Objectives: The p53 tumor suppressor gene encodes a nuclear transcription factor that is critical regulator of cell growth and proliferation through its action in cell-cycle checkpoint control. The wide variety of stressful stmuli which include DNA damage, hypoxia, heat shock, metabolic changes activate the p53 protein, which in turn drives a series of events that culminate either in cell cycle arrest or apoptosis. Mutations of the p53 gene is the most common genetic alteration in human cancer. This gene is altered in approximately 40-60% of head and neck cancers. Whereas the wild-type form of the p53 protein plays a central role in cell-cycle control in response to DNA damage, most of the mutant forms are unable to do so. The high levels of p53 protein expression in tissues are related to the increased cellular proliferative activity and may be associated with the poor clinical outcome. To determine whether the expression of the p53 protein has prognostic significance and is associated with patterns of treatment failure in head and neck squamous cell carcinoma (HNSCC), We analyzed p53 overexpression in 40 cases of HNSCC. Materials and Methods: Immunohistochemical analysis with a monoclonal antibody (DO7) specific for p53 protein was used to detect expression of the protein in formalin-fixed, paraffin-embedded tumor samples from 40 HNSCC. We evaluated p53 protein expression and analyzed the relationship between the p53 overexpression and age, sex, primary tumor site, stage, survival rate, recurrence. All reported P values resulted from two-sided statistical tests. Results: Overexpression of p53 was detected in 20 cases(50%) among 40 cases of HNSCC. The p53 overexpression was not associated with age, sex, primary tumor site, stage, recurrence and survival rate. Conclusions: In our results, p53 was not significant prognostic factor in HNSCC. Based on many previous studies, It is evident that p53 has a certain role in tumorigenesis of HNSCC. So, the further study is needed to evaluate the prognostic significance of p53 in HNSCC.
With the aim of developing and indoor overwintering technique for Pearl oyster, Pinctada fucata martensii, the metabolic rates of young oysters (52.4-83.0 mm in shell length) were measured for 2 weeks at water temperatures of 8, 10, 12, and $14^{\circ}C$. The filtration rate (FR) ranged 0 to $4.84\;L\;h^{-1}gDW^{-1}$ (mean, $0.02{\pm}0.06 $ to $3.12{\pm}1.45$), with significant changes observed over thme except for the case of a water temperature of $14^{\circ}C$. Respiration rate (R) ranged from 0 to $2.370\;mgO2\;h^{-1}gDW^{-1}$ (mean, 0 to $1.77{\pm}0.37$), with significant respiratory disorders observed at temperatures below $12^{\circ}C$; in contrast, the rate increased on the $14^th$ day of the experiment in the case of a temperature of 14$^{\circ}C$. No significant difference was observed among the different water temperatures in terms of excretion rate (E) or absorption efficiency (Abs.eff), except for a significant decrease in aerobic metabolism in the case of water temperature of $8^{\circ}C$. The estimated scope for growth (SFG) ranged from -9.1 to $126.9\;J\;h^{-1}gDW^{-1}$ (mean. $-4.1{\pm}2.6$ to $82.85{\pm}42.6$). A significant energy Joss was found at $8^{\circ}C$, with negative SFG observed throughout the experiment and a gradual energy decrease observed over time at water temperatures of $10^{\circ}C$ and 120C. However. SFG remained positive throughout the experiment in the case of $14^{\circ}C$. The estimated minimum energy requirement, assessed from energy expenditure, is $8.00-34.24\;J\;h^{-1}gDW^{-1}$ (mean, $17.67{\pm}6.17$). In conclusion, the lowest temperature suitable for indoor overwintering is above $14^{\circ}C$.
For evaluating the mutagenic potential of 2-carbomethoxy-4-chlorodiethyl phosphate, three different short-term mutagenicity tests were used; Salmonella typhimurium preincubation assay with and without rat liver microsomal activation, chromosome aberration test in cultured chinese hamster lung fibroblast cell and in vivo micronucleus test in male mice bone marrow. In Salmonella typhimurium reverse mutation assay using TA98, TA100, TAl535 and TAl537, 2-carbomethoxy-4-chlorodiethyl phosphate did not show any mutagenic response in the presence and absence of S9 mix. It did not induce any significant structural chromosome aberrations in the absence of metabolic activation. In micronucleus test using ICR mice, the frequency of micronucleated polychromatic erythrocytes (MNPCE) increased in bone marrow cells treated with positive control, mitomycin-C, but 2-carbomethoxy-4-chlorodiethyl phosphate did not increase micronucleated polychromatic erythrocytes. These results indicate that 2-carbomethoxy-4-chlorodiethyl phosphate does not show any positive responses in short-term genotoxicity assays.
Metabolic alterations including postprandial hyperglycemia have been implicated in the development of obesity-related diseases. Xylose is a sucrase inhibitor suggested to suppress the postprandial glucose surge. The objectives of this study were to assess the inhibitory effects of two different concentrations of xylose on postprandial glucose and insulin responses and to evaluate its efficacy in the presence of other macronutrients. Randomized double-blind cross-over studies were conducted to examine the effect of D-xylose on postprandial glucose and insulin response following the oral glucose tolerance test (OGTT). In study 1, the overnight-fasted study subjects (n = 49) consumed a test sucrose solution (50 g sucrose in 130 ml water) containing 0, 5, or 7.5 g D-xylose powder. In study 2, the overnight-fasted study subjects (n = 50) consumed a test meal (50 g sucrose in a 60 g muffin and 200 ml sucrose-containing solution). The control meal provided 64.5 g of carbohydrates, 4.5 g of fat, and 10 g of protein. The xylose meal was identical to the control meal except 5 g of xylose was added to the muffin mix. In study 1, the 5 g xylose-containing solutions exhibited significantly lower area under the glucose curve (AUCg) and area under the insulin curve (AUCi) values for 0-15 min (P < 0.0001, P < 0.0001), 0-30 min (P < 0.0001, P < 0.0001), 0-45 min (P < 0.0001, P < 0.0001), 0-60 min (P < 0.0001, P < 0.0001), 0-90 min (P < 0.0001, P < 0.0001) and 0-120 min (P = 0.0071, P = 0.0016). In study 2, the test meal exhibited significantly lower AUCg and AUCi values for 0-15 min (P < 0.0001, P < 0.0001), 0-30 min (P < 0.0001, P < 0.0001), 0-45 min (P < 0.0001, P = 0.0005), 0-60 min (P = 0.0002, P = 0.0025), and 0-90 min (P = 0.0396, P = 0.0246). In conclusion, xylose showed an acute suppressive effect on the postprandial glucose and insulin surges.
Several physiological responses were investigated in plants treated with TOPE as a preliminary step to know its action site. Unlike photo-dependent diphenylethers, herbicidal activity of TOPE appeared slowly and its typical symptoms were both burning of leaf blades and abnormal division of meristem in grasses, Similarly, both leakage of cell electrolytes and the curling of cotyledon margin were also shown in cucumber(Cucumis sativus L.). Biosynthesis of chlorophyll in etiolated cucumber cotyledon was not inhibited directly by treatment of TOPE at low light intensity(5.5${\mu}$ mol $m^{-2}s^{-1}$ PAR) and protoporphyrin IX was not also accumulated. The contents of phytoene, phytofluene and ${\beta}$-carotene were abnormaly increased. Photosynthesis was inhibited only at high concentration. Mitochondrial respiration was inhibited at high concentration but rather increased significantly at 10${\mu}$M of TOPE. However, respiration inhibitors did not alleviate the two symptoms of TOPE in cucumber cotyledon. In the same experiments, using inhibitors of protein or nucleic acid biosynthesis, only one of the two symptoms was alleviated by chloramphenicol and cycloheximide. In contrast, both symptoms were alleviated by actinomycin-D and hydroxyurea, suggesting that nucleic acid metabolism might be preferentially related to the mode of action of TOPE. DNA, RNA and protein contents were accumulated in both cucumber cotyledon and rice (Oryza sativa L.) routs treated with TOPE, and the DNA of them was increased at first. Thus, it is conjectured that TOPE increase nucleic acid metabolism directly or indirectly, and then disturb various metabolic pathways causing abnormal physiological and morphological effects followed by final death.
Phosphosugars are found in all living organisms and are commercially valuable compounds with possible applications in the development of a wide range of specialty chemicals and medicines. In carbohydrate metabolism, fructose 6-phosphate (F6P) is an essential intermediate formed by phosphorylation of 6' position of fructose in glycolysis, gluconeogenesis, pentose phosphate pathway and Calvin cycle. In glycolysis, F6P lies within the glycolysis metabolic pathway and is produced by isomerisation of glucose 6-phosphate. For large-scale production, F6P could be produced from starch using many enzymes such as pullulanase, starch phosphorylase, isomerase and mutase. In enzymatic reactions carried out at high temperatures, the solubility of starch is increased and microbial contamination is minimized. Thus, thermophile-derived enzymes are preferred over mesophile-derived enzymes for industrial applications using starch. Recently, we reported the production of glucose 1-phosphate (G1P) from starch by Thermus caldophilus GK24 enzymes. Here we report the production of F6P from starch through three steps; from starch to glucose 1-phosphate (glucan phosphorylase, GP), then glucose 6-phosphate (phosphoglucomutase, GM) and then F6P (phosphoglucoisomerase, GI). Using 200 L of 1.2% soluble starch solution in potassium phosphate buffer, 1,253 g of G1P were produced. Then, 30% yields of F6P were attained at the optimum reaction conditions of GM : G1 (1 : 2.3), 63.5$^{\circ}C$, and pH 6.85. The optimum conditions were found by response surface methodology and the theoretical values were confirmed by the experiments. The optimum starch concentrations were 20 g/L under the given conditions.
Periodontal disease is a major oral disorder and comprises a group of infections that lead to inflammation of the gingiva and the destruction of periodontal tissues. $PPAR{\gamma}$ plays an important role in the regulation of several metabolic pathways and has recently been implicated in inflammatory response pathways. However, its effects on periodontal inflammation have yet to be clarified. In our current study, we evaluated the anti-inflammatory effects of $PPAR{\gamma}$ on periodontal disease. Human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) showed high levels of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), matrix metalloproteinase-2 (MMP-2), and -9 (MMP-9). Moreover, these cells also showed upregulated activities for extracellular signal regulated kinase (ERK1/2), inducible nitric oxide synthase (iNOS) and cyclooxygnase-2. However, cells treated with Ad/$PPAR{\gamma}$ and rosiglitazone in same culture system showed reduced ICAM-1, VCAM-1, MMP-2, -9 and COX-2. Finally, the anti-inflammatory effects of $PPAR{\gamma}$ appear to be mediated via the suppression of the ERK1/2 pathway and consequent inhibition of NF-kB translocation. Our present findings thus suggest that $PPAR{\gamma}$ indeed has a pivotal role in gingival inflammation and may be a putative molecular target for future therapeutic strategies to control chronic periodontal disease.
Choi, Hyeong Sim;Jeong, Eun-Hui;Lee, Tae-Gul;Kim, Seo Yun;Kim, Hye-Ryoun;Kim, Cheol Hyeon
Tuberculosis and Respiratory Diseases
/
v.75
no.1
/
pp.9-17
/
2013
Background: In cancer cells, autophagy is generally induced as a pro-survival mechanism in response to treatment-associated genotoxic and metabolic stress. Thus, concurrent autophagy inhibition can be expected to have a synergistic effect with chemotherapy on cancer cell death. Monensin, a polyether antibiotic, is known as an autophagy inhibitor, which interferes with the fusion of autophagosome and lysosome. There have been a few reports of its effect in combination with anticancer drugs. We performed this study to investigate whether erlotinib, an epidermal growth factor receptor inhibitor, or rapamycin, an mammalian target of rapamycin (mTOR) inhibitor, is effective in combination therapy with monensin in non-small cell lung cancer cells. Methods: NCI-H1299 cells were treated with rapamycin or erlotinib, with or without monensin pretreatment, and then subjected to growth inhibition assay, apoptosis analysis by flow cytometry, and cell cycle analysis on the basis of the DNA contents histogram. Finally, a Western blot analysis was done to examine the changes of proteins related to apoptosis and cell cycle control. Results: Monensin synergistically increases growth inhibition and apoptosis induced by rapamycin or erlotinib. The number of cells in the sub-$G_1$ phase increases noticeably after the combination treatment. Increase of proapoptotic proteins, including bax, cleaved caspase 3, and cleaved poly(ADP-ribose) polymerase, and decrease of anti-apoptotic proteins, bcl-2 and bcl-xL, are augmented by the combination treatment with monensin. The promoters of cell cycle progression, notch3 and skp2, decrease and p21, a cyclin-dependent kinase inhibitor, accumulates within the cell during this process. Conclusion: Our findings suggest that concurrent autophagy inhibition could have a role in lung cancer treatment.
During sleep, relatively major respiratory physiological changes occur in healthy subjects. The contributions and interactions of voluntary and metabolic breathing control systems during waking and sleep are quite different Alterations of ventilatory control occur in chemosensitivity, response to mechanical loads, and stability of ventilation. The activities of intercostal muscles and muscles involved in regulating upper airway size are decreased during sleep. These respiratory physiological changes during sleep compromise the nocturnal ventilatory function, and sleep is an important physiological cause of the nocturnal alveolar hypoventilation. There are several causes of chronic alveolar hypoventilation including cardiopulmonary, neuromuscular diseases. Obstructive sleep apnea syndrome (OSAS) is an important cause of nocturnal hypoventilation and hypoxia. Coexistent cardiopulmonary or neuromuscular disease in patients with OSAS contributes to the development of diurnal alveolar hypoventilation, diurnal hypoxia and hypercapnia. The existing data indicates that nocturnal recurrent hypoxia and fragmentation of sleep in patients with OSAS contributes to the development of systemic hypertension and cardiac bradytachyarrhythmia, and diurnal pulmonary hypertension and cor pulmonale in patients with OSAS is usually present in patients with coexisting cardiac or pulmonary disease. Recent studies reported that untreated patients with OSAS had high long-term mortality rates, cardiovascular complications of OSAS had a major effect on mortality, and effective management of OSAS significantly decreased mortality.
The purpose of this study was to investigate the effect of body fat on energy metabolic response and subjective sensations under the hot environment. Fifteen female university students volunteered as subjects. We organized subjects into three groups: low body fat group(group L : less than 20% of body fat), medium body fat group(group M : 20%~30% of body fat) and high body fat group(group H: more than 30% of body fat). The experiment was conducted with $32^{\circ}C$, 60%RH. The subjects repeated 'Exercise' and 'Rest' period. The results of this study are as follows ; The oxygen uptake value of AM is higher than PM. The value of group H is the highest in three fat groups. But it showed group L is the highest in oxygen uptake per weight. %body fat is the lower, oxygen uptake is the higher. In Calorie, group L has higher value in AM in than in PM. In M group and group H, a value of PM is higher than AM. In group H, difference of AM and PM is the highest. From a view point of three groups, a value of group H is the highest. This support that calorie increases as oxygen uptake increase. The heart rate values of group L and group H are the higher in AM than in PM. This support that heart rate was relation to oxygen uptake. In all three groups, the value of blood pressure is higher in AM than in PM. Subjective sensations of temperature sensation, thermal comfort, and wetness sensation are higher in Am than in Pm. This explains that subject sensations are similar to experimental data, such as oxygen uptake, heart rate, blood pressure. In oxygen uptake, heart rate and blood pressure, general tend to showed higher AM than PM. This showed that heart rate, oxygen uptake increase in AM, as blood pressure increase, too. From a view point of %body fat, group H is higher than the others in oxygen uptake, heart rate and blood pressure.
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