The transcriptional response of cortical neurons to concussion reveals divergent fates after injury.

Traumatic brain injury (TBI) is a risk factor for neurodegeneration, however little is known about how this kind of injury alters neuron subtypes. In this study, we follow neuronal populations over time after a single mild TBI (mTBI) to assess long ranging consequences of injury at the level of single, transcriptionally defined neuronal classes. We find that the stress-responsive Activating Transcription Factor 3 (ATF3) defines a population of cortical neurons after mTBI.

Structural and functional characterization of a histidylated liposome for mRNA delivery.

The development of lipid-based mRNA delivery systems has significantly facilitated recent advances in mRNA-based therapeutics. Liposomes, as the pioneering class of mRNA vectors, continue to lead in clinical trials. We previously developed a histidylated liposome that demonstrated efficient nucleic acid delivery.

The role of river connectivity in the distribution of fish in an anthropized watershed.

The ongoing biodiversity crisis is especially severe in freshwater habitats. Anthropized watersheds, such as the Seine-Normandie basin in France, are particularly affected by human interference. The study of fish species distribution in watersheds often relies on environmental drivers such as land use or climate.

DLK-dependent axonal mitochondrial fission drives degeneration after axotomy.

Currently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we develop a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma.

Biophysical characterization of microRNA mixtures based on Molecular Beacons.

Diverse studies have shown a relationship between dysregulated microRNAs (miRNAs), including miRNA-29b and miRNA-9, and several diseases. So, it is hypothesized that miRNAs can be studied as potential agents to be exploited in biomedical applications, due to their ability to take part in gene expression regulation at a post-transcriptional level. Considering the possibility of using miRNAs, it is important to characterize and validate this bioproduct, structurally and functionally.

A new approach for extracellular RNA recovery from Rhodovulum sulfidophilum.

The development of RNA-based drugs is highly pursued due to the possibility of creating viable and effective therapies. However, their translation to clinical practice strongly depends on efficient technologies to produce substantial levels of these biomolecules, with high purity and high quality. RNAs are commonly produced by chemical or enzymatic methods, displaying these limitations.

[The therapeutic stay, a rewarding experience both professionally and personally].

The organization of a therapeutic stay by four mental health caregivers was a rich learning experience. This experience, a first for them, enabled them to expand their knowledge and adapt their professional posture over the long term. It also helped them to get to know themselves better on a personal level, to be more attuned to their emotions and aware of their limits.

Enhancing natural killer cells proliferation and cytotoxicity using imidazole-based lipid nanoparticles encapsulating interleukin-2 mRNA.

mRNA applications have undergone unprecedented applications-from vaccination to cell therapy. Natural killer (NK) cells are recognized to have a significant potential in immunotherapy. NK-based cell therapy has drawn attention as allogenic graft with a minimal graft-versus-host risk leading to easier off-the-shelf production.

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.

FUS-mediated BBB opening leads to transient perfusion decrease and inflammation without acute or chronic brain lesion.

The permeabilization of the BBB to deliver therapeutics with MR-guided FUS redefines therapeutic strategies as it improves patient outcomes. To ensure the best translation towards clinical treatment, the evaluation of hemodynamic modifications in the CNS is necessary to refine treatment parameters. MR-guided FUS was applied at 1.

Messenger RNA Lipid-Based Nanoparticles: Optimization of Formulations in the Lab.

Among the large variety of messenger RNA (mRNA) delivery systems, those developed with lipid-based formulations were the most widely used and efficient. In our lab, we produced different mRNA formulations made with liposomes, hybrid lipid polymer, and lipid nanoparticles. Our formulations were made with lipids bearing imidazole groups that trigger the endosomal escape of nanoparticles once protonated inside the mild acidic milieu of endosomes upon their cell uptake.

Therapeutic Vaccines for HPV-Associated Cervical Malignancies: A Systematic Review.

Importance: Despite widespread prophylactic vaccination, cervical cancer continues to be a major health problem with considerable mortality. Currently, therapeutic vaccines for HPV-associated cervical malignancies are being evaluated as a potential complement to the standard treatment.

Objective: The present systematic review was conducted on randomized controlled trials (RCTs) to investigate the effects of therapeutic vaccines on the treatment of patients with cervical cancer and cervical intraepithelial neoplasia (CIN) of Grades 2 and 3.

The transcriptional response of cortical neurons to concussion reveals divergent fates after injury.

Traumatic brain injury (TBI) is a risk factor for neurodegeneration, however little is known about how different neuron types respond to this kind of injury. In this study, we follow neuronal populations over several months after a single mild TBI (mTBI) to assess long ranging consequences of injury at the level of single, transcriptionally defined neuronal classes. We find that the stress responsive Activating Transcription Factor 3 (ATF3) defines a population of cortical neurons after mTBI.

Neoantigen vaccine nanoformulations based on Chemically synthesized minimal mRNA (CmRNA): small molecules, big impact.

Recently, chemically synthesized minimal mRNA (CmRNA) has emerged as a promising alternative to in vitro transcribed mRNA (IVT-mRNA) for cancer therapy and immunotherapy. CmRNA lacking the untranslated regions and polyadenylation exhibits enhanced stability and efficiency. Encapsulation of CmRNA within lipid-polymer hybrid nanoparticles (LPPs) offers an effective approach for personalized neoantigen mRNA vaccines with improved control over tumor growth.

Local production of reactive oxygen species drives vincristine-induced axon degeneration.

Neurological side effects arising from chemotherapy, such as severe pain and cognitive impairment, are a major concern for cancer patients. These major side effects can lead to reduction or termination of chemotherapy medication in patients, negatively impacting their prognoses. With cancer survival rates improving dramatically, addressing side effects of cancer treatment has become pressing.

Creation of de novo cryptic splicing for ALS/FTD precision medicine.

A system enabling the expression of therapeutic proteins specifically in diseased cells would be transformative, providing greatly increased safety and the possibility of pre-emptive treatment. Here we describe "TDP-REG", a precision medicine approach primarily for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which exploits the cryptic splicing events that occur in cells with TDP-43 loss-of-function (TDP-LOF) in order to drive expression specifically in diseased cells. In addition to modifying existing cryptic exons for this purpose, we develop a deep-learning-powered algorithm for generating customisable cryptic splicing events, which can be embedded within virtually any coding sequence.

Impact of net charge, targeting ligand amount and mRNA modification on the uptake, intracellular routing and the transfection efficiency of mRNA lipopolyplexes in dendritic cells.

Targeting mRNA formulations to achieve cell specificity is one of the challenges that must be tackled to mettle their therapeutic potential. Here, lipopolyplexes (LPR) bearing tri-mannose-lipid (TM) are used to target mannose receptor on dendritic cells. We investigated the impact of the net charge and percentage of TM units on the binding, uptake, transfection efficiency (TE) and RNA sensors activation.

Recent Advances Using Genetic Therapies Against Infectious Diseases and for Vaccination.

The development of prophylatic or therapeutic medicines for infectious diseases is one of the priorities for health organizations worldwide. Innovative solutions are required to achieve effective, safe, and accessible treatments for most if not all infectious diseases, particularly those that are chronic in nature or that emerge unexpectedly over time. Genetic technologies offer versatile possibilities to design therapies against pathogens.

Oncolytic virotherapy with intratumoral injection of vaccinia virus TG6002 and 5-fluorocytosine administration in dogs with malignant tumors.

TG6002 is an oncolytic vaccinia virus expressing FCU1 protein, which converts 5-fluorocytosine into 5-fluorouracil. The study objectives were to assess tolerance, viral replication, 5-fluorouracil synthesis, and tumor microenvironment modifications to treatment in dogs with spontaneous malignant tumors. Thirteen dogs received one to three weekly intratumoral injections of TG6002 and 5-fluorocytosine.

Murine Breast Cancer Radiosensitization Using Oxygen Microbubbles and Metformin: Vessels Are the Key.

Radiotherapy is a cornerstone of cancer treatment, but tumor hypoxia and resistance to radiation remain significant challenges. Vascular normalization has emerged as a strategy to improve oxygenation and enhance therapeutic outcomes. In this study, we examine the radiosensitization potential of vascular normalization using metformin, a widely used anti-diabetic drug, and oxygen microbubbles (OMBs).

Two-Photon Light Trigger siRNA Transfection of Cancer Cells Using Non-Toxic Porous Silicon Nanoparticles.

The concept of using two-photon excitation in the NIR for the spatiotemporal control of biological processes holds great promise. However, its use for the delivery of nucleic acids has been very scarcely described and the reported procedures are not optimal as they often involve potentially toxic materials and irradiation conditions. This work prepares a simple system made of biocompatible porous silicon nanoparticles (pSiNP) for the safe siRNA photocontrolled delivery and gene silencing in cells upon two-photon excitation.