• Title/Summary/Keyword: Release effect

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Role of p-38 MAP Kinase in apoptosis of hypoxia-induced osteoblasts (저산소 상태로 인한 조골세포 고사사기전에서 p-38 MAP kinase의 역할에 관한 연구)

  • Yoon, Jeong-Hyeon;Jeong, Ae-Jin;Kang, Kyung-Hwa;Kim, Sang-Cheol
    • The korean journal of orthodontics
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    • v.33 no.3 s.98
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    • pp.169-183
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    • 2003
  • Tooth movement by orthodontic force effects great tissue changes within the periodontium, especially by shifting the blood flow in the pressure side and resulting in a hypoxic state of low oxygen tension. The aim of this study is to elucidate the possible mechanism of apoptosis in response to hypoxia in MC3T3El osteoblasts, the main cells in bone remodeling during orthodontic tooth movement. MC3T3El osteoblasts under hypoxic conditions ($2\%$ orygen) resulted in apoptosis in a time-dependent manner as estimated by DNA fragmentation assay and nuclear morphology stained with fluorescent dye, Hoechst 33258. Pretreatment with Z-VAD-FMK, a pancaspase inhibitor, or Z-DEVD-CHO, a specific caspase-3 inhibitor, completely suppressed the DNA ladder in response to hypoxia. An increase in caspase-3-like protease (DEVDase) activity was observed during apoptosis, but no caspase-1 activity (YVADase) was detected. To confirm what caspases are involved in apoptosis, Western blot analysis was performed using anti-caspase-3 or -6 antibodies. The 10-kDa protein, corresponding to the active products of caspase-3, and the 10-kDa protein of the active protein of caspase-6 were generated in hypoxia-challenged cells in which the processing of the full length form of caspase-3 and -6 was evident. While a time course similar to this caspase-3 and -6 activation was evident, hypoxic stress caused the cleavage of lamin A, which was typical of caspase-6 activity. In addition, the stress elicited the release of cytochrome c into the cytosol during apoptosis. Furthermore, we observed that pre-treatment with SB203580, a selective p38 mitogen activated protein kinase inhibitor, attenuated the hypoxia-induced apoptosis. The addition of SB203S80 suppressed caspase-3 and -6-like protease activity by hypoxia up to $50\%$. In contrast, PD98059 had no effect on the hypoxia-induced apoptosis. To confirm the involvement of MAP kinase, JNK/SAPK, ERK, or p38 kinase assay was performed. Although p38 MAPK was activated in response to hypoxic treatment, the other MAPK -JNK/SAPK or ERK- was either only modestly activated or not at all. These results suggest that p38 MAPK is involved in hypoxia-induced apoptosis in MC3T3El osteoblasts.

Effects of Green Manure on Soil Properties and Grain Yield of Sorghum (Sorghum bicolor Moench) (수수 재배 시 풋거름작물 이용이 토양특성 변화와 수수의 수량에 미치는 영향)

  • Kim, Sung-Kook;Jung, Gun-Ho;Shin, Sung-Hyu;Kim, Min-Tae;Kim, Chung-Guk;Shim, Kang-Bo
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.61 no.4
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    • pp.290-296
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    • 2016
  • Green manure has been used as alternative to chemical fertilizer. To evaluate the effect of green manure on the chemical properties of top-soil and sorghum yield, hairy vetch (Vicia villosa Roth, HV), manure barley (MB), and a mixture of hairy vetch and manure barley (HV+MB) were incorporated into the soil at a rate of $100kg-N\;N\;ha-1$ before the sorghum was transplanted. Total biomass of sorghum grown in the HV, MB, and HV+MB treatments was 13.1, 31.6, and $25.2t\;ha^{-1}$, respectively, and the nitrogen production of the treatments was 81, 74, and $145kg\;ha^{-1}$, respectively. The SPAD value of the uppermost leaf of sorghum plants grown in the soils with HV, MB, or HV+MB were very similar until heading stage; however, at maturity, the SPAD value of sorghum cultivated in the soils with HV was lower than that of sorghum in the soils with MB or HV+MB. This could be because the nitrogen release from HV was too rapid to supply nitrogen to sorghum during the later stage of grain filling. Compared with chemical fertilizers, the incorporation of green manure increased the pH, exchangeable cations ($K^+$, $Mg{^{+}^{+}}$, and $Ca{^{+}^{+}}$), and total nitrogen in soil postharvest, indicating an improvement in soil chemical properties. Total carbon content increased in soil with green manure incorporated, but decreased in the chemical fertilized soil, suggesting that sorghum cultivation using green manure may sequester carbon in soils. The yield of sorghum cultivated with green manure was not different from the yield of sorghum cultivated with chemical fertilizers. These results suggest that the mixture of hairy vetch and manure barley can be a useful chemical fertilizer alternative in sorghum cultivation.

Study on the Consequence Effect Analysis & Process Hazard Review at Gas Release from Hydrogen Fluoride Storage Tank (최근 불산 저장탱크에서의 가스 누출시 공정위험 및 결과영향 분석)

  • Ko, JaeSun
    • Journal of the Society of Disaster Information
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    • v.9 no.4
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    • pp.449-461
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    • 2013
  • As the hydrofluoric acid leak in Gumi-si, Gyeongsangbuk-do or hydrochloric acid leak in Ulsan, Gyeongsangnam-do demonstrated, chemical related accidents are mostly caused by large amounts of volatile toxic substances leaking due to the damages of storage tank or pipe lines of transporter. Safety assessment is the most important concern because such toxic material accidents cause human and material damages to the environment and atmosphere of the surrounding area. Therefore, in this study, a hydrofluoric acid leaked from a storage tank was selected as the study example to simulate the leaked substance diffusing into the atmosphere and result analysis was performed through the numerical Analysis and diffusion simulation of ALOHA(Areal Location of Hazardous Atmospheres). the results of a qualitative evaluation of HAZOP (Hazard Operability)was looked at to find that the flange leak, operation delay due to leakage of the valve and the hose, and toxic gas leak were danger factors. Possibility of fire from temperature, pressure and corrosion, nitrogen supply overpressure and toxic leak from internal corrosion of tank or pipe joints were also found to be high. ALOHA resulting effects were a little different depending on the input data of Dense Gas Model, however, the wind direction and speed, rather than atmospheric stability, played bigger role. Higher wind speed affected the diffusion of contaminant. In term of the diffusion concentration, both liquid and gas leaks resulted in almost the same $LC_{50}$ and ALOHA AEGL-3(Acute Exposure Guidline Level) values. Each scenarios showed almost identical results in ALOHA model. Therefore, a buffer distance of toxic gas can be determined by comparing the numerical analysis and the diffusion concentration to the IDLH(Immediately Dangerous to Life and Health). Such study will help perform the risk assessment of toxic leak more efficiently and be utilized in establishing community emergency response system properly.

Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p

  • Lu, Feng-Bin;Chen, Da-Zhi;Chen, Lu;Hu, En-De;Wu, Jin-Lu;Li, Hui;Gong, Yue-Wen;Lin, Zhuo;Wang, Xiao-Dong;Li, Ji;Jin, Xiao-Ya;Xu, Lan-Man;Chen, Yong-Ping
    • Molecules and Cells
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    • v.42 no.12
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    • pp.906-918
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    • 2019
  • MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

Effects of Garcinia cambogia Extract on the Adipogenic Differentiation and Lipotoxicity (가르시니아 캄보지아 추출물의 지방세포 분화 및 지방 독성에 미치는 영향)

  • Kang, Eun Sil;Ham, Sun Ah;Hwang, Jung Seok;Lee, Chang-Kwon;Seo, Han Geuk
    • Food Science of Animal Resources
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    • v.33 no.3
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    • pp.411-416
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    • 2013
  • This study aimed to examine the mechanisms underlying the effects of Garcinia cambogia extract on the adipogenic differentiation of 3T3-L1 cells and long-chain saturated fatty acid-induced lipotoxicity of HepG2 cells. 3T3-L1 preadipocytes, mouse embryonic fibroblast-adipose like cell line, were treated with MDI solution (0.5 mM IBMX, 1 ${\mu}M$ dexamethasone, 10 ${\mu}g/mL$ insulin) to generate a cellular model of adipocyte differentiation. Using this cellular model, the anti-obesity effect of Garcinia cambogia extract was evaluated. MDI-induced lipid accumulation and expression of adipogenesis-related genes were detected by Oil red O staining, Nile Red staining, and Western blot analysis. Effects Garcinia cambogia extract on palmitate-induced lipotoxicity was also analyzed by MTT assay, LDH release, and DAPI staining in HepG2 cells. Garcinia cambogia extract significantly suppressed the adipogenic differentiation of preadipocytes and intracellular lipid accumulation in the differentiating adipocytes. Garcinia cambogia extract also markedly inhibited the expression of peroxisome proliferator- activated receptor ${\gamma}2$ ($PPAR{\gamma}2$), CCAT/enhancer-binding protein ${\alpha}$ ($C/EBP{\alpha}$), and adipocyte protein aP2 (aP2). In addition, Garcinia cambogia extract significantly attenuated palmitate-induced lipotoxicity in HepG2 cells. Palmitateinduced cellular damage and reactive aldehydes were also significantly reduced in the presence of Garcinia cambogia extract. These findings suggest that the Garcinia cambogia extract inhibits the adipogenic differentiation of 3T3-L1 preadipocytes, probably by regulating the expression of multiple genes associated with adipogenesis such as $PPAR{\gamma}2$, $C/EBP{\alpha}$, aP2, and thereby modulating fatty acid-induced lipotoxicity to reduce cellular injury in hepatocytes.

Study on K Activity ratio of Upland soils as Influenced by Lime application (석회시용(石灰施用)이 밭토양의 K Activity ratio에 미치는 영향(影響))

  • Kim, Tai-Soon;Han, Kang-Wan;Song, Ki-Joon;U, Zang-Kual
    • Korean Journal of Soil Science and Fertilizer
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    • v.11 no.2
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    • pp.67-73
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    • 1979
  • The effect of liming on the potassium equilibrium activity ratio ($AR^k_e$) of Chinese cabbage cultivated soil and on the potassium uptake by the plant summarize as follows: 1. $AR^k_e$ is raised by the application of 1.6 ton of $Ca(OH)_2$ per hectare that required amount to adjust pH 6 for the soil. Generally, it could be confirmed that both liming and potassium placement to the soil show the combined effects to raise $AR^k_e$. 2. The exchangeable potassium and the electrical conductivity increase by liming. The mean value of the exchangeable potassium is 0.71 m. equ. per 100g of limed soils while the control give 0.64 m. equ. per 100g. For the electrical conductivity, limed soil show $766{\mu}mho$ and $750{\mu}mho$ is for the control. 3. The reason $AR^k_e$ value increase by liming could be considered that concentrations of $K^+$ and $Ca^{{+}{+}}+Mg^{{+}{+}}$ in the equilibrium solution are increased owing to release both K and $Ca^+$ Mg into the liquid from solid phase in the potassium equilibrium system of the soil. 4. For considering that the energies of exchange of calcium by potassium in the limed soils at different potassium treatment, that is without K, 200 kg $K_2O/ha$ and 350 kg $K_2O/ha$, give -3887 and -3778 and -3737 calories per chemical equivalent respectively. On the other hand in case of the controls which received the same amounts of potassium as mentioned above, energy values are -3983, -4392 and -4228 calories respectively. 5. The absorbed amount of potassium and weights of dry matters of the plant which grown in the limed soils show little higher values than the controls.

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Destabilization of TNF-α mRNA by Rapamycin

  • Park, Jong-Woo;Jeon, Ye-Ji;Lee, Jae-Cheol;Ahn, So-Ra;Ha, Shin-Won;Bang, So-Young;Park, Eun-Kyung;Yi, Sang-Ah;Lee, Min-Gyu;Han, Jeung-Whan
    • Biomolecules & Therapeutics
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    • v.20 no.1
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    • pp.43-49
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    • 2012
  • Stimulation of mast cells through the high affinity IgE receptor (Fc${\varepsilon}$RI) induces degranulation, lipid mediator release, and cytokine secretion leading to allergic reactions. Although various signaling pathways have been characterized to be involved in the Fc${\varepsilon}$RI-mediated responses, little is known about the precious mechanism for the expression of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in mast cells. Here, we report that rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR), reduces the expression of TNF-${\alpha}$ in rat basophilic leukemia (RBL-2H3) cells. IgE or specific antigen stimulation of RBL-2H3 cells increases the expression of TNF-${\alpha}$ and activates various signaling molecules including S6K1, Akt and p38 MAPK. Rapamycin specifically inhibits antigeninduced TNF-${\alpha}$ mRNA level, while other kinase inhibitors have no effect on TNF-${\alpha}$ mRNA level. These data indicate that mTOR signaling pathway is the main regulation mechanism for antigen-induced TNF-${\alpha}$ expression. TNF-${\alpha}$ mRNA stability analysis using reporter construct containing TNF-${\alpha}$ adenylate/uridylate-rich elements (AREs) shows that rapamycin destabilizes TNF-${\alpha}$ mRNA via regulating the AU-rich element of TNF-${\alpha}$ mRNA. The antigen-induced activation of S6K1 is inhibited by specific kinase inhibitors including mTOR, PI3K, PKC and $Ca^{2+}$chelator inhibitor, while TNF-${\alpha}$ mRNA level is reduced only by rapamycin treatment. These data suggest that the effects of rapamycin on the expression of TNF-${\alpha}$ mRNA are not mediated by S6K1 but regulated by mTOR. Taken together, our results reveal that mTOR signaling pathway is a novel regulation mechanism for antigen-induced TNF-${\alpha}$ expression in RBL-2H3 cells.

Effects of Potassium-Channel Opener on Thallium-201 Kinetics: In-vitro Study in Rat Myocyte Preparations and In-vivo Mice Biodistribution Study (K-통로개방제가 배양심근세포와 생쥐 체내의 Thallium-201역동학에 미치는 영향)

  • Lee, Jae-Tae;Kim, Eun-Ji;Ahn, Byeong-Cheol;Sohn, Kang-Kyun;Lee, Kyu-Bo;Ha, Jeoung-Hee;Kim, Chun-K.
    • The Korean Journal of Nuclear Medicine
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    • v.30 no.4
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    • pp.507-515
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    • 1996
  • Background : Potassium channel opener (K-opener) opens ATP-sensitive K'-channel located at cell membrane and induces potassium efflux from cytosol, resulting in intracellular hyperpolarization. Newly synthesized K-opener is currently examined for pharmacologic potency by means of rubidium release test from smooth muscle strip pre-incubated with Rb-86. Since in-vivo behavior of thallium is similar to that of rubidium, we hypothesized that K-opener can alter T1-201 kinetics in vivo. Purpose : This study was prepared to investigate the effects of pinacidil (one of potent K-openers) on the T1-201 uptake and clearance in cultured myocyte, and in-vivo biodistribution in mice. Methods : Spontaneous contracting myocytes were prepared to imitate in-vivo condition from 20 hearts of 3-5 days old Sprague-Dawley rat and cultured for 3-5 days before use ($5{\times}10^5$ cells/ml). Pinacidil was dissolved in 10% DMSO solution at a final concentration of 100nM or l0uM and was co-incubated with T1-201 in HBSS buffer for 20-min to evaluate its effect on cellular T1-uptake, or challenged to cell preparation pre-incubated with T1-201 for washout study. Two, 40 or $100{\mu}g$ of pinacidil was injected intravenously into ICR mice at 10 min after $5{\mu}Ci$ T1-201 injection, and organ uptake and whole body retention rate were measured at different time points. Results : Co-incubation of pinacidil with T1-201 resulted in a decrease in T1-201 uptake into cultured myocyte by 1.6 to 2.5 times, depending on pinacidil concentration and activity of T1-201 used. Pinacidil enhanced T1-201 washout by 1.6-3.1 times from myocyte preparations pre-incubated with T1-201. Pinacidil treatment appears to be resulted in mild decreases in blood and liver activity in normal mice, in contrast, renal and cardiac uptake were mildly decreased in a dose dependent manner. Whole body retention ratios of T1-201 were lower at 24 hour after injection with $100{\mu}g$ of pinacidil than control. Conclusion : These results suggest that treatment with K-opener may affect the interpretation of T1-201 myocardial images, due to decreasing thallium accumulation and enhancing washout from myocardium.

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Bioequivalence of Carvelol Tablet to Dilatrend Tablet (Carvedilol 25 mg) (딜라트렌 정(카르베딜롤 25 mg)에 대한 카베롤 정의 생물학적 동등성)

  • Cho, Hea-Young;Lee, Moon-Seok;Park, Soon-Cheol;Lim, Dong-Koo;Moon, Jai-Dong;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.31 no.4
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    • pp.289-295
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    • 2001
  • Carvedilol is an antihypertensive and antianginal compound that combines nonselective beta-adrenoceptor blocking and vasodilation properties and is devoid of intrinsic sympathomimetic activity. The purpose of the present study was to evaluate the bioequivalence of two carvedilol tablets, $Dilatrend^{TM}$ (Chong Kun Dang Pharmaceutical Co., Ltd.) and $Carvelol^{TM}$ (Dae Won Pharmaceutical Co., Ltd.), according to the prior and revised guidelines of Korea Food and Drug Administration (KFDA). The carvedilol release from the two carvedilol tablets in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution, water and blend of PSB80 into water). Eighteen normal male volunteers, $24.22{\pm}1.86$ years in age and $64.81{\pm}4.56\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 25 mg of carvedilol was orally administered, blood was taken at predetermined time intervals and the concentrations of carvedilol in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two carvedilol tablets were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using non-transformed and logarithmically transformed $AUC_t$ and $C_{max}$. The results showed that the differences in $AUC_t$, $C_{max}$ and $T_{max}$ between two tablets based on the $Dilatrend^{TM}$ were 2.23%, -2.00% and 0.00%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 13.55% and 17.61% for $AUC_t$ and $C_{max}$, respectively). The powers $(l-{\beta})$ at ${\alpha}=0.05$, ${\Delta}=0.2$ for $AUC_t$ and $C_{max}$ were 98.08% and 88.81%, respectively. The 90% confidence intervals were within ${\pm}20%$ (e.g., $-5.69{\sim}10.16$ and $-12.30{\sim}8.30$ for $AUC_t$ and $C_{max}$, respectively). There were no sequence effect between two tablets in logarithmically transformed $AUC_t$ and $C_{max}$. The 90% confidence intervals using logarithmically transformed were within the acceptance range of log(0.8) to log(1.25) (e.g., $0.95{\sim}1.11$ and $0.89{\sim}1.09$ for $AUC_t$ and $C_{max}$, respectively). Two parameters met the criteria of prior and revised KFDA guideline for bioequivalence, indicating that $Carvelol^{TM}$ tablet is bioequivalent to $Dilatrend^{TM}$ tablet.

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Evaluation of Internal Phosphorus Loading through the Dynamic Monitoring of Dissolved Oxygen in a Shallow Reservoir (수심이 얕은 저수지에서 용존산소 동적 모니터링을 통한 인 내부부하 평가)

  • Park, Hyungseok;Choi, Sunhwa;Chung, Sewoong;Ji, Hyunseo;Oh, Jungkuk;Jun, Hangbae
    • Journal of Environmental Impact Assessment
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    • v.26 no.6
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    • pp.553-562
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    • 2017
  • In these days, agricultural reservoirs are considered as a useful resource for recreational purposes, tour and cultural amenity for vicinity communities as well as irrigation water supply. However, many of the agricultural reservoirs are showing a eutrophic or hyper-eutrophic state and high level of organic contamination. In particular, about 44.7% of the aged agricultural reservoirs that constructed before 1945 exceed the water quality criteria for irrigational water use. In addition to external loading, internal nutrient loading from bottom sediment may play an important role in the nutrient budget of the aged reservoirs. The objectives of this study were to characterize variations of thermal structure of a shallow M reservoir (mean depth 1.7 m) and examine the potential of internal nutrient loading by continuous monitoring of vertical water temperature and dissolved oxygen (DO) concentration profiles in 2015 and 2016. The effect of internal loading on the total loading of the reservoir was evaluated by mass balance analysis. Results showed that a weak thermal stratification and a strong DO stratification were developed in the shallow M Reservoir. And, dynamic temporal variation in DO was observed at the bottom of the reservoir. Persistent hypoxic conditions (DO concentrations less than 2 mg/L) were established for 87 days and 98 days in 2015 and 2016, respectively, during the no-rainy summer periods. The DO concentrations intermittently increased during several events of atmospheric temperature drop and rainfall. According to the mass balance analysis, the amount of internal $PO_4-P$ loading from sediment to the overlying water were 37.9% and 39.7% of total loading during no-rainy season in 2015 and 2016, respectively on August when algae growth is enhanced with increasing water temperature. Consequently, supply of DO to the lower layer of the reservoir could be effective countermeasure to reduce nutrient release under the condition of persistent DO depletion in the bottom of the reservoir.