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

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

A REVIEW ON GREEN-SYNTHESIS OF CERIUM OXIDE NANOPARTICLES: FOCUS ON CENTRAL NERVOUS SYSTEM DISORDERS

Green Synthesized Cerium oxide nanoparticles (CeO2NPs) have sparked a lot of interest in numerous disciplines of science and Technology during the past decade. A wide range of biological resources has been employed in synthesizing CeO2NPs, including plants, microorganisms, and other biological products. Biosynthesis procedures, current knowledge, and prospects in the synthesis of Green synthesis of CeO2NPs are also discussed. Neurodegenerative diseases, such as aging, trauma, Alzheimer's and Parkinson's, and other neurological problems, are linked to higher oxidative stress and superoxide radicals generation. Cerium oxide nanoparticles' antioxidant properties suggest that they may be useful in the treatment of CNS diseases. The biological antioxidant benefits of cerium oxide nanoparticles on extending cell and organism lifespan, preventing a free radical attack, and preventing trauma-induced neurological damage are discussed in this section. CeO2NPs, an aspect of nanotechnology, would emerge as a novel drug delivery carrier through therapeutic strategies. In several diseases oxidative stress and inflammation. CeO2NPs exhibited a remarkable ability to switch between+3 and+4 oxidation states making this an efficient therapeutic option and an effective drug delivery agent. Further Reactive oxygen and nitrogen species. The overall goal of this study is to provide reasonable insight into CeO2NPs as new therapeutic agents and to solve the challenges, of safely and effectively employing these CeO2NPs for efficient management of Central Nervous System diseases

ANTIOXIDANT AND ANTI-PROLIFERATIVE EFFECTS OF AN ETHYL ACETATE FRACTION OF THE HYDRO-ETHANOLIC EXTRACT OF SYNEDRELLA NODIFLORA (L) GAERTN

Objective: Synedrella nodiflora is traditionally used in the treatment of several ailments. Pharmacologically, this plant has anticonvulsant, sedative, anti-nociceptive and anti-proliferative effects. This study further investigated S. nodiflora for its antioxidant and in vitro inhibition of cancerous cell lines. Methods: Phytochemical assays, and the DPPH radical scavenging method were employed in preliminary screening for antioxidant activities of the crude hydro-ethanolic extract (SNE) and resulting fractions. The potent ethyl acetate fraction (EAF), was further investigated for total phenol and flavonoid contents, reducing power, lipid peroxidation potential, and cytotoxic effects on human breast cancer (MCF-7), leukemic (Jurkat), and normal liver (Chang’s liver) cell lines. Results: The extract contained phenols, flavonoids, tannins, glycosides, sterols, terpenoids, and alkaloids. It scavenged for DPPH with an IC50 of 114 µg/ml, whereas that of EAF was 8.9 µg/ml. EAF prevented peroxidation of egg lecithin at an IC50 of 24.01±0.08 µg/ml. These IC50s are four and three times lower than the reference standards. EAF produced anti-proliferative effects against MCF-7, and Jurkat cell lines with IC50s of 205.2 and 170.9 µg/ml, respectively. EAF had a high IC50 of 252.2 µg/ml against Chang’s liver cells. At 0.1 mg/ml EAF had similar total flavonoid content to SNE, but a significantly higher total phenol content. Conclusion: The ethyl acetate fraction of S. nodiflora, exhibited the most potent antioxidant activity. It inhibited the proliferation of breast and leukemic cancer cell lines, whiles having weak cytotoxic effect on normal liver cells. These can be explored for further drug development

The potential of siRNA based drug delivery in respiratory disorders: recent advances and progress

© 2019 Wiley Periodicals, Inc. Lung diseases are the leading cause of mortality worldwide. The currently available therapies are not sufficient, leading to the urgent need for new therapies with sustained anti-inflammatory effects. Small/short or silencing interfering RNA (siRNA) has potential therapeutic implications through post-transcriptional downregulation of the target gene expression. siRNA is essential in gene regulation, so is more favorable over other gene therapies due to its small size, high specificity, potency, and no or low immune response. In chronic respiratory diseases, local and targeted delivery of siRNA is achieved via inhalation. The effectual delivery can be attained by the generation of aerosols via inhalers and nebulizers, which overcomes anatomical barriers, alveolar macrophage clearance and mucociliary clearance. In this review, we discuss the different siRNA nanocarrier systems for chronic respiratory diseases, for safe and effective delivery. siRNA mediated pro-inflammatory gene or miRNA targeting approach can be a useful approach in combating chronic respiratory inflammatory conditions and thus providing sustained drug delivery, reduced therapeutic dose, and improved patient compliance. This review will be of high relevance to the formulation, biological and translational scientists working in the area of respiratory diseases

Phase 2 study of vismodegib, a hedgehog inhibitor, combined with gemcitabine and nab-paclitaxel in patients with untreated metastatic pancreatic adenocarcinoma

Background: The Hedgehog (Hh) signalling pathway is overexpressed in pancreatic ductal adenocarcinoma (PDA). Preclinical studies have shown that Hh inhibitors reduce pancreatic cancer stem cells (pCSC), stroma and Hh signalling. Methods: Patients with previously untreated metastatic PDA were treated with gemcitabine and nab-paclitaxel. Vismodegib was added starting on the second cycle. The primary endpoint was progression-free survival (PFS) as compared with historical controls. Tumour biopsies to assess pCSC, stroma and Hh signalling were obtained before treatment and after cycle 1 (gemcitabine and nab-paclitaxel) or after cycle 2 (gemcitabine and nab-paclitaxel plus vismodegib). Results: Seventy-one patients were enrolled. Median PFS and overall survival (OS) were 5.42 months (95% confidence interval [CI]: 4.37–6.97) and 9.79 months (95% CI: 7.85–10.97), respectively. Of the 67 patients evaluable for response, 27 (40%) had a response: 26 (38.8%) partial responses and 1 complete response. In the tumour samples, there were no significant changes in ALDH + pCSC following treatment. Conclusions: Adding vismodegib to chemotherapy did not improve efficacy as compared with historical rates observed with chemotherapy alone in patients with newly diagnosed metastatic pancreatic cancer. This study does not support the further evaluation of Hh inhibitors in this patient population. Trial registration: ClinicalTrials.gov Identifier: NCT01088815