Biomedical and photocatalytic applications of biosynthesized silver nanoparticles: Ecotoxicology study of brilliant green dye and its mechanistic degradation pathways

© 2020 Elsevier B.V. The preparation of nanoparticles from biological materials is an economic and environmentally friendly strategy with several advantages. The current study is focused to synthesize silver nanoparticles using Petroselinum crispum plant extract. Various characteristics of biologically synthesized AgNPs were determined with UV–Visible (UV/Vis) Spectroscopy, X-ray Diffraction (XRD), Fourier Transform Infrared (FTIR) Spectroscopy, and High-Resolution Transmission Electron Microscopy (HRTEM). The plasmonic resonance peak at 425 nm ensured the formation of AgNPs. The FTIR analysis showed that the as-synthesized particles contain alcoholic and polyphenolic constituents, which are responsible for their capping and reduction. The HRTEM results revealed spherical shape of AgNPs with size ranging from 25 to 90 nm. The as-synthesized particles demonstrated excellent antibacterial properties against Gram positive and Gram-negative bacteria. The antioxidant applications of the particles were determined with 2,2-diphenyle-1-picrylhydrazyl (DPPH). Moreover, the photocatalytic application of the synthesized AgNPs was evaluated for brilliant green dye (BG). The results demonstrated high degradation of BG due to small size and well-dispersed nature of AgNPs. Degradation products of BG were identified to suggest degradation pathways. The eco-toxicity of the BG and constituents derived from the dye were studied with Ecological Structure Activity Relationship (ECOSAR) software

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

Bioinformatics: A rational combine approach used for the identification and in-vitro activity evaluation of potent β-Glucuronidase inhibitors.

Identification of hotspot drug-receptor interactions through in-silico prediction methods (Pharmacophore mapping, virtual screening, 3DQSAR, etc), is considered as a key approach in drug designing and development process. In the current design study, advanced in-silico based computational techniques were used for the identification of lead-like molecules against the targeted receptor β-glucuronidase. The binding pattern of a potent inhibitor in the ligand-receptor X-ray co-crystallize complex was used to identify and extract the structure-base Pharmacophore features. Based on these observations; five structure-based pharmacophore models were derived to conduct the virtual screening of ICCBS in-house data-base. Top-ranked identified Hits (33 compounds) were selected to subject for in-vitro biological activity evaluation against β-glucuronidase enzyme; out of them, twenty compounds (61% of screened compounds) evaluated as actives, however eleven compounds were found to have significantly higher inhibitory activity, including compounds 1, 5-8, 10, 12-13, and 17-19 with IC50 values ranging from 1.2 μM to 34.9 μM. Out of the eleven potent inhibitors, seven compounds 1, 5, 6, 7, 8, 13, and 19 were found new, and evaluated first time for the β-glucuronidase inhibitory activity. Compounds 1, 5 and 19 exhibited a highly potent inhibition in uM of β-glucuronidase enzyme with non-cytotoxic behavior against the mouse fibroblast (3T3) cell line. Our combined in-silico and in-vitro results revealed that the binding pattern analysis of the eleven potent inhibitors, showed almost similar non-covalent interactions, as observed in case of our validated pharmacophore model. The obtained results thus demonstrated that the virtual screening minimizes false positives, and provide a template for the identification and development of new and more potent β-glucuronidase inhibitors with non-toxic effects

Functionally graded additive manufacturing for orthopedic applications

Background: Additive Manufacturing due to its benefits in developing parts with complex geometries and shapes, has evolved as an alternate manufacturing process to develop implants with desired properties. The structure of human bones being anisotropic in nature is biologically functionally graded i,e. The structure possesses different properties in different directions. Therefore, various orthopedic implants such as knee, hip and other bone plates, if functionally graded can perform better. In this context, the development of functionally graded (FG) parts for orthopedic application with tailored anisotropic properties has become easier through the use of additive manufacturing (AM). Objectives: and Rationale: The current paper aims to study the various aspects of additively manufactured FG parts for orthopedic applications. It presents the details of various orthopedic implants such as knee, hip and other bone plates in a structured manner. A systematic literature review is conducted to study the various material and functional aspects of functionally graded parts for orthopedic applications. A section is also dedicated to discuss the mechanical properties of functionally graded parts. Conclusion: The literature revealed that additive manufacturing can provide lot of opportunities for development of functionally graded orthopedic implants with improved properties and durability. Further, the effect of various FG parameters on the mechanical behavior of these implants needs to be studied in detail. Also, with the advent of various AM technologies, the functional grading can be achieved by various means e.g. density, porosity, microstructure, composition, etc. By varying the AM parameters. However, the current limitations of cost and material biocompatibility prevent the widespread exploitation of AM technologies for various orthopedic applications

Tuning of electrical conduction properties of natural fibers and TiO2 based flexible paper composite sheets by electrodeposition of metallic nanolayers

In an era of modern smart technology, flexible electrodes are of great interest for different energy conversion as well as energy storage applications like solar cells, all solid-state batteries, and supercapacitors. Flexible metal oxide-based paper electrodes are advantageous in comparison to conventional electrodes due to their economical synthesis, biocompatibility, and environment-friendly characteristics. However, the electrical conductivity of paper electrodes is limited because of the insulating nature of natural fibers employed as a binder for the flexible matrix of metal oxides. The current study is an attempt to tune the electrical properties of lignocelluloses (natural fibers) and titanium dioxide (TiO2) based paper electrodes by facile electrodeposition technique. The crystalline parts (e.g., TiO2, Ag, and Au) of the prepared composite sheets were characterized by XRD analysis while the surface morphology was studied by SEM. FTIR was used to characterize the organic matter in LC fibers by identifying various molecular stretching and vibrational modes of C, H, and O-containing molecules. Electric permittivity was measured as a function of electric field frequency at room temperature which revealed the value of 23. 5 (at 1 kHz) for the sample LC/TiO2/Ag 9000s indicating the best charge storing capability of the sample. Impedance analysis was employed to identify various charge carrier mechanisms active in the sheets. It was found through impedance analysis that there is an active diffusion-controlled impedance mechanism of Au-coated samples causing an increased conductivity via the ionic diffusion. This diffusion-controlled conduction was modeled by the Warburg element. The enhanced conductivity due to ionic diffusion makes these samples more useful as electrodes. Cyclic voltammetry (CV) measurements of the electrodeposited samples established the increase in conductive properties and efficient kinetics of LC/TiO2 paper sheets. The current study suggests that Ag and Au-coated paper electrodes can be potential candidates for energy conversion and storage applications

Synthesis of 2-Aminopyrimidine Derivatives and Their Evaluation as &beta;-Glucuronidase Inhibitors: In Vitro and In Silico Studies

Currently the discovery and development of potent &beta;-glucuronidase inhibitors is an active area of research due to the observation that increased activity of this enzyme is associated with many pathological conditions, such as colon cancer, renal diseases, and infections of the urinary tract. In this study, twenty-seven 2-aminopyrimidine derivatives 1&ndash;27 were synthesized by fusion of 2-amino-4,6-dichloropyrimidine with a variety of amines in the presence of triethylamine without using any solvent and catalyst, in good to excellent yields. All synthesized compounds were characterized by EI-MS, HREI-MS and NMR spectroscopy. Compounds 1&ndash;27 were then evaluated for their &beta;-glucuronidase inhibitory activity, and among them, compound 24 (IC50 = 2.8 &plusmn; 0.10 &micro;M) showed an activity much superior to standard D-saccharic acid 1,4-lactone (IC50 = 45.75 &plusmn; 2.16 &micro;M). To predict the binding mode of the substrate and &beta;-glucuronidase, in silico study was performed. Conclusively, this study has identified a potent &beta;-glucuronidase inhibitor that deserves to be further studied for the development of pharmaceutical products