• Title/Summary/Keyword: Glucose Toxicity

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Targeting cell surface glucose-regulated protein 94 in gastric cancer with an anti-GRP94 human monoclonal antibody

  • Hyun Jung Kim;Yea Bin Cho;Kyun Heo;Ji Woong Kim;Ha Gyeong Shin;Eun-bi Lee;Seong-Min Park;Jong Bae Park;Sukmook Lee
    • BMB Reports
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    • v.57 no.4
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    • pp.188-193
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    • 2024
  • Gastric cancer (GC), a leading cause of cancer-related mortality, remains a significant challenge despite recent therapeutic advancements. In this study, we explore the potential of targeting cell surface glucose-regulated protein 94 (GRP94) with antibodies as a novel therapeutic approach for GC. Our comprehensive analysis of GRP94 expression across various cancer types, with a specific focus on GC, revealed a substantial overexpression of GRP94, highlighting its potential as a promising target. Through in vitro and in vivo efficacy assessments, as well as toxicological analyses, we found that K101.1, a fully human monoclonal antibody designed to specifically target cell surface GRP94, effectively inhibits GC growth and angiogenesis without causing in vivo toxicity. Furthermore, our findings indicate that K101.1 promotes the internalization and concurrent downregulation of cell surface GRP94 on GC cells. In conclusion, our study suggests that cell surface GRP94 may be a potential therapeutic target in GC, and that antibody-based targeting of cell surface GRP94 may be an effective strategy for inhibiting GRP94-mediated GC growth and angiogenesis.

The acute toxicity and efficacy evaluation against Aeromonas salmonicida of aquatic drugs oxolinic acid, neomycin-oxytetracycline, and florfenicol in guppy (Poecilia reticulata) (구피(Poecilia reticulata)에서 수산용의약품 oxolinic acid, neomycin-oxytetracycline, florfenicol의 급성독성 및 Aeromonas salmonicida에 대한 약효 평가)

  • Jun Sung Bae;Chae Won Lee;Chan Yeong Yang;Eun Ha Jeong;Areum Kim;Young-Sik Chae;Jung-Jin Park;Kwan Ha Park
    • Journal of fish pathology
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    • v.36 no.2
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    • pp.293-302
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    • 2023
  • This study evaluated the acute toxicity induced by oxolinic acid (OA), neomycin-oxytetracycline combination (NEO-OTC) and florfenicol (FF) administered to guppy (Poecilia reticulata) by comparing standard formulations with commercial preparations (COOaqua curinpotion, COOaqua terafinpotion and COOaqua profenpotion, respectively) for ornamental fish at concentrations of 2-4%. NEO-OTC exhibited the highest acute toxicity in guppy, with no difference observed between the pstandard formulation and commercial preparation (LC50 = 126.08 mg/L and 112.44 mg/L, respectively). OA acute toxicity was assessed in the form of sodium salt, with an LC50 of 504.61 mg/L for the standard formulation and a slightly increased toxicity of 316.11 mg/L for the commercial preparation. In contrast, no mortality was observed during the 96-hour exposure period with the standard formulation in the form of oxolinic acid. The acute toxicity of FF was measured to be above 1,000 mg/L for the standard formulation; however, the commercial preparation significantly increased to 158.53 mg/L. These results indicate that toxicity can significantly increase in commercial formulations, especially those with low levels of active ingredients. This is presumed to be attributed to the organic solvents or solubilizing agents present in the commercial preparations, which may enhance toxicity. Additionally, guppy infected with Aeromonas salmonicida were effectively protected against mortality by administering OA, NEO-OTC and FF at concentrations of 50 mg/L, 100 mg/L and 15 mg/L, respectively, for 2 hours and at half the dose for 24 hours. This result indicates that liquid formulations containing low concentrations of antibiotics may partially increase toxicity, but there is no problem in effectively treating diseases in ornamental fish.

Hepatoprotective Activity of Bacopa monniera on D-galactosamine Induced Hepatotoxicity in Rats

  • Ramakrishnan, S.;Sumathi, T.
    • Natural Product Sciences
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    • v.13 no.3
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    • pp.195-198
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    • 2007
  • Hepatoprotective action of alcoholic extract of Bacopa monniera (BME) was evaluated on Dgalactosamine (D-GalN) induced rat liver toxicity. Bacopa monniera extract reduced the elevated serum enzyme activities of ALT, AST, ALP, LDH, ${\gamma}-GT$ and the formation of hepatic malondialdehyde induced by D-GalN. The alcholic extract of Bacopa monniera also significantly restored the decreased levels of glutathione and the decreased activities of glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase and glucose-6-phosphatase. Therefore these results suggest that Bacopa monniera has hepatoprotective effect against D-GalN induced hepatotoxicity.

Effect of pH on the Degradation of 2, 4-Dinitrophenol in Sequencing Batch Reactor Process (연속회분식(連續回分式) 처리공정(處理工程)에 의한 2, 4-Dinitrophenol분해시(分解時) pH의 영향(影響))

  • Jo, Kwan-Hyung
    • Journal of Korean Society of Water and Wastewater
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    • v.12 no.1
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    • pp.96-101
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    • 1998
  • Substrate inhibition of 2,4-dinitrophenol (DNP) degradation was investigated using activated sludge which had been adapted to mineralize DNP. DNP is a metabolic uncoupler, preventing cells from making energy for growth and it has been suggested that pH may be important in mitigating effects of uncouplers. After acclimation of the activated sludge, the effect of pH on toxicity of DNP at high concentration (75 mg/L) was investigated, over a pH range of 5 to 9. DNP inhibition was found to be strongly dependent on mixed liquor pH. The DNP degradation rate was highest in the pH range of 6.95 to 7.84; at pH 5.94 degradation of 75 mg/L DNP was significantly inhibited; at pH < 5.77, DNP degradation was completely inhibited after approximately 30% of the DNP was degraded. By comparison, no significant effect of pH variation in the same range was seen on glucose uptake by the activated sludge culture.

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The Effects of Some Oriental Herbs Which Have Been Used in the Treatment of Alcoholic Diseases on Alcoholic Metabolism and Alcoholic Liver Damages (주상에 활용되는 수종의 한약물이 알콜올대사 및 간장해에 미치는 영향)

  • 박형규;이장훈;우홍정
    • The Journal of Korean Medicine
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    • v.21 no.3
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    • pp.186-198
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    • 2000
  • Objectives : This experiment was conducted to verify the effects of some oriental herbs(Alny Cortex et Ramulus, Artemisiae Capillaris Herba, Aurantii Nobilis Pericarpium, Giseng Radix, Hoveniae Semen, Puerariae Flos, Puerariae Radix, and Xanthii Fructus) which have been used in the treatment of alcoholic diseases, on alcoholic metabolism, and on alcoholic liver damage. Methods : The effects of the herbs on the activities of alcohol dehydrogenase(ADH), aldehyde dehydrogenase(ALDH) were evaluated and their protective effects of liver function and cells from alcoholic damage were analysed. For the evaluation of the protective effects, the levels of glucose, triglyceride, BUN, AST, and ALT in serum of rats were measured. Results and Conclusions : It is concluded that Puerariae Radix interferes with the ADH activity directly, thereby reducing the toxicity of alcohol, resulting in enhancing alcohol-tolerance and protecting liver functions. Also Artemisiae Capillaris Herba interferes both ADH and ALDH activities. Isolation of the biologically active compounds from Puerariae Radix and its detailed characterization are matters for future research.

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Peroxynitrite Scavenging Mechanism of Alaternin and Nor-rubrofusarin glucose from Cassia tora

  • Park, Tae-Hyun;Jung, Hyun-Ah;Choi, Jae-Sue;Chung, Hae-Young
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.318.3-319
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    • 2002
  • Peroxynitrite(ONOO-), formed from the reaction of superoxide(O2-) and nitric oxide(NO), is a potent oxidant that contributes to oxidation of various cellular constituents including lipids. amino acids, sulphydryls and nucleotides. It can cause cellular injury such as DNA fragmentation and apoptotic cell death. Also. the toxicity of ONOO- has been reported to be involved in inflammatory and nurodegenerative diseases such as Alzheimer's disease, Parkinson's disease. and atherosclerosis. (omitted)

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Effects of Yukmijihwang-Tang on the Hepatic Microsomal Function of Cd-poisoned Rat (육미지황탕이 카드뮴 중독된 흰쥐의 간장 약물대사 기능에 미치는 영향)

  • Suh, Eun-Sil;Lim, Jong-Pil
    • YAKHAK HOEJI
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    • v.44 no.6
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    • pp.552-557
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    • 2000
  • In order to investigate the effects of Yukmijihwang-Tang on the hepatic microsomal function of Cd-poisoned rats, 3 mg/kg of cadmium (Cd) and 500 mg/kg of Yukmijihwang-Tang extract (YJT), a herbal hepatoprotective medicine, were administered concurrently to rats for 4 weeks. The levels of protein, aniline hydroxylase (AH) and malondialdehyde (MDA) were increased in Cd-treated group. This increase was suppressed by treatment or YJT. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose-6-phosphatase (G-6-P) and ${\delta}-aminolevulinic$ acid dehydratase (ALAD) of Cd-treated group were decreased. This decrease was inhibited by treatment of YJT. Treatment with YJT significantly protects cadmium-induced hepatotoxicity.

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Effects of acute dibutyl phthalate administration on hepatic lipid peroxidation and gamma-glutamyl transferase activity in mice (마우스에서 dibutyl phthalate 급성 투여가 간 지질과산화와 gamma-glutamyl transferase 활성에 미치는 효과)

  • 최달웅;김영환
    • Journal of environmental and Sanitary engineering
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    • v.19 no.1
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    • pp.50-56
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    • 2004
  • Dibutyl phthalate (DBP) is used extensively in the plastic industry and has been known as an endocrine disruptor. Present study was undertaken to examine whether DBP can induce oxidative stress in mice. In this study, oxidative stress was measured in terms of the modification of lipid peroxidation and gamma-glutamyl transferase (GGT) activity. The serum toxicity index, level of lipid peroxidation and triglyceride (TG), and activity of GGT were measured in male ICR mice after a single administration of DBP (5 g/kg, po). DBP did not alter serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, glucose and cholesterol level. However, the treatment with DBP was found to significantly increase the level of lipid peroxidation in liver and lung. The TG content and activity of GGT in the liver of DBP-exposed animals was also increased. These results indicate that DBP can induce mild oxidative stress in mice. The GGT activity is considered to be increased as one of the adaptive defense mechanisms to oxidative stress induced by DBP.

Production and Application of Sophorolipid, A Microbial Surfactant (소포로리피드[미생물계면활성제]의 생산과 응용)

  • Cho, Kwi-Joon;Kim, Young-Bum;Kim, Eun-Ki
    • KSBB Journal
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    • v.14 no.6
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    • pp.747-753
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    • 1999
  • Microbial surfactants are more effective and environmentally friendly than many synthetic surfactants. Sophorolipid, a glycolipid type microbial surfactant, is produced from C. bombiocola. Cultivation techniques to increase the productivity have been developed using various carbon sources and reactor setup, reaching its concentration upto 100-300 g/L. Due to its high productivity and non-toxicity, sophorolipid became one of the most promising alternative to synthetic surfactants. Fermentative production of sophorolipid depends primarily on the carbon sources, such as glucose and vegetable oils, and nitrogen sources. Chemical modification of the sophorolipid produces various derivative with different physical properties including hydrophile-liphophilie balance(HLB), emulsion formation, surface tension and dispersing ability. Commercial potentials of sophorolipid in the cosmetic, health care and environment clean-up industries have been discussed.

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Preventive Mechanism of Sodium Molybdate Against Peripheral Neurotoxicity of Lead (Sodium molybdate의 납중독성 말초 신경계독성 예방기전)

  • Chung, Myung-Kiu;Kang, Soon-Kook;Kim, Myung-Nyu
    • Journal of Environmental Science International
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    • v.9 no.3
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    • pp.209-214
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    • 2000
  • The preventive effects of sodium molybdate on the acute toxicity of lead were studied by investigating tissue accumulation of lead, changes of nerve conduction velocity and concentrations of metabolites related to function of sciatic nerve in rats treated with lead, sodium molybdate and both, respectively. In lead-intoxicated rat, the conduction velocity, myo-inositol concentration and $Na^{+}/K^{+}$ ATPase activity of sciatic nerve were decreased by about 33 %, 48 % and 58 %, respectively. However, sodium molybdate treatment significantly normalized the conduction velocity, $Na^{+}/K^{+}$ ATPase activity and myo-inositol concentration of sciatic nerve in lead-intoxicated rat. Also, sodium molybdate treatment decreased the contents of lead in blood and sciatic nerve through promotion of urinary excretion of lead. But sodium molybdate treatment did not affect the glucose concentration in sciatic nerve. These results suggest that sodium molybdate prevented peripheral neuropathy not only by reducing lead contents in sciatic nerve and blood, but also by enhancing $Na^{+}/K^{+}$ ATPase activity in sciatic nerve.

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