Palbociclib (PD 0332991) Interaction with Kinases. Theoretical and Comparative Molecular Docking Study.

The optimized geometry of palbociclib, (PD 0332991) (8-cyclopentyl-6-ethanoyl-5-methyl-2-(5-(piperazin-1-yl)pyridin-2-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one), electrostatic potential map, molecular orbitals were calculated using the density functional theory. The geometry was used in a molecular docking study of palbociclib-kinase complexes, results could be explained by the charge of the nitrogen and oxygen atoms within the palbociclib. Energy gap of HOMO-LUMO surfaces, could help to explain the reactivity of the ligand and the hydrogen bonding with three different kinases, two of CDK6 and one of CDK4 type. Docking results are similar and complementary with literature reports using molecular dynamics, were hydrogen bonding was obtained and analyzed. The promiscuity of three kinases with palbociclib was detected by the docking results, thus, palbociclib could be used in other types of cancer besides myeloid leukemia. Some similarities are found with CDK4/CDK6 kinases which allow us to determine that palbociclib could be used to control other resistant inhibitor types of cancer.

Experimental Pharmacology for COVID-19 Treatment: A Geoanalytical Bibliometric Analysis.

OBJECTIVE: The objective of this study is to produce a geo-referenced map of the status of R&D in COVID-related studies in the world. METHODS: Spatial mapping of bibliometric data of Cortellis Drug Discovery Intelligence through a spatial bibliometric model with the aid of a GIS (Geographic Information System) called ArcGIS and the software. RESULTS: We show the countries that have the most studies related to COV ID-19 and their degree of collaboration. No drug discovery-related activity was found in South America and Africa. A geo-referenced map of the most active countries in COVID research was constructed as well as conceptual maps of the 11 most representative drugs employed for COVID treatment. CONCLUSION: The georeferenced conceptual maps produced in the present report allow not only to better understand the leading institutions in R&D in COVID-19 related drugs but also to visualize their interactions and research relationships. This could offer, in addition to a coherent, organized multinational effort, the possibility of searching for other drugs that have been employed for other diseases and that, in terms of their conceptual relations, could represent some possibilities for treating the coronavirus SARS-2.

Opioids for pain treatment of cancer: A knowledge maturity mapping.

The conceptual structure of opioids, based on the bibliometric analysis of 4,935 articles of the Web of Science using the following indices: Science Citation Index Expanded (SCI-EXPANDED), Social Sciences Citation Index (SSCI), Conference Proceedings Citation Index-Science (CPCI-S), Conference Proceedings Citation Index- Social Science and Humanities (CPCI-SSH), Book Citation Index-Science (BKCI-S), Book Citation Index-Social Sciences and Humanities (BKCI-SSH) and Emerging Sources Citation Index (ESCI), was constructed. We analyzed the available articles with the words "Opioids" and "Cancer." We show the evolution and the state of the art in countries where these treatments are implemented. The results were processed identifying the most cited articles to extract the main connections and frequencies of keywords, authors, journals, countries, institutions, and their tendencies and their connection and degree of collaboration. The temporal tendencies, the word cloud, the keyword network, the evolution of words, author's production, and the scientific production by country are analyzed in terms of the increasing frequency in which opioids are employed to treat both cancerous and non-cancerous pain.

Electrostatic Spray Disinfection Using Nano-Engineered Solution on Frequently Touched Surfaces in Indoor and Outdoor Environments.

The COVID-19 pandemic has resulted in high demand for disinfection technologies. However, the corresponding spray technologies are still not completely optimized for disinfection purposes. There are important problems, like the irregular coverage and dripping of disinfectant solutions on hard and vertical surfaces. In this study, we highlight two major points. Firstly, we discuss the effectiveness of the electrostatic spray deposition (ESD) of nanoparticle-based disinfectant solutions for systematic and long-lasting disinfection. Secondly, we show that, based on the type of material of the substrate, the effectiveness of ESD varies. Accordingly, 12 frequently touched surface materials were sprayed using a range of electrostatic spray system parameters, including ion generator voltage, nozzle spray size and distance of spray. It was observed that for most cases, the surfaces become completely covered with the nanoparticles within 10 s. Acrylic, Teflon, PVC, and polypropylene surfaces show a distinct effect of ESD and non-ESD sprays. The nanoparticles form a uniform layer with better surface coverage in case of electrostatic deposition. Quantitative variations and correlations show that 1.5 feet of working distance, an 80 µm spray nozzle diameter and an ion generator voltage of 3-7 kV ensures a DEF (differential electric field) that corresponds to an optimized charge-to-mass ratio, ensuring efficient coverage of nanoparticles.

Tomographic analysis of the temporomandibular joint in patients with arthritis: a case of disease translation in Yucatan, Mexico.

Computed tomography imaging of the temporomandibular joint was carried out in 22 previously-diagnosed arthritis patients (3 men, 19 women). This descriptive, cross-sectional observational, qualitative study allowed to characterize the type of condylar morphology condition, the space between temporomandibular joint, the erosion of the cortical and osteophytes formation. The joint characteristics found were cortical erosion, osteophytes and decrease of joint space, which reveals, for the first time in the literature, a correlation between arthritis and temporomandibular joint disease.

The emergence and evolution of the research fronts in HIV/AIDS research.

In this paper, we have identified and analyzed the emergence, structure and dynamics of the paradigmatic research fronts that established the fundamentals of the biomedical knowledge on HIV/AIDS. A search of papers with the identifiers "HIV/AIDS", "Human Immunodeficiency Virus", "HIV-1" and "Acquired Immunodeficiency Syndrome" in the Web of Science (Thomson Reuters), was carried out. A citation network of those papers was constructed. Then, a sub-network of the papers with the highest number of inter-citations (with a minimal in-degree of 28) was selected to perform a combination of network clustering and text mining to identify the paradigmatic research fronts and analyze their dynamics. Thirteen research fronts were identified in this sub-network. The biggest and oldest front is related to the clinical knowledge on the disease in the patient. Nine of the fronts are related to the study of specific molecular structures and mechanisms and two of these fronts are related to the development of drugs. The rest of the fronts are related to the study of the disease at the cellular level. Interestingly, the emergence of these fronts occurred in successive "waves" over the time which suggest a transition in the paradigmatic focus. The emergence and evolution of the biomedical fronts in HIV/AIDS research is explained not just by the partition of the problem in elements and interactions leading to increasingly specialized communities, but also by changes in the technological context of this health problem and the dramatic changes in the epidemiological reality of HIV/AIDS that occurred between 1993 and 1995.

Green synthesis of nanosilver-decorated graphene oxide sheets.

A green facile method has been successfully used for the synthesis of graphene oxide sheets decorated with silver nanoparticles (rGO/AgNPs), employing graphite oxide as a precursor of graphene oxide (GO), AgNO3 as a precursor of Ag nanoparticles (AgNPs), and geranium (Pelargonium graveolens) extract as reducing agent. Synthesis was accomplished using the weight ratios 1:1 and 1:3 GO/Ag, respectively. The synthesised nanocomposites were characterised by scanning electron microscopy, transmission electron microscopy, atomic force microscopy, X-ray diffraction, UV-visible spectroscopy, Raman spectroscopy, energy dispersive X-ray spectroscopy and thermogravimetric analysis. The results show a more uniform and homogeneous distribution of AgNPs on the surface of the GO sheets with the weight ratio 1:1 in comparison with the ratio 1:3. This eco-friendly method provides a rGO/AgNPs nanocomposite with promising applications, such as surface enhanced Raman scattering, catalysis, biomedical material and antibacterial agent.

Biosynthesis of catechol melanin from glycerol employing metabolically engineered Escherichia coli.

BACKGROUND: Melanins comprise a chemically-diverse group of polymeric pigments whose function is related to protection against physical and chemical stress factors. These polymers have current and potential applications in the chemical, medical, electronics and materials industries. The biotechnological production of melanins offers the possibility of obtaining these pigments in pure form and relatively low cost. In this study, Escherichia coli strains were engineered to evaluate the production of melanin from supplemented catechol or from glycerol-derived catechol produced by an Escherichia coli strain generated by metabolic engineering. RESULTS: It was determined that an improved mutant version of the tyrosinase from Rhizobium etli (MutmelA), could employ catechol as a substrate to generate melanin. Strain E. coli W3110 expressing MutmelA was grown in bioreactor batch cultures with catechol supplemented in the medium. Under these conditions, 0.29 g/L of catechol melanin were produced. A strain with the capacity to synthesize catechol melanin from a simple carbon source was generated by integrating the gene MutmelA into the chromosome of E. coli W3110 trpD9923, that has been modified to produce catechol by the expression of genes encoding a feedback inhibition resistant version of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase, transketolase and anthranilate 1,2-dioxygenase from Pseudomonas aeruginosa PAO1. In batch cultures with this strain employing complex medium with 40 g/L glycerol as a carbon source, 1.21 g/L of catechol melanin were produced. The melanin was analysed by employing Fourier transform infrared spectroscopy, revealing the expected characteristics for a catechol-derived polymer. CONCLUSIONS: This constitutes the first report of an engineered E. coli strain and a fermentation process for producing a catechol melanin from a simple carbon source (glycerol) at gram level, opening the possibility of generating a large quantity of this polymer for its detailed characterization and the development of novel applications.

Hierarchy of Knowledge Translation: From Health Problems to Ad-Hoc Drug Design.

An innovative approach to analyze the complexity of translating novel molecular entities and nanomaterials into pharmaceutical alternatives (i.e., knowledge translation, KT) is discussed. First, some key concepts on the organization and translation of the biomedical knowledge (paradigms, homophily, power law distributions, hierarchy, modularity, and research fronts) are reviewed. Then, we propose a model for the knowledge translation (KT) in Drug Discovery that considers the complexity of interdisciplinary communication. Specifically, we address two highly relevant aspects: 1) A successful KT requires the emergence of organized bodies of inter-and transdisciplinary research, and 2) The hierarchical and modular topological organization of these bodies of knowledge. We focused on a set of previously-published studies on KT which rely on a combination of network analysis and computer-assisted analysis of the contents of scientific literature and patents. The selected studies provide a duo of complementary perspectives: the demand of knowledge (cervical cancer and Ebola hemorrhagic fever) and the supply of knowledge (liposomes and nanoparticles to treat cancer and the paradigmatic Doxil, the first nano- drug to be approved).

Geostatistical characterization of the soil of Aguascalientes, México, by using spatial estimation techniques.

Four spatial estimation techniques available in commercial computational packages are evaluated and compared, namely: regularized splines interpolation, tension splines interpolation, inverse distance weighted interpolation, and ordinary Kriging estimation, in order to establish the best representation for the shallow stratigraphic configuration in the city of Aguascalientes, in Central Mexico. Data from 478 sample points along with the software ArcGIS (Environmental Systems Research Institute, Inc. (ESRI), ArcGIS, ver. 9.3, Redlands, California 2008) to calculate the spatial estimates. Each technique was evaluated based on the root mean square error, calculated from a validation between the generated estimates and measured data from 64 sample points which were not used in the spatial estimation process. The present study shows that, for the estimation of the hard-soil layer, ordinary Kriging offered the best performance among the evaluated techniques.

Production of micro- and nanosilica from soil inhabiting Folsomia candida fed with treated rice husk.

Rice husk was employed as a source for producing silica micro- and nanoparticles through its digestion by soil fauna. Although many physicochemical methods for producing nanostructures have been studied, the biological processes remain mostly unexplored. Alkaline hydrogen peroxide with continuous control of reaction pH allowed removal of lignin bonds while preserving most of the cell wall and the silica present in the rice husk. The accessibility of lignocellulose was achieved without removing appreciable amounts of lignin, so this agricultural byproduct can be employed as feeding material for microarthropods Folsomia candida (Collembola). When these microarthropods are placed on a substrate of treated rice husk, more than 85% of degraded material is obtained, as compared to the untreated rice husk substrate, while the silica particles obtained show a slight decrease in average size.

Hegemonic structure of basic, clinical and patented knowledge on Ebola research: a US army reductionist initiative.

BACKGROUND: Ebola hemorrhagic fever (Ebola) is still a highly lethal infectious disease long affecting mainly neglected populations in sub-Saharan Africa. Moreover, this disease is now considered a potential worldwide threat. In this paper, we present an approach to understand how the basic, clinical and patent knowledge on Ebola is organized and intercommunicated and what leading factor could be shaping the evolution of the knowledge translation process for this disease. METHODOLOGY: A combination of citation network analysis; analysis of Medical heading Subject (MeSH) and Gene Ontology (GO) terms, and quantitative content analysis for patents and scientific literature, aimed to map the organization of Ebola research was carried out. RESULTS: We found six putative research fronts (i.e. clusters of high interconnected papers). Three research fronts are basic research on Ebola virus structural proteins: glycoprotein, VP40 and VP35, respectively. There is a fourth research front of basic research papers on pathogenesis, which is the organizing hub of Ebola research. A fifth research front is pre-clinical research focused on vaccines and glycoproteins. Finally, a clinical-epidemiology research front related to the disease outbreaks was identified. The network structure of patent families shows that the dominant design is the use of Ebola virus proteins as targets of vaccines and other immunological treatments. Therefore, patents network organization resembles the organization of the scientific literature. Specifically, the knowledge on Ebola would flow from higher (clinical-epidemiology) to intermediated (cellular-tissular pathogenesis) to lower (molecular interactions) levels of organization. CONCLUSION: Our results suggest a strong reductionist approach for Ebola research probably influenced by the lethality of the disease. On the other hand, the ownership profile of the patent families network and the main researches relationship with the United State Army suggest a strong involvement of this military institution in Ebola research.

Finite element/percolation theory modelling of the micromechanical behavior of clayey soils.

A hybrid model for soils, which combines percolation theory and finite element method is presented. The internal soil structure is modelled via the finite element method, and percolation networks are used for analyzing its mechanical behaviour. Through a microscopic characterization of elastic properties of soil grains, the model is generated. The effective percolation threshold obtained is lower than that of the network geometric percolation. The effective mechanical properties predicted are successfully compared to published experimental results.

Mapping knowledge translation and innovation processes in Cancer Drug Development: the case of liposomal doxorubicin.

We explored how the knowledge translation and innovation processes are structured when theyresult in innovations, as in the case of liposomal doxorubicin research. In order to map the processes, a literature network analysis was made through Cytoscape and semantic analysis was performed by GOPubmed which is based in the controlled vocabularies MeSH (Medical Subject Headings) and GO (Gene Ontology). We found clusters related to different stages of the technological development (invention, innovation and imitation) and the knowledge translation process (preclinical, translational and clinical research), and we were able to map the historic emergence of Doxil as a paradigmatic nanodrug. This research could be a powerful methodological tool for decision-making and innovation management in drug delivery research.

Liposomes versus metallic nanostructures: differences in the process of knowledge translation in cancer.

This research maps the knowledge translation process for two different types of nanotechnologies applied to cancer: liposomes and metallic nanostructures (MNs). We performed a structural analysis of citation networks and text mining supported in controlled vocabularies. In the case of liposomes, our results identify subnetworks (invisible colleges) associated with different therapeutic strategies: nanopharmacology, hyperthermia, and gene therapy. Only in the pharmacological strategy was an organized knowledge translation process identified, which, however, is monopolized by the liposomal doxorubicins. In the case of MNs, subnetworks are not differentiated by the type of therapeutic strategy, and the content of the documents is still basic research. Research on MNs is highly focused on developing a combination of molecular imaging and photothermal therapy.

Hierarchical structure of biological systems: a bioengineering approach.

A general theory of biological systems, based on few fundamental propositions, allows a generalization of both Wierner and Berthalanffy approaches to theoretical biology. Here, a biological system is defined as a set of self-organized, differentiated elements that interact pair-wise through various networks and media, isolated from other sets by boundaries. Their relation to other systems can be described as a closed loop in a steady-state, which leads to a hierarchical structure and functioning of the biological system. Our thermodynamical approach of hierarchical character can be applied to biological systems of varying sizes through some general principles, based on the exchange of energy information and/or mass from and within the systems.

Therapeutic proteins and nanotechnology: immune response and stealth bioengineered constructs.

With unique potentials for organ drug delivery and targeting, intravenous administration of drugs has represented a key tool in biomedicine. A major concern of this route is the rapid capture and destruction of foreign substances by circulating immune cells. Knowledge about the inter-relationships between drugs and blood cells is essential for a better control in drug stability and bioavailability. In this review, both classical pathways and novel insights into the immune mechanisms leading to drug clearance after systemic delivery are described. Drug surface chemistry and size have been identified as critical factors for the activation of host immune responses, and their modification has been extensively explored in order to evade immune surveillance. Common strategies to camouflage drug surfaces through polymer-grafting are presented, with special emphasis on Poly(Ethylene Glycol) (PEG) linkages, one of the most diverse strategies for modifying biomolecular surfaces. Finally, the use of "smart shields", such as PEG attachments shed at particular intracellular conditions, is briefly overviewed as an interesting approach for balancing circulation half lives VS bioavailability in polymer-grafted formulations.