• Journal of Yeungnam Medical Science
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• v.40 no.2
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• pp.136-145
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• 2023

Hepatic encephalopathy (HE) is a severe neuropsychiatric abnormality in patients with either acute or chronic liver failure. Typical brain magnetic resonance imaging findings of HE are bilateral basal ganglia high signal intensities due to manganese deposition in chronic liver disease and hyperintensity in T2, fluid-attenuated inversion recovery, or diffusion-weighted imaging (DWI) with hemispheric white matter changes including the corticospinal tract. Low values on apparent diffusion coefficient mapping of the affected area on DWI, indicating cytotoxic edema, can be observed in acute HE. However, neuropsychological impairment in HE ranges from mild deficits in psychomotor abilities affecting quality of life to stupor or coma with higher grades of hepatic dysfunction. In particular, the long-lasting compensatory mechanisms for the altered metabolism in chronic liver disease make HE imaging results variable. Therefore, the clinical relevance of imaging findings is uncertain and differentiating HE from other metabolic diseases can be difficult. The recent introduction of concepts such as "acute-on-chronic liver failure (ACLF)," a new clinical entity, has led to a change in the clinical view of HE. Accordingly, there is a need to establish a corresponding concept in the field of neuroimaging diagnosis. Herein, we review HE from a historical and etiological perspective to increase understanding of brain imaging and help establish an imaging approach for advanced new concepts such as ACLF. The purpose of this manuscript is to provide an understanding of HE by reviewing neuroimaging findings based on pathological and clinical concepts of HE, thereby assisting in neuroimaging interpretation.

• Journal of Environmental Science International
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• v.33 no.1
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• pp.1-8
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• 2024

When situated in green landscapes, water bodies play a crucial role in positively influencing mood and mental health, yet research on the cognitive mechanisms underlying these therapeutic effects is lacking. This study is intended to examine differences in brain function among adult males exposed to forest landscapes with or without water bodies. The wooded landscapes included views of a waterfall, a valley, and a forest without water. The control group was exposed to a local urban landscape. Twelve adult males participated in a field experiment in which prefrontal cortex (PFC) activity was measured using near-infrared spectroscopy (NIRS). In the experiment, participants engaged in low-intensity walking in three forested areas with similar vegetation and climatic conditions. Participants showed significant differences in left PFC activity depending on whether they were in the three forested landscapes or in the control landscape (P < 0.01). An analysis of variance (ANOVA) confirmed that significantly lower left PFC activity was recorded in the wooded landscape containing a water view . Notably, the lowest PFC values recorded in the landscape with a waterfall view suggest that landscapes with dynamic water flow may be associated with greater therapeutic benefits in terms of PFC activity than static landscapes. Our results underscore that water is a critical aspect of a landscape due to its therapeutic benefits and should be incorporated in the planning and design of green spaces for health promotion.

• Molecules and Cells
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• v.47 no.1
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• pp.100001.1-100001.8
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• 2024

In eukaryotes, a primary protein quality control (PQC) process involves the destruction of conformationally misfolded proteins through the ubiquitin-proteasome system. Because approximately one-third of eukaryotic proteomes fold and assemble within the endoplasmic reticulum (ER) before being sent to their destinations, the ER plays a crucial role in PQC. The specific functions and biochemical roles of several E3 ubiquitin ligases involved in ER-associated degradation in mammals, on the other hand, are mainly unknown. We identified 2 E3 ligases, ubiquitin protein ligase E3 component N-recognin 1 (UBR1) and ubiquitin protein ligase E3 component N-recognin 2 (UBR2), which are the key N-recognins in the N-degron pathway and participate in the ER stress response in mammalian cells by modulating their stability. Cells lacking UBR1 and UBR2 are hypersensitive to ER stress-induced apoptosis. Under normal circumstances, these proteins are polyubiquitinated through Lys48-specific linkages and are then degraded by the 26S proteasome. In contrast, when cells are subjected to ER stress, UBR1 and UBR2 exhibit greater stability, potentially as a cellular adaptive response to stressful conditions. Although the precise mechanisms underlying these findings require further investigation, our findings show that cytoplasmic UBR1 and UBR2 have anti-ER stress activities and contribute to global PQC in mammals. These data also reveal an additional level of complexity within the mammalian ER-associated degradation system, implicating potential involvement of the N-degron pathway.

• Molecules and Cells
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• v.26 no.5
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• pp.503-513
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• 2008

The vomeronasal organ (VNO) is a sensory organ that influences social and/or reproductive behavior and, in many cases, the survival of an organism. The VNO is believed to mediate responses to pheromones; however, many mechanisms of signal transduction in the VNO remain elusive. Here, we examined the expression of proteins involved in signal transduction that are found in the main olfactory system in the VNO. The localization of many signaling molecules in the VNO is quite different from those in the main olfactory system, suggesting differences in signal transduction mechanisms between these two chemosensory organs. Various signaling molecules are expressed in distinct areas of VNO sensory epithelium. Interestingly, we found the expressions of groups of these signaling molecules in glandular tissues adjacent to VNO, supporting the physiological significance of these glandular tissues. Our finding of high expression of signaling proteins in glandular tissues suggests that neurohumoral factors influence glandular tissues to modulate signaling cascades that in turn alter the responses of the VNO to hormonal status.

• Herbal Formula Science
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• v.25 no.4
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• pp.471-481
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• 2017

Objectives : Noemyeong-san (NMS) is a novel herbal prescription composed of five oriental medicinal herbs including Prunellae Spica, Betulae Cortex, Foeniculi Fructus, Asiasari Radix, and Clematidis Radix for treating Alzheimer's disease. In the present study, we investigated the effects and molecular mechanisms of NMS on BV2 microglia to evaluate the potential action of this formula for preventing or treating neurodegenerative disease such as Alzheimer's disease. Methods : To determine the cytotoxicity of NMS on BV2 microglia, the MTT assay was performed. The effects of NMS on lipopolysaccharide (LPS)-stimulated BV2 microglia were determined with a nitric oxide (NO) assay and western blots for inflammatory mediator-related proteins, mitogen activated protein kinases (MAPKs), nuclear factor kappa B (NF-${\kappa}B$) pathway-related proteins, and heme oxygenase-1 (HO-1). Result : NMS inhibited induction of iNOS and COX-2 as well as NO production without affecting the cell viability in LPS-stimulated BV2 microglia. NMS also suppressed activation of ERK and p38 MAPK among main kinases of MAPKs as well as NF-${\kappa}B$ by LPS stimulation. Furthermore, NMS dose-dependently induced the expression of HO-1 and the inhibitory effect of NMS on the production of NO were blocked by pretreatment with an HO-1 inhibitor, Snpp. Conclusions : These results demonstrate that NMS has potent anti-neuroinflammatory effect on the LPS-stimulated microglia. These findings provide evidences for NMS to be considered as a new prescription for preventing or treating neurodegenerative disease such as Alzheimer's disease.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.4
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• pp.321-329
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• 2013

Rodents exposed to a 15-min pretest swim in the forced swimming test (FST) exhibit prolonged immobility in a subsequent 5-min test swim, and antidepressant treatment before the test swim reduces immobility. At present, neuronal circuits recruited by antidepressant before the test swim remain unclear, and also less is known about whether antidepressants with different mechanisms of action could influence neural circuits differentially. To reveal the neural circuits associated with antidepressant effect in the FST, we injected desipramine or citalopram 0.5 h, 19 h, and 23 h after the pretest swim and observed changes in c-Fos expression in rats before the test swim, namely 24 h after the pretest swim. Desipramine treatment alone in the absence of pretest swim was without effect, whereas citalopram treatment alone significantly increased the number of c-Fos-like immunoreactive cells in the central nucleus of the amygdala and bed nucleus of the stria terminalis, where this pattern of increase appears to be maintained after the pretest swim. Both desipramine and citalopram treatment after the pretest swim significantly increased the number of c-Fos-like immunoreactive cells in the ventral lateral septum and ventrolateral periaqueductal gray before the test swim. These results suggest that citalopram may affect c-Fos expression in the central nucleus of the amygdala and bed nucleus of the stria terminalis distinctively and raise the possibility that upregulation of c-Fos in the ventral lateral septum and ventrolateral periaqueductal gray before the test swim may be one of the probable common mechanisms underlying antidepressant effect in the FST.

• Clinical and Experimental Pediatrics
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• v.60 no.6
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• pp.181-188
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• 2017

Purpose: Hypoxic-ischemic encephalopathy is a significant cause of neonatal morbidity and mortality. Erythropoietin (EPO) is emerging as a therapeutic candidate for neuroprotection. Therefore, this study was designed to determine the neuroprotective role of recombinant human EPO (rHuEPO) and the possible mechanisms by which mitogen-activated protein kinase (MAPK) signaling pathway including extracellular signal-regulated kinase (ERK1/2), JNK, and p38 MAPK is modulated in cultured cortical neuronal cells and astrocytes. Methods: Primary neuronal cells and astrocytes were prepared from cortices of ICR mouse embryos and divided into the normoxic, hypoxia (H), and hypoxia-pretreated with EPO (H+EPO) groups. The phosphorylation of MAPK pathway was quantified using western blot, and the apoptosis was assessed by caspase-3 measurement and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Results: All MAPK pathway signals were activated by hypoxia in the neuronal cells and astrocytes (P<0.05). In the neuronal cells, phosphorylation of ERK-1/-2 and apoptosis were significantly decreased in the H+EPO group at 15 hours after hypoxia (P<0.05). In the astrocytes, phosphorylation of ERK-1/-2, p38 MAPK, and apoptosis was reduced in the H+EPO group at 15 hours after hypoxia (P<0.05). Conclusion: Pretreatment with rHuEPO exerts neuroprotective effects against hypoxic injury reducing apoptosis by caspase-dependent mechanisms. Pathologic, persistent ERK activation after hypoxic injury may be attenuateed by pretreatment with EPO supporting that EPO may regulate apoptosis by affecting ERK pathways.

• Molecules and Cells
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• v.37 no.6
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• pp.467-472
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• 2014

Obesity is known to be strongly associated with cardiovascular disease and cancer, the leading causes of mortality worldwide, and develops owing to interactions between genes and the environment. DNA methylation can act as a downstream effector of environmental signals, and analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. Global DNA methylation of peripheral blood cells has recently been proposed as a potential biomarker for disease risk. Repetitive element DNA methylation has been shown to be associated with prominent obesity-related chronic diseases, but little is known about its relationship with weight status. In this study, we quantified the methylation of Alu elements in the peripheral blood DNA of 244 healthy women with a range of body mass indexes (BMIs) using pyrosequencing technology. Among the study participants, certain clinical laboratory parameters, including hemoglobin, serum glutamic oxaloacetic transaminase, serum glutamic- pyruvic transaminase, total cholesterol, and triglyceride levels were found to be strongly associated with BMI. Moreover, a U-shaped association between BMI and Alu methylation was observed, with the lowest methylation levels occurring at BMIs of between 23 and $30kg/m^2$. However, there was no significant association between Alu methylation and age, smoking status, or alcohol consumption. Overall, we identified a differential influence of BMI on global DNA methylation in healthy Korean women, indicating that BMI-related changes in Alu methylation might play a complex role in the etiology and pathogenesis of obesity. Further studies are required to elucidate the mechanisms underlying this relationship.

• International Journal of Oral Biology
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• v.30 no.3
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• pp.91-98
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• 2005

Gamma-aminobutyric acid (GABA) is known as an inhibitory neurotransmitter in the neurons of the central nervous system. However, its detailed action mechanisms in the rostral gustatory zone of the nucleus tractus solitarius (rNTS) have not been established. The present study was aimed to investigate the distribution, role and action mechanisms of GABA in rNTS. Membrane potentials were recorded by whole cell recordings in isolated brain slices of the rat medulla. Superfusion of GABA resulted in a concentration-dependent reduction in input resistance in the neurons in rNTS. The change in input resistance ws accompanied by response to a depolarizing pulse were diminished by GABA. Superfusion of the slices with either $GABA_A$ agonist, muscimol, $GABA_B$ agonist, baclofen or $GABA_C$ agonist, TACA, decreased input resistance and reduced the nerve activity in association with membrane hyperpolarization. It is suggested that inhibitory signals playa role in sensory processing by the rNTS, in that GABA actions occur through activation of $GABA_A,\;GABA_B\;and\;GABA_C$ receptor. These results suggest that GABA has an inhibitory effect on the rNTS through an activation of $GABA_A,\;GABA_B\;and\;GABA_C$ receptors and that the GABAergic inhibition probably plays an important role in sensory processing by the rNTS.

• Journal of Trauma and Injury
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• v.21 no.2
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• pp.78-84
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• 2008

Purpose: Recently, the incidence of blast injury has been on the increase worldwide. The purpose of this study was to evaluate and analyze blast injuries in South Korea. Methods: This was a retrospective multi-center study of blast injuries in three tertiary military centers. The medical records of patients with blast injuries from January 2003 to December 2007 were reviewed. The injury severity was evaluated according to the Injury Severity Score (ISS), the Revised Trauma Score (RTS), and the Trauma Score and the Injury Severity Score (TRISS). Results: This study revealed epidemiological data of blast injury in the three tertiary military hospital. A total of 94 cases of blast injury had occurred. Various body regions were involved. The most frequently injured site was the upper extremity (52.1%). The mechanisms for the blast injuries were primary (41.5%), secondary (74.5%), tertiary (7.4%), and quaternary (29.8%). The mean injury-to-hospital arrival time was $3.2{\pm}1.7hour$. The rate of admission was 88.3%, and the rate of ICU admission was 32.5%. Thirty-six (36) cases required an emergency operation. Most were performed by an Orthopedist (55.6%), an Ophthalmologist (19.4%), or a general surgeon (13.9%). The mortality rate from blast injury was 4.3%. Conclusion: This was the first paper to present data on the type of injury, the site of injury, the cause of death, and the mortality from blast injury in South Korea. Chest injury, brain injury, tertiary injury mechanisms, $ISS{\geq_-}16$, and a Maximal Abbreviated Injury Scale Score $(ABI){\geq_-}4$ were significantly associated with death.