Safety, Tolerability and Pharmacokinetic-Pharmacodynamic Relationship of NX210c Peptide in Healthy Elderly Volunteers: Randomized, Placebo-Controlled, Double-Blind, Multiple Ascending Dose Study.

Introduction: Blood-brain barrier (BBB) integrity is fundamental to brain homeostasis, enabling control of substance exchange and safeguarding neurons against harmful toxins, pathogens, and immune cells that lead to dysregulation and inflammation involved in ageing and neurodegenerative diseases (NDD). The cyclized peptide NX210c is a thrombospondin type 1 repeat analogue derived from subcommissural organ-spondin. It exerts beneficial effects in animal models of NDD owing to its effects on neurons and endothelial cells.

EGHRIN conclusions on pandemic preparedness: no whole-of-society approach without society.

Pandemic preparedness necessitates a multifaceted approach that emphasizes societal factors, such as building trust and acknowledges cultural and societal differences, with a focus on protecting vulnerable groups. To support these goals, the European Global Health Research Institutes Network has outlined a comprehensive transdisciplinary approach through a set of multilevel recommendations.

Bioactive hydrogels based on lysine dendrigrafts as crosslinkers: tailoring elastic properties to influence hMSC osteogenic differentiation.

Dendrigrafts are multivalent macromolecules with less ordered topology and higher branching than dendrimers. Exhibiting a high density of terminal amines, poly-L-lysine dendrigrafts of the fifth generation (DGL G5) allow hydrogel formation with tailorable crosslinking density and surface modification. This work presents DGL G5 as multifunctional crosslinkers in biomimetic PEG hydrogels to favour the osteogenic differentiation of human mesenchymal stem cells (hMSCs).

Four-year evaluation of neonatal cystic fibrosis screening in Southern Belgium.

Unlabelled: Newborn screening for cystic fibrosis (CF-NBS) using an IRT-DNA algorithm with a 12 CFTR-variant panel and an IRT/IRT failsafe was officially implemented in the French-speaking Community of Belgium in January 2020. This screening protocol was evaluated after 4 years according to the criteria defined by the European Cystic Fibrosis Society's working group on neonatal screening. Immunoreactive trypsinogen concentration (IRT) was measured on dried blood spots collected between the second and the fourth day of life.

ST8Sia2 polysialyltransferase protects against infection by Trypanosoma cruzi.

Glycosylation is one of the most structurally and functionally diverse co- and post-translational modifications in a cell. Addition and removal of glycans, especially to proteins and lipids, characterize this process which has important implications in several biological processes. In mammals, the repeated enzymatic addition of a sialic acid unit to underlying sialic acids (Sia) by polysialyltransferases, including ST8Sia2, leads to the formation of a sugar polymer called polysialic acid (polySia).

Uncovering the Hidden Cause of Recurrent Chest Infections in a Child: A Case Report.

Recurrent chest infections can present diagnostic challenges, especially when the underlying cause remains elusive despite initial evaluations and treatments. This case report details the clinical journey of a patient experiencing recurrent chest infections over several months, during which conventional diagnostic approaches initially failed to provide lasting relief. Here, we present the case of a 16-month-old female child who had been experiencing recurrent chest infections since the age of 10 months, ultimately diagnosed as a case of Partial Anomalous Pulmonary Venous Return (PAPVR).

Comparative safety and efficacy of autogenous vaccine administrated by different routes against furunculosis caused by Aeromonas salmonicida sub. salmonicida in large Rainbow trout (Oncorhynchus mykiss).

The development and growth of fish farming are hindered by viral and bacterial infectious diseases, which necessitate effective disease control measures. Furunculosis, primarily caused by Aeromonas salmonicida, stands out as a significant bacterial disease affecting salmonid fish farms, particularly rainbow trout. Vaccination has emerged as a crucial tool in combating this disease.

[F]2-fluoro-2-deoxy-sorbitol ([F]FDS) PET imaging repurposed for quantitative estimation of blood-brain barrier permeability in a rat model of Alzheimer's disease.

Numerous studies suggest that blood-brain barrier (BBB) dysfunction may contribute to the progression of Alzheimer's disease (AD). Clinically available neuroimaging methods are needed for quantitative "scoring" of BBB permeability in AD patients. [F]2-fluoro-2-deoxy-sorbitol ([F]FDS), which can be easily obtained from simple chemical reduction of commercial [F]2-fluoro-2-deoxy-glucose ([F]FDG), was investigated as a small-molecule marker of BBB permeability, in a pre-clinical model of AD using in vivo PET imaging.

Insight on novel oxindole conjugates adopting different anti-inflammatory investigations and quantitative evaluation.

A dual COX/5-LOX strategy was adopted to develop new oxindole derivatives with superior anti-inflammatory activity. Three series of oxindoles - esters -, - and imines - - were synthesized and evaluated for their anti-inflammatory and analgesic activities. Molecular docking and predicted pharmacokinetic parameters were done for the most active compounds.

Post-COVID-19 condition: systemic inflammation and low functional exercise capacity.

Introduction: Post-COVID-19 condition (PCC) is characterised by a plethora of symptoms, with fatigue appearing as the most frequently reported. The alterations that drive both the persistent and post-acute disease newly acquired symptoms are not yet fully described. Given the lack of robust knowledge regarding the mechanisms of PCC we have examined the impact of inflammation in PCC, by evaluating serum cytokine profile and its potential involvement in inducing the different symptoms reported.

Mass Spectrometry-Based Characterization of Protein Aggregates in Tissues and Biofluids.

Protein aggregation is a common mechanism in multiple neurodegenerative and heart diseases and the accumulation of proteins in aggregates is toxic to cells, causing injury and death. The degree of protein aggregation directly correlates with the severity of the disease. Misfolded proteins present thermodynamic barriers that culminate in the loss of structure and function and the exposure of hydrophobic residues.

Isolation of Extracellular Vesicles Using Titanium Dioxide Microspheres.

Extracellular vesicles (EVs) are bilayer membrane particles released from several cell types to the extracellular environment. EVs have a crucial role in cell-cell communication, involving different biological processes in health and diseases. Due to the potential of biomarkers for several diseases as diagnostic and therapeutic tools, it is relevant to understand the biology of the EVs and their content.

DBS are suitable for 1,5-anhydroglucitol monitoring in GSD1b and G6PC3-deficient patients taking SGLT2 inhibitors to treat neutropenia.

Glycogen storage disease type Ib (GSD1b) and G6PC3-deficiency are rare autosomal recessive diseases caused by inactivating mutations in SLC37A4 (coding for G6PT) and G6PC3, respectively. Both diseases are characterized by neutropenia and neutrophil dysfunction due to the intracellular accumulation of 1,5-anhydroglucitol-6-phosphate (1,5-AG6P), a potent inhibitor of hexokinases. We recently showed that the use of SGLT2 inhibitor therapy to reduce tubular reabsorption of its precursor, 1,5-anhydroglucitol (1,5-AG), a glucose analog present in blood, successfully restored the neutropenia and neutrophil function in G6PC3-deficient and GSD1b patients.

Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas.

Background: Glioblastoma (GBM) is an aggressive brain tumor that exhibits resistance to current treatment, making the identification of novel therapeutic targets essential. In this context, cellular prion protein (PrP) stands out as a potential candidate for new therapies. Encoded by the PRNP gene, PrP can present increased expression levels in GBM, impacting cell proliferation, growth, migration, invasion and stemness.

Exploring new imines as anti-inflammatory COX and 5-LOX inhibitors with an improved pharmacokinetic profile.

Dual COX/5-LOX inhibition is a bright strategy for developing new potent and safe anti-inflammatory agents. New imines were synthesized and evaluated for their anti-inflammatory activity. The most active compounds were further investigated for their safety profile.

Biomechanical requirements of meat cutting tasks: A pilot study quantifying tasks sustainability and assistance required at the wrist.

The meat processing industry is particularly affected by distal upper limb musculoskeletal disorders. This pilot study aims at proposing a methodology able to quantify biomechanical requirements of meat cutting tasks at butchers' dominant wrist and, when necessary, at estimating the assistance needed to reach sustainability. Six professional butchers repeatedly cut pieces of pork.

A novel program of infiltrative control in astrocytomas: ADAM23 depletion promotes cell invasion by activating -secretase complex.

Background: Infiltration is a life-threatening growth pattern in malignant astrocytomas and a significant cause of therapy resistance. It results in the tumor cell spreading deeply into the surrounding brain tissue, fostering tumor recurrence and making complete surgical resection impossible. We need to thoroughly understand the mechanisms underlying diffuse infiltration to develop effective therapies.

Effect of atorvastatin on muscle tissues of dermatomyositis and antisynthetase syndrome patients with dyslipidemia.

Introduction: In a recent study, we have shown that atorvastatin is clinically safe for dermatomyositis (DM) and antisynthetase syndrome (ASS) patients with dyslipidemia. Herein, we showed in an unprecedented way, the safety of atorvastatin on the muscular tissues of these patients.

Methods: Transcriptome analysis was performed on samples of the vastus lateralis muscle obtained at baseline and after 12 weeks of atorvastatin (20 mg/day) intervention in DM or ASS patients with dyslipidemia [6DM and 5ASS received atorvastatin, and 2DM and 3ASS received placebo].