Bioengineered Nanomedicines Targeting the Intestinal Fc Receptor Achieve the Improved Glucoregulatory Effect of Semaglutide in a Type 2 Diabetic Mice Model.

The oral administration of the glucagon-like peptide-1 analogue, semaglutide, remains a hurdle due to its limited bioavailability. Herein, neonatal Fc receptor (FcRn)-targeted nanoparticles (NPs) were designed to enhance the oral delivery of semaglutide. The nanocarriers were covalently linked to the FcRn-binding peptide FcBP or the affibody molecule Z that specifically binds to the human FcRn (hFcRn) in a pH-dependent manner.

Stimuli-Responsive Multifunctional Nanomedicine for Enhanced Glioblastoma Chemotherapy Augments Multistage Blood-to-Brain Trafficking and Tumor Targeting.

Minimal therapeutic advances have been achieved over the past two decades for glioblastoma (GBM), which remains an unmet clinical need. Here, hypothesis-driven stimuli-responsive nanoparticles (NPs) for docetaxel (DTX) delivery to GBM are reported, with multifunctional features that circumvent insufficient blood-brain barrier (BBB) trafficking and lack of GBM targeting-two major hurdles for anti-GBM therapies. NPs are dual-surface tailored with a i) brain-targeted acid-responsive Angiopep-2 moiety that triggers NP structural rearrangement within BBB endosomal vesicles, and ii) L-Histidine moiety that provides NP preferential accumulation into GBM cells post-BBB crossing.

Recent advances in long-acting drug delivery systems for anticancer drug.

The use of systemic anticancer chemotherapy is intrinsically limited by its toxicity. Whether dealing with small molecules or biopharmaceuticals, after systemic administration, small doses fail to reach effective intratumoral concentrations, while high doses with significant tumor inhibition effects may also drive the death of healthy cells, endangering the patients. Therefore, strategies based on drug delivery systems (DDSs) for avoiding the systemic toxicity have been designed.

Towards the rate limit of heterologous biotechnological reactions in recombinant cyanobacteria.

Background: Cyanobacteria have emerged as highly efficient organisms for the production of chemicals and biofuels. Yet, the productivity of the cell has been low for commercial application. Cyanobacterial photobiotransformations utilize photosynthetic electrons to form reducing equivalents, such as NADPH-to-fuel biocatalytic reactions.

Glioblastoma immuno-endothelial multicellular microtissue as a 3D in vitro evaluation tool of anti-cancer nano-therapeutics.

Despite being the most prevalent and lethal type of adult brain cancer, glioblastoma (GBM) remains intractable. Promising anti-GBM nanoparticle (NP) systems have been developed to improve the anti-cancer performance of difficult-to-deliver therapeutics, with particular emphasis on tumor targeting strategies. However, current disease modeling toolboxes lack close-to-native in vitro models that emulate GBM microenvironment and bioarchitecture, thus partially hindering translation due to poorly predicted clinical responses.

Multifunctional nanomedicine strategies to manage brain diseases.

Brain diseases represent a substantial social and economic burden, currently affecting one in six individuals worldwide. Brain research has been focus of great attention in order to unravel the pathogenesis and complexity of brain diseases at the cellular, molecular, and microenvironmental levels. Due to the intrinsic nature of the brain, the presence of the highly restrictive blood-brain barrier (BBB), and the pathophysiology of most diseases, therapies can hardly be considered successful purely by the administration of one drug to a patient.

Edinger-Westphal peptidergic neurons enable maternal preparatory nesting.

Optimizing reproductive fitness in mammalians requires behavioral adaptations during pregnancy. Maternal preparatory nesting is an essential behavior for the survival of the upcoming litter. Brain-wide immediate early gene mapping in mice evoked by nesting sequences revealed that phases of nest construction strongly activate peptidergic neurons of the Edinger-Westphal nucleus in pregnant mice.

Heterologous Production of Glycine Betaine Using sp. PCC 6803-Based Chassis Lacking Native Compatible Solutes.

Among compatible solutes, glycine betaine has various applications in the fields of nutrition, pharmaceuticals, and cosmetics. Currently, this compound can be extracted from sugar beet plants or obtained by chemical synthesis, resulting in low yields or high carbon footprint, respectively. Hence, in this work we aimed at exploring the production of glycine betaine using the unicellular cyanobacterium sp.

Bringing vascularization into glioblastoma in vitro models.

Tumor blood vessels create optimal conditions for glioblastoma (GBM) growth and therapy resistance. Therefore, tissue engineering techniques evolved towards allowing its inclusion in preclinical in vitro GBM models. In comparison with conventional ones, less representative of tumor biology, these new tools might significantly improve GBM treatment, contributing to a higher throughput screening in drug research and to the clinical translation of these therapies.

CRISPRi as a Tool to Repress Multiple Copies of Extracellular Polymeric Substances (EPS)-Related Genes in the Cyanobacterium sp. PCC 6803.

The use of the versatile cyanobacterial extracellular polymeric substances (EPS) for biotechnological/biomedical applications implies an extensive knowledge of their biosynthetic pathways to improve/control polymer production yields and characteristics. The multiple copies of EPS-related genes, scattered throughout cyanobacterial genomes, adds another layer of complexity, making these studies challenging and time-consuming. Usually, this issue would be tackled by generating deletion mutants, a process that in cyanobacteria is also hindered by the polyploidy.

Expression and activity of heterologous hydroxyisocaproate dehydrogenases in sp. PCC 6803 Δ.

Exploiting light to drive redox reactions is currently a hot topic since light is considered as an environmentally friendly source of energy. Consequently, cyanobacteria, which can use light e.g.

Design and Validation of Tools for Microbial Synthetic Biology Applications.

Synthetic Biology (SynBio) is a multidisciplinary field that brings together science, technology and engineering to expedite the design, creation and modification of genetic materials to be applied in living organisms or in vitro systems [...

Comparison of alternative integration sites in the chromosome and the native plasmids of the cyanobacterium Synechocystis sp. PCC 6803 in respect to expression efficiency and copy number.

Background: Synechocystis sp. PCC 6803 provides a well-established reference point to cyanobacterial metabolic engineering as part of basic photosynthesis research, as well as in the development of next-generation biotechnological production systems. This study focused on expanding the current knowledge on genomic integration of expression constructs in Synechocystis, targeting a range of novel sites in the chromosome and in the native plasmids, together with established loci used in literature.

Lipid nanocapsules to enhance drug bioavailability to the central nervous system.

The central nervous system (CNS), namely the brain, still remains as the hardest area of the human body to achieve adequate concentration levels of most drugs, mainly due to the limiting behavior of its physical and biological defenses. Lipid nanocapsules emerge as a versatile platform to tackle those barriers, and efficiently delivery different drug payloads due to their numerous advantages. They can be produced in a fast, solvent-free and scalable-up process, and their properties can be fine-tuned for to make an optimal brain drug delivery vehicle.

Expanding the toolbox for sp. PCC 6803: validation of replicative vectors and characterization of a novel set of promoters.

Cyanobacteria are promising 'low-cost' cell factories since they have minimal nutritional requirements, high metabolic plasticity and can use sunlight and CO as energy and carbon sources. The unicellular sp. PCC 6803, already considered the 'green' , is the best studied cyanobacterium but to be used as an efficient and robust photoautotrophic chassis it requires a customized and well-characterized toolbox.

Modulation of Intracellular O Concentration in Escherichia coli Strains Using Oxygen Consuming Devices.

The use of cell factories for the production of bulk and value-added compounds is nowadays an advantageous alternative to the traditional petrochemical methods. Nevertheless, the efficiency and productivity of several of these processes can improve with the implementation of micro-oxic or anoxic conditions. In the industrial setting, laccases are appealing catalysts that can oxidize a wide range of substrates and reduce O to HO.

Identification of inner membrane translocase components of TolC-mediated secretion in the cyanobacterium Synechocystis sp. PCC 6803.

Cyanobacteria were the first organisms ever to perform oxygenic photosynthesis and still significantly contribute to primary production on a global scale. To assure the proper functioning of their primary metabolism and cell homeostasis, cyanobacteria must rely on efficient transport systems to cross their multilayered cell envelope. However, cyanobacterial secretion mechanisms remain largely unknown.

Improving a Synechocystis-based photoautotrophic chassis through systematic genome mapping and validation of neutral sites.

The use of microorganisms as cell factories frequently requires extensive molecular manipulation. Therefore, the identification of genomic neutral sites for the stable integration of ectopic DNA is required to ensure a successful outcome. Here we describe the genome mapping and validation of five neutral sites in the chromosome of Synechocystis sp.

HesF, an exoprotein required for filament adhesion and aggregation in Anabaena sp. PCC 7120.

Here, we report on the identification and characterization of a protein (Alr0267) named HesF, found in the extracellular milieu of Anabaena sp. PCC 7120 grown diazotrophically. hesF was found to be highly upregulated upon transition from non-nitrogen-fixing to nitrogen-fixing conditions, and the highest transcript levels were detected towards the end of the heterocyst differentiation process.

Selection of suitable reference genes for RT-qPCR analyses in cyanobacteria.

Cyanobacteria are a group of photosynthetic prokaryotes that have a diverse morphology, minimal nutritional requirements and metabolic plasticity that has made them attractive organisms to use in biotechnological applications. The use of these organisms as cell factories requires the knowledge of their physiology and metabolism at a systems level. For the quantification of gene transcripts real-time quantitative polymerase chain reaction (RT-qPCR) is the standard technique.

Infection levels and diversity of anisakid nematodes in blackspot seabream, Pagellus bogaraveo, from Portuguese waters.

The blackspot seabream, Pagellus bogaraveo, is a sparid fish of great economic importance in the northeast Atlantic. The main aim of this work was to assess the infection levels and diversity of anisakid nematodes parasitizing P. bogaraveo from Portuguese waters.