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.
Journal of Korean Society of Environmental Engineers
/
v.35
no.6
/
pp.422-429
/
2013
It is generally known that the increase of the Earth surface temperature due to the global warming together with the land desertification by rapid urban development has caused severe climate and weather change. In desert or desertification land, it is observed that there are always severe flooding phenomena, even if desert sand has the high porosity, which could be believed as the favorable condition of rain water infiltration into ground water. The high runoff feature causes possibly another heavy rain by quick evaporation with the depletion of underground water due to the lack of infiltration. The basic physics of desert flooding is reasonably assumed due to the thermal buoyancy of the higher temperature of the soil temperature than that of the rain drop. Considering the importance of this topic associated with water resource management and climate disaster prevention, no systematic investigation has, however, been reported in literature. In this study, therefore, a laboratory scale experiment together with the effort of numerical calculation have been performed to evaluate quantitatively the basic hypothesis of run-off mechanism caused by the increase of soil temperature. To this end, first, of all, a series of experiment has been made repeatedly with the change of soil temperature with well-sorted coarse sand having porosity of 35% and particle diameter, 2.0 mm. In specific, in case 1, the ground surface temperature was kept at $15^{\circ}C$, while in case 2 that was high enough at $70^{\circ}C$. The temperature of $70^{\circ}C$ was tested as this try since the informal measured surface temperature of black sand in California's Coachella Valley up to at 191 deg. $^{\circ}F$ ($88^{\circ}C$). Based on the experimental study, it is observed that the amount of runoff at $70^{\circ}C$ was higher more than 5% compared to that at $15^{\circ}C$. Further, the relative amount of infiltration by the decrease of the surface temperature from 70 to $15^{\circ}C$ is about more than 30%. The result of numerical calculation performed was well agreed with the experimental data, that is, the increase of runoff in calculation as 4.6%. Doing this successfully, a basic but important research could be made in the near future for the more complex and advanced topic for this topic.
Cortisol is present in high concentration in the ovary and its receptor is expressed in the ovarian cells. Moreover, cortisol is known to have a role in steroid synthesis and cell metabolism in human granulosa and lutein cells. However, little is known of the role of cortisol presenting in high concentration in the follicles after LH surge on the granulosa-lutein cells. Therefore, the this study we evaluated the apoptosis and the production of progesterone $(P_4)$ and estradiol $(E_2)$ in the granulosa-lutein cells that are obtained during oocyte-retrieval after treatment with 5, 50, and $500{\mu}g/m\ell$ cortisol and 1 IU/$m\ell$ FSH. Results of DNA fragment analysis and TUNEL assay demonstrated that DNA fragmentation and the rate of apoptotic cells were increased in a dose-dependent manner showing a significant increase in 50 and $500{\mu}g/m\ell$ cortisol treated cells. We found, however, that FSH did not suppress the apoptosis of the cells induced by cortisol. In the results of chemiluminescence assay for $P_4$ and $E_2$, $P_4$ production was decreased by cortisol treatment, whereas $E_2$ was not changed. We also demonstrated that FSH did not inhibit the suppressive effect of GnRH on $P_4$ production as the result of apoptosis. The present study suggests that cortisol of high concentration could cause the apoptosis of human granulosa-lutein cells by suppressing the production of $P_4$. However, we need more studies to elucidate the mechanism by which cortisol induces apoptosis in human granulosa-lutein cells in view of the fact that our results are inconsistent with previous reported data.
In order to reveal the mechanism of heavy metal behavior in soils relating to factors such as soil pH, organic matter, C.E.C. and soil minerals influencing the activities of heavy metals, Cd, Cu and Zn were applied to soil columns filled with 8 different soils with adjusted soil pH to several levels between 3.0 to 11.0 and the amounts of adsorption and desorption of these heavy metals were measured. 1. At the adsorption maxima of three heavy metals(Cd, Cu and Zn) soil pH appeared to be near 6.0 regardless of properties of the 8 soils, and adsorption gradually decreased above and below pH 6.0. This phenomenon was the same in both heavy metal solutions and mixed solutions, and the mixed solution, containing three heavy metals, revealed slightly higher amounts of Cu adsorption and Cd adsorption. 2. It was also found that the adsorption of Cu and Zn by soils was positively correlated with C.E.C. and the organic matter of soils, respectively. However, the pH values showing maxima of heavy metal adsorption were negatively correlated with organic matter content by contrast with the correlation between the maxima and the C.E.C. values in soils. 3. The adsorption of Cu by soils markedly increased more with $Ca(OH)_2$ application than with NaOH application for soil pH adjusment. This was probably because of Ca effects in Cu precipitation in soils, in addition to the effect of the simple soil pH itself on Cu adsorption 4. It was also revealed that adsorbed Cu was hardly desorbed by $N-NH_4OAC$ solution from the Daejeong soil series compared to the Jeonbug and Yechun soil series. This was because the Daejeong soil series consisted of large amounts of expanding type Vermiculite minerals and also was high in C.E.C. and soil organic matter.
This study was conducted to investigate effects of the brown seaweed waste(BSW) supplementation on milk production and related endocrine response in serum in Holstein dairy cows. A total of 14 Holstein dairy cows(initial mean live weight 625kg, average lactation days 225, Reproduction 2.4) were randomly allocated into control(basal diet) and treatment groups (4% BSW/basal diet) with 7 replications for 90 days. Dry matter intake was not affected by brown seaweed waste supplementation, but daily milk yield(kg) at the last experiment significantly increased (6.25kg) in treatment group compared with control group(p<0.05) at the last experiment. The plasma insulin-like growth factor(IGF)-1, triiodothyronine($T_3$) and thyroxine($T_4$) levels were significantly increased in treatment group compared with control group(p<0.05), although the concentration of plasma growth hormone(GH) was not significantly different. Milk composition was not significantly different between groups. The somatic cell count(SCC) in milk were significantly reduced in treatment group compared with control group(p<0.05), but antibodies(total IgG, G1, G2) were not significantly different between groups. Therefore we strongly believe that the increased milk yield is related to metabolic hormones as IGF-1, $T_3$ and $T_4$ and the mechanism of reducing SCC in milk must do more study related nonspecific immunsystem in the future.
In order to examine the effect of SO$_2$, which is the major component of acid rain, on the peroxidase activity, rice (Oryza sativa) seedlings were grown on the media containing various concentrations of Na$_2$SO$_3$. Na$_2$SO$_3$ concentrations needed for the 50% inhibition of rice seed germination were determined to be 300$\mu\textrm{g}$/ml at pH 7, 8$\mu\textrm{g}$/ml at pH 5 and 2$\mu\textrm{g}$/ml at pH 3. Notably, about 8 fold and 4 fold increase of the specific activity of the enzyme were observed with the seedlings treated with 8$\mu\textrm{g}$/ml Na$_2$SO$_3$ at pH 5 and 2$\mu\textrm{g}$/ml Na$_2$SO$_3$ at pH 3, respectively. The effects of Cd and Pb on the peroxidase activities and chlorophyll contents were also examined. About 3.9 fold higher peroxidase activities were found at 0.03mM Cd, and the chlorophyll contents were reduced to 63% of the control seedlings. At 0.04mM Pb, 2.5 fold higher enzyme activities were found and the chlorophyll contents were reduced to 72%. Therefore, the increases of rice peroxidase activities might be involved in the defense mechanism of the cell against various environmental stresses such as Na$_2$SO$_3$, Cd and Pb. The effects of Cu and Fe, which are the inducers of oxidative stresses by the generations of reactive oxygen species, on the peroxidase activities were also investigated. About 57% and 65% activity losses were found at 0.5mM CuSO$_4$ and 0.5mM FeSO$_4$, respectively, and radical scavenger ethanol almost completely protected both inactivations. However, dimethyl sulfoxide, mannitol, thiourea and histidine showed different radical scavenging effects one another against Cu and Fe inactivation.
Licochalcone (LC), isolated from the roots of Glycyrrhiza inflata has multiple pharmacological effects including anti-inflammatory and anti-tumor activities. To date, Licochalcone C (LCC) has induced apoptosis and inhibited cell proliferation in oral and bladder cancer cells, but lung cancer has not yet been studied. In addition, no study reported LCC-induced autophagy in cancer until now. The present study was designed to investigate the effect of LCC on gefitinib-sensitive and -resistant lung cancer cells and elucidate the mechanism of its action. The 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay data showed that LCC significantly inhibited cell viability in non-small cell lung cancer (NSCLC) HCC827 (gefitinib-sensitive) and HCC827GR (gefitinib-resistant) cell lines. Interestingly, Annexin V/7-aminoactinomycin D double staining and cell cycle analysis showed an apoptosis rate within about 20% at the highest concentration of LCC. LCC induced G2/M arrest by reducing the expression of the cell cycle G2/M related proteins cyclin B1 and cdc2 in NSCLC cell lines. Treatment of LCC also induced autophagy by increasing the expression of the autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3) and the protein autophagy-related gene 5 involved in the autophagy process. In addition, LCC increased the production of reactive oxygen species (ROS), and the cell viability was partially restored by treatment with the ROS inhibitor N-acetyl-L-cysteine. In western blotting analysis, the expression of cdc2 was increased and LC3 was decreased by the simultaneous treatment of NAC and LCC. These results indicate that LCC may contribute to anti-tumor effects by inducing ROS-dependent G2/M arrest and autophagy in NSCLC. In conclusion, LCC treatment may be useful as a potential therapeutic agent against NSCLC.
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.
Objectives : Iron (Fe) is an essential element in biological processes; however excessive Fe is harmful to human health. Some air pollutants contain a high level of Fe, and the human lung could therefore be over-exposed to Fe through inhaled air pollutants. This study was performed to investigate the role of metal transporters (divalent metal transporter 1, DMT1, and metal transporter protein 1, MTP1) in the lung under the environments of Fe deficiency in the body and Fe over-exposure in the lung. Methods : Rats were fed Fe deficient (FeD, 2-6 mg Fe/kg) or Fe supplemented (FeS, 120 mg Fe/kg) diet for 4 weeks, followed by a single intratracheal instillation of ferrous sulfate at low (10 mg/kg) or high (20 mg/kg) dose. Fe concentration was analyzed in the serum, lung and liver, and histopathological findings were observed in the lung at 24 hours after Fe administration. The level of DMT1 and MTP1 expression in the lung was analyzed by RT-PCR. Also, the effect of Fe deficiency in the body was evaluated on the level of Fe concentration and metal transporters compared to FeS-diet fed rats at the end of 4-week FeD or FeS diet. Results : The 4-week FeD diet in rats induced an Fe deficiency anemia with decreased serum total Fe, increased unsaturated Fe binding capacity and hypochromic microcytic red blood cells. The concentration of Fe in the lung and liver was lower in the FeD-diet fed rats than in the FeS-diet fed rats. The level of metal transporters mRNA expression was higher in the FeD-diet fed rats than in the FeS-diet. The concentration of Fe in the lung was increased in a dose-dependent pattern after intratracheal instillation of Fe into the rats, while the level of Fe in the serum and liver was not increased in the low-dose Fe administered rats. Therefore, DMT1 and MTP1 mRNA was highly expressed in both FeD-diet and FeS-diet fed rats, after intratracheal instillation of Fe. Conclusions : DMT1 and MTP1 mRNA were more highly expressed in FeD-diet fed rats than in FeS-diet fed rats. The over-exposure of Fe intratracheally induced high expression of metal transporters and increased Fe deposition in the lung in both FeD-diet and FeS-diet fed rats, but did not increase the Fe level of the serum and liver in low-dose Fe administered rats. These results suggest that the role of metal transporters in the lung might be different in a part from the duodenum under the environment of over-exposure to Fe.
Previous researches on technological innovation have several limitations such as lack of general mechanism for technological innovation(inputs, throughputs and outputs of technological innovation), large company oriented studies, and ignoring importance of technology management capabilities. So, this study suggested a new model using resource-based theory and system theory, and empirically applied that to SMEs. Structural equation model analysis by using 223 SMEs in Daegu region provided a support for most of hypotheses. Research results showed that all of factors on technological innovation were significantly and positively related with each other: inputs(R&D leadership, innovation strategy, R&D investment, R&D human resource management, external network), throughputs(portfolio management, project management, technology commercialization) and output(technological innovation). In case of technological innovation inputs, R&D leadership influenced on innovation strategy positively and significantly. And R&D leadership and innovation strategy had positive and significant effects on R&D investment, R&D human resource management and external network. R&D human resource management and external network exerted positive and significant influences on technological innovation throughputs such as portfolio management and project management. But R&D investment did not significant impacts on technological innovation throughputs. Among technological innovation throughputs, both portfolio management and project management had positive and significant effect on technology commercialization. In addition, technology commercialization acted positively and significantly technological innovation output. This study suggests necessary of efforts to implement innovation strategy and manage R&D human resource effectively based on CEO's innovativeness and entrepreneurship. Also, if SMEs want to develop technology and commercialize it, they have to cooperate with external technology resources and informations. Research results revealed that proper level of R&D investment, internal and external communication, information sharing, and learning and cooperative culture were very important for improvement of technological innovation performance in SMEs. Especially, this research suggested that if SMEs manage technological innovation process effectively based on resource-based and system approaches, then they can overcome their resource limitations and gain high technological innovation performance. Also, useful policy support for technological innovation of central or regional government by this research model is important factor for SMEs' technological innovation performance.
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