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. Molecular modeling and docking studies were performed to develop the recombinant protein sequence. Subsequently, the DNA plasmid was produced and HEK-293T cells were transfected to evaluate the designed vector. The obtained results demonstrated that the plasmid construction is robust and can be expressed in the selected cell line. The multidisciplinary integrated in silico and experimental strategy adopted for the construction of a recombinant protein which can be used in HER2+-targeted therapy paves the way towards the production of other therapeutic proteins in a more cost-effective way.

One of the actions that has been implemented to support the recovery of the panmictic population of European eel is stocking of waterbodies where natural recruitment is low or null. However, growth conditions of the stocked eels can vary greatly. This circumstance emphasises the importance to determine ideal habitat conditions to contribute to the success of stocking actions and, consequently, to increase the production of silver eels. This study aims to evaluate the early settlement and growth of stocked glass eels in the upper reaches of a fragmented river. Stocking was carried out, in 2014, at three sites of an inland tributary of the Mondego river basin (Central Portugal), and its monitoring was conducted during the following two years, until 2016, along with the collection of environmental and hydromorphological parameters. The results showed a successful dispersion throughout the study area. Growth varied spatially, although environmental parameters have not clearly explained this variation, but overall with high growth rates and a positive allometric growth in this early stage of stocking, suggesting a good condition of the stocked individuals. This study showed that these upper reaches of fragmented watercourses, a shared feature amongst most European rivers that are currently inaccessible for natural recruitment, may be suitable habitats for eel stocking.

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. Virus-like particles (VLPs) arise as auspicious NPs due to their intrinsic properties. The lack of viral genetic material and the inability to replicate, together with tropism conservation and antigenicity characteristic of the native virus prompted extensive interest in their use as vaccines or as delivery systems for therapeutic and/or imaging agents. Owing to its simplicity and non-complex structure, one of the viruses currently under study for the construction of VLPs is the human immunodeficiency virus type 1 (HIV-1). Typically, HIV-1-based VLPs are used for antibody discovery, vaccines, diagnostic reagent development and protein-based assays. This review will be centered on the use of HIV-1-based VLPs and their potential biomedical applications.

This study estimated the length–weight relationships of 16 fish species occurring close to the shores of sandy beaches along the lower Negro River basin, Brazilian Amazon. The specimens were captured for one day each month, in October to November 2016, early in the morning and early evening, using trawl net (20 m taken for standard length (SL – 0.1 cm precision) and total weight (TW – 0.01 g precision). The parameters a and b of the equation WT = a.LTb were estimated. The a values ranged from 0.0018 to 0.0226 and b values ranged from 2.5271 to 3.3244. This study also provides new data on of maximum lengths for six species, Amazonsprattus scintilla, Brycon pesu, Moenkhausia megalops, Pachyurus paucirastrus, Reganella depressa and Trachydoras microstomus, and new reports of the LWRs parameters of 15 fish species.

Background Qualitative research investigating pharmacists' participation in Long-Term Care (LTC) within interdisciplinary teams is scarce. Aim To characterize how pharmacists' participation in a national network of LTC is perceived by healthcare professionals and other key stakeholders. Method Individual, in-depth, semi-structured interviews of participants (nurses, physicians, pharmacists, and LTC researchers) enrolled purposively or through snowballing sampling techniques, with the final sample being comprised of fourteen participants. Data analysis followed a deductive coding approach framed by Role Theory and supplemented with an inductive coding for additional themes. Results Four Role Theory constructs were identified from the primary data-role identity, overqualification, ambiguity, underqualification. Clinical pharmacy services, logistics and educational activities were pointed out as representing the identity of pharmacists' interventions. Despite the clear identification of LTC pharmacists' interventions, pharmacist expertise on medicine optimization seemed to be underused (role overqualification), as a result of lack of time, lower proactivity in healthcare teams' integration, and the absence of a legal framework targeted to LTC pharmacy practice (role ambiguity). Additional clinical training, including in the management of older people's health conditions, nutrition, and palliative care were missing (role underqualification). Conclusion LTC pharmacists can provide essential services (e.g., clinical pharmacy, logistics, educational interventions), although additional training and a clearer legal framework are missing to better define pharmacists' roles in LTC pharmacy practice.

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. A vector containing the scFv of an antibody, aimed at the human epidermal growth factor receptor 2 (HER2) and fused to the human immunodeficiency virus (HIV) protein gp41, was previously constructed. The work herein describes the early results concerning the production and the characterization of HIV-1-based VLPs expressing this protein, which could function as potential non-toxic tools for transporting drugs and/or imaging agents.

Block copolymer micelles (BCMs) can be used to improve the solubility of lipophilic drugs and increase their circulation half-life. Hence, BCMs assembled from MePEG-b-PCL were evaluated as drug delivery systems of gold(III) bis(dithiolene) complexes (herein AuS and AuSe) to be employed as antiplasmodial drugs. These complexes exhibited remarkable antiplasmodial activity against liver stages of the Plasmodium berghei parasite, and low toxicity in a model of zebrafish embryos. To improve the complexes’ solubility, BCMs were loaded with AuS, AuSe, and the reference drug primaquine (PQ). PQ-BCMs (Dh = 50.9 ± 2.8 nm), AuSe-BCMs (Dh = 87.1 ± 9.7 nm), and AuS-BCMs (Dh = 72.8 ± 3.1 nm) were obtained with a loading efficiency of 82.5%, 55.5%, and 77.4%, respectively. HPLC analysis and UV–Vis spectrophotometry showed that the compounds did not suffer degradation after encapsulation in BCMs. In vitro release studies suggest that AuS/AuSe-BCMs present a more controlled release compared with PQ-loaded BCMs. The antiplasmodial hepatic activity of the drugs was assessed in vitro and results indicate that both complexes present higher inhibitory activity than PQ, although encapsulated AuS and AuSe presented lower activity than their non-encapsulated counterparts. Nevertheless, these results suggest that the use of BCMs as delivery vehicles for lipophilic metallodrugs, particularly AuS and AuSe, could enable the controlled release of complexes and improve their biocompatibility, constituting a promising alternative to conventional antimalarial treatments.

Gold(III) bisdithiolate complexes have been reported as potential antimicrobial and antitumoral agents. The complex [Au(cdc)2]− (cdc=cyanodithioimido carbonate) displayed antimicrobial and outstanding antitumor activity against the ovarian cancer cells A2780 and A2780cisR, which are sensitive and resistant to cisplatin, respectively. However, poor water solubility may hamper its clinical use. Block copolymer micelles (BCMs) may solubilize hydrophobic drugs, improving their bioavailability and circulation time in blood. Aiming to provide water solubility, prolonged availability, and enhanced therapeutic indexes, BCMs loaded with [Au(cdc)2]− were synthesized and characterized. The BCM-[Au(cdc)2] micelles were prepared with a loading efficiency of 64.6% and a loading content of 35.3 mg [Au(cdc)2]−/gBCM. A hydrodynamic diameter of 77.31 ± 27.00 nm and a low polydispersity index of 0.18 indicated that the micelles were homogenous and good candidates for drug delivery. Cytotoxic activity studies against A2780/A2780cisR cells showed that BCM-[Au(cdc)2] maintained relevant cytotoxic activity comparable to the cytotoxicity observed for the same concentration of gold complexes. The Au uptake in A2780 cells, determined by PIXE, was ca. 17% higher for BCMs-[Au(cdc)2] compared to [Au(cdc)2]−. The BCMs-[Au(cdc)2] presented antimicrobial activity against S. aureus Newman and C. glabrata CBS138. These results evidenced the potential of BCM-[Au(cdc)2] for drug delivery and its promising anticancer and antimicrobial activities.