p53 modeling as a route to mesothelioma patients stratification and novel therapeutic identification

Background Malignant pleural mesothelioma (MPM) is an orphan disease that is difficult to treat using traditional chemotherapy, an approach which has been effective in other types of cancer. Most chemotherapeutics cause DNA damage leading to cell death. Recent discoveries have highlighted a potential role for the p53 tumor suppressor in this disease. Given the pivotal role of p53 in the DNA damage response, here we investigated the predictive power of the p53 interactome model for MPM patients’ stratification. Methods We used bioinformatics approaches including omics type analysis of data from MPM cells and from MPM patients in order to predict which pathways are crucial for patients’ survival. Analysis of the PKT206 model of the p53 network was validated by microarrays from the Mero-14 MPM cell line and RNA-seq data from 71 MPM patients, whilst statistical analysis was used to identify the deregulated pathways and predict therapeutic schemes by linking the affected pathway with the patients’ clinical state. Results In silico simulations demonstrated successful predictions ranging from 52 to 85% depending on the drug, algorithm or sample used for validation. Clinical outcomes of individual patients stratified in three groups and simulation comparisons identified 30 genes that correlated with survival. In patients carrying wild-type p53 either treated or not treated with chemotherapy, FEN1 and MMP2 exhibited the highest inverse correlation, whereas in untreated patients bearing mutated p53, SIAH1 negatively correlated with survival. Numerous repositioned and experimental drugs targeting FEN1 and MMP2 were identified and selected drugs tested. Epinephrine and myricetin, which target FEN1, have shown cytotoxic effect on Mero-14 cells whereas marimastat and batimastat, which target MMP2 demonstrated a modest but significant inhibitory effect on MPM cell migration. Finally, 8 genes displayed correlation with disease stage, which may have diagnostic implications. Conclusions Clinical decisions related to MPM personalized therapy based on individual patients’ genetic profile and previous chemotherapeutic treatment could be reached using computational tools and the predictions reported in this study upon further testing in animal models

Characterization of MTAP gene expression in breast cancer patients and cell lines

MTAP is a ubiquitously expressed gene important for adenine and methionine salvage. The gene is located at 9p21, a chromosome region often deleted in breast carcinomas, similar to CDKN2A, a recognized tumor suppressor gene. Several research groups have shown that MTAP acts as a tumor suppressor, and some therapeutic approaches were proposed based on a tumors\ub4 MTAP status. We analyzed MTAP and CDKN2A gene (RT-qPCR) and protein (western-blotting) expression in seven breast cancer cell lines and evaluated their promoter methylation patterns to better characterize the contribution of these genes to breast cancer. Cytotoxicity assays with inhibitors of de novo adenine synthesis (5-FU, AZA and MTX) after MTAP gene knockdown showed an increased sensitivity, mainly to 5-FU. MTAP expression was also evaluated in two groups of samples from breast cancer patients, fresh tumors and paired normal breast tissue, and from formalin-fixed paraffin embedded (FFPE) core breast cancer samples diagnosed as Luminal-A tumors and triple negative breast tumors (TNBC). The difference of MTAP expression between fresh tumors and normal tissues was not statistically significant. However, MTAP expression was significantly higher in Luminal-A breast tumors than in TNBC, suggesting the lack of expression in more aggressive breast tumors and the possibility of using the new approaches based on MTAP status in TNB

Transcriptional analysis of Rhazya stricta in response to jasmonic acid

Background: Jasmonic acid (JA) is a signal transducer molecule that plays an important role in plant development and stress response; it can also efficiently stimulate secondary metabolism in plant cells. Results: RNA-Seq technology was applied to identify differentially expressed genes and study the time course of gene expression in Rhazya stricta in response to JA. Of more than 288 million total reads, approximately 27% were mapped to genes in the reference genome. Genes involved during the secondary metabolite pathways were up- or downregulated when treated with JA in R. stricta. Functional annotation and pathway analysis of all up- and downregulated genes identified many biological processes and molecular functions. Jasmonic acid biosynthetic, cell wall organization, and chlorophyll metabolic processes were upregulated at days 2, 6, and 12, respectively. Similarly, the molecular functions of calcium-transporting ATPase activity, ADP binding, and protein kinase activity were also upregulated at days 2, 6, and 12, respectively. Time-dependent transcriptional gene expression analysis showed that JA can induce signaling in the phenylpropanoid and aromatic acid pathways. These pathways are responsible for the production of secondary metabolites, which are essential for the development and environmental defense mechanism of R. stricta during stress conditions. Conclusions: Our results suggested that genes involved in flavonoid biosynthesis and aromatic acid synthesis pathways were upregulated during JA stress. However, monoterpenoid indole alkaloid (MIA) was unaffected by JA treatment. Hence, we can postulate that JA plays an important role in R. stricta during plant development and environmental stress conditions. How to cite: Hajrah, NH, Rabah SO, Alghamdi MK, et al. Transcriptional analysis of Rhazya stricta in response to jasmonic acid. Electron J Biotechnol 2021;50. https://doi.org/10.1016/j.ejbt.2021.01.00

Green Synthesized Cu2O-Cu(OH)2@Cu Nanocomposites with Fenton-like Catalytic Properties for the Degradation of Cationic and Anionic Dyes

In this work, we introduce an environmental and sustainable approach to grow free standing heterogeneous Cu2O-Cu(OH)2 nanocomposites on a Cu mesh using spinach leaf extract and glycerol. Structural characterizations for samples annealed at 200 °C revealed that there is more Cu(OH)2 than Cu2O on the mesh surface. The photocatalytic activity of the green synthesized catalyst was studied for degradation of a cationic dye methylene blue (MB), an anionic dye methyl orange (MO) and a mixture of both dyes. The effect of changing the dye’s initial pH value on the photodegradation process was explored. After 40 min of irradiation under sunlight, with a maximum intensity of 5 mW/cm2, a basic MB dye (pH-11) showed about 80% color removal with an average kinetic rate of 94.5 m·min−1. In contrast, 93% of the acidified MO dye (pH-2) was degraded with an average kinetic rate of 126.5 m·min−1. Moreover, the versatility of the Cu2O-Cu(OH)2@Cu mesh was evaluated using a remarkable selective separability for a mixture of MB and MO at pH = 2, in the dark and under normal sunlight. Such promising outcomes indicate the potential of our green composites to degrade dyes as both photocatalysts under daylight and as Fenton-like catalysts in darkness

Green Synthesized Cu₂O-Cu(OH)₂@Cu Nanocomposites with Fenton-like Catalytic Properties for the Degradation of Cationic and Anionic Dyes

In this work, we introduce an environmental and sustainable approach to grow free standing heterogeneous Cu2O-Cu(OH)2 nanocomposites on a Cu mesh using spinach leaf extract and glycerol. Structural characterizations for samples annealed at 200 °C revealed that there is more Cu(OH)2 than Cu2O on the mesh surface. The photocatalytic activity of the green synthesized catalyst was studied for degradation of a cationic dye methylene blue (MB), an anionic dye methyl orange (MO) and a mixture of both dyes. The effect of changing the dye’s initial pH value on the photodegradation process was explored. After 40 min of irradiation under sunlight, with a maximum intensity of 5 mW/cm2, a basic MB dye (pH-11) showed about 80% color removal with an average kinetic rate of 94.5 m·min−1. In contrast, 93% of the acidified MO dye (pH-2) was degraded with an average kinetic rate of 126.5 m·min−1. Moreover, the versatility of the Cu2O-Cu(OH)2@Cu mesh was evaluated using a remarkable selective separability for a mixture of MB and MO at pH = 2, in the dark and under normal sunlight. Such promising outcomes indicate the potential of our green composites to degrade dyes as both photocatalysts under daylight and as Fenton-like catalysts in darkness

Structural and Electrochemical Properties of Physically and Chemically Activated Carbon Nanoparticles for Supercapacitors

The demand for supercapacitors has been high during the integration of renewable energy devices into the electrical grid. Although activated carbon materials have been widely utilized as supercapacitor electrodes, the need for economic and sustainable processes to extract and activate carbon nanomaterials is still crucial. In this work, the biomass waste of date palm fronds is converted to a hierarchical porous nanostructure of activated carbon using simple ball-milling and sonication methods. Chemical and physical activation agents of NaOH and CO2, receptively, were applied on two samples separately. Compared with the specific surface area of 603.5 m2/g for the CO2-activated carbon, the NaOH-activated carbon shows a higher specific surface area of 1011 m2/g with a finer nanostructure. Their structural and electrochemical properties are functionalized to enhance electrode–electrolyte contact, ion diffusion, charge accumulation, and redox reactions. Consequently, when used as electrodes in an H2SO4 electrolyte for supercapacitors, the NaOH-activated carbon exhibits an almost two-fold higher specific capacitance (125.9 vs. 56.8 F/g) than that of the CO2-activated carbon at the same current density of 1 A/g. Moreover, using carbon cloth as a current collector provides mechanical flexibility to our electrodes. Our practical approach produces cost-effective, eco-friendly, and flexible activated carbon electrodes with a hierarchical porous nanostructure for supercapacitor applications

Printed Electrodes Based on Vanadium Dioxide and Gold Nanoparticles for Asymmetric Supercapacitors

Printed energy storage components attracted attention for being incorporated into bendable electronics. In this research, a homogeneous and stable ink based on vanadium dioxide (VO2) is hydrothermally synthesized with a non-toxic solvent. The structural and morphological properties of the synthesized material are determined to be well-crystalline monoclinic-phase nanoparticles. The charge storage mechanisms and evaluations are specified for VO2 electrodes, gold (Au) electrodes, and VO2/Au electrodes using cyclic voltammetry, galvanostatic charge–discharge, and electrochemical impedance spectroscopy. The VO2 electrode shows an electrical double layer and a redox reaction in the positive and negative voltage ranges with a slightly higher areal capacitance of 9 mF cm−2. The VO2/Au electrode exhibits an areal capacitance of 16 mF cm−2, which is double that of the VO2 electrode. Due to the excellent electrical conductivity of gold, the areal capacitance 18 mF cm−2 of the Au electrode is the highest among them. Based on that, Au positive electrodes and VO2 negative electrodes are used to build an asymmetric supercapacitor. The device delivers an areal energy density of 0.45 μWh cm−2 at an areal power density of 70 μW cm−2 at 1.4 V in the aqueous electrolyte of potassium hydroxide. We provide a promising electrode candidate for cost-effective, lightweight, environmentally friendly printed supercapacitors