A study on the flexibility of enzyme active sites

<p>Abstract</p> <p>Background</p> <p>A common assumption about enzyme active sites is that their structures are highly conserved to specifically distinguish between closely similar compounds. However, with the discovery of distinct enzymes with similar reaction chemistries, more and more studies discussing the structural flexibility of the active site have been conducted.</p> <p>Results</p> <p>Most of the existing works on the flexibility of active sites focuses on a set of pre-selected active sites that were already known to be flexible. This study, on the other hand, proposes an analysis framework composed of a new data collecting strategy, a local structure alignment tool and several physicochemical measures derived from the alignments. The method proposed to identify flexible active sites is highly automated and robust so that more extensive studies will be feasible in the future. The experimental results show the proposed method is (a) consistent with previous works based on manually identified flexible active sites and (b) capable of identifying potentially new flexible active sites.</p> <p>Conclusions</p> <p>This proposed analysis framework and the former analyses on flexibility have their own advantages and disadvantage, depending on the cause of the flexibility. In this regard, this study proposes an alternative that complements previous studies and helps to construct a more comprehensive view of the flexibility of enzyme active sites.</p

The transcription factor CREB is involved in sorafenib-inhibited renal cancer cell proliferation, migration and invasion

Our previous reports showed that the cyclic-AMP-response element-binding protein (CREB) served as a proto-oncogene in the process of tumorigenesis and mediated the growth and metastatic activity of renal cancer cells. Our study, therefore, explored the role of CREB in sorafenib-inhibited cell proliferation, migration and invasion. Renal cancer cells were cultured in medium containing sorafenib for 12, 24, 48 and 72 h. The MTT assay was used to study the cytotoxic effects of sorafenib. Cell invasion and migration were assayed in wound healing and transwell experiments, respectively. Protein expression levels were evaluated by western blotting. The results show that sorafenib treatment decreased cell viability in a dose- and time-dependent manner. Sorafenib inhibited cell migration and invasion and decreased the expression of MMP-2 and MMP-9. Moreover, addition of the recombinant plasmid pCI-neo/CREB (PN) reversed the sorafenib-induced inhibition of cell proliferation, migration and invasion. These results show that CREB is associated with the sorafenib-induced inhibition of proliferation, migration and invasion

Comparative Evaluation Research on the Carrying Capacity of Multi-regional Distribution Network Owner Project Departments Based on Combined Weights

This paper proposes a comparative evaluation method for the carrying capacity of the owner's project department based on combined weights. This method first combines the current grid companies’ requirements for the construction of the owner’s project department and the current distribution network construction management issues to systematically construct the owner’s project department’s carrying capacity evaluation index system. Through comprehensive evaluation and collection of indicator-related data, it is determined based on the coefficient of variation method. The objective weight of the indicator is determined based on the analytic hierarchy process; then the integrated scoring model is used to comprehensively calculate the normalized indicator value and weight value to obtain the evaluation analysis result; finally, the method is verified by empirical analysis Effectiveness

PO-066 The Function of t Lycium Barbarum Juice Supplemen in Exercise Stress Regulation during Increasing Resistance Training

Objective The purpose of this study was to explore the function of Lycium Barbarum juice on exercise stress regulation when male university students drank Lycium Barbarum juice during increasing resistance exercise, by observing the effects of oral Lycium Barbarum juice on the blood glucose, serum Adrenocorticotropic Hormone (ACTH), insulin and glucagon concentration. Methods 21 to 22, healthy, 28 male university students participated in the study. They were randomly divided into a control group (n=16)and an experimental group(n=12). All participants completed four-stage incremental load movement for a total of 32 days. The exercise intensity of four stages was 60% VO2max, 70% VO2max, 80% VO2max and 90% VO2max, respectively. Each stage was exercised every-other-day, 4 times per stage and 1 hour each time. During the exercise, each subject in the experimental group drank 100 ml of 100% Lycium Barbarum juice before going to bed every day. Before the experiment and the morning after the end of each phase, a participant’s elbow-venous blood was collected to separate the serum. In all serum substances, the concentrations of ACTH, insulin, glucagon were detected by ELISA system. Fasting blood glucose concentration was detected by a blood glucose meter (Kyoto GT-1640 glucose meter, Japan). SPSS 17.0 software was used for statistical analysis. Results 1) The serum ACTH concentration of the subjects continually increased with the progress of the incremental load exercise and reached the highest at the end of the fourth stage. Compared with the increase in the control group (P&lt;0.05), the experimental group was more significant (P&lt;0.01). 2) Compared with before the experiment, both control group and experimental group were no obvious changes of blood glucose concentration in the first and second stages, and the control group was significantly decreased in the third and fourth stages (P&lt;0.05), while the experimental group was not (P&gt;0.05). 3) During the increasing load exercise, the changes of insulin in serum of the participants were basically the same. The insulin level increased significantly at the end of the first stage and decreased successively at the end of the last three stages. At the end of the fourth stage, the serum insulin level of the control group decreased more significantly (P&lt;0.05) than the experimental group (P&gt;0.05). 4) The glucagon concentration in the control group continued to increase with the increase of the load. By contrast, the glucagon concentration in the experimental group gradually decreased at the end of the first stage and then increased at the end of the fourth stage. However, all of the increase and decrease are not statistically significant. Conclusions During increasing resistance exercise, drinking Lycium Barbarum juice can increase the ability of the body to regulate Adrenocorticotropic Hormone (ACTH), insulin and glucagon through the exercise stress regulation systems, the Hypothalamic-Pituitary-Adrenal Cortical Hormone system (HPA) and the Sympathetic-Adrenal Medullary system. It plays an important role in maintaining blood sugar levels during increasing resistance exercise and accelerating post-exercise function recovery after exercise

PO-067 Effects of oral Lycium barbarum juice in red blood cell antioxidant biomarkers and physical function during 8 days of aerobic exercise

Objective Lycium barbarum polysaccharide (LBP) is the main active components of Lycium barbarum, its benefits to anti-aging, vision, kidney, and liver functions. Nevertheless, there is still a scarcity of experimental evidence to support the effect of Lycium barbarum on aerobic exercise.This a randomized controlled trial was observed the effects of oral Lycium barbarum juice in red blood cell antioxidant biomarkers and physical function during 8 days&nbsp;of&nbsp;aerobic exercise. Methods 28 healthy male college students were divided into control group（16）and experimental group（12），and underwent interval running once every other day，total of 8 days. Exercise program: An exercise session includes two 30-minute aerobic exercises at 60%VO2max and a five-minute break. For the duration of the 8 days period, participants exercised one time every other day and the experimental group drank 100ml Lycium barbarum juice (each LBP content 360-440mg%) at bedtime every night. In ninth days, all the experimenters did exhaustive exercise with 80%VO2max on a treadmill with 8°.simultaneous recording of motion duration. The levels of red blood cell SOD, MDA, GSH-PX, serum CAT, serum TAC and other oxygenation stress markers and BLA, Glu, Urea, CK, Urine eight items and other physical function indexes of the subjects were determined before the experiment and after the completion of each intensity exercise. Differences between before and after intervention values were tested using a paired t test.And to compare the mean of outcomes in quantitative variables between the 2 groups, a&nbsp;independent t-test was used. The SPSS software (version 17, SPSS Inc, Chicago, IL, USA) was applied for data analysis and statistical significance was accepted at P &lt; 0.05. Results (1)After 8 days of oral Lycium barbarum juice, the exhaustion time of exercise force in the experimental group was 30.76 ±12.19min, while the control group was 23.64±8.56min. Compared with the control group, the average exercise exhaustion time of the experimental group was prolonged 7.12min. (2)The red blood cell SOD in the two groups after 8 days of aerobic exercise had significant and significant improvement (P &lt; 0.05, P &lt; 0.01), and moreover, the increase of the experimental group was significantly higher than that of the control group (P &lt; 0.05).As well as, the blood erythrocyte GSH-PX and serum TAC were significantly enhanced after the experiment (P &lt; 0.01).It is suggested that increasing the levels of SOD and GSH-PX in vivo is beneficial in scavenging the free radicals produced by body movement. (3)After the 8 days oral Lycium barbarum juice, the decrease of MDA in blood red blood cells in the experimental group was greater than that of the control group (P &lt; 0.01), indicating that the juice of Lycium barbarum could reduce the production of lipid peroxide products. (4) Exhaustion exercise after 8 days of oral Lycium barbarum juice, the physical function indexes of the experimental group, such as BLA, Urea, and CK were reduced. The positive rate of eight urine items was less than that in the control group, 8 in the control group, 2 for bilirubin positive, 3 in the urinary occult blood and 5 in the urine protein, while only 1 in the experimental group were positive for urine protein. &nbsp; Conclusions Oral Lycium barbarum juice can improve the activity of antioxidant enzymes during aerobic exercise, reduce the formation of lipid peroxides in the body, protect the biological function of red blood cells, improve the physical function and postpone the production of sports fatigue