Direct observation of DNA threading in flap endonuclease complexes

Maintenance of genome integrity requires that branched nucleic acid molecules are accurately processed to produce double-helical DNA. Flap endonucleases are essential enzymes that trim such branched molecules generated by Okazaki fragment synthesis during replication. Here, we report crystal structures of bacteriophage T5 flap endonuclease in complexes with intact DNA substrates, and products, at resolutions of 1.9–2.2 Å. They reveal single-stranded DNA threading through a hole in the enzyme enclosed by an inverted Vshaped helical arch straddling the active site. Residues lining the hole induce an unusual barb-like conformation in the DNA substrate juxtaposing the scissile phosphate and essential catalytic metal ions. A series of complexes and biochemical analyses show how the substrate’s single-stranded branch approaches, threads through, and finally emerges on the far side of the enzyme. Our studies suggest that substrate recognition involves an unusual “flycasting, thread, bend and barb” mechanis

Tannin Nanoparticles (NP99) Enhances the Anticancer Effect of Tamoxifen on ER+ Breast Cancer Cells

International audienc

Green Fabrication of Zinc Oxide Nanoparticles Using Phlomis Leaf Extract: Characterization and In Vitro Evaluation of Cytotoxicity and Antibacterial Properties

Green nanoparticle synthesis is an environmentally friendly approach that uses natural solvents. It is preferred over chemical and physical techniques due to the time and energy savings. This study aimed to synthesize zinc oxide nanoparticles (ZnO NPs) through a green method that used Phlomis leaf extract as an effective reducing agent. The synthesis and characterization of ZnO NPs were confirmed by UV-Vis spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Dynamic light scattering (DLS), Zeta potential, and Field Emission Scanning Electron Microscope (FESEM) techniques. In vitro cytotoxicity was determined in L929 normal fibroblast cells using MTT assay. The antibacterial activity of ZnO nanoparticles was investigated using a disk-diffusion method against S. aureus and E. coli, as well as minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) content concentrations. XRD results confirmed the nanoparticles’ crystalline structure. Nanoparticle sizes were found to be around 79 nm by FESEM, whereas the hydrodynamic radius of nanoparticles was estimated to be around 165 ± 3 nm by DLS. FTIR spectra revealed the formation of ZnO bonding and surfactant molecule adsorption on the surface of ZnO NPs. It is interesting to observe that aqueous extracts of Phlomis leave plant are efficient reducing agents for green synthesis of ZnO NPs in vitro, with no cytotoxic effect on L929 normal cells and a significant impact on the bacteria tested

Recent Advances in Plant-Mediated Zinc Oxide Nanoparticles with Their Significant Biomedical Properties

Compared to traditional physical and chemical approaches, nanobiotechnology and plant-based green synthesis procedures offer significant advantages, as well as having a greater range of medical and biotechnological applications. Nanoparticles of zinc oxide (ZnO NPs) have recently been recognized as a promising option for many industries, including optics, electrics, packaged foods, and medicine, due to their biocompatibility, low cytotoxicity, and cost-effectiveness. Several studies have shown that zinc ions are important in triggering cell apoptosis by promoting the generation of reactive oxygen species (ROSs) and releasing zinc ions (Zn2+), which are toxic to cells. The toxic nature of the chemicals used in the synthesis of ZnO nanoparticles limits their clinical utility. An overview of recent developments in green ZnO NP synthesis is presented in this review, emphasizing plant parts as reducing agents and their medical applications, including their antimicrobial, anticancer, antioxidant, and anti-inflammatory properties, as well as key mechanisms of action for these applications to facilitate further research on the biomedical fields in the future

Gold nanoparticles loaded TNF-alpha and CALNN peptide as a drug delivery system and promising therapeutic agent for breast cancer cells

We investigated the anti-cancer properties of gold nanoparticles loaded TNF- and CALNN peptides, which we proposed as a potential drug delivery system using in vitro and in vivo models. The binding of GNPs-TNF- and GNPs-TNF-CALNN was characterized using a UV, ELISA and SEM analysis. The outcomes demonstrated that a novel drug delivery system had an anti-proliferative activity against breast cancer cell lines through a mechanism of apoptosis induction. In vivo model involved studying the cytotoxic influence of a drug delivery system GNPs, GNPs-TNF-alpha and GNPs-TNF-alpha-CALNN when applied to the transplanted AN-3 cell line. tumor sections were examined using microarray. In-vivo studies demonstrated that GNPs alone had less of a growth inhibitory effect on tumors implanted in mice when compared to GNPs-TNF-CALNN combined therapy. The cytotoxic assay showed that GNPs, GNPs-TNF-alpha and GNPs-TNF-alpha-CALNN exhibit selective toxicity towards cancer cells, inducing cell apoptosis through activation of caspase-3 and 7, p53 protein

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population