The Journal of the Korean Society for Microbiology
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v.34
no.6
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pp.501-512
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1999
Gliotoxin, a fungal metabolite, is one of the epipolythiodioxopiperazine classes and has a variety of effects including immunomodulatory and apoptotic agents. This study is designed to evaluate the effect of zinc on gliotoxin-induced death of HL-60 cells. Here, we demonstrated that treatment of gliotoxin decreased cell viability in a dose and time-dependent manner. Gliotoxin-induced cell death was confirmed as apoptosis characterized by chromatin margination, fragmentation and ladder-pattern digestion of genomic DNA. Gliotoxin increased the proteolytic activities of caspase 3, 6, 8, and 9. Caspase-3 activation was further confirmed by the degradation of procaspase-3 and PARP in gliotoxin-treated HL-60 cells. Zinc compounds including $ZnCl_2$ and $ZnSO_4$ markedly inhibited gliotoxin-induced apoptosis in HL-60 cells (from 30% to 90%). Consistent with anti-apoptotic effects, zinc also suppressed the enzymatic activities of caspase-3 and -9 proteases. In addition, cleavage of both PARP and procaspase 3 in gliotoxin-treated HL-60 cells was inhibited by the addition of zinc compounds. We further demonstrated that expression of Fas ligand by gliotoxin was suppressed by zinc compounds. These data suggest that zinc may prevent gliotoxin-induced apoptosis via inhibition of Fas ligand expression as well as suppression of caspase family cysteine proteases-3 and -9 in HL-60 cells.
Proceedings of the Korean Society of Applied Pharmacology
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1996.04a
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pp.272-272
/
1996
While ranitidine is well known to be absorbed rapidly, the underlying cause of variable bioavailability in intra- and inter-subjects has not been clarified yet. Intestinal permeability is a key controlling factor for oral absorption of highly soluble drugs, In the present study, intestinal ferfusions have been conducted to determine the intestinal permeabilities(Peffs) of ranitidine in the rats, dogs and humans and compared to the estimated fractions of dose absorbed (FAs) in humans. A new in vivo methodology, using a regional segmental perfusion technique, has been used in the dogs and humans. In situ single-pass perfusion experiments have been performed in the rats. In the dog and human studies, perfusion experiments have been conducted on two periods to determine the intrasubject variability, There was low significant intrasubject variation as compared to intersubject variation. The Peffs of ranitidine were 33%, 51%, and 45% inthe rats, dogs and humans, respectively. The FAs were approximately the same for all three species models, suggesting rats and dogs are good animal models for estimating the oral absorption of ranitidine in humans. In addition, the estimated extent of absorption of this drug is consistent with the average bioavailability, indicating that ranitidine has permeability-limited absorption characteristics. Supported by FDA Grant FD01462.
Some physicochemical characteristics like nutritional values, sugar content, and fatty acid composition (FAs) in fruits of four papaya (Carica papaya L.) cultivars ('Red Lady', 'Sunrise Solo', 'Tainung', and 'BH-65') grown under plastic greenhouse conditions in the Mediterranean region of Turkey were evaluated. The chemical characteristics, except acidity in the fruits, significantly varied among the cultivars. Nitrogen (N) was the most abundant mineral in all papaya cultivars and ranged from $0.80\;g{\cdot}100\;g^{-1}$ in 'Red Lady' to $1.28\;g{\cdot}100\;g^{-1}$ in 'BH-65' in fresh weight. Potassium (K) and calcium (Ca) were found the highest amount in dry weight. Glucose and fructose were identified as the main sugars in all cultivars. Sucrose was in trace amounts in the three cultivars, but not detectable in cultivar 'Red Lady'. Twenty-five FAs were detected in the papaya fruits. Polyunsaturated fatty acids (PUFAs) were found to be in a highest amounts compared to the saturated fatty acid (SFAs) and monounsaturated fatty acids (MUFAs). Palmitic (C16:0), oleic (C18:1), and linoleic (C18:2n6) acids were the major fatty acids detected in all cultivars. The results of this study implied that dietary intake of papayas may supply substantial nutrient components necessary for human health.
Ta Van Thuong;O.L. Tashlykov;S.M. Glukhov;D.E. Shumkov;Yu.V. Volchikhina
Nuclear Engineering and Technology
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v.55
no.6
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pp.2088-2095
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2023
The safety of nuclear installations is largely determined by the tightness of fuel elements cladding. As the Fukushima nuclear accident showed, the main task in case of loss of power supply is to ensure reliable removal of residual heat release from spent fuel pool (SFP) with irradiated fuel assemblies (IFAs). The paper presents the results of calculated-experimental studies and thermal-hydraulic modeling of temperature storage modes of IFAs in SFP. Experimental studies of SFP's temperature regime and calculated evaluation of residual heat removal due to the thermal conductivity of building structures surrounding the SFP were performed. To ensure the safe operation of research reactors, it's necessary to know the IFA's residual heat power (RHP) in the reactor and SFP, which is determined depending on the operating time of fuel assemblies (FAs) and the IFAs calculated holding time. The FAs operating time depends on the reactor energy output. The IFAs calculated holding time is determined by the fuel burnup, U-235 mass in the fuel, and reactor utilization factor. The IFAs fuel burnup was calculated using the MCU-PTR program. Also presented are the RHP's calculation results using some of the empirical dependencies. The concept of a passive heat removal system (PHRS) based on thermosyphon's operating principle was proposed.
Background: Although pulmonary resection is the standard approach for the management of pulmonary metastases from soft tissue sarcoma, most of them are unresectable and chemotherapy remains the only option. The effectiveness of the cytotoxic drugs may be limited by the toxicities that occur before the therapeutic dose is reached. The regional administration of doxorubicin using pulmonary arterial perfusion in a rodent model can produce 10 to 25 times higher concentrations in the lung than systemic administration with minimal systemic toxicities. However, it is unclear whether a high concentration of doxorubicin has beneficial effects for killing cancer cells. Material and Method: We studied this to evaluate the dose-dependent cytotoxic and apoptotic effects of doxorubicin on methylcholanthrene-induced rat fibrosarcoma(MCA) cells. This study examined the cytotoxicity and apoptosis-related gene expressions(Fas, FasL, Bax, caspase 1, caspase 2, caspase 8, Bcl-2, Bcl-xL, Bcl-xS) in MCA cells after 24 hours exposure to various concentrations of doxorubicin such as 1, 5, 10, 50, and 100 $\mu$M. Result: Dose-dependent cytotoxicity was observed after 24 hours exposure to doxorubicin. However, peak apoptosis after 24 hours exposure was observed at 5 $\mu$M of doxorubicin. Above 5 $\mu$M, apoptotic activity was decreased with dose-increment. All mRNA levels of apoptosis-related genes after 24 hours exposure were up-regulated above the control level at 1 $\mu$M of doxorubicin and then decreased by doxorubicin dose-increment except caspase 8, which showed higher levels than the control level at 5 $\mu$M. Apoptosis-related protein levels were highest at 1 $\mu$M of doxorubicin and then decreased by doxorubicin dose-increment. However, Bax and Bcl-xL proteins steadily showed higher levels than the control throughout the different concentrations of doxorubicin. Conclusion: These results suggest that apoptosis is the main cytotoxic mechanism in low concentrations of doxorubicin in MCA cells and apoptosis-related genes, such as Bax, caspase 8, and Bcl-xL, are involved. At high concentrations, doxorubicin still can kill MCA cells, even when apoptosis is inhibited, and have its propriety for achieving much cytotoxicity against MCA cells.
Nam, Gun He;Wee, Ji-Hyang;Kim, Sang Yung;Baek, Ji-Young;Kim, Young Min
Journal of Life Science
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v.29
no.10
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pp.1152-1158
/
2019
Rudbeckia laciniata var. hortensis Bailey is used in home remedy for colic and gastritis in South Korea. Although Rudbeckia laciniata var. hortensis Bailey is used extensively for home remedies, no single study on its efficacy exists. In this study, we investigated the anti-obesity effects of Rudbeckia laciniata var. hortensis Bailey. The anti-obesity effect of a 70% ethanol extract from Rudbeckia laciniata var. hortensis Bailey on the differentiation of 3T3-L1 pre-adipocytes to adipocytes was investigated with an Oil Red O assay, western blot analysis, and mRNA analysis. Compared to the control (only treated with DM), the 70% ethanol extract of Rudbeckia laciniata var. hortensis Bailey significantly inhibited adipocyte differentiation and intracellular triglyceride (TG) levels at a concentration of $100{\mu}g/ml$. To determine how the TG content was reduced, we measured the level of protein and mRNA expression of obesityrelated agents, such as peroxisome proliferators-activated receptor ${\gamma}$ ($PPAR{\gamma}$), CCAAT/enhancer- binding protein ${\alpha}$ ($C/EBP{\alpha}$), AMP-activated protein kinase (AMPK) phosphorylation, LPL, and FAS. As a result, the 70% ethanol extract of Rudbeckia laciniata var. hortensis Bailey significantly increased the expression of AMPK and decreased the expression of genes related to adipogenesis and fat storage, such as $PPAR{\gamma}$, $C/EBP{\alpha}$, LPL, and FAS.
Hwang, Donghyun;Lee, Hana;Lee, Minjoo;Cho, Seungkwan;Kim, Han Sung
Journal of Biomedical Engineering Research
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v.41
no.6
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pp.235-246
/
2020
This study aimed to evaluate the inhibitory effect of micro-current stimulation(MCS) on adipogenesis regarding with Wnt/β-catenin pathway using the ob/ob mouse and 3T3-L1 cell line. 6-week old ob/ob male mice were equally assigned to four groups: obese group(ob), obese with MCS groups(50 μA, 200 μA, and 400 μA). 6-week old C57BL/6J male mice were assigned to the control group(CON). We analyzed abdominal adipose tissue volume by using in vivo micro-CT and measured the body weight, feed intake, liver weight and triglycerides in serum. All the MCS groups showed that significantly reduced body weight and triglycerides in serum. In the case of liver weight and abdominal adipose tissue volume, the inhibitory effect of adipogenesis was shown in the 200 μA and 400 μA groups. To elucidate the anti-obesity effect of MCS, β-catenin, C/EBPα and FAS protein expressions were analyzed by western blotting. β-catenin expression was upregulated, C/EBPα and FAS expression were down-regulated in the relatively high-intensity groups(200 μA and 400 μA). Thus, the 200 μA and 400 μA for the intensity of MCS were chosen for cell experiments. In the 3T3-L1 cell line, Wnt/β-catenin pathway including Wnt10b, Wnt3a, β-catenin and Cyclin D1 was activated in all MCS groups. Accordingly, the expression level of C/EBPα was decreased during the differentiation and lipid droplet was significantly reduced in Oil red O staining results. These results suggest that the Wnt/β-catenin signaling might be activated by MCS with current intensities between 200-400 μA and it may lead to anti-obesity effects.
Ana Sandra Llera-Romero;Milagros Adobes-Martin;Jose Enrique Iranzo-Cortes;Jose Maria Montiel-Company;Daniele Garcovich
The korean journal of orthodontics
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v.53
no.6
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pp.374-392
/
2023
Objective: Assess and evaluate the different indicators of oral health-related quality of life (OHRQoL) among patients treated with clear aligners (CAs) versus those treated with conventional fixed orthodontics (FAs). Methods: An electronic search was performed on the database is Web of Science, Scopus, and Embase databases. Randomized and non-randomized control trials, cross-sectional, prospective cohort and retrospective trials were included. Quality was assessed with risk of bias tool and risk of bias in non-randomised studies. Meta-analyses were performed with random effects models, estimating the standardized and non-standardized mean differences, odds ratio and risk ratio as the measure of effect. The effect on time was determined using a meta-regression model. Results: Thirty one articles were included in the qualitative synthesis and 17 in the meta-analysis. CAs had a significantly lower negative impact on QoL, with an "important" effect size, while the influence of time was not significant. Periodontal indicators plaque index (PI), gingival index (GI), probing depth (PD), and bleeding on probing show significantly better values in patients treated with CAs, with moderate to large effect sizes. PI and GI have a significant tendency to improve over time. In microbiological indicators, CAs present a lower biofilm mass without differences in the percentage of patients with high counts of Streptococcus mutans and Lactobacilli bacteria. The risk of white spot lesion onset is ten times lower in carriers of CAs. Conclusions: Patients wearing CAs show better periodontal indicators, less risk of white spot development, less biofilm mass and a better QoL than patients with FAs.
BACKGROUND/OBJECTIVES: Adipogenesis is part of the cell differentiation process in which undifferentiated fibroblasts (pre-adipocytes) become mature adipocytes with the accumulation of lipid droplets and subsequent cell morphological changes. Several transcription factors and food components have been suggested to be involved in adipogenesis. The aim of this study was to determine whether mulberry leaf ethanol extract (MLEE) affects adipogenesis in 3T3-L1 adipocytes. MATERIALS/METHODS: The 3T3-L1 adipocytes were treated with different doses of MLEE for 8 days starting 2 days post-confluence. Cell viability, fat accumulation, and adipogenesis-related factors including CCAAT-enhancer-binding protein alpha ($C/EBP{\alpha}$), peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$), $PPAR{\gamma}$ coactivator 1 alpha (PGC-$1{\alpha}$), fatty acid synthase (FAS), and adiponectin were analyzed. RESULTS: Results showed that MLEE treatments at 10, 25, 50, and $100{\mu}g/ml$ had no effect on cell morphology and viability. Without evident toxicity, all MLEE treated cells had lower fat accumulation compared with control as shown by lower absorbances of Oil Red O stain. MLEE at 50 and $100{\mu}g/ml$ significantly reduced protein levels of $PPAR{\gamma}$, PGC-$1{\alpha}$, FAS, and adiponectin in differentiated adipocytes. Furthermore, protein level of $C/EBP{\alpha}$ was significantly decreased by the treatment of $100{\mu}g/ml$ MLEE. CONCLUSION: These results demonstrate that MLEE treatment has an anti-adipogenic effect in differentiated adipocytes without toxicity, suggesting its potential as an anti-obesity therapeutic.
Journal of Physiology & Pathology in Korean Medicine
/
v.31
no.6
/
pp.348-355
/
2017
Aster yomena (AY) have been used as a traditional medicine to treat cough, bronchial asthma, and insect bites in Korea. In this study, we evaluated the inhibition of adipogenesis in 3T3-L1 cells and in high-fat diet (HFD)-induced obese mice by AY ethanol extract. Lipid accumulation measurement indicates that AY markedly inhibited adipogenesis in a dose-dependent manner. qRT-PCR results demonstrated that the mRNA expression of adipogenic transcription factors such as peroxisome proliferator-activated receptor-${\gamma}$ ($PPAR-{\gamma}$) in 3T3-L1 cells were significantly down-regulated by AY treatment. And inhibited the expression of FAS, a protein responsible for lipid synthesis, transport and storage. Oral administration of AY (100, 250, and 500 mg/kg, P.O/daily for 4 weeks) was conducted in high-fat diet induced obese mice and C57BL/6 mice. AY was orally administered for 4 weeks to extract liver and epididymal fat, and hematoxylin and eosin staining(H&E staining) was observed. Observation showed that the fat concentration of liver tissue tended to decrease dose-dependently and decreased significantly at 500 mg/kg concentration. The AY-administered group of HFD-induced mice had a lower body weight gain, along with decreased triglycerides and total cholesterol compared with the control mice, however, the HDL-cholesterol/total cholesterol ratio was increased. These results indicate that AY exhibits anti-obesity effects in obese mice by decreasing in serum lipid levels and lipogenesis related gene.
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