• Sleep Medicine and Psychophysiology
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• v.6 no.1
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• pp.19-25
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• 1999

Sleep alters both breathing pattern and the ventilatory responses to external stimuli. These changes during sleep permit the development or aggravation of sleep-related hypoxemia in patients with respiratory disease and contribute to the pathogenesis of apneas in patients with the sleep apnea syndrome. Fundamental effects of sleep on the ventilatory control system are 1) removal of wakefulness input to the upper airway leading to the increase in upper airway resistance, 2) loss of wakefulness drive to the respiratory pump, 3) compromise of protective respiratory reflexes, and 4) additional sleep-induced compromise of ventilatory control initiated by reduced functional residual capacity on supine position assumed in sleep, decreased $CO_2$ production during sleep, and increased cerebral blood flow in especially rapid eye movement(REM) sleep. These effects resulted in periodic breathing during unsteady non-rapid eye movement(NREM) sleep even in normal subjects, regular but low ventilation during steady NREM sleep, and irregular breathing during REM sleep. Sleep-induced breathing instabilities are divided due primarily to transient increase in upper airway resistance and those that involve overshoots and undershoots in neural feedback mechanisms regulating the timing and/or amplitude of respiratory output. Following ventilatory overshoots, breathing stability will be maintained if excitatory short-term potentiation is the prevailing influence. On the other hand, apnea and hypopnea will occur if inhibitory mechanisms dominate following the ventilatory overshoot. These inhibitory mechanisms include 1) hypocapnia, 2) inhibitory effect from lung stretch, 3) baroreceptor stimulation, 4) upper airway mechanoreceptor reflexes, 5) central depression by hypoxia, and 6) central system inertia. While the respiratory control system functions well during wakefulness, the control of breathing is commonly disrupted during sleep. These changes in respiratory control resulting in breathing instability during sleep are related with the pathophysiologic mechanisms of obstructive and/or central apnea, and have the therapeutic implications for nocturnal hypoventilation in patients with chronic obstructive pulmonary disease or alveolar hypoventilation syndrome.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.10
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• pp.1552-1559
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• 2013

Rubus coreanus Miquel (RCM) has been used as one of the Korean traditional medicines for prostate health. In addition, recent studies have reported that RCM reduced chronic inflammatory diseases such as cancer, and rheumatoid arthritis. Therefore, in this study, we investigated the effects of unripe and ripe RCM on inflammationrelated gene expressions in LPS-stimulated mouse peritoneal macrophages. Mice were fed with 2% unripe RCM (U2), 10% unripe RCM (U10), 2% ripe RCM (R2), and 10% ripe RCM (R10) for 8 weeks. Peritoneal macrophages were isolated and stimulated with LPS then proinflammatory mediators (TNF-${\alpha}$, IL-$1{\beta}$, and IL-6), and prostaglandin E2 ($PGE_2$) productions were assessed. Moreover, gene expression profiles were analyzed by cDNA microarray method. Unripe and ripe RCM significantly reduced TNF-${\alpha}$ production but only unripe RCM decreased IL-$1{\beta}$ and IL-6 production. RCM intake significantly reduced inflammatory-related gene expressions such as arachidonate 5-lipoxygenase, interleukin 11, and nitric oxide synthase 2. Furthermore, unripe and ripe RCM significantly decreased ceruloplasmin, tissue plasminogen activator, thrombospondin 1, and vascular endothelial growth factor A expression which modulates symptoms of chronic inflammatory diseases. RCM intake also significantly increased hypoxia inducible factor 3, alpha which is the negative regulators of hypoxia-inducible gene expression. Furthermore, only unripe RCM reduced chemokine (C-C motif) ligand 8, chemokine (C-X-C motif) ligand 14, and phospholipase A2 expression. In this study, we showed that RCM had anti-inflammatory effects by suppression of pro-inflammatory mediator expressions and may reduce chronic inflammatory disease progress through regulation of gene expressions. These findings suggest that RCM might be used as a potential functional material to reduce chronic inflammatory responses.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.3
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• pp.229-236
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• 2016

Resveratrol (RSV) may provide numerous protective effects against chronic inflammatory diseases. Due to local hypoxia and hypertonicity, the renal medulla is subject to extreme oxidative stress, and aldehyde products formed during lipid peroxidation, such as 4-hydroxy-2-hexenal (HHE), might be responsible for tubular injury. This study aimed at investigating the effects of RSV on renal and its signaling mechanisms. While HHE treatment resulted in decreased expression of Sirt1, AQP2, and nuclear factor erythroid 2-related factor 2 (Nrf2), mouse cortical collecting duct cells (M1) cells treated with HHE exhibited increased activation of p38 MAPK, extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and increased expression of NOX4, $p47^{phox}$, Kelch ECH associating protein 1 (Keap1) and COX2. HHE treatment also induced $NF-{\kappa}B$ activation by promoting $I{\kappa}B-{\alpha}$ degradation. Meanwhile, the observed increases in nuclear $NF-{\kappa}B$, NOX4, $p47^{phox}$, and COX2 expression were attenuated by treatment with Bay 117082, N-acetyl-l-cysteine (NAC), or RSV. Our findings indicate that RSV inhibits the expression of inflammatory proteins and the production of reactive oxygen species in M1 cells by inhibiting $NF-{\kappa}B$ activation.

• Journal of Oral Medicine and Pain
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• v.40 no.2
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• pp.63-71
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• 2015

Purpose: To investigate the relationship between headache and sleep by evaluating sleep quality, daytime sleepiness, and specific features related to sleep-disordered breathing (SDB). Methods: One hundred one subjects with headache and 118 healthy controls were enrolled. To collect various information on headache attacks, headache group completed self-reported questionnaire about the characteristics of headache attacks and the migraine disability assessment (MIDAS) questionnaire. The subjective quality of sleep was evaluated in all of the subjects using the Pittsburgh sleep quality index (PSQI) and Epworth sleepiness scale (ESS). In addition, the following specific features of sleep were evaluated in 28 subjects selected randomly from each group: apnea-hypopnea index (AHI), prevalence of SDB, nocturnal oxygen saturation (SaO2), and oxygen desaturation index (ODI) as measured using a portable monitoring device. Results: The global PSQI and the prevalence of poor sleeping (global PSQI >5), ESS scores and the prevalence of daytime sleepiness (ESS score >10) were significantly higher in the headache group (both p<0.0001, respectively). The mean scores on the numerical rating scale and the MIDAS were significantly higher in the poor-sleeper group than in the good-sleeper group (p=0.0347 and p=0.0016, respectively). The global PQSI and prevalence of daytime sleepiness were significantly higher in the chronic-headache group than in the acute-headache group (p=0.0003 and p=0.0312, respectively). Conclusions: There is a significant association between headache and sleep. Especially, severity and chronicity of headache were significantly associated with sleep quality and daytime sleepiness.

• Archives of Plastic Surgery
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• v.35 no.2
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• pp.174-180
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• 2008

Purpose: While radiotherapy remains an essential part of the multidisciplinary treatment of cancers, it may cause unwanted consequences such as tissue break down and chronic non-healing wounds as a result of hypoxia, hypovascularity, and hypocellularity. The conservative treatment of osteoradionecrosis was effective only in the early stages or has a limited result. The surgical treatment of osteoradionecrosis includes various local fasciocutaneous flaps, local myocutaneous flaps and different kinds of free flaps with cancellous bone graft or alloplastic material after removal of all devitalized tissue. This study reviews recent cases of osteoradionecrosis in Severance hospital and investigates the use of various flaps for reconstruction of osteoradionecrosis. Methods: From 2000 to 2006, a total of 29 patients, nine men and twenty women with a mean age of 60.4 years were identified and included in the study. Fasciocutaneous flaps were used on 7 patients and myocutaneous flaps were used on the remaining patients. Mean follow-up period was 10.4 months. Results: In the fasciocutaneous flap group, we noted two complications including total flap failure and a partial flap necrosis. In the myocutaneous flap group, four complications were noted including a partial flap necrosis and 3 cases of wound dehiscence. Considering the complications noted in this study, the natural history of progression to flap necrosis appeared to follow the following sequence of events: marginal flap necrosis, infection, wound dehiscence, flap floating and partial flap necrosis, serially. Conclusion: Successful surgical treatment of osteoradionecrosis includes wide radical debridement and reconstruction with a well vascularized flap like myocutaneous flap or fasciocutaneous flap.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.6
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• pp.533-543
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• 2021

Myocardial fibrosis (MF) is the result of persistent and repeated aggravation of myocardial ischemia and hypoxia, leading to the gradual development of heart failure of chronic ischemic heart disease. Triptolide (TPL) is identified to be involved in the treatment for MF. This study aims to explore the mechanism of TPL in the treatment of MF. The MF rat model was established, subcutaneously injected with isoproterenol and treated by subcutaneous injection of TPL. The cardiac function of each group was evaluated, including LVEF, LVFS, LVES, and LVED. The expressions of ANP, BNP, inflammatory related factors (IL-1β, IL-18, TNF-α, MCP-1, VCAM1), NLRP3 inflammasome factors (NLRP3, ASC) and fibrosis related factors (TGF-β1, COL1, and COL3) in rats were dete cted. H&E staining and Masson staining were used to observe myocardial cell inflammation and fibrosis of rats. Western blot was used to detect the p-P65 and t-P65 levels in nucleoprotein of rat myocardial tissues. LVED and LVES of MF group were significantly upregulated, LVEF and LVFS were significantly downregulated, while TPL treatment reversed these trends; TPL treatment downregulated the tissue injury and improved the pathological damage of MF rats. TPL treatment downregulated the levels of inflammatory factors and fibrosis factors, and inhibited the activation of NLRP3 inflammasome. Activation of NLRP3 inflammasome or NF-κB pathway reversed the effect of TPL on MF. Collectively, TPL inhibited the activation of NLRP3 inflammasome by inhibiting NF-κB pathway, and improved MF in MF rats.

• Korean Journal of Biological Psychiatry
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• v.23 no.2
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• pp.63-68
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• 2016

Objectives Haenyeo are Korean professional women breath-hold divers in Jeju island. The aim of this study was to investigate the clinical characteristics of depressed Haenyeo group, compared to non-Haenyeo depressed group. Methods This study included 75 Haenyeo and 340 non-Haenyeo with depressive disorders recruited from the Dementia Early Detection Program in Jeju island. Structural diagnostic interviews were performed using the Korean version of Mini International Neuropsychiatric Interview. All patients completed the questionnaires, including the Subjective Memory Complaints Questionnaire (SMCQ), the Patient Health Questionnaire-15 (PHQ-15), and the Blessed dementia scale. Depression was evaluated by the Korean version of short form the Geriatric Depression Scale (K-SGDS) and cognition was assessed by the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) assessment packet. Results Although the mean scores of the K-SGDS were similar between Haenyeo and non-Haenyeo depressed groups, the Haenyeo group showed a higher mean score on the PSQ-15 (p < 0.001, ANCOVA adjusting for age, the K-SGDS and education). The Haenyeo group showed poorer performance on the Korean Version of Frontal Assessment Batter (p < 0.001), the Mini-Mental State Examination in the Korean version of the CERAD Assessment Packet (p < 0.018), the word fluency test (p < 0.001), and the word list memory test (p = 0.012) in ANCOVA adjusting for age and education. The mean SMCQ score was higher in the Haenyeo depressed group than in the non-Haenyeo depressed group. Conclusions The Haenyeo depressed group shows cognitive dysfunction, especially frontal lobe dysfunction, compared to the non-Haenyeo depressed group, indicating the Haenyeo depressed group may have more severe frontolimbic dysfunction due to chronic exposure to hypoxia. The Haenyeo depressed group suffers more somatic symptoms than the non-Haenyeo depressed group.

• Journal of Veterinary Clinics
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• v.28 no.1
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• pp.52-56
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• 2011

Acute renal injury induced by ischemia is a major cause of high morbidity and mortality in hospitalized patients and a common complication in hospitalized patients. Thus, the work with acute renal failure and renal ischemia has been studied for many years. Although serum creatinine concentration that is widely used as an index of renal function performs fairly well for estimating kidney function in patients with stable chronic kidney disease, it performs poorly in the setting of acute disease. Thus, an ideal biomarker for acute kidney injury would help clinicians and scientists diagnose the most common form of acute kidney injury in hospitalized patients, acute tubular necrosis, early and accurately, and may aid to risk-stratify patients with acute kidney injury by predicting the need for renal replacement therapy, the duration of acute kidney injury, the length of stay and mortality. In this study, renal ischemia and reperfusion were performed by clapming and un-clamping right renal artery in miniature pigs. Plasma blood urea nitrogen (BUN) and creatinine were examined at pre- clamping, after-clamping at 0, 1 and 3 hours. And we searched initial indicators in these samples. Also, renal tissue was collected and searched the initial indicator by PCR and western blotting. As a result, hypoxia inducible factor $1{\alpha}$ ($HIF1{\alpha}$), nuclear factor kappa-B ($NF{\kappa}B$), $I{\kappa}B$, erythropoietin (EPO), erythropoietin receptor (EPOR), angiopoietin-1 and vascular endothelial growth factor (VEGF) were showed significant changes among the renal protein. $HIF1{\alpha}$, EPO, and EPOR were showed significant changes among the renal gene. Thus, these markers will be used as initial diagnosis of acute renal failure.

• Sleep Medicine and Psychophysiology
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• v.4 no.2
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• pp.129-139
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• 1997

The data collected to date indicate that sleep-related breathing disorders, including sleep-disordered breathing(sleep apnea) and underlying respiratory system diseases, are one of the important risk factors for cardiovascular dysfunction. Sleep-disordered breathing(sleep apnea) is now recognized as one of the leading causes of systemic hypertension, cardiac arrhythmias, coronary heart disease, pulmonary hypertension, right heart failure, and stroke. Sleep may exert a profound effect on breathing in patients with underlying respiratory system disease including bronchopumonary diseases, chest wall abnormalities, central alveolar hypoventilation syndromes or respiratory neuromuscular disorders. Chronic hypoxia and hypercapnia in these patients may accelerate the development of long term cardiovascular complications such as cardiac arrhythmias, pulmonary hypertension, and right heart failure(cor pulmonale). Several recent studies reported that sleep-related breathing disorders are associated with long-term cardiovascular morbidity and mortality. Careful assessment of respiratory and cardiovascular function in these patients is critical. Aggressive and highly effective treatment of sleep-related breathing disorders using tracheostomy, mechanical ventilation, nasal continuous positive airway pressure therapy(nCPAP), intercurrent oxygen therapy or other interventions can reduce the prevalence of cardiovascular dysfunction and the long-term mortality.

• Journal of Ginseng Research
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• v.48 no.1
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• pp.31-39
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• 2024

Background: Ginsenoside Rg3, a primary bioactive component of red ginseng, has anti-cancer effects. However, the effects of Rg3-enriched ginseng extract (Rg3RGE) on apoptosis and autophagy in breast cancer have not yet been investigated. In the present study, we explored the anti-tumor effects of Rg3RGE on breast cancer cells stimulated CoCl₂, a mimetic of the chronic hypoxic response, and determined the operative mechanisms of action. Methods: The inhibitory mechanisms of Rg3RGE on breast cancer cells, such as apoptosis, autophagy and ROS levels, were detected both in vitro. To determine the anti-cancer effects of Rg3RGE in vivo, the cancer xenograft model was used. Results: Rg3RGE suppressed CoCl₂-induced spheroid formation and cell viability in 3D culture of breast cancer cells. Rg3RGE promoted apoptosis by increasing cleaved caspase 3 and cleaved PARP and decreasing Bcl2 under the hypoxia mimetic conditions. Further, we identified that Rg3RGE promoted apoptosis by inhibiting lysosomal degradation of autophagosome contents in CoCl₂-induced autophagy. We further identified that Rg3RGE-induced apoptotic cell death and autophagy inhibition was mediated by increased intracellular ROS levels. Similarly, in the in vivo xenograft model, Rg3RGE induced apoptosis and inhibited cell proliferation and autophagy. Conclusion: Rg3RGE-stimulated ROS production promotes apoptosis and inhibits protective autophagy under hypoxic conditions. Autophagosome accumulation is critical to the apoptotic effects of Rg3RGE. The in vivo findings also demonstrate that Rg3RGE inhibits breast cancer cell growth, suggesting that Rg3RGE has potential as potential as a putative breast cancer therapeutic.