Enhancement efficiency delivery of antiviral Molnupiravir-drug via the loading with self-assembly nanoparticles of pycnogenol and cellulose which are decorated by zinc oxide nanoparticles for COVID-19 therapy.

The target of the study is to modify the efficiency of Molnupiravir-drug (MOL) for COVID-19 therapy via the rearrangement of the building engineering of MOL-drug by loading it with self-assembly biomolecules nanoparticles (NPs) of pycnogenol (Pyc) and cellulose (CNC) which are decorated by zinc oxide nanoparticles. The synthesis and characterization of the modified drug are performing successfully, the loading and release process of the MOL drug on a nano surface is measured by UV-Vis spectroscopy under room temperature and different pH. The release efficiency of the MOL drug is calculated to be 65% (pH 6.8) and 69% (pH 7.4). The modified MOL drug displays 71% (pH 6.8) and 78% (pH 7.4) for CNC@Pyc.MOL nanocomposite, while CNC@Pyc.MOL.ZnO nanocomposite gave values at 76% (pH 6.8) and 78% (pH 7.4), the efficiency recorded after 19 h. The biological activity of the MOL-drug and modified MOL-drug is measured, and the cytotoxicity is performed by SRB technique, where the self-assembly (CNC@Pyc) appears to be a safe healthy, and high viability against the examined cell line. The antioxidant activity and anti-inflammatory are evaluated, where the nanocomposite that has ZnO NPs (CNC@Pyc.MOL.ZnO) gave high efficiency compared to the composite without ZnO NPs. The CPE-inhibition assay is used to identify potential antivirals against CVID-19 (229E virus), the viral inhibition (%) was reported at 37.6 % (for 800 µg/ml) and 18.02 % (for 400 µg/ml) of CNC@Pyc.MOL.ZnO. So, the modified MOL-drug was suggested as a replacement drug for the therapy of COVID-19 compared to MOL-drug, but the results need clinical trials.

Clinicopathologic Impact of NANOG, ZEB1, and EpCAM Biomarkers on Prognosis of Serous Ovarian Carcinoma.

OBJECTIVES: Serous ovarian carcinoma (SOC) is a biologically heterogeneous with different genomic and molecular profiles, beside clinical response to the chemotherapy with subsequent in obstacles in starting unified, acceptable treatments and so we assess immunoexpression of Nanog, ZEB1, and EpCAM in SOC. METHODS: In this study, the immunoexpression of Nanog, ZEB1, and EpCAM was studied in 60 cases of SOC. Overall survival (OS), disease-free survival (DFS) data and response to chemotherapy were  analyzed. RESULTS: NANOG was immunostained in 65% of the cases with a significant association with tumor grade, lymph node metastasis, and FIGO stage (p < 0.001 for each). ZEB1 showed moderate- high expression in 58.3% of the cases with significant up-regulation of ZEB1 expression with SOC grade, nodal metastasis, and SOC FIGO stage (p<0.001). EpCAM revealed high expression in 60% of the cases with significant association with higher grade, nodal metastasis, and advanced stage (p < 0.001 for each). Up-regulation of Nanog was significantly associated with response to chemotherapy, relapse, shorter OS and DFS (p < 0.001 for each). ZEB1 overexpression exhibited a significant association with response to chemotherapy (p= 0.012), relapse, shorter OS and DFS (p<0.001 for each). Moreover, the high EpCAM had a significant association with response to chemotherapy (p= 0.043), relapse (p < 0.001) shorter OS (p=0.006) and DFS (p< 0.001). CONCLUSIONS: Up-regulation of Nanog and ZEB-1 and EpCAM perhaps promote an aggressive SOC with a high risk of relapse and unfavorable response to standard chemotherapy regimen.

MIR-379-5p Expression in Endometrial Cancer and Its Correlation with ROR1 Expression.

OBJECTIVE: To asses miR-379-5p expression in endometrial cancer (EC) and its correlation with ROR1 expression and to investigate the relation between miR-379-5p and ROR1 expressions and the clinicopathological picture of EC. METHODS: Fifty female of EC were joined to this study. The gene expression of miR-379-5p (by quantitative real time-PCR) and ROR1 (by quantitative real time-PCR and immunohistochemistry) were studied in EC and normal nearby endometrial tissue. RESULTS: The gene expression of miR-379-5p was significantly downregulated while that of ROR1 was significantly upregulated in EC tissues compared to adjacent normal endometrial tissues. Furthermore, miR-379 and ROR1 expressions significantly associated with tumor stage (P< 0.045), grade (P< 0.001), myometrial invasion (P <0.001) and LN metastasis (P< 0.034). In addition, miR-3795p and ROR1 gene expression were negatively correlated (r = -0.746, P < 0.001). CONCLUSIONS: In EC, miR-379-5p can be used as a diagnostic marker, and ROR1 could be a potential target of miR-379-5p.

Drug delivery of sofosbuvir drug capsulated with the ß-cyclodextrin basket loaded on chitosan nanoparticle surface for anti-hepatitis C virus (HCV).

The present work-study the improvement of the loading and release efficiency of sofosbuvir drug (SOF) for anti-hepatitis C virus (HCV) by the combination process with ß-cyclodextrin (ßCD) basket to form a novel self-assembly ßCD-SOF which load on the chitosan nanoparticle (Cs NPs) to form a novel hybrid composite (Cs@ßCD-SOF). The characterization process performs for confirming the formation of hybrid composite with various methods. The loading efficiency of SOF is performed by UV-Vis spectroscopy, which is reported at 94.54% for Cs@ßCD-SOF, while in the reverse case the efficiency is ßCD-SOF@Cs 65.2%. The binding constant (Kb) was reported at 1.33 ± 0.02, and 0.1069 ± 0.03 min-1for Cs@ßCD-SOF and ßCD-SOF@Cs, respectively. The release process of SOF is reported by UV-Vis spectra at 271 nm with 30 min intervals, at pH 7.4 the release efficiency is 67% after 6 h, and 78% after 21 h, while it gave 61% release efficiency at pH 6.8 after time 6 h, and 63% after 21 h. The cytotoxicity assay of the SOF capsulated hybrid materials (ßCD-SOF and Cs@ßCD-SOF) has been detected with three different types of cell lines like mouse normal liver cells (BNL), hepatocellular carcinoma (HepG2), and breast adenocarcinoma (MCF-7). SRB method for the quick screening is used for the cytotoxicity assay of the SOF capsulated materials, where the examined composites appear a safety status and high viability against the examined cell line. The FRAP method is used to detect the antioxidant activities of SOF capsulated materials. The recommendation for using a safe alternative SOF drug based on Cs NPs and ßCD which give on loading and release efficiency compared to SOF drugs, but the clinical trials are an important step.

Self-assembly of porphyrin on graphene oxide in aqueous medium: fabrication, characterization, and photocatalytic studies.

We herein report the supramolecular self-assembly of a water soluble porphyrin, namely, 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin-tetra(p-toluenesulfonate) (TMPyP), on the surface of graphene oxide (GO). The fabricated GO nanosheet and GO@TMPyP hybrid material composite have been characterized by using various spectroscopic and analytical techniques, e.g., scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), and Fourier transform infrared (FT-IR) spectroscopy. The steady state absorption measurements of the GO@TMPyP self-assembly showed a significant red shift (∼20 nm) compared to those of the control TMPyP in water. The steady state fluorescence measurements showed a significant fluorescence quenching of the singlet excited state of TMPyP in the presence of GO. These findings suggest the electron transfer reaction from TMPyP to GO. The time resolved fluorescence measurements showed a considerable decrease in the lifetime of the singlet state of TMPyP in the presence of GO, from which the rate and efficiency of the electron transfers from TMPyP to GO were determined to be 1.93 × 109 s-1 and 91%, respectively. The transient absorption measurements showed a considerable quenching of the triplet excited state of TMPyP in the self-assembly. All these findings confirm the occurrence of efficient electronic interactions between TMPyP and GO in both the ground and excited states. In addition, the fabricated GO@TMPyP showed high photocatalytic activity for the degradation of methylene blue (MB) and methyl orange (MO) mixed dye pollutants in water under visible light irradiation.

Graphene oxide-metal oxide nanocomposites: fabrication, characterization and removal of cationic rhodamine B dye.

The fabrication and characterization of graphene oxide (GO) nanosheets and their reaction with Fe3O4 and ZrO2 metal oxides to form two nanocomposites, namely graphene oxide-iron oxide (GO-Fe3O4) and graphene oxide-iron oxide-zirconium oxide (GO-Fe3O4@ZrO2), have been examined. The fabricated nanocomposites were examined using different techniques, e.g.transmission electron microscopy, X-ray diffraction, zeta potential measurement and Fourier transform infrared spectroscopy. Compared to GO, the newly fabricated GO-Fe3O4 and GO-Fe3O4@ZrO2 nanocomposites have the advantage of smaller band gaps, which result in increased adsorption capacity and photocatalytic effects. The results also showed the great effect of the examined GO-metal oxide nanocomposites on the decomposition of cationic rhodamine B dye, as indicated by steady-state absorption and fluorescence, time correlated single photon counting and nanosecond laser photolysis techniques. The antibacterial activity of the fabricated GO and GO-metal oxides has been studied against Gram-positive and Gram-negative bacteria.