A Bioinspired Cu-Responsive Magnetic Resonance Imaging Contrast Agent with Unprecedented Turn-On Response and Selectivity.

Imaging extracellular Cu in vivo is of paramount interest due to its biological importance in both physiological and pathological states. Magnetic resonance imaging (MRI) is a powerful technique to do so. However, the development of efficient MRI contrast agents selective for Cu, particularly versus the more abundant Zn ions, is highly challenging.

Thermodynamic and kinetic study of palladium(II) complexation with 1-methyl-2-mercaptoimidazole (methimazole) and their importance for structural design of metallodrugs.

The acidobasic and complexing properties of 1-methyl-2-mercaptoimidazole (Methimazole, an anti-thyroid drug) were investigated. The pK 11.49 ± 0.

Non-invasive in vivo imaging of changes in Collagen III turnover in myocardial fibrosis.

Heart failure (HF) affects 64 million people globally with enormous societal and healthcare costs. Myocardial fibrosis, characterised by changes in collagen content drives HF. Despite evidence that collagen type III (COL3) content changes during myocardial fibrosis, in vivo imaging of COL3 has not been achieved.

Enabling Visible Light Sensitization of Yb, Nd and Er in Dimeric Ln/Ga Metallacrowns through Functionalization with Ru Complexes for NIR-II Multiplex Imaging.

Multiplex imaging in the second near-infrared window (NIR-II, 1000-1700 nm) provides exciting opportunities for more precise understanding of biological processes and more accurate diagnosis of diseases by enabling real-time acquisition of images with improved contrast and spatial resolution in deeper tissues. Today, the number of imaging agents suitable for this modality remains very scarce. In this work, we have synthesized and fully characterized, including theoretical calculations, a series of dimeric Ln/Ga metallacrowns bearing Ru polypyridyl complexes, LnRu-3 (Ln=Y, Yb, Nd, Er).

Ubiquitylation of nucleic acids by DELTEX ubiquitin E3 ligase DTX3L.

The recent discovery of non-proteinaceous ubiquitylation substrates broadened our understanding of this modification beyond conventional protein targets. However, the existence of additional types of substrates remains elusive. Here, we present evidence that nucleic acids can also be directly ubiquitylated via ester bond formation.

Small, Fluorinated Mn Chelate as an Efficient H and F MRI Probe.

We explore the potential of fluorine-containing small Mn chelates as alternatives to perfluorinated nanoparticles, widely used as F MRI probes. In MnL1, the cyclohexanediamine skeleton and two piperidine rings, involving each a metal-coordinating amide group and an appended CF moiety, provide high rigidity to the complex. This allows for good control of the Mn-F distance (r=8.

Oil/Water Biphasic Solvent System for the Eco-Extraction and Cosmetic Formulation of L.

Annatto, obtained from the seeds of achiote ( L.), is a widely used orange pigment rich in bixin and other apocarotenoids. This work reports the optimisation of a green extraction method of pigments and antioxidant compounds from achiote as well as its integration in a one-step green extraction-cosmetic formulation process.

Tuning white light emission using single-component tetrachroic Dy metallacrowns: the role of chromophoric building blocks.

White light production is of major importance for ambient lighting and technological displays. White light can be obtained by several types of materials and their combinations, but single component emitters remain rare and desirable towards thinner devices that are, therefore, easier to control and that require fewer manufacturing steps. We have designed a series of dysprosium(iii)-based luminescent metallacrowns (MCs) to achieve this goal.

Investigation of Ln complexation by a DOTA derivative substituted by an imidazothiadiazole: synthesis, solution structure, luminescence and relaxation properties.

We investigated the coordination properties of original macrocyclic Ln complexes comprising an imidazothiadiazole heterocycle. The thermodynamic stability of the Gd complex was determined by a combination of potentiometric and photophysical measurements. The kinetic inertness was assessed in highly acidic media.

Comprehensive literature review of oral and intravenous contrast-enhanced PET/CT: a step forward?

The integration of diagnostic CT scans into PET/CT facilitates a comprehensive single examination, presenting potential advantages for patients seeking a thorough one-shot check-up. The introduction of iodinated contrast media during PET scanning raises theoretical concerns about potential interference with uptake quantification, due to the modification of tissue density on CT. Nevertheless, this impact appears generally insignificant for clinical use, compared to the intrinsic variability of standardized uptake values.

Lanthanide-Based Probes for Imaging Detection of Enzyme Activities by NIR Luminescence, T1- and ParaCEST MRI.

Applying a single molecular probe to monitor enzymatic activities in multiple, complementary imaging modalities is highly desirable to ascertain detection and to avoid the complexity associated with the use of agents of different chemical entities. We demonstrate here the versatility of lanthanide (Ln) complexes with respect to their optical and magnetic properties and their potential for enzymatic detection in NIR luminescence, CEST and T1 MR imaging, controlled by the nature of the Ln ion, while using a unique chelator. Based on X-ray structural, photophysical, and solution NMR investigations of a family of Ln DO3A-pyridine model complexes, we could rationalize the luminescence (Eu, Yb), CEST (Yb) and relaxation (Gd) properties and their variations between carbamate and amine derivatives.

DELTEX E3 ligases ubiquitylate ADP-ribosyl modification on nucleic acids.

Although ubiquitylation had traditionally been considered limited to proteins, the discovery of non-proteinaceous substrates (e.g. lipopolysaccharides and adenosine diphosphate ribose (ADPr)) challenged this perspective.

Integrins regulate hERG1 dynamics by girdin-dependent Gαi3: signaling and modeling in cancer cells.

The hERG1 potassium channel is aberrantly over expressed in tumors and regulates the cancer cell response to integrin-dependent adhesion. We unravel a novel signaling pathway by which integrin engagement by the ECM protein fibronectin promotes hERG1 translocation to the plasma membrane and its association with β1 integrins, by activating girdin-dependent Gαi3 proteins and protein kinase B (Akt). By sequestering hERG1, β1 integrins make it avoid Rab5-mediated endocytosis, where unbound channels are degraded.

["New Modalities in Cancer Imaging and Therapy" XVth edition of the workshop organized by the network "Tumor Targeting, Imaging, Radiotherapies" of the Cancéropôle Grand-Ouest, 5-8 October 2022, France].

The fifteenth edition of the international workshop organized by the "Tumour Targeting and Radiotherapies network" of the Cancéropôle Grand-Ouest focused on the latest advances in internal and external radiotherapy from different disciplinary angles: chemistry, biology, physics, and medicine. The workshop covered several deliberately diverse topics: the role of artificial intelligence, new tools for imaging and external radiotherapy, theranostic aspects, molecules and contrast agents, vectors for innovative combined therapies, and the use of alpha particles in therapy.

Zinc-sensitive MRI contrast agents: importance of local probe accumulation in zinc-rich tissues.

We present the characterisation of a Gd-based contrast agent that responds to Zn upon interaction with Human Serum Albumin. We show that the contradictory behaviour is related to Gd-accumulation in Zn-rich tissues. This highlights the importance of the biodistribution of such contrast agents.

Gd Complexes for MRI Detection of Zn in the Presence of Human Serum Albumin: Structure-Activity Relationships.

Zn-responsive magnetic resonance imaging (MRI) contrast agents are typically composed of a Gd chelate conjugated to a Zn-binding moiety via a linker. They allow for Zn detection in the presence of human serum albumin (HSA). In order to decipher the key parameters that drive their Zn-dependent MRI response, we designed a pyridine-based ligand, , and compared the properties of to those of analogue complexes with varying Gd core, Zn-binding moiety, or linker sizes.

An efficient site-selective, dual bioconjugation approach exploiting N-terminal cysteines as minimalistic handles to engineer tailored anti-HER2 affibody conjugates.

Site-selective, dual-conjugation approaches for the incorporation of distinct payloads are key for the development of molecularly targeted biomolecules, such as antibody conjugates, endowed with better properties. Combinations of cytotoxic drugs, imaging probes, or pharmacokinetics modulators enabled for improved outcomes in both molecular imaging, and therapeutic settings. We have developed an efficacious dual-bioconjugation strategy to target the N-terminal cysteine of a chemically-synthesized, third-generation anti-HER2 affibody.

A new automatic method for tracking rats in the Morris water maze.

Morris water maze (MWM) test is widely used to evaluate the learning and memory deficits in rodents. Image processing and pattern recognition can be used to analyse videos and recognize automatically the tracking in MWM. There are several commercial and free access software that allows analyzing the behavioral tasks although they also have limitations such as automation, cost, user intervention among other things.

Structural Variations in Carboxylated Bispidine Ligands: Influence of Positional Isomerism and Rigidity on the Conformation, Stability, Inertness and Relaxivity of their Mn Complexes.

Mn complexes of 2,4-pyridyl-disubstituted bispidine ligands have emerged as more biocompatible alternatives to Gd -based MRI probes. They display relaxivities comparable to that of commercial contrast agents and high kinetic inertness, unprecedented for Mn complexes. The chemical structure, in particular the substituents on the two macrocyclic nitrogens N3 and N7, are decisive for the conformation of the Mn complexes, and this will in turn determine their thermodynamic, kinetic and relaxation properties.

Water-Soluble Gd(III)-Porphyrin Complexes Capable of Both Photosensitization and Relaxation Enhancement.

With the aim of developing more stable Gd(III)-porphyrin complexes, two types of ligands and with carboxylic acid anchors were synthesized. Due to the N-substituted pyridyl cation attached to the porphyrin core, these porphyrin ligands were highly water-soluble and formed the corresponding Gd(III) chelates, and . was sufficiently stable in neutral buffer, presumably due to the preferred conformation of the carboxylate-terminated anchors connected to nitrogen in the position of the pyridyl group helping to stabilize Gd(III) complexation by the porphyrin center.

A seven-coordinate Mn(II) complex with a pyridine-based 15-membered macrocyclic ligand containing one acetate pendant arm: structure, stability and relaxation properties.

A new 15-membered pyridine-based macrocyclic ligand containing one acetate pendant arm (-carboxymethyl-3,12,18-triaza-6,9-dioxabicyclo[12.3.1]octadeca-1(18),14,16-triene, L1) was synthesized and its Mn(II) complex MnL1 was investigated in the context of MRI contrast agent development.

A phosphorylated zinc finger peptide bearing a gadolinium complex for zinc detection by MRI.

Two zinc finger peptides, namely ZFQD and ZFQE (Ln = Tb or Gd), with an appended Ln chelate and a phosphoserine able to coordinate the Ln ion are presented. The two peptides differ by the amino acid anchorage of the chelate, either aspartate (D) or glutamate (E). Both peptides are able to bind Zn and adopt the ββα fold.

Optimized Methods for the Surface Immobilization of Collagens and Collagen Binding Assays.

Fibrosis occurs in various tissues as a reparative response to injury or damage. If excessive, however, fibrosis can lead to tissue scarring and organ failure, which is associated with high morbidity and mortality. Collagen is a key driver of fibrosis, with type I and type III collagen being the primary types involved in many fibrotic diseases.