Anti-cancer and potential chemopreventive actions of ginseng by activating Nrf2 (NFE2L2) anti-oxidative stress/anti-inflammatory pathways

This article reviews recent basic and clinical studies of ginseng, particularly the anti-cancer effects and the potential chemopreventive actions by activating the transcriptional factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2 or NFE2L2)-mediated anti-oxidative stress or anti-inflammatory pathways. Nrf2 is a novel target for cancer prevention as it regulates the antioxidant responsive element (ARE), a critical regulatory element in the promoter region of genes encoding cellular phase II detoxifying and anti-oxidative stress enzymes. The studies on the chemopreventive effects of ginseng or its components/products showed that Nrf2 could also be a target for ginseng's actions. A number of papers also demonstrated the anti-inflammatory effects of ginseng. Targeting Nrf2 pathway is a novel approach to the investigation of ginseng's cancer chemopreventive actions, including some oxidative stress and inflammatory conditions responsible for the initiation, promotion and progression of carcinogenesis

A class of optimal state-delay control problems

We consider a general nonlinear time-delay system with state-delays as control variables. The problem of determining optimal values for the state-delays to minimize overall system cost is a non-standard optimal control problem – called an optimal state-delay control problem – that cannot be solved using existing optimal control techniques. We show that this optimal control problem can be formulated as a nonlinear programming problem in which the cost function is an implicit function of the decision variables. We then develop an efficient numerical method for determining the cost function’s gradient. This method, which involves integrating an auxiliary impulsive system backwards in time, can be combined with any standard gradient-based optimization method to solve the optimal state-delay control problem effectively. We conclude the paper by discussing applications of our approach to parameter identification and delayed feedback control

Developing 21st Century Skills through a Constructivist-Constructionist Learning Environment

Science and technology innovation and 21st century skills are increasingly important in the 21st century workplace. The purpose of this study is to propose an instructional strategy that develop constructivist-constructionist learning environment that simultaneously develop chemistry knowledge and 21st century skills. Based on constructivist and constructionist learning theories, we identified three central guiding principles for this study: (1) engage students in discovery and problem solving task through teamwork, (2) provide opportunities for communicating ideas, and (3) involve students in the process of design. An intervention module, Malaysian Kimia (chemistry) Digital Game known as MyKimDG, was developed as a mechanism for creating the learning environment. In this study, students were required to work collaboratively to design educational media that help their peers who face difficulty in learning particular concept. They were guided to go through the IDPCR (Inquiry, Discover, Produce, Communicate and Review) phases. It is hypothesized that MyKimDG can create learning environment that allows students to deepen subject content knowledge and practice various 21st century skills in real situation. This study employed quasi-experimental study with non-equivalent control group pretest-posttest control group design. Results suggest that this approach is able to improve the acquisition of chemistry knowledge and high productivity skill

Toe clearance and velocity profiles of young and elderly during walking on sloped surfaces

Background Most falls in older adults are reported during locomotion and tripping has been identified as a major cause of falls. Challenging environments (e.g., walking on slopes) are potential interventions for maintaining balance and gait skills. The aims of this study were: 1) to investigate whether or not distributions of two important gait variables [minimum toe clearance (MTC) and foot velocity at MTC (VelMTC)] and locomotor control strategies are altered during walking on sloped surfaces, and 2) if altered, are they maintained at two groups (young and elderly female groups). Methods MTC and VelMTC data during walking on a treadmill at sloped surfaces (+3°, 0° and -3°) were analysed for 9 young (Y) and 8 elderly (E) female subjects. Results MTC distributions were found to be positively skewed whereas VelMTC distributions were negatively skewed for both groups on all slopes. Median MTC values increased (Y = 33%, E = 7%) at negative slope but decreased (Y = 25%, E = 15%) while walking on the positive slope surface compared to their MTC values at the flat surface (0°). Analysis of VelMTC distributions also indicated significantly (p < 0.05) lower minimum and 25th percentile (Q1) values in the elderly at all slopes. Conclusion The young displayed a strong positive correlation between MTC median changes and IQR (interquartile range) changes due to walking on both slopes; however, such correlation was weak in the older adults suggesting differences in control strategies being employed to minimize the risk of tripping

The Effects of Achievement Motivation and Perceived Teacher Involvement in Academic Tasks on the Academic Achievement and Psychological Well-being of Rural Students in the Interior Sabah Division, Malaysia

This study examines the effects of achievement motivation and perceived teacher involvement on academic achievement and psychological well-being of rural students in the Interior Sabah Division (Beaufort, Keningau, Kuala Penyu, Membakut, Pensiangan, Sipitang, Tambunan & Tenom). We predicted that achievement motivation contributes to both academic achievement and psychological well-being. We also predicted teachers’ involvement in students’ academic work also contributes to both dependent variables. A total of 1586 students participated in this study from 21 rural schools in the Interior Division Sabah. A questionnaire, divided into four sections, was used to measure all the variables. Section A measured the demographic variables, such as the academic achievement, academic level, age, gender and location; Section B; measured achievement motivation; Section C measured the perception of teacher involvement in students’academic work and Section D measured psychological well-being. Hierarchical regression analyses were used to analyze the data. The study found that achievement motivation contributed 4% to the variance in academic achievement and 16% on psychological well-being. In regards to teachers’ involvement in academic studies, it contributed 6% to students’ psychological well-being but not in academic achievement. These significant findings may create awareness and bring the matter to the attention of the Ministry of Education, the schools and Parent-Teacher Association. From this study, it is our hope that the Educational Institution may provide more achievement motivational programs to enhance rural students’ psychological well-being and academic achievement

The Influence of Context Aspects towards Input Aspects of Science Practical among Science Teachers in Rural Secondary Schools of Sabah

This study aims to explore the influence of science practical context towards the input of science practical among the science teachers in 69 rural secondary schools in Sabah. A total of 357 science teachers were selected by stratified sampling method. This study is a quantitative non-experimental study using the survey method to collect data. The instrument of science practical context aspects and science practical input aspects questionnaires were used to collect data. Statistical Package for Social Science (SPSS) version 21.0 for Windows and the software of 'Smart Partial Least Square (SmartPLS) version 3.2.7 was used to analyze the collected quantitative data. The findings show that the level of the science practical context aspects and science practical input aspects are at the stage of 'High' (3:46- 4.64) among the science teachers at rural secondary schools in Sabah. The value of composite reliability for context aspects is 0.984 and for input aspects is 0.939. The results also showed there is a significant positive correlation between the science practical context aspects and the science practical input aspects (β=0.473, p<0.05). There is a modest positive effect and significant between the science practical context aspects towards the science practical input aspects (β = 0.473, p <0.05). A total of 16% of science practical context can affect the science practical input aspects. The implications of this study showed that science teachers should examine the science practical input aspects coincides with the implementation of science practical in addition to considering the science practical process and product aspects

Suitable reference genes for real-time PCR in human HBV-related hepatocellular carcinoma with different clinical prognoses

<p>Abstract</p> <p>Background</p> <p>Housekeeping genes are routinely used as endogenous references to account for experimental differences in gene expression assays. However, recent reports show that they could be de-regulated in different diseases, model animals, or even under varied experimental conditions, which may lead to unreliable results and consequently misinterpretations. This study focused on the selection of suitable reference genes for quantitative PCR in human hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with different clinical outcomes.</p> <p>Methods</p> <p>We evaluated 6 commonly used housekeeping genes' expression levels in 108 HBV-related HCCs' matched tumor and non-tomor tissue samples with different clinical outcomes and 26 normal liver specimens by real-time PCR. The expression stability of the 6 genes was compared using the software programs geNorm and NormFinder. To show the impact of reference genes on data analysis, we took PGK1 as a target gene normalized by each reference gene, and performed one-way ANOVA and the equivalence test.</p> <p>Results</p> <p>With the geNorm and NormFinder software programs, analysis of TBP and HPRT1 showed the best stability in all tissue samples, while 18s and ACTB were less stable. When 18s or ACTB was used for normalization, no significant difference of PGK1 expression (p > 0.05) was found among HCC tissues with and without metastasis, and normal liver specimens; however, dramatically differences (p < 0.001) were observed when either TBP or the combination of TBP and HPRT1 were selected as reference genes.</p> <p>Conclusion</p> <p>TBP and HPRT1 are the most reliable reference genes for q-PCR normalization in HBV-related HCC specimens. However, the well-used ACTB and 18S are not suitable, which actually lead to the misinterpretation of the results in gene expression analysis.</p

Suitable reference genes for real-time PCR in human HBV-related hepatocellular carcinoma with different clinical prognoses

<p>Abstract</p> <p>Background</p> <p>Housekeeping genes are routinely used as endogenous references to account for experimental differences in gene expression assays. However, recent reports show that they could be de-regulated in different diseases, model animals, or even under varied experimental conditions, which may lead to unreliable results and consequently misinterpretations. This study focused on the selection of suitable reference genes for quantitative PCR in human hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with different clinical outcomes.</p> <p>Methods</p> <p>We evaluated 6 commonly used housekeeping genes' expression levels in 108 HBV-related HCCs' matched tumor and non-tomor tissue samples with different clinical outcomes and 26 normal liver specimens by real-time PCR. The expression stability of the 6 genes was compared using the software programs geNorm and NormFinder. To show the impact of reference genes on data analysis, we took PGK1 as a target gene normalized by each reference gene, and performed one-way ANOVA and the equivalence test.</p> <p>Results</p> <p>With the geNorm and NormFinder software programs, analysis of TBP and HPRT1 showed the best stability in all tissue samples, while 18s and ACTB were less stable. When 18s or ACTB was used for normalization, no significant difference of PGK1 expression (p > 0.05) was found among HCC tissues with and without metastasis, and normal liver specimens; however, dramatically differences (p < 0.001) were observed when either TBP or the combination of TBP and HPRT1 were selected as reference genes.</p> <p>Conclusion</p> <p>TBP and HPRT1 are the most reliable reference genes for q-PCR normalization in HBV-related HCC specimens. However, the well-used ACTB and 18S are not suitable, which actually lead to the misinterpretation of the results in gene expression analysis.</p

A Densely Interconnected Genome-Wide Network of MicroRNAs and Oncogenic Pathways Revealed Using Gene Expression Signatures

MicroRNAs (miRNAs) are important components of cellular signaling pathways, acting either as pathway regulators or pathway targets. Currently, only a limited number of miRNAs have been functionally linked to specific signaling pathways. Here, we explored if gene expression signatures could be used to represent miRNA activities and integrated with genomic signatures of oncogenic pathway activity to identify connections between miRNAs and oncogenic pathways on a high-throughput, genome-wide scale. Mapping >300 gene expression signatures to >700 primary tumor profiles, we constructed a genome-wide miRNA–pathway network predicting the associations of 276 human miRNAs to 26 oncogenic pathways. The miRNA–pathway network confirmed a host of previously reported miRNA/pathway associations and uncovered several novel associations that were subsequently experimentally validated. Globally, the miRNA–pathway network demonstrates a small-world, but not scale-free, organization characterized by multiple distinct, tightly knit modules each exhibiting a high density of connections. However, unlike genetic or metabolic networks typified by only a few highly connected nodes (“hubs”), most nodes in the miRNA–pathway network are highly connected. Sequence-based computational analysis confirmed that highly-interconnected miRNAs are likely to be regulated by common pathways to target similar sets of downstream genes, suggesting a pervasive and high level of functional redundancy among coexpressed miRNAs. We conclude that gene expression signatures can be used as surrogates of miRNA activity. Our strategy facilitates the task of discovering novel miRNA–pathway connections, since gene expression data for multiple normal and disease conditions are abundantly available