Post-traumatic osteoarthritis in mice following mechanical injury to the synovial joint

We investigated the spectrum of lesions characteristic of post-traumatic osteoarthritis (PTOA) across the knee joint in response to mechanical injury. We hypothesized that alteration in knee joint stability in mice reproduces molecular and structural features of PTOA that would suggest potential therapeutic targets in humans. The right knees of eight-week old male mice from two recombinant inbred lines (LGXSM-6 and LGXSM-33) were subjected to axial tibial compression. Three separate loading magnitudes were applied: 6N, 9N, and 12N. Left knees served as non-loaded controls. Mice were sacrificed at 5, 9, 14, 28, and 56 days post-loading and whole knee joint changes were assessed by histology, immunostaining, micro-CT, and magnetic resonance imaging. We observed that tibial compression disrupted joint stability by rupturing the anterior cruciate ligament (except for 6N) and instigated a cascade of temporal and topographical features of PTOA. These features included cartilage extracellular matrix loss without proteoglycan replacement, chondrocyte apoptosis at day 5, synovitis present at day 14, osteophytes, ectopic calcification, and meniscus pathology. These findings provide a plausible model and a whole-joint approach for how joint injury in humans leads to PTOA. Chondrocyte apoptosis, synovitis, and ectopic calcification appear to be targets for potential therapeutic intervention

Modification of bauxite residue with oxalic acid for improved performance in intumescent coatings

Valorization of bauxite residue (BR) enhances the dynamics of its application in intumescent coating for fire retarding systems. This BR, an alumina production waste could contain up to 45% ferrous oxide along with residual aluminous minerals. In an attempt to optimize the fire retardant properties of these minerals in intumescent systems, BR was treated in oxalic acid, varying the heating temperature between 50 °C and 100 °C at a constant pH of 2.65. X-ray florescence spectrometry revealed up to 80% reduction in iron content and total dissolution of desilication products (DSPs). The process temperature was found to affect the efficiency with which iron oxide was removed and with which the dissolved DSPs were precipitated as aluminum hydrates. X-ray diffraction revealed increased crystallinity and a gibbsite-dominated compound. Incorporation of the modified bauxite residues into a control intumescing formulation resulted in improved endothermic cooling, increased char expansion and char reinforcement. An inverse relationship appeared to exist between aluminum hydrates and iron as removal of iron led to enhanced intumescence and increased char expansion while higher iron content led to a compact, less expanded char. A balance of the fire retarding minerals occurred at a leaching temperature of 75 °C in oxalic acid. Best heat shielding performance thus occurred at XBR75-IC5 as char expansion increased by 12% and the substrate temperature reduced by 31% over the control IC system. Thus, BR may act as alternative fire retardant filler for intumescing systems

Natural Products-Based Drug Design against SARS-CoV-2 Mpro 3CLpro

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has received global attention due to the serious threat it poses to public health. Since the outbreak in December 2019, millions of people have been affected and its rapid global spread has led to an upsurge in the search for treatment. To discover hit compounds that can be used alone or in combination with repositioned drugs, we first analyzed the pharmacokinetic and toxicological properties of natural products from Brazil’s semiarid region. After, we analyzed the site prediction and druggability of the SARS-CoV-2 main protease (Mpro), followed by docking and molecular dynamics simulation. The best SARS-CoV-2 Mpro complexes revealed that other sites were accessed, confirming that our approach could be employed as a suitable starting protocol for ligand prioritization, reinforcing the importance of catalytic cysteine-histidine residues and providing new structural data that could increase the antiviral development mainly against SARSCoV-2. Here, we selected 10 molecules that could be in vitro assayed in response to COVID-19. Two compounds (b01 and b02) suggest a better potential for interaction with SARS-CoV-2 Mpro and could be further studied.Research Dean and Graduate Studies of the Federal University of Pará (PROPESP/UFPA)Brazilian National Council for Scientific and Technological Development (CNPq)Brazilian Coordination for Improvement of Personnel Higher Education (CAPES)Bahia Research Foundation (FAPESB, grant numbers APP071/2011, JCB-0039/2013, and RED-008/2013

In Silico Study to Identify New Antituberculosis Molecules from Natural Sources by Hierarchical Virtual Screening and Molecular Dynamics Simulations

The authors acknowledge the Graduate Program in Biotechnology/UEFS for academic support.Tuberculosis (TB) is an infection caused by Mycobacterium tuberculosis, responsible for 1.5 million documented deaths in 2016. The increase in reported cases of M. tuberculosis resistance to the main drugs show the need for the development of new and efficient drugs for better TB control. Based on these facts, this work aimed to use combined in silico techniques for the discovery of potential inhibitors to β-ketoacyl-ACP synthase (MtKasA). Initially compounds from natural sources present in the ZINC database were selected, then filters were sequentially applied by virtual screening, initially with pharmacophoric modeling, and later the selected compounds (based on QFIT scores) were submitted to the DOCK 6.5 program. After recategorization of the variables (QFIT score and GRID score), compounds ZINC35465970 and ZINC31170017 were selected. These compounds showed great hydrophobic contributions and for each established system 100 ns of molecular dynamics simulations were performed and the binding free energy was calculated. ZINC35465970 demonstrated a greater capacity for the KasA enzyme inhibition, with a ΔGbind = −30.90 kcal/mol and ZINC31170017 presented a ΔGbind = −27.49 kcal/mol. These data can be used in other studies that aim at the inhibition of the same biological targets through drugs with a dual action

Winning or not winning: the influence on coach-athlete relationships and goal achievement

This study analyses the relation between sports success and athletes’ perception of coaches’ leadership, athletes’ satisfaction with coaches’ leadership, coach-athlete compatibility, and goal achievement. Sixty-six athletes who qualified for the final Division I play-offs of a professional volleyball championship were grouped into winning (n = 21) and non-winning teams (n = 45). Leadership styles, satisfaction with leadership, coach-athlete compatibility, and goal achievement were evaluated. Analysis of variance with repeated-measures revealed that the winning teams evaluated their coaches’ vision, inspiration, technical instruction, positive feedback, and active management more positively than non-winning teams and that their satisfaction with coaches’ strategies increased over time. A multivariate analysis of variance (MANOVA) indicated that the winning teams’ perceived achievement of personal and team goals was greater than that of the non-winning teams. Sports success was associated with athletes’ positive evaluation of coaches’ leadership, satisfaction with coaches’ strategy, and higher perceived goal attainment

Identification of Potential Inhibitors from Pyriproxyfen with Insecticidal Activity by Virtual Screening

Aedes aegypti is the main vector of dengue fever transmission, yellow fever, Zika, and chikungunya in tropical and subtropical regions and it is considered to cause health risks to millions of people in the world. In this study, we search to obtain new molecules with insecticidal potential against Ae. aegypti via virtual screening. Pyriproxyfen was chosen as a template compound to search molecules in the database Zinc_Natural_Stock (ZNSt) with structural similarity using ROCS (rapid overlay of chemical structures) and EON (electrostatic similarity) software, and in the final search, the top 100 were selected. Subsequently, in silico pharmacokinetic and toxicological properties were determined resulting in a total of 14 molecules, and these were submitted to the PASS online server for the prediction of biological insecticide and acetylcholinesterase activities, and only two selected molecules followed for the molecular docking study to evaluate the binding free energy and interaction mode. After these procedures were performed, toxicity risk assessment such as LD50 values in mg/kg and toxicity class using the PROTOX online server, were undertaken. Molecule ZINC00001624 presented potential for inhibition for the acetylcholinesterase enzyme (insect and human) with a binding affinity value of -10.5 and -10.3 kcal/mol, respectively. The interaction with the juvenile hormone was -11.4 kcal/mol for the molecule ZINC00001021. Molecules ZINC00001021 and ZINC00001624 had excellent predictions in all the steps of the study and may be indicated as the most promising molecules resulting from the virtual screening of new insecticidal agents.Federal University of Amapá, Program in Biotechnology and Biodiversity-Network BIONORTE, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for funding in the publication of this article

Silver colloidal nanoparticles : effect on matrix composition and structure of Candida albicans and Candida glabrata biofilms

Aim : The aim of this study was to assess the effect of different silver nanoparticles (SN) concentrations on the matrix composition and structure of Candida albicans and Candida glabrata biofilms. Methods and Results : Candida biofilms were developed in 6-well microtiter plates during 48 h. After, these biofilms were exposed to 13·5 or 54 μg SN ml−1 for 24 h. Then, extracellular matrices were extracted from biofilms and analysed chemically in terms of proteins, carbohydrates and DNA. To investigate the biofilm structure, scanning electron microscopy (SEM) and epifluorescence microscopy were used. SN interfered with the matrix composition of Candida biofilms tested in terms of protein, carbohydrate and DNA, except for the protein content of C. albicans biofilm. By SEM, Candida biofilms treated with SN revealed structural differences, when compared with the control groups. Further, SN showed a trend of agglomeration within the biofilms. Epifluorescence microscopy images suggest that SN induced damage on cell walls of the Candida isolates tested. Conclusions : In general, irrespective of concentration, SN affected the matrix composition and structure of Candida biofilms and these findings may be related to the mechanisms of biocide action of SN. Significance and Impact of the Study : This study reveals new insights about the behaviour of SN when in contact with Candida biofilms. SN may contribute to the development of therapies to prevent or control Candida infections.We thank David Williams (Cardiff University, Cardiff, UK) for providing strain 324LA/94. The authors also thank CAPES (grant BEX 1221/10-8) and FAPESP (2009/15146-5), Brazil, for supporting Douglas Roberto Monteiro work. The colloidal suspension of silver nanoparticles used herein was prepared and characterized by LIEC-CMDMC and INCTMN/FAPESP-CNPq, Sao Carlos, Brazil

An environmentally benign antimicrobial nanoparticle based on a silver-infused lignin core

Silver nanoparticles have antibacterial properties, but their use has been a cause for concern because they persist in the environment. Here, we show that lignin nanoparticles infused with silver ions and coated with a cationic polyelectrolyte layer form a biodegradable and green alternative to silver nanoparticles. The polyelectrolyte layer promotes the adhesion of the particles to bacterial cell membranes and, together with silver ions, can kill a broad spectrum of bacteria, including Escherichia coli, Pseudomonas aeruginosa and quaternary-amine-resistant Ralstonia sp. Ion depletion studies have shown that the bioactivity of these nanoparticles is time-limited because of the desorption of silver ions. High-throughput bioactivity screening did not reveal increased toxicity of the particles when compared to an equivalent mass of metallic silver nanoparticles or silver nitrate solution. Our results demonstrate that the application of green chemistry principles may allow the synthesis of nanoparticles with biodegradable cores that have higher antimicrobial activity and smaller environmental impact than metallic silver nanoparticles