proteins and proteins related to endoplasmic reticulum-associated degradation (ERAD). On the other hand, the proteins involved with folate metabolism, purine and methionine biosynthesis, and translation were reduced. In addition, we analyzed the insoluble protein fractions and identified the fragments of Idh1p and Pgk1p, as well as several ribosomal assembly-related proteins. This suggests that intracellular iron depletion induces imperfect translation of proteins. Although the proteins identified above result from changes in iron metabolism (i.e., iron deficiency), definitive evidence for iron-related proteins remains insufficient. Nevertheless, this study is the first to present a molecular model for iron deficiency, and the results may provide valuable information on the regulatory network of iron metabolism.