Tailored Viral-like Particles as Drivers of Medical Breakthroughs.

Despite the recognized potential of nanoparticles, only a few formulations have progressed to clinical trials, and an even smaller number have been approved by the regulatory authorities and marketed. Virus-like particles (VLPs) have emerged as promising alternatives to conventional nanoparticles due to their safety, biocompatibility, immunogenicity, structural stability, scalability, and versatility. Furthermore, VLPs can be surface-functionalized with small molecules to improve circulation half-life and target specificity.

Impact of concerning excipients on animal safety: insights for veterinary pharmacotherapy and regulatory considerations.

Objectives: Veterinarians and pharmacists are familiar with the efficacy and safety aspects attributed to active pharmaceutical ingredients included in medicines, but they are rarely concerned with the safety of excipients present in medicines. Although generally recognized as safe, excipients are not chemically inert and may produce adverse events in certain animal populations. This review aims to present excipients of concern to these populations and highlight their relevance for rational veterinary pharmacotherapy.

The World of GPCR dimers - Mapping dopamine receptor D homodimers in different activation states and configuration arrangements.

G protein-coupled receptors (GPCRs) are known to dimerize, but the molecular and structural basis of GPCR dimers is not well understood. In this study, we developed a computational framework to generate models of symmetric and asymmetric GPCR dimers using different monomer activation states and identified their most likely interfaces with molecular details. We chose the dopamine receptor D (DR) homodimer as a case study because of its biological relevance and the availability of structural information.

Construction of HER2-Specific HIV-1-Based VLPs.

Virus-like particles (VLPs) are nanoplatforms comprised of one or more viral proteins with the capacity to self-assemble without viral genetic material. VLPs arise as promising nanoparticles (NPs) that can be exploited as vaccines, as drug delivery vehicles or as carriers of imaging agents. Engineered antibody constructs, namely single-chain variable fragments (scFv), have been explored as relevant molecules to direct NPs to their target.

How promising are HIV-1-based virus-like particles for medical applications.

New approaches aimed at identifying patient-specific drug targets and addressing unmet clinical needs in the framework of precision medicine are a strong motivation for researchers worldwide. As scientists learn more about proteins that drive known diseases, they are better able to design promising therapeutic approaches to target those proteins. The field of nanotechnology has been extensively explored in the past years, and nanoparticles (NPs) have emerged as promising systems for target-specific delivery of drugs.

Enhanced neuronal differentiation by dynamic piezoelectric stimulation.

Electroactive smart materials play an important role for tissue regenerative applications. Poly(vinylidene fluoride) (PVDF) is a specific subtype of piezoelectric electroactive material that generates electrical potential upon mechanical stimulation. This work focuses on the application of piezoelectric PVDF films for neural differentiation.

Ultrasonication Improves Solid Phase Synthesis of Peptides Specific for Fibroblast Growth Factor Receptor and for the Protein-Protein Interface RANK-TRAF6.

Considering our interest in the use of peptides as potential target-specific drugs or as delivery vectors of metallodrugs for various biomedical applications, it is crucial to explore improved synthetic methodologies to accomplish the highest peptide crude purity in the shortest time possible. Therefore, we compared "classical" fluorenylmethoxycarbonyl (Fmoc)-solid phase peptide synthesis (SPPS) with ultrasound(US)-assisted SPPS based on the preparation of three peptides, namely the fibroblast growth factor receptor 3(FGFR3)-specific peptide Pep1 (VSPPLTLGQLLS-NH) and the novel peptides (RQMATADEA-NH) and (AAVALLPAVLLALLAPRQMATADEA-NH), which are being developed aimed at interfering with the intracellular protein-protein interaction(PPI) RANK-TRAF6. Our results demonstrated that US-assisted SPPS led to a 14-fold () and 4-fold time reduction () in peptide assembly compared to the "classical" method.

Soil actinobacteria inhibit antagonistic fungi of leafcutter ant colonies.

Founder females of the leaf-cutting ant species Atta sexdens experience high mortality during the founding and establishment of their colonies. The foundation site is crucial for the success of a new colony. In this study, we isolated and identified actinobacteria from fungus garden chambers of A.

In Silico End-to-End Protein-Ligand Interaction Characterization Pipeline: The Case of SARS-CoV-2.

SARS-CoV-2 triggered a worldwide pandemic disease, COVID-19, for which an effective treatment has not yet been settled. Among the most promising targets to fight this disease is SARS-CoV-2 main protease (M), which has been extensively studied in the last few months. There is an urgency for developing effective computational protocols that can help us tackle these key viral proteins.

Decoding Partner Specificity of Opioid Receptor Family.

This paper describes an exciting big data analysis compiled in a freely available database, which can be applied to characterize the coupling of different G-Protein coupled receptors (GPCRs) families with their intracellular partners. Opioid receptor (OR) family was used as case study in order to gain further insights into the physiological properties of these important drug targets, known to be associated with the opioid crisis, a huge socio-economic issue directly related to drug abuse. An extensive characterization of all members of the ORs family ( (MOR), (DOR), (KOR), nociceptin (NOP)) and their corresponding binding partners (ARRs: Arr2, Arr3; G-protein: G, G, G, G, G, G, G, G, G, G, G, G, G) was carried out.

Integrated in Silico and Experimental Approach towards the Design of a Novel Recombinant Protein Containing an Anti-HER2 scFv.

Biological therapies, such as recombinant proteins, are nowadays amongst the most promising approaches towards precision medicine. One of the most innovative methodologies currently available aimed at improving the production yield of recombinant proteins with minimization of costs relies on the combination of in silico studies to predict and deepen the understanding of the modified proteins with an experimental approach. The work described herein aims at the design and production of a biomimetic vector containing the single-chain variable domain fragment (scFv) of an anti-HER2 antibody fragment as a targeting motif fused with HIV gp41.

Biological evaluation of new TEM1 targeting recombinant antibodies for radioimmunotherapy: In vitro, in vivo and in silico studies.

The tumour endothelial marker 1 (TEM1/endosialin/CD248) is a receptor overexpressed in several human solid tumours and silenced in normal adult tissues, representing a suitable and potentially safe target for radioimmunotherapy of sarcoma. To develop new tools with improved TEM1 targeting properties, a new panel of antibody fragments was for the first time evaluated preclinically following I radiolabelling. The antibody fragment 1C1m-Fc, with the highest human/murine TEM1 binding affinity, was extensively characterized in vitro and in vivo in a Ewing's sarcoma human xenograft mouse model.

Understanding the Binding Specificity of G-Protein Coupled Receptors toward G-Proteins and Arrestins: Application to the Dopamine Receptor Family.

G-Protein coupled receptors (GPCRs) are involved in a myriad of pathways key for human physiology through the formation of complexes with intracellular partners such as G-proteins and arrestins (Arrs). However, the structural and dynamical determinants of these complexes are still largely unknown. Herein, we developed a computational big-data pipeline that enables the structural characterization of GPCR complexes with no available structure.

The Central Role of Non-Structural Protein 1 (NS1) in Influenza Biology and Infection.

Influenza (flu) is a contagious viral disease, which targets the human respiratory tract and spreads throughout the world each year. Every year, influenza infects around 10% of the world population and between 290,000 and 650,000 people die from it according to the World Health Organization (WHO). Influenza viruses belong to the Orthomyxoviridae family and have a negative sense eight-segment single-stranded RNA genome that encodes 11 different proteins.

Prediction and targeting of GPCR oligomer interfaces.

GPCR oligomerization has emerged as a hot topic in the GPCR field in the last years. Receptors that are part of these oligomers can influence each other's function, although it is not yet entirely understood how these interactions work. The existence of such a highly complex network of interactions between GPCRs generates the possibility of alternative targets for new therapeutic approaches.

Dynamical Rearrangement of Human Epidermal Growth Factor Receptor 2 upon Antibody Binding: Effects on the Dimerization.

Human epidermal growth factor 2 (HER2) is a ligand-free tyrosine kinase receptor of the HER family that is overexpressed in some of the most aggressive tumours. Although it is known that HER2 dimerization involves a specific region of its extracellular domain, the so-called "dimerization arm", the mechanism of dimerization inhibition remains uncertain. However, uncovering how antibody interactions lead to inhibition of HER2 dimerization is of key importance in understanding its role in tumour progression and therapy.

Operationality of concepts in Heideggerian phenomenological investigation: epistemological reflection on Nursing.

Objective: To describe the investigative path of analysis and the operationality of concepts based on Martin Heidegger's theoretical and philosophical framework.

Method: Theoretical reflection on the phenomenon of pregnancy in a woman with heart disease.

Results: Stages of the investigative movement were evidenced based on the pre-reflection related to the object of study and to the search for the phenomenal meaning, using the existential and analytical Hermeneutics as the approach and resulting in the reach of the phenomenal totality.

Less Exploited GPCRs in Precision Medicine: Targets for Molecular Imaging and Theranostics.

Precision medicine relies on individually tailored therapeutic intervention taking into account individual variability. It is strongly dependent on the availability of target-specific drugs and/or imaging agents that recognize molecular targets and patient-specific disease mechanisms. The most sensitive molecular imaging modalities, Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET), rely on the interaction between an imaging radioprobe and a target.

An Overview of Antiretroviral Agents for Treating HIV Infection in Paediatric Population.

Paediatric Acquired ImmunoDeficiency Syndrome (AIDS) is a life-threatening and infectious disease in which the Human Immunodeficiency Virus (HIV) is mainly transmitted through Mother-To- Child Transmission (MTCT) during pregnancy, labour and delivery, or breastfeeding. This review provides an overview of the distinct therapeutic alternatives to abolish the systemic viral replication in paediatric HIV-1 infection. Numerous classes of antiretroviral agents have emerged as therapeutic tools for downregulation of different steps in the HIV replication process.

Computational Approaches in Antibody-drug Conjugate Optimization for Targeted Cancer Therapy.

Cancer has become one of the main leading causes of morbidity and mortality worldwide. One of the critical drawbacks of current cancer therapeutics has been the lack of the target-selectivity, as these drugs should have an effect exclusively on cancer cells while not perturbing healthy ones. In addition, their mechanism of action should be sufficiently fast to avoid the invasion of neighbouring healthy tissues by cancer cells.

Root distribution and its association with bean growth habit.

Associations between root distribution and bean growth habit may contribute to the selection of genotypes adapted to restrictive environments. The present work aimed to relate and compare root distribution with the growth habit in beans. 10 bean genotypes of different growth habits (I, II and III) were evaluated for root distribution in two agricultural years (2014/15 and 2015/16).

In Silico Studies Targeting G-protein Coupled Receptors for Drug Research Against Parkinson's Disease.

Parkinson's Disease (PD) is a long-term neurodegenerative brain disorder that mainly affects the motor system. The causes are still unknown, and even though currently there is no cure, several therapeutic options are available to manage its symptoms. The development of novel antiparkinsonian agents and an understanding of their proper and optimal use are, indeed, highly demanding.

CXCR7 participates in CXCL12-mediated migration and homing of leukemic and normal hematopoietic cells.

CXCR4 was the first receptor identified for CXCL12, but a second receptor, CXCR7, has also been described and its function in hematopoietic cells remains unknown. By inhibition of CXCR4 and/or CXCR7, we showed that CXCR7 participates in normal CD34 and U937 cell migration and prevents downregulation of CXCR4 by CXCL12 stimulation. In addition, CXCR7 contributes to homing of acute myeloid leukemia and normal progenitor cells to the bone marrow and spleen of NOD/SCID mice.

Recovery of phenolic compounds from multi-component solution by a synthesized activated carbon using resorcinol and formaldehyde.

The adsorption of four phenolic compounds (gallic acid, protocatechuic acid, vanillic acid and syringic acid) is investigated using a synthesized mesoporous carbon on both single and multi-component synthetic solutions. Some correlation of the adsorption capacity of the carbon and the nature of adsorbate could be made, except for gallic acid whose concentration decrease seems to be not exclusively due to adsorption but also to polymerization reaction. In the multi-component mixture, negative effects in the adsorption capacity are observed probably due to competition for the active centers of the adsorbent surface.

Oxidation of clofibric acid in aqueous solution using a non-thermal plasma discharge or gamma radiation.

In this work, we study degradation of clofibric acid (CFA) in aqueous solution using either ionizing radiation from aCo source or a non-thermal plasma produced by discharges in the air above the solution. The results obtained with the two technologies are compared in terms of effectiveness of CFA degradation and its by-products. In both cases the CFA degradation follows a quasi-exponential decay in time well modelled by a kinetic scheme which considers the competition between CFA and all reaction intermediates for the reactive species generated in solution as well as the amount of the end product formed.