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

Clinical profile of Dengue patients in a rural tertiary care centre of coastal Kerala

Background: Dengue epidemic is a major health problem in India. According to the directorate of National Vector Borne Disease Control Programme (NVBDCP) over 18,700 cases of dengue have been reported in India in 2017.Kerala has reported the highest number of dengue related deaths in the country. The aim of the present study is to find out the clinical profile of patients admitted with dengue fever during the epidemic in 2017 in a rural tertiary care centre in coastal Kerala.Methods: 341 patients who were admitted in the medicine department of a rural tertiary care centre in Kerala with Dengue were included in the study. W.H.O case definitions were used for the diagnosis. Complete blood counts, RBS, serum creatinine and liver function tests and E.C.G were carried out in all patients. Chest X ray, Echocardiogram, ultrasonogram, MRI and CSF study were done when indicated.Results: Males predominated. 317 were diagnosed as dengue fever, 12 as dengue hemorrhagic fever and 12 had dengue shock syndrome. Only four patients succumbed to death. Aminotransferases were elevated in 74.4%. In all cases AST was more than ALT. Head ache and myalgia were the common symptoms at the time of presentation. 72 patients had abnormal ECG, but all had normal ECG at the time of discharge, indicating a transient change during the episode.Conclusions: Careful monitoring of clinical and biochemical parameters is necessary during dengue epidemics. Atypical manifestations of dengue should also be considered in the differential diagnosis of various diseases in different organ systems

Glimpses of Semantic Web Technologies and Related Case Studies

Semantic web is a platform of new evolution in rapidly developing World Wide Web. Semantic web refers to extracting knowledge from large amount of data. The purpose of this paper is to give a first-hand information and description for the semantic web technology. Although several research works have been carried out in the high semantic web technology, the semantic web is yet vastly unexplored. A semantic web technological innovation is rapidly changing traditional methods of searching data and how search engines work. Few prominent semantic web case studies are presented. One of the popular applications of XML RDF is Really Simple Syndication (RSS) feed which is discussed in detail

New World Health Organization labour care guide in reducing intrapartum caesarean section rates at tertiary care hospital-Hassan institute of medical sciences, Hassan

Background: The Aim of this study was to assess whether labour monitoring using new WHO LCG will result in reducing intra partum caesarean sections. Methods: A analytical study was conducted from the month of September 2022 to January 2023 among 1735 pregnant women admitted at Hassan institute of Medical Sciences, in active phase of labour (5cm cervical dilatation and above) after obtaining informed consent. Results: In the present study, the New WHO Labour Care guide was plotted for 1735 pregnant women among which 1668 (96%) of the total patients had vaginal delivery, while 67 (4%) of the patients underwent Cesarean Section. Among the patients who underwent Cesarean Section it was found that1082 (94%) of the total Cesarean Sections were in latent phase of labour before plotting of the new WHO Labour care guide whereas only about 67 (6%) of Cesarean Section were conducted in active phase of labour. Among the patients who underwent LSCS in the active phase of labour majority were due to fetal distress 29(43%), 21(31%) due to Cephalopelvic disproportion, 13(20%) due to Non progression of labour and about 4(6%) due to Deep Transverse Arrest Conclusions: Majority of the caesarean sections were conducted in the latent phase of labour. The New WHO Labour Care guide has reduced the occurrence of intrapartum caesarean sections in the active phase of labour. However the overall rate of caesarean section must be controlled by reducing the number of Cesarean Sections conducted in latent phase of labour, that is before plotting the New WHO labour care guide

Concrete Roughness Characterization using Laser Profilometry for Fiber-Reinforced Polymer Sheet Application

The failure of a reinforced concrete member strengthened with fiberreinforced polymer (FRP) laminates may be caused by crushing of concrete, rupture of FRP laminates, or delamination of the FRP sheet. Therefore, the effectiveness and failure mode of FRP sheets applied to beams and columns is related to the degree of adhesion of the epoxy to the concrete surface. When a peeling or delamination failure can be avoided, a more effective engagement of the FRP sheet occurs, which results in more efficient use of the material. One of the principal factors affecting the bond behavior between the concrete and epoxy is the roughness of the concrete substrate. To prepare the bond surface, sand blasting or grinding is typically used to roughen the concrete. To that end, a portable device has been developed to measure the roughness of concrete surfaces. This device can be used as a quality-control tool to characterize surface roughness and identify when an adequate surface preparation has been attained. The method uses laser striping and image analysis. The method was tested on six slabs of sandblasted concrete, which were sandblasted to varying degrees of surface roughness, and a series of nine plastic model concrete surface profiles

Coronary Artery Calcification (CAC) and Post-Trial Cardiovascular Events and Mortality Within the Women's Health Initiative (WHI) Estrogen-Alone Trial.

BackgroundAmong women aged 50 to 59 years at baseline in the Women's Health Initiative (WHI) Estrogen-Alone (E-Alone) trial, randomization to conjugated equine estrogen-alone versus placebo was associated with lower risk of myocardial infarction and mortality, and, in an ancillary study, the WHI-CACS (WHI Coronary Artery Calcification Study) with lower CAC, measured by cardiac computed tomography ≈8.7 years after baseline randomization. We hypothesized that higher CAC would be related to post-trial coronary heart disease (CHD), cardiovascular disease (CVD), and total mortality, independent of baseline randomization or risk factors.Methods and resultsWHI-CACS participants (n=1020) were followed ≈8 years from computed tomography scan in 2005 (mean age=64.4) through 2013 for incident CHD (myocardial infarction and fatal CHD, n=17), CVD (n=69), and total mortality (n=55). Incident CHD and CVD analyses excluded women with CVD before scan (n=89). Women with CAC=0 (n=54%) had very low age-adjusted rates/1000 person-years of CHD (0.91), CVD (5.56), and mortality (3.45). In comparison, rates were ≈2-fold higher for women with any CAC (>0). Associations were not modified by baseline randomization to conjugated equine estrogen-alone versus placebo. Adjusted for baseline randomization and risk factors, the hazard ratio (95% confidence interval) for CAC >100 (19%) was 4.06 (2.11, 7.80) for CVD and 2.70 (1.26, 5.79) for mortality.ConclusionsAmong a subset of postmenopausal women aged 50 to 59 years at baseline in the WHI E-Alone Trial, CAC at mean age of 64 years was strongly related to incident CHD, CVD, and to total mortality over ≈8 years, independent of baseline randomization to conjugated equine estrogen-alone versus placebo or CVD risk factors.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00000611

Temperature influences of the interfacial layer in MOS (Pt/TiO2/Si) structures

In this paper present I-V and C-V electrical characteristics of MOS (Pt/TiO2/Si) were reported. In the I-V characteristics the various electric parameter estimated such as the ideality factor (n), barrier height (FB), leakage current (Ic) and saturation current (Io) were estimated and further analyzed with Cheung functions. These electrical parameters were observed to be varying with heat treatment. The C-V characteristics, flat band voltage (VFB), interface trap density (Dit), effective charge density (Neff) and oxide trapped charge (Qot) were estimated and analyzed. The variation of these values with annealing temperature was correlated with restructuring and rearrangement of TiO2/SiO2 atoms at the metal/silicon interface. The hysteresis loop in counter clock wise voltage between -1 V to 1 V at 1 MHz frequency, after 600 °C heat treatment show the strong accumulation region, this may be due to the reduced interface trapped charge and dangling bon

Endothelial Nitric Oxide Synthase Gene Polymorphism (G894T) and Diabetes Mellitus (Type II) among South Indians

The objective of the study is to find out whether the endothelial nitric oxide synthase (eNOS) G894T single-nucleotide polymorphism is associated with type 2 diabetes mellitus in South Indian (Tamil) population. A total number of 260 subjects comprising 100 type 2 diabetic mellitus patients and 160 healthy individuals with no documented history of diabetes were included for the study. DNA was isolated, and eNOS G894T genotyping was performed using the polymerase chain reaction followed by restriction enzyme analysis using Ban II. The genotype distribution in patients and controls were compatible with the Hardy-Weinberg expectations (P > 0.05). Odds ratio indicates that the occurrence of mutant genotype (GT/TT) was 7.2 times (95% CI = 4.09–12.71) more frequent in the cases than in controls. Thus, the present study demonstrates that there is an association of endothelial nitric oxide synthase gene (G894T) polymorphism with diabetes mellitus among South Indians

A STUDY ON EFFECTIVENESS OF THE RURAL DEVELOPMENT PROJECT PROVIDING RURAL EMPLOYMENT, MANDYA

The Shri Kshethra Dharmasthala Rural Development Project (SKDRDP) has been a cornerstone of rural development efforts in India aimed at improving the socio-economic conditions of rural communities. This study explores the effectiveness of the SKDRDP in providing rural employment opportunities and the impact it has had on the livelihoods of the beneficiaries. The study indicates that the SKDRDP has played a pivotal role in providing rural employment opportunities to the local population. Through various initiatives, including skill development programs, micro-enterprise support, and infrastructure development projects, the project has significantly increased rural employment. Beneficiaries reported improved income levels and quality of result of their involvement in SKDRDP activities. The SKDRDP has proven to be effective in providing rural employment opportunities and enhancing the livelihoods of the rural population. It acts as a model for comprehensive rural development, emphasizing skill-building, self-reliance, and community empowerment. The study's conclusions underscore the importance of continued support for such initiatives to further rural development and reduce poverty in India

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