Emerging role of nuclear factor erythroid 2-related factor 2 in the mechanism of action and resistance to anticancer therapies

Nuclear factor E2-related factor 2 (NRF2), a transcription factor, is a master regulator of an array of genes related to oxidative and electrophilic stress that promote and maintain redox homeostasis. NRF2 function is well studied in in vitro, animal and general physiology models. However, emerging data has uncovered novel functionality of this transcription factor in human diseases such as cancer, autism, anxiety disorders and diabetes. A key finding in these emerging roles has been its constitutive upregulation in multiple cancers promoting pro-survival phenotypes. The survivability pathways in these studies were mostly explained by classical NRF2 activation involving KEAP-1 relief and transcriptional induction of reactive oxygen species (ROS) neutralizing and cytoprotective drug-metabolizing enzymes (phase I, II, III and 0). Further, NRF2 status and activation is associated with lowered cancer therapeutic efficacy and the eventual emergence of therapeutic resistance. Interestingly, we and others have provided further evidence of direct NRF2 regulation of anticancer drug targets like receptor tyrosine kinases and DNA damage and repair proteins and kinases with implications for therapy outcome. This novel finding demonstrates a renewed role of NRF2 as a key modulatory factor informing anticancer therapeutic outcomes, which extends beyond its described classical role as a ROS regulator. This review will provide a knowledge base for these emerging roles of NRF2 in anticancer therapies involving feedback and feed forward models and will consolidate and present such findings in a systematic manner. This places NRF2 as a key determinant of action, effectiveness and resistance to anticancer therapy

A real-time assay for monitoring nucleic acid cleavage by quadruplex formation

Direct and straightforward methods to follow nucleic acid cleavage are needed. A spectrophotometric quadruplex formation assay (QFA) was developed, which allows real-time monitoring of site-specific cleavage of nucleic acids. QFA was applied to study both protein and nucleic acid restriction enzymes, and was demonstrated to accurately determine Michaelis–Menten parameters for the cleavage reaction catalyzed by EcoRI. QFA can be used to study the mechanisms of protein–nucleic acid recognition. QFA is also a useful tool for dissecting individual nicking rates of a double-stranded cleavage

Differential in University Academic Performance of Students from Public and Private Secondary Schools Studying in Federal University Dutsin-Ma

There exists a serious controversy over the University performance of students attending public and private secondary schools. This study aimed to assess the differential in university academic performance of students from public and private secondary schools studying in Federal University Dutsin-Ma. The research design of this study is an ex post facto research design. The population is made up of all 300 level students of Federal University Dutsin-Ma, Katsina, Katsina State during the 2020/2021 academic session. The sample size was 183 (Male 120 & Female 63) students, simple random sampling technique was used to select sample from each programme in Science Education Department, Federal University Dutsin-Ma, Katsina State. The students’ cumulative grade point average (CGPA) at the end of the 300 level 2020/2021 academic session was collected. The data collected were analyzed using t-test inferential statistic. Results obtained showed that there is no difference between university academic performance of private and public secondary school students in Federal university Dutsin-Ma., and recommended that, parents could take their children to any school type irrespective of public or private secondary school

Adsorption of Methylene Blue using Activated Carbon Made from Watermelon Rinds

This work reports the possibility of using sustainable waste from watermelon rinds as a potential candidate for the removal of methylene blue (MB) from aqueous solution in batch mode. The adsorbent was characterized by FTIR and SEM where the FTIR analysis shows peaks at 3370 cm-1 that corresponds to –OH stretching vibration for lignin, pectin and cellulose, at 1728 cm-1 corresponds to –C=O stretching of esters, carboxylic acids, and as well peak in the range of 1350 – 1000 cm-1 which indicates stretching vibration of alcohols and carboxylic acids. The availability of hydroxyl and carboxyl groups enhance high MB uptake at lower pH. The SEM image of raw adsorbent shows no development of pores, but after carbonization the pores were developed due to escape of volatile groups during carbonization and activation process. Adsorption studies using batch mode were performed by varying adsorption parameters such as adsorbent dosage, contact time, pH of the solution and initial dye concentration. The maximum capacity of the adsorbent was found to be 0.4g dosage, pH 4, 20mg/L of initial MB concentration and 60 minutes contact time that removes maximum of 197.5 mg g-1. The results indicated that watermelon rind is a successful agricultural waste that could be utilized for sustainable removal of cationic dyes in aqueous solutions

Bobst Library. La biblioteca central de la Universidad de Nueva York

[ES] En este artículo se explica el origen de Bobst Libray, la biblioteca central de la Universidad de Nueva York. Dedicada a servir a la comunidad universitaria, esta biblioteca se ha convertido en el principal centro de investigación de la ciudad. Se describe cuáles son sus servicios y se exponen sus perspectivas de futuro

NRF2 regulates HER1 signaling pathway to modulate the sensitivity of ovarian cancer cells to lapatinib and erlotinib

NF-E2-related factor 2 (NRF2) regulates the transcription of a battery of metabolic and cytoprotective genes. NRF2 and epidermal growth factor receptors (EGFRs/HERs) are regulators of cellular proliferation and determinants of cancer initiation and progression. NRF2 and HERs confer cancers with resistance to several therapeutic agents. Nevertheless, there is limited understanding of the regulation of HER expression and activation and the link between NRF2 and HER signalling pathways. We show that NRF2 regulates both basal and inducible expression of HER1, as treatment of ovarian cancer cells (PEO1, OVCAR3, and SKOV3) with NRF2 activator tBHQ inducing HER1, while inhibition of NRF2 by siRNA knockdown or with retinoid represses HER1. Furthermore, treatment of cells with tBHQ increased total and phosphorylated NRF2, HER1, and AKT levels and compromised the cytotoxic effect of lapatinib or erlotinib. Treatment with siRNA or retinoid antagonised the effect of tBHQ on NRF2 and HER1 levels and enhanced the sensitivity of ovarian cancer cells to lapatinib or erlotinib. Pharmacological or genetic inhibition of NRF2 and/or treatment with lapatinib or erlotinib elevated cellular ROS and depleted glutathione. This extends the understanding of NRF2 and its regulation of HER family receptors and opens a strategic target for improving cancer therapy

Adherence to antihypertensive medications in patients attending public hospitals in Kano State, Nigeria

Hypertension is a chronic medical condition characterized by an elevated arterial blood pressure with increasing prevalence in developing countries including Nigeria. One of the integral elements in management of hypertension is adherence to medication and life-style modification. This study aimed to assess adherence level for anti-hypertensive medications among adult hypertensive patients attending public hospitals in Kano State, Nigeria. The study was a cross sectional prospective survey involving 600 patients from six public healthcare facilities selected by multistage sampling technique. Adherence status was assessed using Morisky medication adherence scale. Sociodemographic data and other factors that may influence adherence to hypertension medications were evaluated. Out of the 598 patients that participated in the study, only 178 (29.8%) have their BP controlled based on JNC8. Three hundred and thirty two (55.5%) out of 598 patients have good adherence, while 266 (45.5%) have poor adherence. Of the 178 patients who had good BP control, 120 (67.5%) have good adherence while 58 (32.5%) have poor adherence. BP control was significantly higher in those that adhered to antihypertensive medication compared with non-adhering patients (χ2 = 14.526; df = 1; p-value = < 0.001). Additionally, Chi-square test showed significant association between number of antihypertensives and blood pressure control. (χ2=37.556, df=3, p<0.001). The study established that 55.5% of the respondents have good adherence to their antihypertensive medication while 29.8% had their BP controlled. Adherence and number of antihypertensive medication a patient is taking were found to have significant relationship with BP control. Keywords: Medication, adherence, hypertension, antihypertensiv

Nuclear factor erythroid 2-related factor 2 modulates HER4 receptor in ovarian cancer cells to influence their sensitivity to tyrosine kinase inhibitors

Aim: Nuclear factor erythroid 2-related factor 2 (NRF2) is a key component in the cell’s response to oxidative and electrophilic stress and is a transcription factor regulating the expression of a collection of anti-oxidative and cytoprotective genes. Human epidermal growth factor receptor 4 (HER4/erbB4) regulates growth and differentiation in many cancer types. Here, NRF2 and HER4 receptor interactions were investigated in a panel of ovarian cancer cell lines.Methods: Pharmacological [tert-butylhydroquinone (tBHQ) and retinoid/rexinoid, bexarotene] and genetic [small interfering RNA (siRNA)] manipulations were used to activate or inhibit NRF2 function in the cell line panel (PE01, OVCAR3, SKOV3). Activity of the HER-targeted tyrosine kinase inhibitors, erlotinib (ERL) and lapatinib (LAP), was evaluated after NRF2 activation.Results: While tBHQ increased the levels of both phosphorylated-NRF2 (pNRF2) and HER4 in PE01, OVCAR3 and SKOV3 cells, bexatorene and NRF2-target siRNA treatment decreased pNRF2 and total HER4 levels. The tBHQ-dependent pharmacological activation of NRF2 attenuated the therapeutic effectiveness of ERL and LAP. Analyses of gene expression data from a HER4 driven reporter system and in vitro or in vivo cancer models, support NRF2 regulation of HER4 expression.Conclusions: These results support the presence of signaling interaction between the NRF2 and HER4 receptor pathways and suggest that intervention modulating this cross-talk could have anticancer therapeutic value

NRF2 regulates HER2 and HER3 signaling pathway to modulate sensitivity to targeted immunotherapies

NF-E2 related factor-2 (NRF2) is an essential transcription factor for multiple genes encoding antioxidants and detoxification enzymes. NRF2 is implicated in promoting cancer therapeutic resistance by its detoxification function and crosstalk with proproliferative pathways. However, the exact mechanism of this intricate connectivity between NRF2 and growth factor induced proliferative pathway remains elusive. Here, we have demonstrated that pharmacological activation of NRF2 by tert-butylhydroquinone (tBHQ) upregulates the HER family receptors, HER2 and HER3 expression, elevates pAKT levels, and enhances the proliferation of ovarian cancer cells. Preactivation of NRF2 also attenuates the combined growth inhibitory effects of HER2 targeting monoclonal antibodies, Pertuzumab and Trastuzumab. Further, tBHQ caused transcriptional induction of HER2 and HER3, while SiRNA-mediated knockdown of NRF2 prevented this and further caused transcriptional repression and enhanced cytotoxicity of the HER2 inhibitors. Hence, NRF2 regulates both HER2 and HER3 receptors to influence cellular responses to HER2 targeting monoclonal antibodies. This deciphered crosstalk mechanism reinforces the role of NRF2 in drug resistance and as a relevant anticancer target