Electron beam irradiation developed cinnamon oil- (polyvinyl alcohol/gum tragacanth)/graphene oxide dressing hydrogels: Antimicrobial and healing assessments.

This study aimed to develop hydrogel dressings for wound healing composed of gum tragacanth (TG) and polyvinyl alcohol (PVA) loaded with Graphene oxide (GO) and Cinnamon oil (CMO) using electron beam irradiation. The impact of the preparation conditions and the incorporation of GO and CMO on the characteristic properties of the prepared CMO-(PVA/TG)-GO wound dressings was evaluated. The healing-related characteristics were assessed, including fluid absorption and retention, water vapor transmission rate (WVTR), hemolytic assay, and antimicrobial potential. Wound healing efficacy was evaluated using a scratch wound healing assay. FTIR analysis verified the chemical structure, whereas scanning electron microscopy demonstrated an appropriate porosity structure necessary for optimal wound healing. The gel content increases with the initial total polymer concentration and the irradiation dose increases. Higher GO and CMO content improve the gel content and decreases swelling. WVTR decreases with the rise in CMO content. In vitro, cytotoxicity and hemolytic potency assessments confirmed their biocompatibility. The incorporation of GO and CMO enhances the antimicrobial activity and wound-healing capability. Based on the above findings, CMO-(PVA/TG)-GO dressings show promising potential as candidates for wound care.

Silver decorated nickel oxide nanoflake/carbon nanotube nanocomposite as an efficient electrocatalyst for ethanol oxidation.

The higher energy density and lesser toxicity of ethanol compared to methanol make it an ideal combustible renewable energy source in fuel cells. Finding suitable cost-effective electrocatalysts that can oxidize ethanol in ethanol-based fuel cells is a major challenge. With their high catalytic activity and stability in alkaline media, transition metal-based catalysts are ideal candidates for alkaline direct ethanol fuel cells. Nickel-based nanomaterials and composites exhibit high electrocatalytic activity, which makes them predominant candidates for the electrochemical oxidation of ethanol. In this study, the electrocatalytic activity of a nickel oxide flower-like structure was explored. Forming a nanocomposite of NiO in combination with carbon nanotubes (CNTs), NiO/CNTs, as a substrate led to an increase in the stability of the electrocatalyst in alkaline media. Furthermore, the electrocatalytic activity of the NiO/CNT nanocomposite was greatly enhanced by decorating the surface with different ratios of silver (Ag). Ag/NiO/CNT composites with different Ag ratios, namely, 25% and 50% by weight, were studied. The Ag 25%/NiO/CNT weight ratio showed a maximum ethanol conversion. At an ethanol concentration of 300 mM, the electrochemical oxidation current density was found to be 57.1 ± 0.2 mA cm-2 for the 25% by weight Ag ratio, with a five-fold increase in the current density (compared to NiO/CNTs (10 ± 0.34 mA cm-2)). Furthermore, the nanocomposite synthesized here (Ag 25%/NiO/CNTs) showed a significantly higher energy conversion (current per ethanol concentration) rate compared to other reported NiO-based catalysts. These results open real opportunities for designing high efficiency ethanol fuel cell catalysts.

Anti-proliferation evaluation of new derivatives of indole-6-carboxylate ester as receptor tyrosine kinase inhibitors.

Aim: The main goal was to create two new groups of indole derivatives, hydrazine-1-carbothioamide (4a and 4b) and oxadiazole (5, and 6a-e) that target EGFR (4a, 4b, 5) or VEGFR-2 (6a-e). Materials & methods: The new derivatives were characterized using various spectroscopic techniques. Docking studies were used to investigate the binding patterns to EGFR/VEGFR-2, and the anti-proliferative properties were tested in vitro. Results: Compounds 4a (targeting EGFR) and 6c (targeting VEGFR-2) were the most effective cytotoxic agents, arresting cancer cells in the G2/M phase and inducing the extrinsic apoptosis pathway. Conclusion: The results of this study show that compounds 4a and 6c are promising cytotoxic compounds that inhibit the tyrosine kinase activity of EGFR and VEGFR-2, respectively.

[Box: see text].

Novel 1,3,4-oxadiazole derivatives of naproxen targeting EGFR: Synthesis, molecular docking studies, and cytotoxic evaluation.

The close association between inflammation and cancer inspired the synthesis of a series of 1,3,4-oxadiazole derivatives (compounds H4-A-F) of 6-methoxynaphtalene. The chemical structures of the new compounds were validated utilizing Fourier-transform infrared, proton nuclear magnetic resonance, and carbon-13 nuclear magnetic resonance spectroscopic techniques and CHN analysis. Computer-aided drug design methods were used to predict the compounds biological target, ADMET properties, toxicity, and to evaluate the molecular similarities between the design compounds and erlotinib, a standard epidermal growth factor receptor (EGFR) inhibitor. The antiproliferative effects of the new compounds were evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, cell cycle analysis, apoptosis detection by microscopy, quantitative reverse transcription-polymerase chain reaction, and immunoblotting, and EGFR enzyme inhibition assay. In silico analysis of the new oxadiazole derivatives indicated that these compounds target EGFR, and that compounds H4-A, H4-B, H4-C, and H4-E show similar molecular properties to erlotinib. Additionally, the results indicated that none of the synthesized compounds are carcinogenic, and that compounds H4-A, H4-C, and H4-F are nontoxic. Compound H4-A showed the best-fit score against EGFR pharmacophore model, however, the in vitro studies indicated that compound H4-C was the most cytotoxic. Compound H4-C caused cytotoxicity in HCT-116 colorectal cancer cells by inducing both apoptosis and necrosis. Furthermore, compounds H4-D, H4-C, and H4-B had potent inhibitory effect on EGFR tyrosine kinase that was comparable to erlotinib. The findings of this inquiry offer a basis for further investigation into the differences between the synthesized compounds and erlotinib. However, additional testing will be needed to assess all of these differences and to identify the most promising compound for further research.

Genomic prediction and genome-wide association study using combined genotypic data from different genotyping systems: application to apple fruit quality traits.

With advances in next-generation sequencing technologies, various marker genotyping systems have been developed for genomics-based approaches such as genomic selection (GS) and genome-wide association study (GWAS). As new genotyping platforms are developed, data from different genotyping platforms must be combined. However, the potential use of combined data for GS and GWAS has not yet been clarified. In this study, the accuracy of genomic prediction (GP) and the detection power of GWAS increased for most fruit quality traits of apples when using combined data from different genotyping systems, Illumina Infinium single-nucleotide polymorphism array and genotyping by random amplicon sequencing-direct (GRAS-Di) systems. In addition, the GP model, which considered the inbreeding effect, further improved the accuracy of the seven fruit traits. Runs of homozygosity (ROH) islands overlapped with the significantly associated regions detected by the GWAS for several fruit traits. Breeders may have exploited these regions to select promising apples by breeders, increasing homozygosity. These results suggest that combining genotypic data from different genotyping platforms benefits the GS and GWAS of fruit quality traits in apples. Information on inbreeding could be beneficial for improving the accuracy of GS for fruit traits of apples; however, further analysis is required to elucidate the relationship between the fruit traits and inbreeding depression (e.g. decreased vigor).

Synthesis, In Silico Prediction, and In Vitro Evaluation of Anti-tumor Activities of Novel 4'-Hydroxybiphenyl-4-carboxylic Acid Derivatives as EGFR Allosteric Site Inhibitors.

INTRODUCTION: Allosteric inhibition of EGFR Tyrosine Kinase (TK) is currently among the most attractive approaches for designing and developing anti-cancer drugs to avoid chemoresistance exhibited by clinically approved ATP-competitive inhibitors. The current work aimed to synthesize new biphenyl-containing derivatives that were predicted to act as EGFR TK allosteric site inhibitors based on molecular docking studies. METHOD: A new series of 4'-hydroxybiphenyl-4-carboxylic acid derivatives, including hydrazine-1-carbothioamide (S3-S6) and 1,2,4-triazole (S7-S10) derivatives, were synthesized and characterized using IR, 1HNMR, 13CNMR, and HR-mass spectroscopy. Compound S4 had a relatively high pharmacophore-fit score, indicating that it may have biological activity similar to the EGFR allosteric inhibitor reference, and it scored a relatively low ΔG against EGFR TK allosteric site, indicating a high likelihood of drug-receptor complex formation. Compound S4 was cytotoxic to the three cancer cell lines tested, particularly HCT-116 colorectal cancer cells, with an IC50 value comparable to Erlotinib. Compound S4 induced the intrinsic apoptotic pathway in HCT-116 cells by arresting them in the G2/M phase. RESULT: All of the new derivatives, including S4, met the in silico requirements for EGFR allosteric inhibitory activity. CONCLUSION: Compound S4 is a promising EGFR tyrosine kinase allosteric inhibitor that warrants further research.

New Carbothioamide and Carboxamide Derivatives of 3-Phenoxybenzoic Acid as Potent VEGFR-2 Inhibitors: Synthesis, Molecular Docking, and Cytotoxicity Assessment.

INTRODUCTION/BACKGROUND: Because of the well-established link between angiogenesis and tumor development, the use of antiangiogenic therapeutics, such as those targeting VEGFR-2, presents a promising approach to cancer treatment. In the current study, a set of five hydrazine-1-- carbothioamide (compounds 3a-e) and three hydrazine-1-carboxamide derivatives (compounds 4a-c) were successfully synthesized from 3-phenoxybenzoic acid. These compounds were specially created as antiproliferative agents with the goal of targeting cancer cells by inhibiting VEGFR-2 tyrosine kinase. MATERIALS AND METHODS: The new derivatives were synthesized by conventional organic methods, and their structure was versified by IR, 1HNMR, 13CNMR, and mass spectroscopy. In silico investigation was carried out to identify the compounds' target, molecular similarity, ADMET, and toxicity profile. The cytotoxic activity of the prepared compounds was evaluated in vitro against three human cancer cell lines (DLD1 colorectal adenocarcinoma, HeLa cervical cancer, and HepG2 hepatocellular carcinoma). The effects of the leading compound on cell cycle progression and apoptosis induction were investigated by flow cytometry, and the specific apoptotic pathway triggered by the treatment was evaluated by RT-PCR and immunoblotting. Finally, the inhibitory activities of the new compounds against VEGFR-2 was measured. RESULTS: The designed derivatives exhibited comparable binding positions and interactions to the VEGFR-2 binding site to that of sorafenib (a standard VEGFR-2 tyrosine kinase inhibitor), as determined by molecular docking analysis. Compound 4b was the most cytotoxic compound, achieving the lowest IC50 against HeLa cells. Compound 4b, a strong representative of the synthesized series, induced cell cycle arrest at the G2/M phase, increased the proportion of necrotic and apoptotic HeLa cells, and activated caspase 3. The EC50 value of compound 4b against VEGFR-2 kinase activity was comparable to sorafenib's. CONCLUSION: Overall, the findings suggest that compound 4b has a promising future as a starting point for the development of new anticancer drugs.

Autonomous differentiation of transgenic cells requiring no external hormone application: the endogenous gene expression and phytohormone behaviors.

The ectopic overexpression of developmental regulator (DR) genes has been reported to improve the transformation in recalcitrant plant species because of the promotion of cellular differentiation during cell culture processes. In other words, the external plant growth regulator (PGR) application during the tissue and cell culture process is still required in cases utilizing DR genes for plant regeneration. Here, the effect of Arabidopsis BABY BOOM (BBM) and WUSCHEL (WUS) on the differentiation of tobacco transgenic cells was examined. We found that the SRDX fusion to WUS, when co-expressed with the BBM-VP16 fusion gene, significantly influenced the induction of autonomous differentiation under PGR-free culture conditions, with similar effects in some other plant species. Furthermore, to understand the endogenous background underlying cell differentiation toward regeneration, phytohormone and RNA-seq analyses were performed using tobacco leaf explants in which transgenic cells were autonomously differentiating. The levels of active auxins, cytokinins, abscisic acid, and inactive gibberellins increased as cell differentiation proceeded toward organogenesis. Gene Ontology terms related to phytohormones and organogenesis were identified as differentially expressed genes, in addition to those related to polysaccharide and nitrate metabolism. The qRT-PCR four selected genes as DEGs supported the RNA-seq data. This differentiation induction system and the reported phytohormone and transcript profiles provide a foundation for the development of PGR-free tissue cultures of various plant species, facilitating future biotechnological breeding.

Synthesis, docking study, and antitumor evaluation of benzamides and oxadiazole derivatives of 3-phenoxybenzoic acid as VEGFR-2 inhibitors.

Current chemotherapeutic agents have several limitations, including lack of selectivity, the development of undesirable side effects, and chemoresistance. As a result, there is an unmet need for the development of novel small molecules with minimal side effects and the ability to specifically target tumor cells. A new series of 3-phenoxybenzoic acid derivatives, including 1,3,4-oxadiazole derivatives (4a-d) and benzamides derivatives (5a-e) were synthesized; their chemical structures were confirmed by Fourier-transform infrared spectroscopy, 1H nuclear magnetic resonance (NMR), 13C NMR, and mass spectra; and various physicochemical properties were determined. The antiproliferative activities of the new derivatives were evaluated by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Three compounds (4b, 4c, and 4d) exhibited cytotoxicity against two of the three cell lines tested, five compounds (3, 4a, 5a, 5b, and 5e) were toxic to one cell line, while two compounds (5c and 5d) were not cytotoxic to any of the three cell lines tested in the current study. Based on docking scores, MTT assay findings, and vascular endothelial growth factor receptor 2 (VEGFR-2) kinase activity data, Compound 4d was selected for further biological investigation. Flow cytometry was used to determine the mode of cell death (apoptosis vs. necrosis) and the effect on cell cycle progression. Compound 4d arrested HepG2 hepatocellular carcinoma cells in the G2/M phase and activated both the intrinsic and extrinsic apoptosis pathways. In conclusion, Compound 4d has shown promising results for future research as a potent VEGFR-2 tyrosine kinase inhibitor.

Biocontrol of multidrug resistant pathogens isolated from fish farms using silver nanoparticles combined with hydrogen peroxide insight to its modulatory effect.

This study was divided into two parts. The first part involved the isolation, and detection of the prevalence and antimicrobial resistance profile of Aeromonas hydrophila, Pseudomonas aeruginosa, and Vibrio species from Nile tilapia fish and marine aquatic water. One hundred freshly dead Nile tilapia fish were collected from freshwater aquaculture fish farms located in Al-Abbassah district, Sharkia Governorate, and 100 samples of marine aquatic water were collected from fish farms in Port Said. The second part of the study focused on determining the in vitro inhibitory effect of dual-combination of AgNPs-H2O2 on bacterial growth and its down regulatory effect on crucial virulence factors using RT-PCR. The highest levels of A. hydrophila and P. aeruginosa were detected in 43%, and 34% of Nile tilapia fish samples, respectively. Meanwhile, the highest level of Vibrio species was found in 37% of marine water samples. Additionally, most of the isolated A. hydrophila, P. aeruginosa and Vibrio species exhibited a multi-drug resistance profile. The MIC and MBC results indicated a bactericidal effect of AgNPs-H2O2. Furthermore, a transcriptional modulation effect of AgNPs-H2O2 on the virulence-associated genes resulted in a significant down-regulation of aerA, exoU, and trh genes in A. hydrophila, P. aeruginosa, and Vibrio spp., respectively. The findings of this study suggest the effectiveness of AgNPs-H2O2 against drug resistant pathogens related to aquaculture.

Efficient photocatalytic remediation of lerui acid brilliant blue dye using radiation- prepared carboxymethyl cellulose/acrylic acid hydrogel supported by ZnO@Ag.

Organic dye pollution from textiles and other industries presents a substantial risk to people and aquatic life. The use of photocatalysis to decolorize water using the strength of UV light is one of the most important remediation techniques. In the present study, a novel nanocomposites hydrogel including carboxymethyl cellulose (CMC), acrylic acid (AAc), Zinc oxide (ZnO), and silver (Ag) nanoparticles was produced using an eco-friendly γ-irradiation technique for photocatalytic decolorization applications. ZnO and Ag nanoparticles were distributed in the CMC/AAc hydrogel matrix without significant aggregation. SEM, XRD, EDX, TEM, and FTIR analyses were used to assess the physicochemical characteristics of the nanocomposite samples. Carboxymethyl cellulose/acrylic acid/Zinc oxide doped silver (CMC/PAAc/ZnO@Ag) nanocomposite hydrogels were developed and utilized in the photocatalytic decolorization of the lerui acid brilliant blue dye (LABB) when exposed to ultraviolet (UV) radiation. UV- Vis spectrophotometry was utilized to analyze the optical properties of the produced nanostructure. Regarding the decolorization of the LABB, the impacts of operational variables were investigated. The optimum conditions for decolorization (93 %) were an initial concentration of 50 mg/L, pH = 4, catalyst dosage of 50 g/L, and exposure time of 90 min. The results illustrated that the LABB acidic dye from wastewater was remarkably decolored.

Chitosan/alginate/pectin biopolymer-based Nanoemulsions for improving the shelf life of refrigerated chicken breast.

This study investigated the use of nanoemulsions and various polymer coatings to enhance the quality and shelf life of chicken breast. This comprehensive study explored the antibacterial activity of essential oils (EOs) against Escherichia coli and Staphylococcus aureus, as well as the characterization of nanoemulsions (Nes) and nanoemulsion-based coatings. The antimicrobial potential of EOs, such as cinnamon, tea tree, jojoba, thyme, and black cumin seed oil, was evaluated against microorganisms, and thyme oil exhibited the highest inhibitory effect, followed by cinnamon and tea tree oil by disk diffusion analysis. The MIC and MBC values of EOs were found between 0.16-2.5 mg/mL and 0.16-5 mg/mL, respectively, while thyme EO resulted in the lowest values showing its antimicrobial potential. Then, the essential oil nanoemulsions (EONe) and their coatings, formulated with thyme oil, alginate, chitosan, and pectin, were successfully characterized. Optical microscope observations confirmed the uniform distribution of droplets in all (EONe), while particle size analysis demonstrated multimodal droplet size distributions. The EONe-chitosan coating showed the highest efficacy in reducing cooking loss, while the EONe-chitosan, EONe-alginate, and EONe-pectin coatings displayed promising outcomes in preserving color stability. Microbial analysis revealed the significant inhibitory effects of the EONe-chitosan coating against mesophilic bacteria, psychrophilic bacteria, and yeasts, leading to an extended shelf life of chicken breast. These results suggest the potential application of thyme oil and NE-based coatings in various industries for antimicrobial activity and quality preservation.

New Indole-6-Carboxylic Acid Derivatives as Multi-Target Antiproliferative Agents: Synthesis, in Silico Studies, and Cytotoxicity Evaluation.

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are commonly overexpressed in cancers making them appealing targets for cancer therapeutics. Two groups of indole-6-carboxylic acid derivatives, hydrazone derivatives targeting EGFR and oxadiazole derivatives targeting VEGFR-2, were synthesized and characterized using FT-IR, 1 H-NMR, 13 CNMR, and HR-MS techniques. Binding patterns to potential molecular targets were studied using molecular docking and compared to standard EGFR and VEGFR-2 inhibitors. The newly synthesized compounds were cytotoxic to the three cancer cell lines tested (HCT-116, HeLa, and HT-29 cell lines) as evaluated by the MTT assay. Compound 3 b (EGFR-targeting) and compound 6 e (VEGFR-2-targeting) possessed the highest antiproliferation activity, were cancer-selective, arrested cancer cells in the G2/M phase, induced the extrinsic apoptosis pathway, and had the highest EGFR/VEGFR-2 enzyme inhibitory activity, respectively. The structure-activity relationships of the new compounds showed that the presence of an aryl or heteroaryl fragment attached to a linker is required for the anti-tumor activity. In conclusion, the findings of the current study suggest that compounds 3 b and 6 e are promising cytotoxic agents that act by inhibiting EGFR and VEGFR-2 tyrosine kinases, respectively.

Electrospun PVA nanofiber mat for topical Deflazacort delivery: accentuated anti-inflammatory efficacy for wound healing.

PURPOSE: Asses the wound healing activity of Polyvinyl alcohol - Deflazacort (PVA-DEF) nanofibers mats synthesized by electrospinning technology. METHODS: PVA-DEF nanofiber mats were created with various PVA polymer concentrations using an electrospinning process. The morphological features and diameter of the electrospun nanofibrous mats were investigated using scanning electron microscopy (SEM). The in vitro DEF release rate from PVA electrospun nanofibrous mats was evaluated. In addition to assessing wound healing activity in vivo, histological, and immunochemical tests were conducted. RESULTS: Results revealed a uniform and smooth surface of the fiber with an average diameter of the selected fibers of 533.9 nm ± 45.83. Also, PVA electrospun nanofiber mats showed an initial burst release of more than 50% of the DEF in 1 h, and the rest of the DEF was released gradually for up to 480 min. Fickian diffusion is the main DEF release mechanism from PVA electrospun nanofiber mats. In male Wistar albino rats with 1 cm2 excision wounds, in vivo studies revealed a significant improvement in wound healing rate via modulation of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) expression. CONCLUSION: PVA-DEF nanofiber mats can be used effectively for improving wound healing.

Insights into the therapeutic outcomes of trimetazidine/doxorubicin combination in Ehrlich solid-phase carcinoma mouse tumor model.

One of the key features of cancer is metabolic reprogramming that can be exploited to sensitize cancer cells to chemotherapy. Trimetazidine (TMZ) is a metabolic anti-ischemic drug that blocks the activity of long-chain 3-ketoacyl CoA thiolase leading to the inhibition of fatty acid oxidation. AIMS: The objective of the current investigation was to evaluate the idea that TMZ could synergize the antitumor activity of doxorubicin (DOX). MAIN METHODS: The hypothesis was examined in vitro using the human breast cancer cell lines MCF-7 and MDA-MB231. In addition, the in vivo experiments were conducted using the Ehrlich solid phase carcinoma model. KEY FINDINGS: In vitro cytotoxicity experiments demonstrated that TMZ improved the potency of DOX in MCF-7 cell lines in a synergistic manner. In vivo testing confirmed that DOX/TMZ combination exhibits synergistic effect at both DOX/TMZ 1:10 and 1:5 ratios, where DOX was administered at one tenth and one fifth of its original dose, respectively. The co-treatment (1:5 ratio) significantly reduced tumor Nicotinamide adenine dinucleotide (NAD)+/NADH ratio (6.1-fold) and Adenosine triphosphate (ATP) levels (61 %) with concurrent activation of AMP-activated protein kinase (AMPK) (2.2-fold) and peroxisome proliferator-activated receptor-gamma coactivator (PGC)1-α (5.5-fold) protein expression versus control. The same treatment decreased the nuclear levels of NF-κB (p65) (57.5 %) and induced tumor apoptosis as evidenced by elevated Bax/Bcl-2 ratio (6.8-fold) along with active caspase-3 levels (6.6-fold) against control. SIGNIFICANCE: The current investigation constitutes a proof-of-concept study that provided preclinical evidence for the anticancer activity of DOX/TMZ combination and warrants further investigation for repurposing TMZ in DOX protocols.

Radiation synthesis and photocatalytic performance of floated graphene oxide decorated ZnO/ alginate-based beads for methylene blue degradation under visible light irradiation.

Organic dye contamination, emanating from pharmaceutical, paper, and textile industries into water resources, severely threatens marine and human life even at low concentrations. Photocatalysis is one of the most important remediation techniques that decolorize water by employing the power of light. In this work, the development of floated beads of Sodium Alginate/hydroxyethyl methacrylate (Alg-g-HEMA) encompass graphene oxide (GO) decorated Zinc oxide (ZnO) utilizing ionizing radiation was designed to function as a photocatalyst when exposed to visible light. Floatability was induced using calcium carbonate. GO was sonochemically decorated with ZnO nanoparticles and the yield was characterized using XRD, FTIR, TEM, SEM, and EDX techniques. Optical characteristics of the developed nanostructure were performed using UV-Vis spectrophotometry. The photocatalytic activity of the floated (Alg-g-HEMA)-ZnO@GO beads was assessed for the photo decolorization of methylene blue dye (MB) under visible light. The upshot of operational factors such as photocatalyst dose, pH, initial dye concentration, and irradiation time on the decolorization of MB was examined. It was observed that 1 g of the developed (Alg-g-HEMA)-ZnO@GO photocatalyst was able to decolorize 1000 ml of 20 ppm of MB within 150 min at pH 9. In terms of kinetics, photo-decolorization follows Langmuir Hinshelwood pseudo-first order.

MALAT-1: Immunomodulatory lncRNA hampering the innate and the adaptive immune arms in triple negative breast cancer.

BACKGROUND: Triple negative breast cancer (TNBC) is known as hot immunogenic tumor. Yet, it is one of the most aggressive BC subtypes. TNBC evolve several tactics to evade the immune surveillance phenomena, one of which is shedding of natural killer (NK) cells activating immune ligands such as MICA/B and/or by inducing the expression of the immune checkpoints such as PD-L1 and B7-H4. MALAT-1 is an oncogenic lncRNA. MALAT-1 immunogenic profile is not well investigated. AIM: The study aims at exploring the immunogenic role of MALAT-1 in TNBC patients and cell lines and to identify its molecular mechanism in altering both innate and adaptive immune cells present at the tumor microenvironment of TNBC METHODS: BC patients (n = 35) were recruited. Primary NK cells and cytotoxic T lymphocytes were isolated from normal individuals using the negative selection method. MDA-MB-231 cells were cultured and transfected by several oligonucleotides by lipofection technique. Screening of ncRNAs was performed using q-RT-PCR. Immunological functional analysis experiments were performed upon co-culturing primary natural killer cells and cytotoxic T lymphocytes using LDH assay. Bioinformatics analysis was performed to identify potential microRNAs targeted by MALAT-1. RESULTS: MALAT-1 expression was significantly upregulated in BC patinets with a profound expression in TNBC patients compared to their normal counterparts. Correlation analysis revealed a positive correlation between MALAT-1, tumor size and lymph node metastasis. Knocking down of MALAT-1 in MDA-MB-231 cells resulted in a significant induction of MICA/B, repression of PD-L1 and B7-H4 expression levels. Enhancement of cytotoxic activity of co-cultured NK and CD8+ cells with MALAT-1 siRNAs transfected MDA-MB-231 cells. In silico analysis revealed that miR-34a and miR-17-5p are potential targets to MALAT-1; accordingly, they were found to be downregulated in BC patients. Forcing the expression of miR-34a in MDA-MB-231 cells resulted in a significant induction in MICA/B levels. Ectopic expression of miR-17-5p in MDA-MB-231 cells significantly repressed the expression of PD-L1 and B7-H4 checkpoints. Validations of MALAT-1/miR-34a" and "MALAT-1/miR-17-5p axes were performed by a series of co-transfections and functional assessment of cytotoxic profile of primary immune cells. CONCLUSION: This study proposes a novel epigenetic alteration exerted by TNBC cells mainly by inducing the expression of MALAT-1 lncRNA. MALAT-1 mediates innate and adaptive immune suppression events partially via targeting miR-34a/MICA/B and miR-175p/PD-L1/B7-H4 axes in TNBC patients and cell lines.

A systematic investigation of four ports MIMO antenna depending on flexible material for UWB networks.

A flexible quad-port MIMO antenna with good isolation features with both flat and bending configurations is presented and investigated in this work. The single unit of the MIMO is composed of a crescent-shaped monopole antenna connected with a curved coplanar waveguide (CPW) fed to enhance the operating bandwidth. A thin and flexible Roger 3003 material with thickness = 0.13 mm, εr = 3, and tan δ = 0.001 is used. To improve the isolation between ports which in turn improves the performance of the MIMO system, the single unit antenna is repeated four times and placed orthogonal to each other. A 54 mm × 54 mm × 0.13 mm (0.63λo × 0.63λo × 0.0015λo @ 3.5 GHz) is the total size of the quad ports MIMO antenna. The flexible MIMO antennas in both flat and bending layouts are simulated, tested and the outcomes achieved S11 < - 10 dB from 3.5 GHz up to 11 GHz with mutual coupling ≤ - 17 dB between ports. The radiation patterns of the MIMO antenna are tested with 5 dB peak gain and with semi-omnidirectional and bidirectional patterns in both two planes. The Diversity Gain (DG) values ≥ 9.9 dB through the designed working band, Envelop Correlation Coefficient (ECC) lower than 0.03 from 3.5 GHz to 4 GHz and lower than 0.01 from 4 to 11 GHz, and Channel Capacity Loss (CCL) value ≤ 0.5 bit/s/Hz over the worked band are calculated and extracted in flat and bending configurations and achieved suitable values which support the suggested antenna in the UWB flexible networks.

Early Diagnosis of Pulmonary Embolism Related to Clinical Presentation and Vital Signs in the Emergency Department at King Saud Medical City.

BACKGROUND: Pulmonary embolism (PE) is a common acute life-threatening cardiovascular disorder. It is the third most common cause of hospital-related death and early detection and management of PE are crucial. The study aimed to evaluate the association between vital signs and laboratory investigations with PE. METHODS: This is a retrospective, hospital records-based, observational study, conducted among patients who were admitted to the emergency department of King Saud Medical City in Riyadh, Saudi Arabia with a suspected diagnosis of PE during the period of March 2021 to March 2022. Data were collected by searching patients' files and recording demographic data, and information about the clinical presentation, workup, and outcome. Data were entered and analyzed using SPSS version 26 (IBM, Armonk, NY), utilizing Chi-square statistics to test differences between groups, and logistic regression analyses to identify predictors of PE. RESULTS: The study included 92 patients, with a preponderance of females (70.7%), and those aged 40-60 years (51.1%). Diabetes mellitus (44.6%), and hypertension (30.4%) were the most common comorbidities among others, while shortness of breath (SOB) (83.7%), and chest pain (44.6%) were among the most commonly reported symptoms. A majority of patients had tachycardia (64.1%), while about half had low oxygen saturation (51.5%), and nearly one-third had tachypnea (29.3%), which was more predominant among those not diagnosed with PE. Logistic regression analysis revealed that SOB, respiratory rate, and oxygen saturation were the only significant predictors of PE. CONCLUSION: Although being an integral part of the initial assessment in the hospital, measuring the vital signs is not always reflective of the likelihood of PE, and they should not be the only metric relied upon to make decisions about treatment approaches in patients with PE. Physicians should ensure the employment of evidence-based clinical prediction rules and guidelines when diagnosing and managing PE.