P2 receptors are a family of transmembrane receptors activated by nucleotides and nucleosides. Two classes have been described in mammals, P2X and P2Y, which are implicated in various diseases. Currently, only P2Y12 has medicines approved for clinical use as antiplatelet agents and natural products have emerged as a source of new drugs with action on P2 receptors due to the diversity of chemical structures. In drug discovery, in silico virtual screening (VS) techniques have become popular because they have numerous advantages, which include the evaluation of thousands of molecules against a target, usually proteins, faster and cheaper than classical high throughput screening (HTS). The number of studies using VS techniques has been growing in recent years and has led to the discovery of new molecules of natural origin with action on different P2X and P2Y receptors. Using different algorithms it is possible to obtain information on absorption, distribution, metabolism, toxicity, as well as predictions on biological activity and the lead-likeness of the selected hits. Selected biomolecules may then be tested by molecular dynamics and, if necessary, rationally designed or modified to improve their interaction for the target. The algorithms of these in silico tools are being improved to permit the precision development of new drugs and, in the future, this process will take the front of drug development against some central nervous system (CNS) disorders. Therefore, this review discusses the methodologies of in silico tools concerning P2 receptors, as well as future perspectives and discoveries, such as the employment of artificial intelligence in drug discovery.

Ovarian cancer is among the seven most common types of cancer in women, being the most fatal gynecological tumor, due to the difficulty of detection in early stages. Aptamers are important tools to improve tumor diagnosis through the recognition of specific molecules produced by tumors. Here, aptamers and their potential targets in ovarian cancer cells were analyzed by in silico approaches. Specific aptamers were selected by the Cell-SELEX method using Caov-3 and OvCar-3 cells. The five most frequent aptamers obtained from the last round of selection were computationally modeled. The potential targets for those aptamers in cells were proposed by analyzing proteomic data available for the Caov-3 and OvCar-3 cell lines. Overexpressed proteins for each cell were characterized as to their three-dimensional model, cell location, and electrostatic potential. As a result, four specific aptamers for ovarian tumors were selected: AptaC2, AptaC4, AptaO1, and AptaO2. Potential targets were identified for each aptamer through Molecular Docking, and the best complexes were AptaC2-FXYD3, AptaC4-ALPP, AptaO1-TSPAN15, and AptaO2-TSPAN15. In addition, AptaC2 and AptaO1 could detect different stages and subtypes of ovarian cancer tissue samples. The application of this technology makes it possible to propose new molecular biomarkers for the differential diagnosis of epithelial ovarian cancer.

INFORMATION AND COMMUNICATION TECHNOLOGIES have become important tools for teaching scientific subjects such as anatomy and histology as well as other, nondescriptive subjects like physiology and pharmacology (8-10). Software has been used to facilitate the learning of specific concepts at the cellular and molecular levels in the biological and health sciences (3, 11, 15). Although educational software, virtual environments, and e-learning are not new, their scope has been expanding to reach the more complex areas of science and higher levels of education. As a case in point, the British Pharmacological Society (6) offers access to Ͼ250 different software packages, not to mention what can be found by searching other databases such as Google, Google Scholar, or ERIC. With so many different programs available, there is a clear need for more rigorous research to provide a scientific and pedagogical foundation for the general content and usability of this software, focusing on an empirical rather than a descriptive software evaluation. Despite the wealth of pharmacology software found on the web, few of these programs are evaluated pedagogically. Developing educational software is quite different from developing noneducational software, such as business applications. Educational software should be designed to facilitate learning for its users, who may not already possess the knowledge being studied (7). In this context, our group developed "PHARMAVIRTUA," a Creative Commons-licensed software package, to help pharmacology teachers by promoting an active and motivated learning environment for students. The present study evaluated the usefulness of the PHARMAVIRTUA educational software package for teaching and learning basic pharmacology. We analyzed subjective (student perception) and objective (student exam results) parameters as well as navigability, usability, friendliness, and other characteristics of the software.

P2X7 is an ATP-activated purinergic receptor implicated in pro-inflammatory responses. It is associated with the development of several diseases, including inflammatory and neurodegenerative conditions. Although several P2X7 receptor antagonists have recently been reported in the literature, none of them is approved for clinical use. However, the structure of the known antagonists can serve as a scaffold for discovering effective compounds in clinical therapy. This study aimed to propose an improved virtual screening methodology for the identification of novel potential P2X7 receptor antagonists from natural products through the combination of shape-based and docking approaches. First, a shape-based screening was performed based on the structure of JNJ-47965567, a P2X7 antagonist, using two natural product compound databases, MEGx (~5.8 × 10³ compounds) and NATx (~32 × 10³ compounds). Then, the compounds selected by the proposed shape-based model, with Shape–Tanimoto score values ranging between 0.624 and 0.799, were filtered for drug-like properties. Finally, the compounds that met the drug-like filter criteria were docked into the P2X7 allosteric binding site, using the docking programs GOLD and DockThor. The docking poses with the best score values were submitted to careful visual inspection of the P2X7 allosteric binding site. Based on our established visual inspection criteria, four compounds from the MEGx database and four from the NATx database were finally selected as potential P2X7 receptor antagonists. The selected compounds are structurally different from known P2X7 antagonists, have drug-like properties, and are predicted to interact with key P2X7 allosteric binding pocket residues, including F88, F92, F95, F103, M105, F108, Y295, Y298, and I310. Therefore, the combination of shape-based screening and docking approaches proposed in our study has proven useful in selecting potential novel P2X7 antagonist candidates from natural-product-derived compounds databases. This approach could also be useful for selecting potential inhibitors/antagonists of other receptors and/or biological targets.

Background: Worldwide, primary care is for most people the gateway into many health systems. Offering solutions to the demands of the communities served requires the constant preparation of professionals, especially doctors and medical undergraduate students. We analyze and propose ways to improve the teaching and learning processes facilitated by the Basic Family Health Units (BFHUs) based on the use of electronic portals with evidence-based medicine criteria. Method: First phase: The authors conducted a qualitative-quantitative study on students and instructors of primary care (PC) medicine by administering a survey of open- and closed-ended questions at medical schools. The closed-ended questions were studied with descriptive statistics, and open-ended questions were analyzed via the creation of categories. Perceptions of major teaching and learning problems were then identified. Second phase: Meetings were held with students and their instructors for 6 months and involved the use of electronic portals and the application of new questionnaires using a Likert scale for pre- and postevaluation. Results: In the first phase, 40% of the students considered local instructor training levels a problem. A similar result was found regarding teachers’ lectures, revealing a lack of adequate PC training and performance. Building on our results, we focused on BFHUs to apply new strategies for teaching and learning, such as the use of the Evidence-Based Health (SBE) Portal, which includes several databases with clinical evidence criteria. In the second phase, the authors identified an improvement in the quality of learning among instructors and students. This outcome improved safety in daily clinical practice in PC, possibly with better results for its users. Conclusions: The use of electronic portals can facilitate BFHU teaching and learning and promote the health of users.

Background: To conduct an analysis and propose ways to improve teaching and learning processes facilitated through Basic Family Health Units (BFHUs). Method: First phase: The authors conducted a qualitative-quantitative study on students and instructors of Primary Care (PC) involving a survey of open- and closed-ended questions administered at medical schools. Closed-ended questions were studied with descriptive statistics and open-ended questions were determined from the creation of categories. Perceptions of major teaching and learning problems were in turn identified. Second phase: Meetings were held with students and respective instructors for 6 months and involved the use of electronic portals and the application of new questionnaires using a Likert scale for pre- and post-evaluation. Results: In the first phase, 40% of the students considered local instructor training levels a problem. A similar result was found regarding teachers’ lectures, revealing a lack of adequate PC training and performance for most of the categories considered. From our results, we used BHFUs to apply new strategies less widely used for teaching and learning to improve health practices such as the use of the Evidence-Based Health Portal, which is more navigable and offers studies based on clinical evidence criteria. In the second phase, the authors identified an improvement in the quality of learning among instructors and students. Conclusions: The use of electronic portals can facilitate BHFU teaching and learning (teaching/learning space).