Bioreduction of silver nanoparticles from aerial parts of Euphorbia hirta L. (EH-ET) and its potent anticancer activities against neuroblastoma cell lines

Euphorbia hirta L. (Family: Euphorbiaceae) is a versatile medicinal plant and enriched with novel bioactive molecules and possess broad-spectrum pharmacological actions. Present work is aiming to synthesis and characterize of silver nanoparticles (AgNPs) by bioreduction method an using ethanolic extract of aerial parts of Euphorbia hirta L. (EH-ET). The synthesized AgNPs observed by a color change of source solution (as AgNPs) and further confirmed by the UV-Visible spectroscopic technique. The AgNPs synthesized were characterized by Scanning Electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR) and Zeta potential analysis. The synthesized AgNPs are polydispersed and some places it’s agglomerated. The particle size EH-ET silver nanoparticles were analyzed using Beckman coulter particle size analyzer (DelsaTM Nano common). The average size of the particles size noted in 2.9-206.3 nm. Anticancer activity of EH-ET Silver nanoparticles was tested against neuroblastoma cells (SH-SY5Y) and breast cancer cells (SH-SY5Y) and cytotoxicity were tested in vero cells by MTT assay. The preliminary confirmation of the synthesized AgNPs by the present method was made by the appearance of reddish brown color and the visible absorption peak at 429.5 nm. SEM image revealed that AgNPs synthesized were spherical in shape and silver nanoparticles were in the size range of 2.9 to 206.3 nm. FT-IR spectra showed the peaks corresponding to functional groups C=O, -C=C and -OH, which actively participated in bio-reduction and subsequent stabilization reactions in the synthesis of AgNPs. The obtained nanoparticles showed promising anticancer activity against neuroblastoma cells (SH-SY5Yc) and breast cancer cells (MCF-7) with IC50 values of 29.85 and 335 µg/mL, respectively. Whereas, the nanoparticles did not show any activity against vero cell lines. The synthesized silver nanoparticles using an ethanolic extract of Euphorbia hirta L. would be helpful for the preparation of potent cytotoxicity agents to destroy cancer cells

Probing and Manipulating the Lateral Pressure Profile in Lipid Bilayers Using Membrane-Active Peptides—A Solid-State 19F NMR Study

The lateral pressure profile constitutes an important physical property of lipid bilayers, influencing the binding, insertion, and function of membrane-active peptides, such as antimicrobial peptides. In this study, we demonstrate that the lateral pressure profile can be manipulated using the peptides residing in different regions of the bilayer. A $^{19}$F-labeled analogue of the amphiphilic peptide PGLa was used to probe the lateral pressure at different depths in the membrane. To evaluate the lateral pressure profile, we measured the orientation of this helical peptide with respect to the membrane using solid-state $^{19}$F-NMR, which is indicative of its degree of insertion into the bilayer. Using this experimental approach, we observed that the depth of insertion of the probe peptide changed in the presence of additional peptides and, furthermore, correlated with their location in the membrane. In this way, we obtained a tool to manipulate, as well as to probe, the lateral pressure profile in membranes

Phosphate-dependent aggregation of [KL]n_{n} peptides affects their membranolytic activity

In this study, we investigate how the length of amphiphilic β-sheet forming peptides affects their interaction with membranes. Four polycationic model peptides with lengths from 6 to 18 amino acids were constructed from simple Lys-Leu repeats, giving [KL]$_{n=3,5,7,9}$. We found that (1) they exhibit a pronounced antimicrobial activity with an intriguing length dependent maximum for [KL]$_{5}$ with 10 amino acids; (2) their hemolytic effect, on the other hand, increases steadily with peptide length. CD analysis (3) and TEM (4) show that all peptides-except for the short [KL]$_{3}$-aggregate into amyloid-like fibrils in the presence of phosphate ions, which in turn has a critical effect on the results in (1) and (2). In fact, (5) vesicle leakage reveals an intrinsic membrane-perturbing activity (at constant peptide mass) of [KL]$_{5}$ > [KL]$_{9}$ > [KL]7 in phosphate buffer, which changes to [KL]$_{5}$ ≈ [KL]$_{7}$ ≈ [KL]$_{9}$ in PIPES. A specific interaction with phosphate ions thus explains the subtle balance between two counteracting effects: phosphate-induced unproductive pre-aggregation in solution versus monomeric membrane binding and vigorous lipid perturbation due to self-assembly of the bound peptides within the bilayer. This knowledge can now be used to control and optimize the peptides in further applications

Antibacterial, antioxidant and anti-proliferative properties and zinc content of five south Portugal herbs

Context: Crataegus monogyna L. (Rosaceae) (CM), Equisetum telmateia L. (Equisataceae) (ET), Geranium purpureum Vil. (Geraniaceae) (GP), Mentha suaveolens Ehrh. (Lamiaceae) (MS), and Lavandula stoechas L. spp. luisieri (Lamiaceae) (LS) are all medicinal. Objective: To evaluate the antioxidant, antiproliferative and antimicrobial activities of plant extracts and quantify individual phenolics and zinc. Material and methods: Aerial part extracts were prepared with water (W), ethanol (E) and an 80% mixture (80EW). Antioxidant activity was measured with TAA, FRAP and RP methods. Phenolics were quantified with a HPLC. Zinc was quantified using voltammetry. Antibacterial activity (after 48 h) was tested using Enterococcus faecalis, Bacillus cereus, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Listeria monocytogenes. Antiproliferative activity (after 24 h) was tested using HEP G2 cells and fibroblasts. Results: Solvents influenced results; the best were E and 80EW. GP had the highest antioxidant activity (TAA and FRAP of 536.90mg AAE/g dw and 783.48mg TE/g dw, respectively). CM had the highest zinc concentration (37.21 mg/kg) and phenolic variety, with neochlorogenic acid as the most abundant (92.91 mg/100 g dw). LS was rich in rosmarinic acid (301.71 mg/100 g dw). GP and LS inhibited the most microorganisms: B. cereus, E. coli and S. aureus. GP also inhibited E. faecalis. CM had the lowest MIC: 5830 mu g/mL. The antibacterial activity is explained by the phenolics present. LS and CM showed the most significant anti-proliferative activity, which is explained by their zinc content. Conclusion: The most promising plants for further studies are CM, LS and GP.FCT, Fundacao para a Ciencia e a Tecnologia of Portugal [SFRH/BSA/139/2014

Membranolytic Mechanism of Amphiphilic Antimicrobial β-Stranded [KL]n_n Peptides

Amphipathic peptides can act as antibiotics due to membrane permeabilization. KL peptides with the repetitive sequence [Lys-Leu]$_n$-NH$_2$ form amphipathic β-strands in the presence of lipid bilayers. As they are known to kill bacteria in a peculiar length-dependent manner, we suggest here several different functional models, all of which seem plausible, including a carpet mechanism, a β-barrel pore, a toroidal wormhole, and a β-helix. To resolve their genuine mechanism, the activity of KL peptides with lengths from 6–26 amino acids (plus some inverted LK analogues) was systematically tested against bacteria and erythrocytes. Vesicle leakage assays served to correlate bilayer thickness and peptide length and to examine the role of membrane curvature and putative pore diameter. KL peptides with 10–12 amino acids showed the best therapeutic potential, i.e., high antimicrobial activity and low hemolytic side effects. Mechanistically, this particular window of an optimum β-strand length around 4 nm (11 amino acids × 3.7 Å) would match the typical thickness of a lipid bilayer, implying the formation of a transmembrane pore. Solid-state $^{15}$N- and $^{19}$F-NMR structure analysis, however, showed that the KL backbone lies flat on the membrane surface under all conditions. We can thus refute any of the pore models and conclude that the KL peptides rather disrupt membranes by a carpet mechanism. The intriguing length-dependent optimum in activity can be fully explained by two counteracting effects, i.e., membrane binding versus amyloid formation. Very short KL peptides are inactive, because they are unable to bind to the lipid bilayer as flexible β-strands, whereas very long peptides are inactive due to vigorous pre-aggregation into β-sheets in solution

QT Interval Prolongation and Torsade De Pointes in Patients with COVID-19 treated with Hydroxychloroquine/Azithromycin

Background: There is no known effective therapy for patients with COVID-19. Initial reports suggesting the potential benefit of Hydroxychloroquine/Azithromycin (HY/AZ) have resulted in massive adoption of this combination worldwide. However, while the true efficacy of this regimen is unknown, initial reports have raised concerns regarding the potential risk of QT prolongation and induction of torsade de pointes (TdP). Objective: to assess the change in QTc interval and arrhythmic events in patients with COVID-19 treated with HY/AZ METHODS: This is a retrospective study of 251 patients from two centers, diagnosed with COVID-19 and treated with HY/AZ. We reviewed ECG tracings from baseline and until 3 days after completion of therapy to determine the progression of QTc and incidence of arrhythmia and mortality. Results: QTc prolonged in parallel with increasing drug exposure and incompletely shortened after its completion. Extreme new QTc prolongation to > 500 ms, a known marker of high risk for TdP had developed in 23% of patients. One patient developed polymorphic ventricular tachycardia (VT) suspected as TdP, requiring emergent cardioversion. Seven patients required premature termination of therapy. The baseline QTc of patients exhibiting extreme QTc prolongation was normal. Conclusion: The combination of HY/AZ significantly prolongs the QTc in patients with COVID-19. This prolongation may be responsible for life threating arrhythmia in the form of TdP. This risk mandates careful consideration of HY/AZ therapy in lights of its unproven efficacy. Strict QTc monitoring should be performed if the regimen is given

Opinions: Business History and Anthropology

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Different expectations: a comparative history of structure, experience, and strategic alliances in the U.S. and U.K. poultry sectors, 1920-1990

This comparative historical analysis demonstrates how memory and reflexive interpretations of the past can shape entrepreneurial willingness to collaborate with larger firms in an industry. Emphasizing the importance of spatial metaphors and periodization for developing historical knowledge, the paper focuses on how the historical space of experience explains how entrepreneurs make strategic choices regarding collaboration under conditions of complexity and uncertainty. Comparing the U.S. and U.K. emerging poultry sectors offers a methodologically novel analysis of an important but little‐studied agribusiness sector, offering a dual reading that compares two versions of historical reasoning both theoretically and empirically