In vitro investigation on synergistic anticancer effects between vitamin E isomers, pure compounds and crude alkaloid plant extracts on human cancerous cells

Anticancer chemotherapeutic treatment using single dose has been limited due to drug resistance and potential metabolic degradation. For instance, high-dose tocotrienols undergo metabolic degradation that limits the availability of therapeutic dose thereby limiting the potency in vivo. Combined treatment of tocotrienols at low dosage has been suggested as alternative to circumventing this limitation. This study was designed to investigate the cytotoxic effects and subsequently the apoptotic mechanisms of individual doses and combined treatments at lower dosages of tocotrienols (delta and gamma), jerantinines (A and B) and extracts (ethanol and alkaloid crude) from leaves and bark of Ficus hispida, Ficus fistulosa and Ficus schwarzii on lung (A549), brain (U87MG) and colon (HT-29) cancer cell lines. Neutral red uptake assay was conducted to evaluate the antiproliferative effect of individual and combined treatments. Staining techniques (histochemical and fluorescence), COMET assay flow cytometric analysis and immunofluorescence were conducted to evaluate cell morphology, DNA damage, cell cycle arrest pattern and antimicrotubule effects. Finally cell and molecular based assays were conducted to investigate the pathways for induction of apoptosis. Cell viability study revealed that alkaloid crude extracts of leaves and bark of F. fistulosa demonstrated the highest potency with IC50 range of 0.96 – 46.81 µg/ml compared to F. schwarzii (8.79 – 107.9 µg/ml) and F. hispida (15.14 – 49.58 µg/ml) on A549, U87MG and HT-29 cells. Both delta- and gamma-tocotrienols induced antiproliferative effects on A549, U87MG and HT-29 cells with IC50 values of 3.12 - 12.40 µg/ml and 3.17 – 16.36 µg/ml, respectively. Potent antiproliferative effects were also evident for jerantinine A (IC50 0.62 – 1.74 µg/ml), jerantinine B (IC50 0.58 – 1.48 µg/ml) and vinblastine (IC50 0.03 – 0.71 µg/ml). However, similar toxic effects on these three compounds were also evident on non-cancerous lung fibroblast (MRC5) cells. The leaf and bark alkaloid crude extracts of F. fistulosa and F. schwarzii were selected for combined treatments. The combined treatment of IC20 doses of F. fistulosa with both delta- and gamma-tocotrienols induced synergistic antiproliferative effects (combination index (CI) 1) were observed for IC20 doses of F. schwarzii extracts combined with delta- and gamma-tocotrienols on HT-29 cells. On the other hand, combined treatments of tocotrienols (delta and gamma) with IC20 doses of jerantinines (A and B) induced synergistic effects (CI < 1) on A549, U87MG and HT-29 cells causing up to 4.48-fold dose reduction of tocotrienols thus reducing toxicity towards MRC5 cells compared to cancer cells. Further morphological and DNA damage assessment focusing on tocotrienols (delta and gamma), jerantinines (A and B) and combined low-dose treatments revealed anticancer features including cell shrinkage, nuclear chromatin condensation and fragmentation, membrane blebbing, apoptotic bodies and induction of predominantly double stranded DNA breaks. Cell cycle analysis demonstrated the induction of G0/G1 and G2/M cell cycle arrests by tocotrienols (delta and gamma) and jerantinines (A and B), respectively on U87MG, A549 and HT-29 cells. Meanwhile, G2/M (A549) and G0/G1 (U87MG and HT-29) cell cycle arrests were evident for combined low-dose treatments of tocotrienols (delta and gamma) with IC20 doses of jerantinines (A and B). Jerantinines A and B and combined low-dose treatments with tocotrienols (delta and gamma) caused disruption of microtubule networks and induction of caspase 8-, 9- and 3-mediated apoptosis with caspase-independent growth inhibition evidenced in the presence of caspase inhibitors on U87MG, A549 and HT-29 cells. In contrast, although treatments of tocotrienols (delta and gamma) alone caused similar apoptotic features as those of combined, disruption of microtubule networks were not characterized on these three cancer cell lines. Further mechanistic study on U87MG cells revealed that the apoptosis triggered by individual doses of tocotrienols (delta and gamma) involved the activation of TRAIL and Bid as well as the release of cytochrome C, thus confirming the recruitment of the death receptor and mitochondria-mediated pathways. On the other hand, individual doses of jerantinines (A and B) and combined low-dose treatments with tocotrienols resulted in the activation of TRAIL, FAS, p53 and Bid, as well as the release of cytochrome C. The activation of both death receptors, p53 and microtubule disruption by combined low-dose treatments demonstrates an improved mechanism of action comparing to individual doses of tocotrienols and jerantinines. In addition, the combined low-dose treatments also caused a reduction of required potent doses thereby minimizing the toxicity of jerantinines (A and B) towards the non-cancerous MRC5 cells. In conclusion, this research has presented valuable combined treatment candidates which are warranted for further investigations as future chemotherapeutic agents against cancers

In vitro investigation on synergistic anticancer effects between vitamin E isomers, pure compounds and crude alkaloid plant extracts on human cancerous cells

Anticancer chemotherapeutic treatment using single dose has been limited due to drug resistance and potential metabolic degradation. For instance, high-dose tocotrienols undergo metabolic degradation that limits the availability of therapeutic dose thereby limiting the potency in vivo. Combined treatment of tocotrienols at low dosage has been suggested as alternative to circumventing this limitation. This study was designed to investigate the cytotoxic effects and subsequently the apoptotic mechanisms of individual doses and combined treatments at lower dosages of tocotrienols (delta and gamma), jerantinines (A and B) and extracts (ethanol and alkaloid crude) from leaves and bark of Ficus hispida, Ficus fistulosa and Ficus schwarzii on lung (A549), brain (U87MG) and colon (HT-29) cancer cell lines. Neutral red uptake assay was conducted to evaluate the antiproliferative effect of individual and combined treatments. Staining techniques (histochemical and fluorescence), COMET assay flow cytometric analysis and immunofluorescence were conducted to evaluate cell morphology, DNA damage, cell cycle arrest pattern and antimicrotubule effects. Finally cell and molecular based assays were conducted to investigate the pathways for induction of apoptosis. Cell viability study revealed that alkaloid crude extracts of leaves and bark of F. fistulosa demonstrated the highest potency with IC50 range of 0.96 – 46.81 µg/ml compared to F. schwarzii (8.79 – 107.9 µg/ml) and F. hispida (15.14 – 49.58 µg/ml) on A549, U87MG and HT-29 cells. Both delta- and gamma-tocotrienols induced antiproliferative effects on A549, U87MG and HT-29 cells with IC50 values of 3.12 - 12.40 µg/ml and 3.17 – 16.36 µg/ml, respectively. Potent antiproliferative effects were also evident for jerantinine A (IC50 0.62 – 1.74 µg/ml), jerantinine B (IC50 0.58 – 1.48 µg/ml) and vinblastine (IC50 0.03 – 0.71 µg/ml). However, similar toxic effects on these three compounds were also evident on non-cancerous lung fibroblast (MRC5) cells. The leaf and bark alkaloid crude extracts of F. fistulosa and F. schwarzii were selected for combined treatments. The combined treatment of IC20 doses of F. fistulosa with both delta- and gamma-tocotrienols induced synergistic antiproliferative effects (combination index (CI) 1) were observed for IC20 doses of F. schwarzii extracts combined with delta- and gamma-tocotrienols on HT-29 cells. On the other hand, combined treatments of tocotrienols (delta and gamma) with IC20 doses of jerantinines (A and B) induced synergistic effects (CI < 1) on A549, U87MG and HT-29 cells causing up to 4.48-fold dose reduction of tocotrienols thus reducing toxicity towards MRC5 cells compared to cancer cells. Further morphological and DNA damage assessment focusing on tocotrienols (delta and gamma), jerantinines (A and B) and combined low-dose treatments revealed anticancer features including cell shrinkage, nuclear chromatin condensation and fragmentation, membrane blebbing, apoptotic bodies and induction of predominantly double stranded DNA breaks. Cell cycle analysis demonstrated the induction of G0/G1 and G2/M cell cycle arrests by tocotrienols (delta and gamma) and jerantinines (A and B), respectively on U87MG, A549 and HT-29 cells. Meanwhile, G2/M (A549) and G0/G1 (U87MG and HT-29) cell cycle arrests were evident for combined low-dose treatments of tocotrienols (delta and gamma) with IC20 doses of jerantinines (A and B). Jerantinines A and B and combined low-dose treatments with tocotrienols (delta and gamma) caused disruption of microtubule networks and induction of caspase 8-, 9- and 3-mediated apoptosis with caspase-independent growth inhibition evidenced in the presence of caspase inhibitors on U87MG, A549 and HT-29 cells. In contrast, although treatments of tocotrienols (delta and gamma) alone caused similar apoptotic features as those of combined, disruption of microtubule networks were not characterized on these three cancer cell lines. Further mechanistic study on U87MG cells revealed that the apoptosis triggered by individual doses of tocotrienols (delta and gamma) involved the activation of TRAIL and Bid as well as the release of cytochrome C, thus confirming the recruitment of the death receptor and mitochondria-mediated pathways. On the other hand, individual doses of jerantinines (A and B) and combined low-dose treatments with tocotrienols resulted in the activation of TRAIL, FAS, p53 and Bid, as well as the release of cytochrome C. The activation of both death receptors, p53 and microtubule disruption by combined low-dose treatments demonstrates an improved mechanism of action comparing to individual doses of tocotrienols and jerantinines. In addition, the combined low-dose treatments also caused a reduction of required potent doses thereby minimizing the toxicity of jerantinines (A and B) towards the non-cancerous MRC5 cells. In conclusion, this research has presented valuable combined treatment candidates which are warranted for further investigations as future chemotherapeutic agents against cancers

Utilisation of Information Security Mechanisms for Combating Pharming on University Websites in Northern Regionsof Nigeria

This paper investigates the“utilisation of information security mechanisms for combating pharming on University Websites in Northern Regions of Nigeria”. Two objectives were formulated: to identify the “type of information security mechanisms employed for combating pharming on University Websites in Northern Regions of Nigeria”; and to determine the “effectiveness of the information security mechanisms employed for combating pharming on University Websites in Northern Regions of Nigeria”. Quantitative research methodology was used for the study. 9 Universities in Northern Regions of Nigeria with 127 ICT personnel were selected. The questionnaire was used as an instrument in collecting the data. Mean and standard deviationwere used to present and analyse the data collected in the study. The research found that “detectives, preventive and mitigative mechanisms” were the types of “mechanisms employed for combating pharming on Universities studied”; it was also found that “mitigative and detective information security mechanisms employed are more effective than preventive mechanisms in combating pharming on University studied”. The paper concludes that, if security safeguards are not adequate, pharmers affect the “functionality of University websites undetected”. They can attack websites using skills the software developers never imagined. The study recommended that to guarantee information effective information security, therefore, ICT personnel need to establish strong preventive measures and quality management practices that will protect data during collection, processing, and storage from pharmers

The Relevance of Entrepreneurial Orientation to Students Entrepreneurial Intention: Evidence from Federal University Dutse (FUD)

This paper examined the dimensions of entrepreneurial orientation and its relevance to student’s entrepreneurial intention among Federal University Dutse final year students as at 2017­­/2018 academic session. The study adopts cross-sectional research design using quantitative questionnaire approach to collect the data. To validate the model, data from 282 final year students were analysed using the Partial Least Squares Structural Equation Modelling (PLS-SEM). Overall, the study revealed that dimensions of innovativeness, pro-activeness and risk-taking are significantly and positively relevance to student entrepreneurial intention. The study used Human Capital Theory (HCT) as a theoretical foundation of the study. This study served as one of the pioneering study with regard to HCT in testing relationship of this nature. This study recommended that other researchers should use this theory to include other dimension of entrepreneurial orientation for further validation. This study also contributes to the current literatures by extending the used of entrepreneurial orientation which is still rare in student entrepreneurial intention literatures. As suggestion to policy, the government should guarantee not only inspiring students with entrepreneurship education but also inculcate the spirit of innovativeness proactiveness, and risk-taking among  youths as it has relevance in explaining students entrepreneurial intention

Impact of Gurara Dam on Land Cover in the Surrounding Communities of Kaduna State, Nigeria

This research focuses on the impact of Gurara Dam on land cover in the surrounding communities of Kaduna state Nigeria. The aim of the study is to assess changes land cover condition in communities surrounding Gurara Dam as a result of the Dam construction. This was achieved by analysing the land cover changes between pre-dam (2000) and the post-dam (2013) in terms of spatial extent and percentage coverage.To assess the impact, Landsat (ETM, TM and MSS) covering the area for 2000 (pre-dam period) and 2013 (post-dam period) was obtained. To interpret and verify the accuracy of the satellite imagery; ground truth observation was conducted on the land cover of the study area. Using ArcGIS 10.0 and AutoCAD Map 2013 software, different image processing techniques and analysis were undertaken to produce land cover maps of the study area for pre-dam and post dam period. The extent of area coverage of each land use/land cover was calculated in hectares and express in percentages. The study discovers that in the post-dam period (between 2000 and 2013) the impact of Gurara dam has resulted in substantial changes in the land cover, with losses in fadama land. Forestry, arable land and Rock outcrop by 58%, 9%, 7%, and 12% respectively. Whereas gains occurred in bare land (26%), water bodies (42%), circulation (28%).  Modern irrigation also witnessed gain by 100% and built up area 26%. It is there recommended that, modern technology (Geographic Information System) be provided as mitigation measure to land cover problems in communities surrounding Gurara Dam. Keywords: Dam Construction, Geographic Information System, land cover, Upstream and Spatial Exten

ASSESSING THE INFLUENCE OF MARKET ORIENTATION AND ENTREPRENEURIAL ORIENTATION ON BUSINESS PERFORMANCE OF WOMEN ENTREPRENEURS IN NIGERIA

The aim of this study is to assess the influence of market orientation and entrepreneurial orientation on the business performance of women entrepreneurs in Nigeria. This study used Kano State, North West Nigeria as a case study. A sample size of 245 women entrepreneurs was drawn using simple random sampling out of the population of 650 registered women entrepreneurs in Kano State, Nigeria. Responses of the subjects were collected through close-ended structured questionnaire. Statistical Package for Social Science (SPSS) software was used to analyze the respondents profile while Structural Equation Modeling (SEM) through Analysis of Moment Structure (AMOS) software was used to test the hypotheses of this study. The finding indicates that market orientation and entrepreneurial orientation have positive and significant influence on business performance of women entrepreneurs in Nigeria. This study suggests that Market Orientation (MO) and Entrepreneurial Orientation (EO) are important variables to business performance. Therefore, adequate attentions have been actualized. The study contribute to the existing body of knowledge, and also it serve as a reference to future research

The Role of Information and Communication Technology (ICT)) Towards Providing Effective Library Services in Special Libraries of Adamawa Broadcasting Corporation Yola, Adamawa State Nigeria

The study examined the role of information and communication technology (ICT)) towards providing effective library services in special libraries of Adamawa broadcasting corporation Yola, Adamawa State Nigeria. The study employed four objectives of the study and four research questions. The study adopted the descriptive survey research method. Questionnaire was used as instrument for data collection. The population of the study consists of fifteen (15) staff. This study adopted purposive sampling technique where. Descriptive statistic was used as the method of data analysis. The study revealed that there is availability of ICTs such as: CDs, hard drives, flash and also photocopier and printers in the library. The study also, revealed that the staff possessed competencies in retrieving document from storage devices. The study also, showed that current awareness services are effective in using ICTS for providing effective services in the library. The study showed that poor funding and facilities are the major problem hindered the effective use of information and communication technology in the library. The study concluded that among others that there is availability of information and communication technologies; also, staff in the library possessed competencies of retrieving document from the storage devices and poor funding and inadequate facilities are the major problems hinders the effective use of the library. The study recommended among others that the management of ABC should make ICTs available and should make sufficient funds available in other to acquire modern ICT facilities for effective services deliver