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Oxaliplatin (Oxa)-associated adverse side effects have considerably limited the clinical use of the drug in colon cancer therapy. Mutant p53 has diverse mutational profiles in colon cancer, and it influences the potencies of various chemotherapeutic drugs, including Oxa. Thus, it would be highly beneficial to identify an alternative therapeutic strategy that not only reduces the toxicity of Oxa, but also exerts a synergistic effect against colon cancers, regardless of their p53 profiles. The present study was aimed at preparing and optimizing Teucrium polium L. essential oil nanoemulsion (TPO-NANO) and investigating its effect on the sensitivity of colon cancer cells with differences in p53 status (HCT116 wild-type and HT-29 mutant-type) to Oxa. The viability of treated cells was determined and the combination index (CI) was calculated. Morphological changes were determined under inverted microscopy, while percentage apoptosis was assayed using flow cytometry. Intracellular ROS and the protein levels of p53 and Bax were measured. The colony-forming potential of treated cells was determined using colony assay. The size of TPO-NANO was markedly increased from 12.90 ± 0.04 nm to 14.47 ± 0.53 nm after loading Oxa (p ≤ 0.05). The combination (Oxa + TPO-NANO) produced a synergetic effect in HCT116 and HT-29, with CI of 0.94 and 0.88, respectively. Microscopic examination and flow cytometric analysis revealed that cells treated with Oxa + TPO-NANO had a higher percentage of apoptosis than cells exposed to monotherapy. Cumulatively, Oxa exerted an apoptotic effect on wild or mutant p53 colon cancer cells when combined with TPO-NANO, through a mechanism involving ROS-mediated mitochondrial apoptosis.

The aqueous extract of Portulaca oleracea was used as a biocatalyst for the reduction of Na2SeO3 to form Se-NPs that appeared red in color and showed maximum surface plasmon resonance at a wavelength of 266 nm, indicating the successful Phyto-fabrication of Se-NPs. A FT-IR chart clarified the role of plant metabolites such as proteins, carbohydrates, and amino acids in capping and stabilizing Se-NPs. TEM, SAED, and XRD analyses indicated the formation of spherical, well-arranged, and crystalline Se-NPs with sizes in the range of 2–22 nm. SEM-EDX mapping showed the maximum peaks of Se at 1.4, 11.3, and 12.4 KeV, with weight and atomic percentages of 36.49 and 30.39%, respectively. A zeta potential of −43.8 mV also indicated the high stability of the synthesized Se-NPs. The Phyto-synthesized Se-NPs showed varied biological activities in a dose-dependent manner, including promising activity against pathogenic bacteria and Candida species with varied MIC values in the range of 12.5−50 µg·mL−1. Moreover, the Se-NPs showed antiviral activity toward HAV and Cox-B4, with percentages of 70.26 and 62.58%, respectively. Interestingly, Se-NPs showed a target orientation to cancer cell lines (HepG2) with low IC50 concentration at 70.79 ± 2.2 µg·mL−1 compared to normal cell lines (WI−38) with IC50 at165.5 ± 5.4 µg·mL−1. Moreover, the as-formed Se-NPs showed high activity against various instar larvae I, II, III, and IV of Culex pipiens, with the highest mortality percentages of 89 ± 3.1, 73 ± 1.2, 68 ± 1.4, and 59 ± 1.0%, respectively, at 50 mg L−1. Thus, P. oleracea-based Se-NPs would be strong potential antimicrobial, anti-viral, anti-cancer, and anti-insect agents in the pharmaceutical and biomedical industries.

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The limitations of gemcitabine (GEM) in cancer therapy are due to its poor pharmacokinetics, which cause undesired adverse effects. The current study was aimed at investigating the anticancer effect and apoptotic mechanism of synthesized nanoemulsion (NE) containing Pulicaria crispa essential oil (PC-EO) and GEM (PC-NE:GEM) on MCF-7 and Hep-G2 cancer cell lines. An optimized NE formulation was selected based on the Box–Behnken method. The droplet size of the optimized PC-NE was 9.93 ± 0.53 nm, but after GEM loading, it was increased to 11.36 ± 0.0.21 nm. Results from FTIR revealed that GEM was successfully loaded onto PC-NE. The antineoplastic effect of PC-NE:GEM on MCF-7 and Hep-G2 cancer cells was increased more than 100-fold relative to that of GEM. A combination index and isobologram based on CompuSyn software revealed the synergistic effect of the formulation produced by a 1:1 ratio combination of PC-NE and GEM. These findings were confirmed by examination of cellular morphologies. The combination formulation strongly induced about 4.48-fold and 2.95-fold increases in apoptosis in MCF-7 and Hep-G2 cells, respectively, when compared with GEM. Moreover, PC-NE:GEM produced a synergistic increase in ROS production in MCF-7 cells (15.23%) and Hep-G2 cells (31.69%), when compared with GEM. In addition, PC-NE:GEM enhanced the activation of the intrinsic apoptosis pathway through upregulation of expressions of p53 and Caspase-3, and downregulation of Bcl-2 expression in MCF-7 cells, while the expressions of Caspase-3, Bax, and p53 were upregulated in HepG2 cells. These results indicate that the GEM-loaded NE containing PC-EO may reduce the dose of GEM and eliminate the associated side effects.

strain AB_11_10 was isolated and identified using microscopy and 16s rRNA sequencing, and its phytochemical constituents were determined using liquid chromatography-quadrupole time-of-flight mass spectrometry. The isolate had a segmented filamentous shape with a blue-green color. Many biomolecules, including organic compounds, amino acids, and fatty acids, were detected. strain AB_11_10 was used to synthesize gold nanoparticles (Ph-AuNPs) by adjusting the optimum reaction conditions. The concentration, algal/precursor ratio, temperature, reaction time, and pH significantly influenced the synthesis of the Ph-AuNPs. Mixing 1 mL of 0.5 mM of HAuCl with 1 mL of algal extract and exposing the mixture to 100 °C for 30 min at pH 5.6 were the optimum conditions for the biosynthesis of Ph-AuNPs at a wavelength of 524.5 nm. The Ph-AuNPs were characterized using TEM, SEM, EDX, and mapping Zeta sizer and FTIR. The Ph-AuNPs had quasi-spherical to triangular shapes with an average diameter of 9.6 ± 4.3 nm. Ph-AuNPs composed of 76.10 ± 3.14% of Au and trace amounts of carbon and oxygen were detected, indicating that the strain AB_11_10 successfully synthesized Ph-AuNPs. The hydrodynamic diameter of the Ph-AuNPs was 28.5 nm, and their potential charge was -17.7 mV. O-H, N-H, C=C, N-O, C-H, and C-O were coated onto the surfaces of the Ph-AuNPs. These groups correspond to algal phytochemicals, which may have been the main reducing and stabilizing substances during the Ph-AuNP synthesis. The therapeutic activity of the Ph-AuNPs against osteosarcoma cancers was examined in MG-63 and SAOS-2 cell lines, while their biocompatibility was tested against Vero cell lines using a sulforhodamine B assay. The Ph-AuNPs had potent antitumor activity against the MG-63 and SAOS-2 cells, with a low toxicity toward Vero cells. Flow cytometry and cell cycle arrest analyses revealed that the Ph-AuNPs enhanced the apoptotic pathway and arrested the cell cycle in the MG-63 and SAOS-2 cells. strain AB_11_10 provides a new source to synthesize small, stable, and biocompatible AuNPs that act as apoptotic enhancers in osteosarcoma.

This study was carried out to extract essential oil from the aerial parts of Teucrium polium L. (TPO) using hydro-distillation, and to determine the chemical composition of the extract with GC-MS analysis. The plant was obtained from Huraymila City in the North-Western Riyadh. Total contents of phenolics (TPC) and flavonoids (TFC) were estimated as gallic acid (GA) equivalent and catechin (CH) equivalent, respectively, whereas the antioxidant activity was measured with DPPH assay. Agar disc diffusion and micro-broth dilution methods were utilized for antibacterial evaluation, while MTT assay was used for cytotoxicity evaluation. The average yield of TPO was 0.26±0.01%(v: w), and the predominant constituents were t-cadinol (25.58%), &agr-fenchene (20.09%), β-eudesmol (11.76%), β-myrcene (8.02%), γ-cadinene (5.22%), α-phellandrene (3.11%), epi-bicyclosesquiphellandrene (3.07%), and caryophyllene oxide (2.48%), all of which accounted for 79.33% of the identified compounds. The TPC and TFC of TPO were 138.33±3.1 pg GA equivalents mL-1 and 19±2.15 µg CH equivalents mL-1, respectively. The oil had good radical-scavenging activity, with IC50 of 61.38± 4.33 µg mL-1. It exhibited antibacterial activity against Gram-positive S. aureus and MRSA at 16.67 % (v/v), with inhibition zones of 13± 0.09 and 11± 0.13 mm, respectively, and MIC: MBC values of 0.26/0.52 and 0.5/21.04, respectively. However, it had no effect on the growth of negative strains (S. sonnei, P. aeruginosa, K. pneumoniae and E. coli). Results of anti-proliferative effects of TPO on two human colon cancer cell lines (HT-29 and HCT116) and hepatic cancer HepG2 cells, showed that it had a more cytotoxic effect on HT-29 and HCT116 cells, with IC50 values of 0.07± 0.03 and 0.14±0.06, respectively than on HepG2 which was markedly inhibited only at higher concentrations (p< 0.001). In conclusion, TPO exerted antimicrobial and antiproliferative properties. Overall, these findings are considered useful addition to biodiversity data and may be useful in food biotechnology and pharmaceutical industries.

The extreme health and economic problems in the world due to the SARS-CoV-2 infection have led to an urgent need to identify potential drug targets for treating coronavirus disease 2019 (COVID-19). The present state-of-the-art tool-based screening was targeted to identify drug targets among clinically approved drugs by uncovering SARS-CoV-2 helicase inhibitors through molecular docking analysis. Helicase is a vital viral replication enzyme, which unwinds nucleic acids and separates the double-stranded nucleic acids into single-stranded nucleic acids. Hence, the SARS-CoV-2 helicase protein 3D structure was predicted, validated, and used to screen the druggable targets among clinically approved drugs such as protease inhibitor, nucleoside reverse transcriptase inhibitor, and non-nucleoside reverse transcriptase inhibitors, used to treat HIV infection using molecular docking analysis. Interaction with SARS-CoV-2 helicase, approved drugs, vapreotide (affinity: -12.88; score: -9.84 kcal/mol), and atazanavir (affinity: -11.28; score: -9.32 kcal/mol), approved drugs for treating AIDS-related diarrhoea and HIV infection, respectively, are observed with significantly low binding affinity and MOE score or binding free energy. The functional binding pockets of the clinically approved drugs on SARS-CoV-2 helicase protein molecule suggest that vapreotide and atazanavir may interrupt the activities of the SARS-CoV-2 helicase. The study suggests that vapreotide may be a choice of drug for wet lab studies to inhibit the infection of SARS-CoV-2.

The SARS-CoV-2 (previously 2019-nCoV) outbreak in Wuhan, China and other parts of the world affects people and spreads coronavirus disease 2019 (COVID-19) through human-to-human contact, with a mortality rate of > 2%. There are no approved drugs or vaccines yet available against SARS-CoV-2. State-of-the-art tools based on in-silico methods are a cost-effective initial approach for identifying appropriate ligands against SARS-CoV-2. The present study developed the 3D structure of the envelope and nucleocapsid phosphoprotein of SARS-CoV-2, and molecular docking analysis was done against various ligands. The highest log octanol/water partition coefficient, high number of hydrogen bond donors and acceptors, lowest non-bonded interaction energy between the receptor and the ligand, and high binding affinity were considered for the best ligand for the envelope (mycophenolic acid: log = 3.00; D = -10.2567 kcal/mol; p = 7.713 µM) and nucleocapsid phosphoprotein (1-[(2,4-dichlorophenyl)methyl]pyrazole-3,5-dicarboxylic acid: log = 2.901; D = -12.2112 kcal/mol; p = 7.885 µM) of SARS-CoV-2. The study identifies the most potent compounds against the SARS-CoV-2 envelope and nucleocapsid phosphoprotein through state-of-the-art tools based on an in-silico approach. A combination of these two ligands could be the best option to consider for further detailed studies to develop a drug for treating patients infected with SARS-CoV-2, COVID-19.

The aim of this study is to investigate the single nucleotide polymorphisms (SNPs) associated with breast cancer in our population of Arab patients. We investigated 26 breast cancer patients and an equal number of healthy age- and sex-matched control volunteers. We examined the exome wide microarray-based biomarkers and screened 243,345 SNPs for their possible significant association with our breast cancer patients. Successfully, we identified the most significant (p value ≤9.14×10−09) four associated SNPs [SNRK and SNRK-AS1-rs202018563G; BRCA2-rs2227943C; ZNF484-rs199826847C; and DCPS-rs1695739G] among persons with breast cancer versus the healthy controls even after Bonferroni corrections (p value <2.05×10−07). Although our patients’ numbers were limited, the identified SNPs might shed some light on certain breast cancer-associated functional multigenic variations in Arab patients. We assert on the importance of more extensive large-scale analysis to confirm the candidate biomarkers and possible target genes of breast cancer among Arab ancestries.

Hemoglobinopathies are common disorders in Saudi Arabia and have an impact on the general health of the affected individuals. The current study aimed to find out the effects of the presence of α 3.7 kb rightward deletion or sickle-cell trait (SCT) on ventilatory and hemodynamic parameters of maximum exercise testing in young Saudi women. In a cross-sectional study, 75 randomly selected female students from different colleges were tested for VO using a COSMED system for maximum exercise testing. Blood parameters and globin genotyping were determined. Hemoglobin genetic studies revealed 28 of the students had 3.7 α-globin deletion only ( α /α α ), five had SCT, and 42 had normal α-globin (α α /α α and no HbS) and were considered the control group. Subjects with α /α α showed significantly lower VO and higher resting systolic blood pressure, while SCT carriers showed no difference in regard to ventilatory parameters, but had higher post-exercise systolic blood pressure than controls. It is concluded that individuals with 3.7 α-globin deletion might have lower fitness capacity, as demonstrated by lower VO , which might explain the general lower VO in the young women of this population. Furthermore, increments in resting systolic and posteexercise systolic blood pressure in 3.7 α-globin deletion and SCT, respectively, might indicate a future risk of cardiovascular diseases and require attention and extensive studies.