Dynamic and multi-pharmacophore modeling for designing polo-box domain inhibitors.

The polo-like kinase 1 (Plk1) is a critical regulator of cell division that is overexpressed in many types of tumors. Thus, a strategy in the treatment of cancer has been to target the kinase activity (ATPase domain) or substrate-binding domain (Polo-box Domain, PBD) of Plk1. However, only few synthetic small molecules have been identified that target the Plk1-PBD. Here, we have applied an integrative approach that combines pharmacophore modeling, molecular docking, virtual screening, and in vitro testing to discover novel Plk1-PBD inhibitors. Nine Plk1-PBD crystal structures were used to generate structure-based hypotheses. A common pharmacophore model (Hypo1) composed of five chemical features was selected from the 9 structure-based hypotheses and used for virtual screening of a drug-like database consisting of 159,757 compounds to identify novel Plk1-PBD inhibitors. The virtual screening technique revealed 9,327 compounds with a maximum fit value of 3 or greater, which were selected and subjected to molecular docking analyses. This approach yielded 93 compounds that made good interactions with critical residues within the Plk1-PBD active site. The testing of these 93 compounds in vitro for their ability to inhibit the Plk1-PBD, showed that many of these compounds had Plk1-PBD inhibitory activity and that compound Chemistry_28272 was the most potent Plk1-PBD inhibitor. Thus Chemistry_28272 and the other top compounds are novel Plk1-PBD inhibitors and could be used for the development of cancer therapeutics

Wirksamkeit der Phototherapie bei Neugeborenen mit einer Hyperbilirubinämie: systematische Literaturreview

Die Hyperbilirubinämie betrifft viele Neugeborene und unbehan-delt kann diese eine Bilirubinencephalopathie auslösen mit gravierenden Folgen. Deshalb ist es wichtig, die Hyperbilirubinämie frühzeitig zu erkennen und zu therapieren. Phototherapie kann zur Behandlung dieser Krankheit genutzt werden und ist eine nichtinvasive Methode. Die Phototherapie ist in der „Nursing Intervention Classification“ als Pflegeintervention aufgeführt. Das Fehlen von aktuellen deutschen systematischen Literaturreviews zeigt die Wichtigkeit des Erstellens dieser Arbeit

Wirksamkeit der Hypnose auf Schmerzen bei Erwachsenen: systematische Literaturreview

Das Ziel dieser systematischen Literaturreview ist es, die Wirksamkeit der Hypnose auf Schmerzen bei Erwachsenen zu überprüfen. Daraus ergibt sich folgende Forschungsfrage: "Wie wird die Wirksamkeit der Hypnose auf Schmerzen bei Erwachsenen in der wissenschaftlichen Literatur beschrieben?

Biological functions of blood group antigens

Os antígenos de grupos sanguíneos eritrocitários são estruturas macromoleculares localizadas na superfície extracelular da membrana eritrocitária. Com o desenvolvimento de estudos moleculares, mais de 250 antígenos são conhecidos e estão organizados em 29 sistemas de grupos sanguíneos reconhecidos pela Sociedade Internacional de Transfusão Sanguínea (ISBT). Estudos têm revelado que os antígenos de grupo sanguíneo estão expressos na membrana eritrocitária com ampla diversidade estrutural, incluindo epítopos de carboidratos em glicoproteínas e/ou glicolipídios e em proteínas inseridas na membrana via um domínio, via domínios de multipassagem ou ligados a glicosilfosfatidinositol. Além das diversidades estruturais, muitas funções importantes têm sido associadas aos antígenos eritrocitários recentemente identificadas, podendo ser esquematicamente divididas em: estruturais, transportadores, receptores e moléculas de adesão, enzimas, proteínas controladoras do complemento e outras. Esta revisão tem como foco as funções potenciais das moléculas que expressam os antígenos eritrocitários.Erythrocyte blood group antigens are macromolecules structures located on the extracellular surface of the red blood cell membrane. The development of molecular studies allowed the recognition of more than 250 antigens by the International Society for Blood Transfusion (ISBT). These studies have also shown that blood group antigens are carried on red blood cell membrane of wide structural diversity, including carbohydrate epitopes on glycoproteins and/or glycolipids and on proteins inserted within the membrane via single or multi-pass transmembrane domains, or via glycosylphosphatidylinositol linkages. In addition, to their structural diversity, many important functions associated with blood group antigens have been recently identified and can be didactically divided into: structural proteins, transporters, receptors and adhesion molecules, enzymes, complement control proteins and others. This review will focus on the potential functions of the molecules that express blood group antigens

Ecology of the non-native snail Sinotaia cf quadrata (Caenogastropoda: Viviparidae). A study in a lowland stream of South America with different water qualities

Sinotaia quadrata is a snail native from Asia recorded for the first time in South America in 2009 in central Argentina. In 2015, this species was also found in a lowland stream with different water qualities. Our aims were to contribute to the knowledge of its population ecology and to compare the individuals from the two locations anatomically. Snails were searched at 6 sites, where physicochemical and hydraulic parameters were measured. Biological samples were also taken at two sites (S3 and S4) to study the population traits of S. cf quadrata (density, size structure, fecundity and sex ratio) and to assess the water quality through macroinvertebrates' biological indices (richness, diversity and IBPamp). Physicochemical and biological parameters allowed us classifying sites as "moderately polluted" (S3) and "heavily polluted" (S4). At S4, the population showed a lower density, larger individuals, higher fecundity and a scarce representation of young snails. The differences observed in the radula and mantle border of snails from the two geographical regions might be attributed to environmental differences. We conclude that this species is tolerant to a wide range of environmental variables which, along with its high fecundity and morphological plasticity, could allow this species to colonize neighbor streams.Fil: Ferreira, Ana Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Paz, Laura Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Rumi Macchi Z., Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Ocon, Carolina Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Altieri, Paula Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Rodrigues Capitulo, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; Argentin

Updates on polyurethane and its multifunctional applications in biomedical engineering

Polyurethanes (PUs) have properties that make them promising in biomedical applications. PU is recognized as one of the main families of blood and biocompatible materials. PU plays a vital role in the design of medical devices in various medical fields. The structure of PU contains two segments: soft and hard. Its elastomeric feature is due to its soft segment, and its excellent and high mechanical property is because of its hard segment. It is possible to achieve specific desirable and targeted properties by changing the soft and hard chemical structures and the ratio between them. The many properties of PU each draw the attention of different medical fields. This work reviews PU highlighted properties, such as biodegradability, biostability, shape memory, and improved antibacterial activity. Also, because PU has a variety of applications, this review restricts its focus to PU's prominent applications in tissue engineering, cardiovascular medicine, drug delivery, and wound healing. In addition, it contains a brief review of PU's applications in biosensors and oral administration