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Effects of long-term tubular HIF-2α overexpression on progressive renal fibrosis in a chronic kidney disease model

  • Dal-Ah Kim;Mi-Ran Lee;Hyung Jung Oh;Myong Kim;Kyoung Hye Kong
    • BMB Reports
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    • v.56 no.3
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    • pp.196-201
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    • 2023
  • Renal fibrosis is the final manifestation of chronic kidney disease (CKD) regardless of etiology. Hypoxia-inducible factor-2 alpha (HIF-2α) is an important regulator of chronic hypoxia, and the late-stage renal tubular HIF-2α activation exerts protective effects against renal fibrosis. However, its specific role in progressive renal fibrosis remains unclear. Here, we investigated the effects of the long-term tubular activation of HIF-2α on renal function and fibrosis, using in vivo and in vitro models of renal fibrosis. Progressive renal fibrosis was induced in renal tubular epithelial cells (TECs) of tetracycline-controlled HIF-2α transgenic (Tg) mice and wild-type (WT) controls through a 6-week adenine diet. Tg mice were maintained on doxycycline (DOX) for the diet period to induce Tg HIF-2α expression. Primary TECs isolated from Tg mice were treated with DOX (5 ㎍/ml), transforming growth factor-β1 (TGF-β1) (10 ng/ml), and a combination of both for 24, 48, and 72 hr. Blood was collected to analyze creatinine (Cr) and blood urea nitrogen (BUN) levels. Pathological changes in the kidney tissues were observed using hematoxylin and eosin, Masson's trichrome, and Sirius Red staining. Meanwhile, the expression of fibronectin, E-cadherin and α-smooth muscle actin (α-SMA) and the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was observed using western blotting. Our data showed that serum Cr and BUN levels were significantly lower in Tg mice than in WT mice following the adenine diet. Moreover, the protein levels of fibronectin and E-cadherin and the phosphorylation of p38 MAPK were markedly reduced in the kidneys of adenine-fed Tg mice. These results were accompanied by attenuated fibrosis in Tg mice following adenine administration. Consistent with these findings, HIF-2α overexpression significantly decreased the expression of fibronectin in TECs, whereas an increase in α-SMA protein levels was observed after TGF-β1 stimulation for 72 hr. Taken together, these results indicate that long-term HIF-2α activation in CKD may inhibit the progression of renal fibrosis and improve renal function, suggesting that long-term renal HIF-2α activation may be used as a novel therapeutic strategy for the treatment of CKD.

Ginsenoside Rb2 suppresses cellular senescence of human dermal fibroblasts by inducing autophagy

  • Kyeong Eun Yang;Soo-Bin Nam;Minsu Jang;Junsoo Park;Ga-Eun Lee;Yong-Yeon Cho;Byeong-Churl Jang;Cheol-Jung Lee;Jong-Soon Choi
    • Journal of Ginseng Research
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    • v.47 no.2
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    • pp.337-346
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    • 2023
  • Background: Ginsenoside Rb2, a major active component of Panax ginseng, has various physiological activities, including anticancer and anti-inflammatory effects. However, the mechanisms underlying the rejuvenation effect of Rb2 in human skin cells have not been elucidated. Methods: We performed a senescence-associated β-galactosidase staining assay to confirm cellular senescence in human dermal fibroblasts (HDFs). The regulatory effects of Rb2 on autophagy were evaluated by analyzing the expression of autophagy marker proteins, such as microtubule-associated protein 1A/1B-light chain (LC) 3 and p62, using immunoblotting. Autophagosome and autolysosome formation was monitored using transmission electron microscopy. Autophagic flux was analyzed using tandem-labeled GFP-RFP-LC3, and lysosomal function was assessed with Lysotracker. We performed RNA sequencing to identify potential target genes related to HDF rejuvenation mediated by Rb2. To verify the functions of the target genes, we silenced them using shRNAs. Results: Rb2 decreased β-galactosidase activity and altered the expression of cell cycle regulatory proteins in senescent HDFs. Rb2 markedly induced the conversion of LC3-I to LC3-II and LC3 puncta. Moreover, Rb2 increased lysosomal function and red puncta in tandem-labeled GFP-RFP-LC3, which indicate that Rb2 promoted autophagic flux. RNA sequencing data showed that the expression of DNA damage-regulated autophagy modulator 2 (DRAM2) was induced by Rb2. In autophagy signaling, Rb2 activated the AMPK-ULK1 pathway and inactivated mTOR. DRAM2 knockdown inhibited autophagy and Rb2-restored cellular senescence. Conclusion: Rb2 reverses cellular senescence by activating autophagy via the AMPK-mTOR pathway and induction of DRAM2, suggesting that Rb2 might have potential value as an antiaging agent.

Effects of Temperature on the Development and Reproduction of Ostrinia scapulalis (Lepidoptera: Crambidae) (콩줄기명나방(Ostrinia scapulalis) (나비목: 포충나방과)의 발육과 산란에 미치는 온도의 영향)

  • Jeong Joon, Ahn;Eun Young, Kim;Bo Yoon, Seo;Jin Kyo, Jung
    • Korean journal of applied entomology
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    • v.61 no.4
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    • pp.577-590
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    • 2022
  • Ostrinia scapulalis is one of important pests in leguminous crops, especially red bean. In order to understand the biological characteristics of the insect, we investigated the effects of temperature on development of each life stage, adult longevity and fecundity of O. scapulalis at eleven constant temperatures of 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, and 36℃. Eggs and larvae successfully developed next life stage at most temperature subjected except 7, 10 and 13℃. The developmental period of egg, larva and pupa decreased as temperature increased. Lower and higher threshold temperature (TL and TH) were calculated by the Lobry-Rosso-Flandrois (LRF) and Sharpe-Schoolfield-Ikemoto (SSI) models. The lower developmental threshold (LDT) and thermal constant (K) from egg hatching to adult emergence of O. scapulalis were estimated by linear regression as 13.5℃ and 384.5DD, respectively. TL and TH from egg hatching to adult emergence using SSI model were 19.4℃ and 39.8℃. Thermal windows, i.e., the range in temperature between the minimum and maximum rate of development, of O. scapulalis was 20.4℃. Adults produced viable eggs at the temperature range between 16℃ and 34℃, and showed a maximum number, ca. 416 offsprings, at 25℃. Adult models including aging rate, age-specific survival rate, age-specific cumulative oviposition, and temperature-dependent fecundity were constructed, using the temperature-dependent adult traits. Temperature-dependent development models and adult oviposition models will be useful components to understand the population dynamics of O. scapulalis and will be expected using a basic data for establishing the strategy of integrated pest management in leguminous crops.

YOLO-based Traffic Signal Detection for Identifying the Violation of Motorbike Riders (YOLO 기반의 교통 신호등 인식을 통한 오토바이 운전자의 신호 위반 여부 확인)

  • Wahyutama, Aria Bisma;Hwang, Mintae
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2022.05a
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    • pp.141-143
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    • 2022
  • This paper presented a new technology to identify traffic violations of motorbike riders by detecting the traffic signal using You Only Look Once (YOLO) object detection. The hardware module that is mounted on the front of the motorbike consists of Raspberry Pi with a camera to run the YOLO object detection, a GPS module to acquire the motorcycle's coordinate, and a LoRa communication module to send the data to a cloud DB. The main goal of the software is to determine whether a motorbike has violated a traffic signal. This paper proposes a function to recognize the red traffic signal colour with its movement inside the camera angle and determine that the traffic signal violation happens if the traffic signal is moving to the right direction (the rider turns left) or moving to the top direction (the riders goes straight). Furthermore, if a motorbike rider is violated the signal, the rider's personal information (name, mobile phone number, etc), the snapshot of the violation situation, rider's location, and date/time will be sent to a cloud DB. The violation information will be delivered to the driver's smartphone as a push notification and the local police station to be used for issuing violation tickets, which is expected to prevent motorbike riders from violating traffic signals.

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Studies on Cropping System of Upland Crop for the Sustainable Agriculture. (환경 농업 실천을 위한 밭작물 작부체계의 적용 조사)

  • Kang, Y.K.
    • Journal of Practical Agriculture & Fisheries Research
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    • v.3 no.1
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    • pp.20-29
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    • 2001
  • This study was carried out to find out basic data of the various cropping systems controlling the soil environment by analysing the historical literature, the changes of cropping system and the expected income of cropping system of the upland crop. The results were summerized as follows ; 1. According to the literature of 'Gumyangjoprok' and 'Sanlimgyungjae', published on 15 to 16 century in Korea, the cropping system of barley, soybean, red bean, and millet, etc. was done together both the 'kunkyong' and 'kanjong'. 2. Since 1970s the staple food grains had been self-sufficient and the setting up of the rice seedbed became faster. However, the cropping system of the rice after barley was rapidly fallen from 83.7% to 4.0% in 1990s. Furthermore, the food production and the rate of arable land utilization were also rapidly fallen. 3. The most prospective cropping system is considered the soybean after barley, and root & tuber crops considering with the soil environment. 4. The expecting income of cropping system ranged from 940,000won to l,970,000won per 10a but that of barley after soybean cropping for 610,000won, and that of barley-after mung bean cropping for 613,000won. 5. The maintenance and the preservation of agricultural environment shall become positive by practicing the Integrated Nutrients Management(INM), and the Integrated Pest Management(IPM) with control using of fertilizer and pesticide presenting the excessive loads to the soil environment.

Assessing the Quality for Blood Transfusion Service since the 1st National Quality Assessment Program in South Korea (국내 1차 수혈 적정성 평가 시행에 따른 수혈서비스 질관리 현황)

  • Jin-Ah Kwon;Eun-Jeong Cho;A-Hyun Jung;Dong-Sook Kim
    • Quality Improvement in Health Care
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    • v.28 no.2
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    • pp.30-38
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    • 2022
  • Purpose: The Health Insurance Review and Assessment Service (HIRA) in South Korea initiated a quality assessment (QA) program for blood transfusion healthcare services in 2020 to ensure patient safety and appropriate blood use. This study examines the quality of blood transfusion services since the first national QA program for blood transfusion services in Korea. Methods: We analyzed HIRA claims and QA investigation data based on inpatient medical records from all tertiary, general, and primary hospitals between October 2020 and March 2021. The target population was patients aged 18 years and older who received either total knee arthroplasty or red blood cell transfusion. The QA indicators for transfusion healthcare service consisted of four quality indicators and four monitoring indicators. Results: We analyzed the results of QA indicators for transfusion service from the medical records of 189,668 patients from 1,171hospitals and expressed indicators as proportions. The average results for evaluation indicators were as follows: transfusion checklist presence, 64.8%; irregular antibody tests, 61.8%; transfusions in which the hemoglobin levels before transfusion met the transfusion guidelines for patients undergoing total knee arthroplasty, 20.6%, and transfusions in patients undergoing total knee arthroplasty, 59.3%. The average results for monitoring indicators were as follows: transfusion management implementation in medical institutions, 56.9%; preoperative anemia management in anemia patients undergoing total knee arthroplasty, 43.9%; one-unit transfusions, 82.5%; and the transfusion index. Conclusion: The quality of blood transfusion healthcare varied and the assessment revealed that there is scope for improvement. Hospitals require more effective blood transfusion management and this can be facilitated by providing feedback on the QA results about blood transfusion healthcare services to medical institutions, and by disclosing the results to the public.

Analysis of enzyme activity changes caused by flooding stress in upland crops (침수 스트레스에 의한 밭작물의 효소활성 변화 분석)

  • Juhyung Shin;Byeonggyu Kim;Kihwan Kim;Tae-An Kang;Won-Chan Kim
    • Korean Journal of Environmental Biology
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    • v.40 no.3
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    • pp.341-351
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    • 2022
  • Among various environmental stresses, humid stress lacks mechanisms and biochemical understanding compared to drought, low temperature, and high salt stresses. The aim of this study was to investigate enzyme activity of field crops under humidity stress. Results of this study could be used as basic data for understanding humidity stress and early diagnosis. Growth and enzyme activities of sesame, perilla, red beans, sorghum, and beans as major field crops in Korea when flooded were investigated. It was confirmed that growths of both shoots and roots were retarded. In plants, anaerobic fermentation occurred due to flooding stress, which increased the activity of alcohol dehydrogenase (ADH) compared to the control group. Increases of reactive oxygen species (ROS) were also observed. All flooded plants showed increased peroxidase (POD) activity and lipid peroxidation. Their dyeing strength was darker than that of the control group, even in 3,3'-diaminobenzidine (DAB) staining. Since enzyme activity changes in plants appear relatively faster than changes in phenotype at the ground level, they could be used as biomarkers for early diagnosis of humidity stress in crops.

Analysis of inflammatory markers in blood related with the occurrence of subcutaneous abscesses in goats (염소의 피하농양 발생에 따른 혈액 내 염증지표 분석)

  • Ku, Ji-yeong;Park, Jun-Hwan;Kim, Seo-Ho;Cho, Yong-il;Kim, Chan-Lan;Cha, Seung-Eon;Shin, Gee-Wook;Park, Jinho
    • Korean Journal of Veterinary Service
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    • v.45 no.1
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    • pp.47-54
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    • 2022
  • Subcutaneous abscesses, which occur mainly in goats and sheep, are lymph node abscesses caused by Corynebacterium pseudotuberculosis infection, and are divided into internal, external, and mixed types depending on the type of occurrence. While diagnostic methods for subcutaneous abscesses have been continuously studied, research reports for effective treatment and management of subcutaneous abscesses are inadequate. Therefore, this study was conducted to determine the changes in biometric information related to the inflammatory markers of goats induced by subcutaneous abscesses by infection with C. pseudotuberculosis. For this, hematological tests, analysis of inflammatory indicators, and analysis of serum proteins through electrophoresis separation of goats with healthy goats and goats inoculated with C. pseudotuberculosis to induce subcutaneous abscesses were compared and analyzed by date, and the differences and characteristics were identified periodically. As a result, in goats induced with subcutaneous abscesses, anemia findings related to a rapid decrease in red blood cell (RBC), hematocrit (HCT), and hemoglobin (Hb) were observed, and a significant increase in inflammatory cells expressed in total white blood cell (WBC), neutrophil, and monocytes was observed. And the levels of acute phase protein (APP) such as fibrinogen, haptoglobin, and serum amyloid A (SAA) were observed to increase rapidly immediately after infection. In addition, in the results of electrophoretic analysis of serum proteins, it was observed that the levels of α-globulin and β-globulin were significantly increased in goats with subcutaneous abscesses. That is, when looking at these changes, it was found that the systemic inflammatory response of goats was rapidly induced immediately after infection with the C. pseudotuberculosis pathogen. Through this study, it was possible to identify changes in the biomarkers of goats with subcutaneous abscesses, which had not been reported. Furthermore, these analyzed data are thoughts to be of great help in identifying, treating, and managing the goats of subcutaneous abscesses.

Quantitative Research Trends for Critical Care Survivors' Health related Quality of Life after Intensive Care Unit Discharge (중환자실 생존 환자의 퇴원 후 건강관련 삶의 질에 관한 국내·외 양적연구 동향)

  • Son, Youn-Jung;Song, Hyo-Suk
    • Asia-pacific Journal of Multimedia Services Convergent with Art, Humanities, and Sociology
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    • v.6 no.12
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    • pp.55-67
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    • 2016
  • Purpose: The aims of this were to analyse the quantitative research trends and describe the factors influencing health related to quality of life (HRQoL) and instruments used to HRQoL after Intensive care units (ICU) discharge. Methods: This study were included 84 published papers regarding HRQoL after ICU discharge from initial data to December 2015. Results: The majority of papers were performed abroad. Only 4 papers with regard to HRQoL of ICU survivors were performed by nurses. 36 studies (42.8%) were used to measure HRQoL ICU survivors using the SF-36. 29 studies (34.5%) were used to measure HRQoL at 3~6 months after ICU discharge. Older age, longer length of stay at ICU, severity of illness, anxiety and depression were main risk factors to lower HRQoL in ICU patients. Conclusions: This study provides a better understanding of quality of life follwing critical illness. Therefore, further stduy is needed to develop patient centered intervention considered patients'health status and recovery phase. Additionally, large prospective multicenter cohort studies should be required.

Analysis of Nutrient Content by Digestion Phase of Legumes using an In Vitro Digestion Model (In Vitro Digestion Model을 활용한 두류 소화 단계별 영양성분 변화 분석)

  • Da Bin Lee;Kyeong A Jang;In Seon Hwang;Min Sook Kang;Mi-Kyung Seo;Haeng Ran Kim;Seon Mi Yoo
    • The Korean Journal of Food And Nutrition
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    • v.36 no.5
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    • pp.368-378
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    • 2023
  • Changes in contents of free sugars, amino acids, and fatty acids of legumes were analyzed for each phase of in vitro digestion. In addition, contents of resistant starch in raw and digested pulses were compared. Soybeans, kidney beans, cowpeas, and chickpeas were analyzed. An in vitro digestion model was used to analyze contents of nutrients using LC-MS and GC-MS. Stachyose in kidneybean, cowpea, and chickpea increased as the digestion phase progressed. In four types of legumes, raffinose slightly decreased or showed no significant difference between the Oral phase and the BBMV phase. Content of glucose, a monosaccharide, increased during the BBMV phase. During the digestion phase, levels of free amino acids and free fatty acids also increased. Content of resistant starch was reduced compared to that in the raw material. It was 0.01g/100 g food in soybean, 1.06 g/100 g food in red kidney bean, 0.77g/ 100g food in cowpea, and 0.76 g/100 g food in chickpea. It was confirmed that nutrients in the in vitro digestion model were liberated at each digestion phase with changes in the content of resistant starch. These results are expected to be used as fundamental data for obtaining bioavailability of nutrients.