Impact of APE1/Ref-1 Redox Inhibition on Pancreatic Tumor Growth

Pancreatic cancer is especially a deadly form of cancer with a survival rate less than 2%. Pancreatic cancers respond poorly to existing chemotherapeutic agents and radiation, and progress for the treatment of pancreatic cancer remains elusive. To address this unmet medical need, a better understanding of critical pathways and molecular mechanisms involved in pancreatic tumor development, progression, and resistance to traditional therapy is therefore critical. Reduction–oxidation (redox) signaling systems are emerging as important targets in pancreatic cancer. AP endonuclease1/Redox effector factor 1 (APE1/Ref-1) is upregulated in human pancreatic cancer cells and modulation of its redox activity blocks the proliferation and migration of pancreatic cancer cells and pancreatic cancer-associated endothelial cells in vitro. Modulation of APE1/Ref-1 using a specific inhibitor of APE1/Ref-1′s redox function, E3330, leads to a decrease in transcription factor activity for NFκB, AP-1, and HIF1α in vitro. This study aims to further establish the redox signaling protein APE1/Ref-1 as a molecular target in pancreatic cancer. Here, we show that inhibition of APE1/Ref-1 via E3330 results in tumor growth inhibition in cell lines and pancreatic cancer xenograft models in mice. Pharmacokinetic studies also show that E3330 attains more than10 μmol/L blood concentrations and is detectable in tumor xenografts. Through inhibition of APE1/Ref-1, the activity of NFκB, AP-1, and HIF1α that are key transcriptional regulators involved in survival, invasion, and metastasis is blocked. These data indicate that E3330, inhibitor of APE1/Ref-1, has potential in pancreatic cancer and clinical investigation of APE1/Ref-1 molecular target is warranted. Mol Cancer Ther; 10(9); 1698–708. ©2011 AACR

HEPATOPROTECTIVE ACTIVITY OF AQUEOUS EXTRACTS OF CHRYSANTHEMUM INDICUM FLOWERS ON PARACETAMOL INDUCED LIVER INJURY IN ALBINO RATS

Objective: The present investigation was evaluated that protective activity of aqueous extract of flowers of Chrysanthemum indicum studied againstparacetamol-induced hepatotoxicity in animal model.Methods: Bioactive functional groups, such as alcohol, carboxylic acid, and amines, were present in the aqueous extract of flowers of C. indicumidentified by Fourier transform infrared spectroscopy. The animals were grouped into 5 and each group has 6 animals and induced the hepatic failure.Silymarin was used as reference standard. Aqueous extract of flowers of C. indicum treated in a different dose which was compared with control groupof animals.Results: Aqueous extract of flowers of C. indicum reduced the level of aspartate transaminase (AST), alanine transaminase (ALT), serum bilirubin,protein, triglycerides, and cholesterol compared than paracetamol treated Group II animals. Histopathological studies were confirmed that reductionof necrosis and inflammation in the liver cells.Conclusion: Thus, these results revealed that the aqueous extract of flowers of C. indicum shown very significant (p<0.01) hepatoprotection againstparacetamol-induced hepatic failure in animal model by reducing AST, ALT, serum total bilirubin, protein, triglycerides, and cholesterol levels.Keywords: Hepatoprotective activity, Chrysanthemum indicum, Paracetamol

Apurinic/Apyrimidinic Endonuclease/Redox Factor-1 (APE1/Ref-1) redox function negatively regulates NRF2

Apurinic/apyrimidinic endonuclease/redox factor-1 (APE1/Ref-1) (henceforth referred to as Ref-1) is a multifunctional protein that in addition to its base excision DNA repair activity exerts redox control of multiple transcription factors, including nuclear factor κ-light chain enhancer of activated B cells (NF-κB), STAT3, activator protein-1 (AP-1), hypoxia-inducible factor-1 (HIF-1), and tumor protein 53 (p53). In recent years, Ref-1 has emerged as a promising therapeutic target in cancer, particularly in pancreatic ductal carcinoma. Although a significant amount of research has centered on Ref-1, no wide-ranging approach had been performed on the effects of Ref-1 inhibition and transcription factor activity perturbation. Starting with a broader approach, we identified a previously unsuspected effect on the nuclear factor erythroid-related factor 2 (NRF2), a critical regulator of cellular defenses against oxidative stress. Based on genetic and small molecule inhibitor-based methodologies, we demonstrated that repression of Ref-1 potently activates NRF2 and its downstream targets in a dose-dependent fashion, and that the redox, rather than the DNA repair function of Ref-1 is critical for this effect. Intriguingly, our results also indicate that this pathway does not involve reactive oxygen species. The link between Ref-1 and NRF2 appears to be present in all cells tested in vitro, noncancerous and cancerous, including patient-derived tumor samples. In particular, we focused on understanding the implications of the novel interaction between these two pathways in primary pancreatic ductal adenocarcinoma tumor cells and provide the first evidence that this mechanism has implications for overcoming the resistance against experimental drugs targeting Ref-1 activity, with clear translational implications

Bio- Matric Intelligent ATM System

Now a day, peoples have multiple bank accounts so money transactions play a vital role in the nature of trade. Today, ATMs and Credit cards are used for this purpose, the authentication of these transactions are unsecure. To overcome this shortcoming of money transactions, we proposes the idea of using fingerprints of customers as login multiple banking password in place of traditional pin number. Here, if the fingerprint is recognized, then it display the multiple banking screen. Then we can choose the bank which we need for transaction. The remaining feature are same as i.e., a reference fingerprint of the nominee or a close family member of the customer can be used if the customer is not available in case of emergencies. This proposed business model helps the society, mainly the rural people, by enhancing the security using Fingerprint recognition in Digital image processing. As the fingerprint of every person is unique and unchangeable, this biometric feature is used over the others

A SWOT Analysis Of The Use Of Social Media Networking Sites In Medical Colleges In Ahmedabad City During The Covid-19 Pandemic Situation: In Reference To The Library

This survey is concerned with trying to measure the SWOT analysis of the role of libraries in the use of social media networking sites on health educational performance during the Covid-19 pandemic situation in medical colleges providing health education in Ahmedabad, for practical reasons, the SWOT analysis was conducted to collect data on that use. To conduct a SWOT analysis to find out the challenges regarding the use of social media networking sites in the context of libraries of social educational networking sites of medical academic libraries using Google form structured questionnaire and personal interview. Keeping in mind the main approach of this case study, a SWOT analysis of the use of social media networking sites on the academic performance of library users of colleges of health sciences during the Covid-19 pandemic situation was conducted. There will be a strategic plan to increase the use of social media and its benefits by evaluating the results of the SWOT analysis. The authors present the results of the study in the form of practical recommendations for short-term and long-term implementation. Future research will provide the most beneficial for libraries on social media and related strategies and may include follow-up studies in academic libraries using the SWOT Framework tool method. In addition, comparing the results of this study with similar studies in other libraries may form a model for other libraries that may attempt to increase their capacity and knowledge through the effective use of social media. The present study attempts to plan a strategy for libraries through SWOT analysis to establish a unique distinction that highlights their strengths and challenges

Monitoring of Soil Parameters and Controlling of Soil Moisture

The proposed system combines advanced sensor technologies with sophisticated machine learning techniques, such Artificial Neural Networks (ANN) and Support Vector Machines (SVM), to provide a reliable real-time monitoring solution for important soil parameters. The system gathers and analyses enormous volumes of data on soil moisture, nutrient levels, and other important factors using cutting-edge sensors and remote sensing capabilities. Complex, non-linear interactions within the data are described by SVM, whereas complex patterns and dependencies are captured by ANN. As a result, projections of soil parameters are more accurate and reliable. This integrated system presents a fresh approach to sustainable agriculture and environmental management by streamlining the supply of accurate insights into soil health and providing farmers and environmentalists with timely information for well-informed decision-making

EFFECT OF COENZYME Q10 ALONE AND ITS COMBINATION WITH ROSUVASTATIN ON STREPTOZOTOCIN-NICOTINAMIDE INDUCED DIABETIC NEUROPATHY IN RATS

Objectives: This study was aimed to investigate the effect of coenzyme Q10 and its combination with rosuvastatin on STZ-nicotinamide induced diabetic neuropathy.Methods: Diabetic neuropathy in rats were induced with streptozotocin-nicotinamide. The diabetic rats were treated with coenzyme Q10 or rosuvastatin or their combination. Various parameters like muscular grip strength, paw withdrawal response, tail flick response and markers of oxidative stress such as malondialdehyde (MDA) level, superoxide dismutase (SOD) and reduced glutathione (GSH) in the sciatic nerve were measured. All treated animal was subjected to histopathological changes of sciatica nerve.Results: In diabetic control group, muscular grip strength was significantly decreased and increased paw withdrawal response, tail flick response as compared to normal control rats. In addition, STZ-nicotinamide caused nerve cell damage with a higher MDA level, depletion of SOD and GSH level along with marked degeneration of the nerve cell. The treatment of diabetic rats with coenzyme Q10 or rosuvastatin or their combination ameliorate STZ-nicotinamide induced nerve damage due to improvement in the muscular grip strength, paw withdrawal response, tail flick response, reduction in oxidative stress along with histopathological changes.Conclusion: This finding suggests that treatment with coenzyme Q10 or rosuvastatin showed significant neuroprotective effect against STZ-nicotinamide induced diabetic neuropathy. However, concomitant administration of both showed a better neuroprotective effect than coenzyme Q10 or rosuvastatin alone treatment.Â

Exploring the potential of amine-functionalized mesoporous silica nanocarrier to conjugate guide RNA for gene delivery

Sugarcane is a key cash crop, with nations such as Brazil, India, and China being the leading producers. The trade of sugar and related products contributes significantly to these economies. Sugarcane is the primary feedstock for producing sugar and ethanol in the sugarcane processing industry, yielding sugarcane bagasse fly ash (SBFA) as a byproduct. This byproduct comes primarily from the combustion of bagasse (the fibrous residue after juice extraction) and contains silica (SiO2), alumina (Al2O3), and other minerals. The use of sugarcane waste materials reduces the need for new raw resources and lowers the environmental impact. Turning waste into valuable nanoparticles also helps manage waste better and reduces the amount that is burnt or dumped in landfills. The fly ash was treated with an alkaline solution (e.g., sodium hydroxide) to extract silica. This process helps dissolve other minerals, leaving a silica-rich residue. After extraction, the silica was purified through acid washing to remove impurities. Mesoporous silica nanoparticles were created using the sol-gel method and 3-aminopropyltriethoxysilane (APTES) was added to them functionally to conjugate sgRNA. The synthesized mesoporous silica nanoparticles were characterized for size and shape, functional groups, and crystallinity using various instruments such as Transmission Electron Microscope (TEM), Fourier Transform Infrared Spectroscopy (FT-IR), Dynamic Light Scattering, Brunauer-Emmett-Teller (BET) Analyzer, and X-Ray Diffractometer (XRD), respectively. Furthermore, synthesized mesoporous silica nanoparticles were bioconjugated with sgRNA of OsEPF1, a gene negative regulation of stomatal development, which in turn, helps reduce yield loss in rice due to drought and heat stress