• Title/Summary/Keyword: low flow hypoxia

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The standardized Korean Red Ginseng extract and its ingredient ginsenoside Rg3 inhibit manifestation of breast cancer stem cell-like properties through modulation of self-renewal signaling

  • Oh, Jisun;Yoon, Hyo-Jin;Jang, Jeong-Hoon;Kim, Do-Hee;Surh, Young-Joon
    • Journal of Ginseng Research
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    • v.43 no.3
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    • pp.421-430
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    • 2019
  • Background: The ginsenoside Rg3, one of active components of red ginseng, has chemopreventive and anticancer potential. Cancer stem cells retain self-renewal properties which account for cancer recurrence and resistance to anticancer therapy. In our present study, we investigated whether the standardized Korean Red Ginseng extract (RGE) and Rg3 could modulate the manifestation of breast cancer stem cell-like features through regulation of self-renewal activity. Methods: The effects of RGE and Rg3 on the proportion of $CD44^{high}/CD24^{low}$ cells, as representative characteristics of stem-like breast cancer cells, were determined by flow cytometry. The mammosphere formation assay was performed to assess self-renewal capacities of breast cancer cells. Aldehyde dehydrogenase activity of MCF-7 mammospheres was measured by the ALDEFLUOR assay. The expression levels of Sox-2, Bmi-1, and P-Akt and the nuclear localization of hypoxia inducible $factor-1{\alpha}$ in MCF-7 mammospheres were verified by immunoblot analysis. Results: Both RGE and Rg3 decreased the viability of breast cancer cells and significantly reduced the populations of $CD44^{high}/CD24^{low}$ in MDA-MB-231 cells. RGE and Rg3 treatment attenuated the expression of Sox-2 and Bmi-1 by inhibiting the nuclear localization of hypoxia inducible $factor-1{\alpha}$ in MCF-7 mammospheres. Suppression of the manifestation of breast cancer stem cell-like properties by Rg3 was mediated through the blockade of Akt-mediated self-renewal signaling. Conclusion: This study suggests that Rg3 has a therapeutic potential targeting breast cancer stem cells.

Complications amd Mortality After Coronary Artery Bypass Graft Surgery; Collective Review of 61 Cases (관상동맥우회수술후 합병증과 사망율에 대한 임상적 고찰;61례 보고)

  • 조건현
    • Journal of Chest Surgery
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    • v.26 no.7
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    • pp.526-531
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    • 1993
  • Sixty-one consecutive patients with coronary artery bypass graft for myocardial revascularization were retrospectively reviewed to analyze various pattern of postoperative complication and death during hospital stay from Nov. 1988 to Oct. 1992. Fortytwo of the patients were male and nineteen female. The mean age was 56 and 51 years in male and female. Preoperative diagnosises were unstable angina in 14 of patients, stable angina in 28, postmyocardial infarction state in 15, and state of failed percutaneous transluminal coronary angioplasty in 4. 141 stenosed coronary arteries were bypassed with use of 20 pedicled internal mammary artery and 124 reversed saphenous vein grafts. Postoperative complications and perioperative death were as follows: 1. Of 61 patients undergoing operation, peri and postoperative over all complication occured in 15 patients [ 25% ]; newly developed myocardial infarction in 4, intractable cardiac arrhythmia including atrial fibrillation and frequent ventricular premature contraction in 3, bleeding from gastrointestinal tract in 2, persistent vegetative state as a sequele of brain hypoxia in 1, wound necrosis in 1, left hemidiaphragmatic palsy in 3 and poor blood flow through graft in 2. 2. Operative mortality was 8%[5 patients]. 3 out of these died in operating room; 1 patient by bleeding from rupture of calcified aortic wall, 1 by air embolism through left atrial vent catheter, 1 by low cardiac output syndrome. 2 patients died during hospital stay; 1 by acute respiratory distress syndrome with multiuple organ failure, 1 by brain death after delayed diagnosis of pericardial tamponade.

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The Effect of Rainfall on the Water Quality of a Small Reservoir (Lake Wangkung, Korea)

  • Hwang, Gil-Son;Kim, Jae-Ok;Kim, Jai-Ku;Kim, Young-Chul;Kim, Bom-Chul
    • Korean Journal of Ecology and Environment
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    • v.38 no.spc
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    • pp.39-43
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    • 2005
  • The dynamics of water quality with the storm events were analyzed in a small reservoir for irrigation, Lake Wangkung. Water quality of the inflowing stream fluctuated seasonally with the variation of flow rate. Thermal stratification was consistent from April to October below 2 m depths and anoxic layer was developed below 2 m depth in summer. The unique feature of temperature showed that thermal stratification was disrupted by a heavy rain event during monsoon, but hypolimnetic hypoxia were reestablished after a few days. Phosphorus and nitrogen increased immediately following storm events. The marked increase may be due to the input of P-rich storm runoff from the watershed. Internal phosphorus loading can be one of the explanations for TP increases in summer. When there was a storm, total populations of phytoplankton and zooplankton was reduced immediately following the storm, indicating possible flushing of algae and zooplankton. After a lag period of low-density the plankton population bloomed to a peak again within five days after the storm. Turbid water in lake became clear again which coincided with the time of the phytoplankton buildup. The results demonstrate that water quality is regulated greatly by rainfall intensity in Lake Wangkung.

Muscle oxygenation, endocrine and metabolic regulation during low-intensity endurance exercise with blood flow restriction

  • Hwang, Hyejung;Mizuno, Sahiro;Kasai, Nobukazu;Kojima, Chihiro;Sumi, Daichi;Hayashi, Nanako;Goto, Kazushige
    • Korean Journal of Exercise Nutrition
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    • v.24 no.2
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    • pp.30-37
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    • 2020
  • [Purpose] The present study investigated the effect of endurance exercise with blood flow restriction (BFR) performed at either 25% maximal oxygen uptake (${\dot{V}}O_2$ max) or 40% ${\dot{V}}O_2$ max) on muscle oxygenation, energy metabolism, and endocrine responses. [Methods] Ten males were recruited in the present study. The subjects performed three trials: (1) endurance exercise at 40% ${\dot{V}}O_2$ max without BFR (NBFR40), (2) endurance exercise at 25% ${\dot{V}}O_2$ max with BFR (BFR25), and (3) endurance exercise at 40% ${\dot{V}}O_2$ max with BFR (BFR40). The exercises were performed for 15 min during which the pedaling frequency was set at 70 rpm. In BFR25 and BFR40, 2 min of pressure phase (equivalent to 160 mmHg) followed by 1 min of release phase were repeated five times (5 × 3 min) throughout 15 minutes of exercise. During exercise, muscle oxygenation and concentration of respiratory gases were measured. The blood samples were collected before exercise, immediately after 15 min of exercise, and at 15, 30, and 60 minutes after completion of exercise. [Results] Deoxygenated hemoglobin (deoxy-Hb) level during exercise was significantly higher with BFR25 and BFR40 than that with NBFR40. BFR40 showed significantly higher total-hemoglobin (total-Hb) than NBFR40 during 2 min of pressure phase. Moreover, exercise-induced lactate elevation and pH reduction were significantly augmented in BFR40, with concomitant increase in serum cortisol concentration after exercise. Carbohydrate (CHO) oxidation was significantly higher with BFR40 than that with NBFR40 and BFR25, whereas fat oxidation was lower with BFR40. [Conclusion] Deoxy-Hb and total Hb levels were significantly increased during 15 min of pedaling exercise in BFR25 and BFR40, indicating augmented local hypoxia and blood volume (blood perfusion) in the muscle. Moreover, low-and moderate-intensity exercise with BFR facilitated CHO oxidation.

Control of Ventilation during Sleep (수면 중 호흡의 조절)

  • Kim, Woo-Sung
    • 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.

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Effects of Differential Distribution of Microvessel Density, Possibly Regulated by miR-374a, on Breast Cancer Prognosis

  • Li, Jian-Yi;Zhang, Yang;Zhang, Wen-Hai;Jia, Shi;Kang, Ye;Tian, Rui
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.3
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    • pp.1715-1720
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    • 2013
  • Background: The discovery that microRNAs (miRNAs) regulate proliferation, invasion and metastasis provides a principal molecular basis of tumor heterogeneity. Microvessel distribution is an important characteristic of solid tumors, with significant hypoxia occurring in the center of tumors with low blood flow. The distribution of miR-374a in breast tumors was examined as a factor likely to be important in breast cancer progression. Methods: Breast tissue samples from 40 patients with breast cancer were classified into two groups: a highly invasive and metastatic group (HIMG) and a low-invasive and metastatic Group (LIMG). Samples were collected from the center and edge of each tumor. In each group, six specimens were examined by microRNA array, and the remaining 14 specimens were used for real-time RT-qPCR, Western blot and immunohistochemical analyses. Correlation analysis was performed for the miRNAs and target proteins. Follow-up was carried out during 28 months to 68 months after surgery, and survival data were analyzed. Results: In the LIMG, the relative content of miR-374a was lower in the center of the tumor than at its edge; in the HIMG, it was lower at the edge of the tumor, and miR-374a levels were lower in breast cancer tissues than in normal tissues. There was no difference between VEGF-A and VCAM-1 mRNA levels at the edge and center of the tumor; however, we observed a significant difference between VEGF-A and VCAM-1 protein expression levels in these two regions. There was a negative correlation between miR-374a and target protein levels. The microvessel density (MVD) was lower in the center of the tumor than at its edge in HIMG, but the LIMG vessels were uniformly distributed. There was a significant positive correlation between MVD and the number of lymph node metastases (Pearson correlation, r=0.912, P<0.01). The median follow-up time was 48.5 months. LIMG had higher rate of disease-free survival (100%, P=0.013) and longer median survival time (66 months) than HIMG, which had a lower rate of 75% and shorter median survival time (54 months). Conclusions: Our data demonstrated miR-374a to be differentially distributed in breast cancer; VEGF-A and VCAM-1 mRNA had coincident distribution, and the distribution of teh respective proteins was uneven and opposite to that for the miR-374a. These data might explain the differences in the distribution of MVD in breast cancer and variation in breast cancer prognosis.

Differential Distribution of miR-20a and miR-20b may Underly Metastatic Heterogeneity of Breast Cancers

  • Li, Jian-Yi;Zhang, Yang;Zhang, Wen-Hai;Jia, Shi;Kang, Ye;Zhu, Xiao-Yu
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.1901-1906
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    • 2012
  • Background: The discovery that microRNA (miRNA) regulates metastasis provide a principal molecular basis for tumor heterogeneity. A characteristic of solid tumors is their heterogenous distribution of blood vessels, with significant hypoxia occurring in regions (centers of tumor) of low blood flow. It is necessary to discover the mechanism of breast cancer metastasis in relation to the fact that there is a differential distribution of crucial microRNA in tumors from centers to edges. Methods: Breast tissues from 48 patients (32 patients with breast cancer) were classified into the high invasive and metastatic group (HIMG), low invasive and metastatic group (LIMG), and normal group. Samples were collected from both the centers and edges of all tumors. The first six specimens were detected by microRNA array, and the second ten specimens were detected by real-time qRT-PCR and Western blot analyses. Correlation analysis was performed between the miRNAs and target proteins. Results: The relative content of miR-20a and miR-20b was lower in the center of the tumor than at the edge in the LIMG, lower at the edge of the tumor than in the center in the HIMG, and lower in breast cancer tissues than in normal tissues. VEGF-A and HIF-1alpha mRNA levels were higher in the HIMG than in the LIMG, and levels were higher in both groups than in the normal group; there was no difference in mRNA levels between the edge and center of the tumor. VEGF-A and HIF-1alpha protein levels were higher in the HIMG than in the LIMG, and protein levels in both groups were higher than in the normal group; there was a significant difference in protein expression between the edge and center of the tumor. Correlation analysis showed that the key miRNAs (miR-20a and miR-20b) negatively correlated with the target proteins (VEGF-A and HIF-1alpha). Conclusions: Our data suggest that miR-20a and miR-20b are differentially distributed in breast cancer, while VEGF-A and HIF-1alpha mRNA had coincident distributions, and VEGF-A and HIF-1alpha proteins had uneven and opposing distributions to the miRNAs. It appears that one of the most important facets underlying metastatic heterogeneity is the differential distribution of miR-20a and miR-20b and their regulation of target proteins.

Effect of Circulation Cycle of Nutrient Solution on the Dissolved Oxygen Concentration, and the Growth and Phytonutrient Contents of Leafy Vegetables Grown in DFT Systems (양액의 순환주기가 담액수경 엽채류의 용존산소 농도, 생육 및 식물영양소의 함량에 미치는 영향)

  • Seo, Tae-Cheol;Rhee, Han-Cheol;Rho, Mi-Young;Choi, Kyeong-Lee;Yun, Hyung-Kwon;Chun, Chang-Hoo
    • Journal of Bio-Environment Control
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    • v.18 no.2
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    • pp.112-118
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    • 2009
  • To determine the effects of circulation frequency of nutrient solution, three frequencies of 10min. on/10min. off; 10min. on/110min. off; and 10min. on/1,430min. off. treatments were applied to leafy vegetable production using deep flow technique (DFT) systems and their growth and phytonutrient content were investigated. In the 10min. on/I,430min. off treatment, dissolved oxygen concentration (DOC) 17 days after treatment decreased to 2.8mg. $L^{-1}$, known to be a low DOC that causes hypoxia, and thereafter decreased to 1.5mg. $L^{-1}$ 20 days after treatment. Fresh weight of 7 leafy vegetables in the 10min. on/1,430min. off treatment was lower by 0${\sim}$24% than those in the 10min. on/110min. off treatment, and those in the 10min. on/10min. off was higher by -2${\sim}$34% than those in the 10min. on/110min. off treatment as control. As the more frequent circulation was applied, the higher phosphorous content and the lower carbon to nitrogen ratio (C/N ratio) and total ascorbic acid contents were resulted. Results indicate that the circulation frequency of 110min, on/110min. off could be recommended for the production of the tested leafy vegetables in DFT systems.

Dynamics of Phosphorus-Turbid Water Outflow and Limno-Hydrological Effects on Hypolimnetic Effluents Discharging by Hydropower Electric Generation in a Large Dam Reservoir (Daecheong), Korea (대청호 발전방류수의 인·탁수 배출 역동성과 육수·수문학적 영향)

  • Shin, Jae-Ki;Hwang, Soon-Jin
    • Korean Journal of Ecology and Environment
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    • v.50 no.1
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    • pp.1-15
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    • 2017
  • Daecheong Reservoir was made by the construction of a large dam (>15 m in height) on the middle to downstream of the Geum River and the discharge systems have the watergate-spillway (WS), a hydropower penstock (HPP), and two intake towers. The purpose of this study was to investigate the limnological anomalies of turbid water reduction, green algae phenomenon, and oligotrophic state in the lower part of reservoir dam site, and compared with hydro-meteorological factors. Field surveys were conducted in two stations of near dam and the outlet of HPP with one week intervals from January to December 2000. Rainfall was closely related to the fluctuations of inflow, outflow and water level. The rainfall pattern was depended on the storm of monsoon and typhoon, and the increase of discharge and turbidity responded more strongly to the intensity than the frequency. Water temperature and DO fluctuations within the reservoir water layer were influenced by meteorological and hydrological events, and these were mainly caused by water level fluctuation based on temperature stratification, density current and discharge types. The discharges of WS and HPP induced to the flow of water bodies and the outflows of turbid water and nutrients such as nitrogen and phosphorus, respectively. Especially, when hypoxic or low-oxygen condition was present in the bottom water, the discharge through HPP has contributed significantly to the outflow of phosphorus released from the sediment into the downstream of dam. In addition, HPP effluent which be continuously operated throughout the year, was the main factor that could change to a low trophic level in the downreservoir (lacustrine zone). And water-bloom (green-tide) occurring in the lower part of reservoir was the result that the water body of upreservoir being transported and diffused toward the downreseroir, when discharging through the WS. Finally, the hydropower effluent was included the importance and dynamics that could have a temporal and spatial impacts on the physical, chemical and biological factors of the reservoir ecosystem.