Liposomes having particle size from several tens to hundreds nanometers are efficient carriers for injectable drug delivery. Enhancement of liposome stability in bloodstream has been studied because of its relatively short circulation time and fast clearance from human body by reticuloendothelial system (RES) in blood vessel. In this study, new disaccharide-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) derivatives in which lactose or sucrose as the disaccharide molecule was conjugated covalently to DSPE were synthesized. Liposomes of which surface had disaccharide molecules were prepared by incorporating the disaccharide-DSPE into liposomes as one of their lipid components. Particle size of the prepared liposomes was approximately 100 nm. The liposomes of which surface were modified with the disaccharide-DSPE showed -25 mV of zeta potential value due to the presence of hydroxyl groups on their surface, while the unmodified control liposomes showed -10 mV of zeta potential value. Loading efficiency of model drug, doxorubicin, into liposomes was about 90%. Stability of the disaccharide-modified liposomes in vitro was evaluated by monitoring the amount of protein adsorption and particle size of the liposomes in serum. Disaccharide-modified liposomes were more stable in serum than unmodified control liposomes or polyethyleneglycol (PEG)-modified liposomes due to less adsorption of serum protein and hence less increase of their particle size. The liposomes of which surface was modified with disaccharide-DSPE conjugate can be used as long-circulating carriers for drugs having high toxicity or short half-life time due to their enhanced stability in blood circulatory system.
Lee, Hyun Ah;Kim, Ji Eun;Choi, Jun Young;Sung, Ji Eun;Youn, Woo Bin;Son, Hong Joo;Lee, Hee Seob;Kang, Hyun-Gu;Hwang, Dae Youn
Journal of Life Science
/
v.30
no.4
/
pp.331-342
/
2020
The suppression of neuroinflammatory responses in microglial cells can be considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Asparagus cochinchinensis has traditionally been used as a medicine to treat fever, cough, kidney disease, breast cancer, inflammatory diseases, and brain diseases. In this study, we investigated the neuroprotective mechanism of an aqueous extract from A. cochinchinensis root (AEAC), particularly its anti-inflammatory effects on lipopolysaccharide (LPS)-activated BV-2 microglial cells. BV-2 cells were treated with four different concentrations of AEAC. No significant toxicity was detected in BV-2 cells treated with AEAC. Nitric oxide (NO), cyclooxygenase-2 (COX-2) mRNA, and inducible nitric oxide synthase (iNOS) mRNA levels were 21% lower in the AEAC+LPS group than in the Vehicle+LPS group. Lower proinflammatory (TNF-α and IL-1β) and anti-inflammatory cytokine (IL-6 and IL-10) levels were also detected in the AEAC+LPS group than in the Vehicle+LPS group, albeit at varying rates. Moreover, the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group compared to the Vehicle+LPS group, enhancement of the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group, while cell cycle arrest at the G2/M phase caused by LPS treatment was less severe in the AEAC+LPS group. The increase in reactive oxygen species (ROS) generation induced by LPS treatment was also lower in the AEAC-pretreated group than in the Vehicle+LPS group. This is the first study to show that AEAC exerts anti-neuroinflammatory activity against LPS stimulation by regulating the MAPK signaling pathway, the cell cycle, and ROS production.
Improper disposal of petroleum and spills from underground storage tanks have created large areas with highly toxic contamination of the soil and groundwater. Methyl tert-butyl ether (MTBE) is widely used as a fuel additive because of its advantageous properties of increasing the octane value and reducing carbon monoxide and hydrocarbon exhausts. However, MTBE is categorized as a possible human carcinogen. This research investigated the Modified Photo-Fenton system which is based on the Modified Fenton reaction and UV light irradiation. The Modified Fenton reaction is effective for MTBE degradation near a neutral pH, using the ferric ion complex composed of a ferric ion and environmentally friendly organic chelating agents. This research was intended to treat high concentrations of MTBE; thus, 1,000 mg/L MTBE was chosen. The objectives of this research are to find the optimal reaction conditions and to elucidate the kinetic and mechanism of MTBE degradation by the Modified Photo-Fenton reaction. Based on the results of experiments, citrate was chosen among eight chelating agents as the candidate for the Modified Photo-Fenton reaction because it has a relatively higher final pH and MTBE removal efficiency than the others, and it has a relatively low toxicity and is rapidly biodegradable. MTBE degradation was found to follow pseudo-first-order kinetics. Under the optimum conditions, [$Fe^{3+}$] : [Citrate] = 1 mM: 4 mM, 3% $H_2O_2$, 17.4 kWh/L UV dose, and initial pH 6.0, the 1000 ppm MTBE was degraded by 86.75% within 6 hours and 99.99% within 16 hours. The final pH value was 6.02. The degradation mechanism of MTBE by the Modified Photo-Fenton Reaction included two diverse pathways and tert-butyl formate (TBF) was identified to be the major degradation intermediate. Attributed to the high solubility, stability, and reactivity of the ferric-citrate complexes in the near neutral condition, this Modified Photo-Fenton reaction is a promising treatment process for high concentrations of MTBE under or near a neutral pH.
Kim, Jin-suk;Lee, Sang-mok;Choi, Seok-wha;Lee, Won-chang
Korean Journal of Veterinary Research
/
v.34
no.2
/
pp.361-368
/
1994
Teratogenic and embryotoxic effects of mercury have been reported, however, there is little information about possible antidotes against mercury exposure during gestation. In order to evaluate therapeutic effects of selenium as an antidote against mercury poisoning, pregnant CD-1 mice were exposed to methylmercury chloride(20ppm) through the drinking water with treatment of sodium selenite (1.0mg, 2.0mg or 3.0mg/kg b.w., subcutaneously) or BAL(5.0mg/kg b.w., subcutaneously) under the single or combination base as the therapeutic agents from day 6 to 15 of gestation. Fetal growth parameters such as body weight and crown-rump length in the mice exposed to mercury, were reduced as was placental weight compared to those in the control. Treatment of selenium(alone, combination with BAL) reduced the harmful effects induced by mercury on the fetal growth parameters even though no specific relationship between dose and therapeutic effect. The incidence of dead fetuses/resorptions and malformed fetuses(especially cleft palate) was also increased in the mercury only treated group. Selenium treatment demonostrated reduced the incidence of abnormal fetuses under the exposure of mercury. Relative maternal organ weights(liver, kidney, spleen) were increased significantly but relative brain weight was decreased as evidenced by decreased in the mercury treated mice compared to that in the control. A subtle indication of maternal mercury toxicity evidenced by changes of relative maternal organ weights, decreased water and feed consumption were also prevented efficiently by selenium treatment. The present study suggests that methylmercuric chloride is embrytoxic and teratogenic in CD-1 mice when exposured during organogenesis and that selenium administration may have therapeutic application for the treatment of mercury poisoning although more applicable study in human should be performed with caution in the future.
Kim, Doh-Hyung;Bae, Gang-U;Yong, Wha-Shim;Choi, Eun-Kyung;Kim, Youn-Seup;Park, Jae-Seuk;Jee, Young-Koo;Lee, Kye-Young
Tuberculosis and Respiratory Diseases
/
v.53
no.3
/
pp.275-284
/
2002
Background : Gemcitabine is a new anti-cancer agent for treating non-small cell lung cancer. Functioning as an antimetabolite, it induces anti-cancer effects by suppressing DNA synthesis after being incorporated into the DNA as a cytosine arabinoside analogue. When Gemcitabine is incorporated into the DNA, the p53 gene may be activated by induction of the DNA defect. However, there are a few studies on the molecular mechanisms of Gemcitabine-induced cell death. This study examined the role of p53 in Gemcitabine-induced cell death. Methods : A549 and NCl-H358 lung cancer cells were used in this study. The cell viability test was done using a MTT assay at Gemcitabine concentrations of 10nM, 100nM, 1uM, 10uM and 100uM. A FACScan analysis with propium iodide staining was used for the cell cycle analysis. Western blot analysis was done to investigate the extent of p53 activation. For the functional knock-out of p53, stable A549-E6 cells and H358-E6 cells were transfected pLXSN-16E6SD which is over expresses the human papilloma virus E6 protein that constantly degrades p53 protein. The functional knock out of p53 was confirmed by Western blot analysis after treatment with a DNA damaging agent, doxorubicine. Results : Gemcitabine exhibited cell toxicity in dose-dependent fashion. The cell cycle analysis resulted in an S phase arrest. Western blot analysis significant p53 activation in time-dependent manner. Gemcitabine-induced cytotoxicity was reduced by 20-30% in the A549-E6 cells and the 30-40% in H358-E6 cells when compared with the A549-neo and H358-neo control cells. Conclusion : Gemcitabine induces an S phase arrest, as expected for the anti-metabolite, and activates the p53 gene, Furthermore, p53 might play an important role in Gemcitabine-induced cell death. Further investigation into the molecular mechanisms on how Gemcitabine activates the p53 gene and its signaling pathway are recommended.
Chung, Mi Yeon;Kwon, Eun-Young;Hwang, Jae-Sam;Goo, Tae-Won;Yun, Eun-Young
Journal of Life Science
/
v.23
no.3
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pp.426-431
/
2013
With the objective of developing a functional food source, we established optimal processing conditions for the larvae of Allomyrina dichotoma, which have been used in traditional medicine to treat hepatic disorders in Korea. Without suitable processing, the larvae are difficult to consume as a food because of their disgusting taste and smell; moreover, in this form they might be a potential microbial hazard. In this study, we investigated the effect of feeding material, sterilization, and powdering after freeze-drying on the food quality of the larvae of A. dichotoma and on cytotoxicity against Raw 264.7 cells. Three to five days feeding with the sawdust from discarded oak-trees is sufficient for the breeding process. The sawdust was sterilized by vapor for five minutes. Sterilization of the larvae at a high temperature ($115^{\circ}C$ for 5 min, 0.9 $kgf/cm^2$) is necessary to eliminate pathogenic bacteria and fungi. The results of the cytotoxicity assay showed no toxicity in the prepared extract from larvae of A. dichotoma. In addition, to prepare the larvae for human consumption, various feeds were used and the smell, color, and taste were evaluated. Our results suggested that larvae of A. dichotoma could be developed as food source when a suitable processing method is established.
Microcystin produced by cyanobacteria in surface waters, such as eutrophic lake and river, is a kind of serious environmental problems due to its toxicity to human and wild animals. Microcystin is synthesized nonribosomally by the large modular multi-functional enzyme complex known as microcystin synthetase encoded by the mcy gene cluster. Amplification of mcy genes by PCR from cultures and environmental samples is a simple and efficient method to detect the toxigenic Microcystis. In order to evaluate primers designed to detect toxic microcystin-producing strains, 17 cyanobacterial strains and 20 environmental samples were examined by PCR with 7 pairs of primers. Some microcystin-producing cyanobacteria were not detected with FAA-RAA, TOX4F-TOX4R and FP-RP primers. The fragment of unexpected size was amplified with NSZW2-NSZW1 primers in Microcystis strains isolated from the lakes in Korea. TOX1P-TOX1F primers failed in amplification of toxin-producing strains. Only MSF-MSR and TOX2P- TOX2F primers amplified the fragments of mcy genes from 11 strains of microcystin-producing Microcystis. The water samples taken from 20 lakes in Korea were analyzed by PCR using each of the primers. In all the water samples, cyanobacteria capable of producing microcystin were detected by the PCR with TOX2P-TOX2F primers. These results indicate that TOX2P-TOX2F primers are better than the other primers for detection of microcystin-producing Microcystis strains in Korea. The nucleotide sequences of mcy gene in Microcystis aeruginosa NIER10010 suggest genetic diversity of Korean isolates.
Park, Si-Hyang;Moon, Sung-Sil;Xie, Cheng-Liang;Choung, Se-Young;Choi, Yeung-Joon
Journal of the Korean Society of Food Science and Nutrition
/
v.43
no.8
/
pp.1166-1173
/
2014
This study investigated the detoxification effects of enzymatic hydrolysate from oyster on acetaminophen-induced toxicity using HepG-2 cells. Oyster hydrolysate was made with 1% Protamex and 1% Neutrase after treatment with transglutaminase (TGPN) or without (PN). Two types of oyster hydrolysate were added to human-derived HepG-2 hepatocytes damaged by acetaminophen, after which the survival rate of HepG-2 cell was measured. In addition, glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities in the culture media were evaluated. The survival rates of HepG-2 cells were $136.2{\pm}1.4%$ at $100{\mu}g/mL$ of TGPN and $179.6{\pm}3.8%$ at $200{\mu}g/mL$ of TGPN. These cell survival rates were higher compared to that of the negative control group ($60.7{\pm}3.2%$) treated only with acetaminophen. GOT activity was $38.3{\pm}0.2$ Karmen/mL in the negative control group, whereas it was $19.9{\pm}0.5$ for TGPN ($200{\mu}g/mL$) and $22.0{\pm}2.4$ Karmen/mL for PN ($200{\mu}g/mL$). GOT and GTP activities were shown to be dependent on TGPN concentration, and significant reduction in activities could be conformed. The detoxification efficacy of TGPN was higher compared to that of PN. These results suggest that oyster hydrolysate has potential as a healthy food or pro-drug for liver protection.
Journal of Korean Home Economics Education Association
/
v.20
no.2
/
pp.75-94
/
2008
The purposes of this paper are to describe the newly established reference values of nutrient intakes: to apply the changed dietary reference intakes to the new text book based on the revised curriculum: and to contrive substantial contents in the domain of dietary life(foods & nutrition) of new text book. Dietary Reference Intakes for Koreans(KDRIs) is newly established reference values of nutrient intakes that are considered necessary to maintain the health of Koreans at the optimal state and to prevent chronic diseases and overnutrition. Unlike previously used Recommended Dietary Allowances for Koreas(KRDA), which presented a single reference value for intake of each nutrient, multiple values are set at levels for nutrients to reduce risk of chronic diseases and toxicity as well as prevention of nutrient deficiency. The new KDRIs include the Estimated Average Requirement(EAR), Recommended Intake(RI), Adequate Intake(AI), and Tolerable Upper Intake Level(UL). The EAR is the daily nutrient intake estimated to meet the requirement of the half of the apparently healthy individuals in a target group and thus is set at the median of the distribution of requirements. The RI is set at two standard deviations above the EAR. The AI is established for nutrients for which existing body of knowledge are inadequate to establish the EAR and RI. The UL is the highest level of daily nutrient intake which is not likely to cause adverse effects for the human health. Age and gender subgroups are established in consideration of physiological characteristics and developmental stages: infancy, toddler, childhood, adolescence, adulthood and old age. Pregnancy and lactation periods were considered separately and gender is divided after early childhood. Reference heights and weights are from the Korean Agency for Technology and Standards, Ministry of Commerce, Industry and Energy. The practical application of DRIs to the new books based on the revision in the 7th curriculum is to assess the dietary and nutrient intake as well as to plan a meal. It can be utilized to set an appropriate nutrient goal for the diet as usually eaten and to develop a plan that the individual will consume using a nutrient based food guidance system in the new books based on the revision in the 7th curriculum.
Lee, Beom Jun;Lee, Sook Jin;Kim, Tae Myoung;Kim, Dae Joong;Nam, Sang Yoon;Hyun, Sang Hwan;Kang, Jong Koo;Hong, Jin Tae;Kim, Cheul Kyu;Yun, Young Won
Korean Journal of Veterinary Research
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v.44
no.4
/
pp.507-513
/
2004
Aflatoxins are produced mainly by Aspergillus flavus and Aspergillus parasiticus that grow in improperly stored cereals. Aflatoxin B1 ($AFB_1$) is a potent hepatocarcinogen in a variety of experimental animals including human beings. In spite of a high attention to the hepatocarcinogenecity of $AFB_1$, the relative toxicity of aflatoxins ($AFB_2$ and $AFG_1$) is not fully clarified. Sprague-Dawley male rats were orally administered with $AFB_1$, $AFB_2$, and $AFG_1$ at the dose of 250 ${\mu}g/kg$ (additionally including a dose of $1250{\mu}g/kg $ for $AFB_1$) body weight. Animals were then killed at 12, 24 or 48 hrs following aflatoxin exposure. Subsequently the immunohistochemical examination of p53, cytochrome p450 1A1 (CYP450 1A1), and glutathione-S-transferase placental form (GST-P) were performed. The level of the 8-OxodG in the liver was determined. Expressions of CYP450 1A1 and p53 were high in the liver of rats through 48 hrs after treatment of $AFB_1$ at the single dose of $250{\mu}g/kg $. This pattern was more clear as increasing doses. The treatment of $AFB_2$ and $AFG_1$ did not affect the expression of CYP450 1A1 but it caused weak expression of p53. The activity of GST were not found in the liver of rats treated with aflatoxins. The formation of 8-OxodG by $AFB_1$ increased in a dose-dependent manner up to 24 hrs after a single treatment of $AFB_1$ thereafter decreased to the level of control. The treatment of $AFB_2$ and $AFG_1$ did not affect the levels of 8-OxodG in the liver of rats with increasing time. These results in the present study indicate that $AFB_1$ among aflatoxins with low comparable levels is the most toxic as determined by early biomarkers such as CYP450 1A1, p53, GST-P, and 8-OxodG.
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