Biology subjects

Godin, B.

Publications and source records attributed to Godin, B..

6 recordsLinked to original sources

bioRxiv2025

Telomerase mRNA-Lipid nanoparticles attenuate neuroinflammation after traumatic brain injury in mice

Traumatic brain injury (TBI) is a leading cause of chronic neurological disability, yet no disease-modifying therapy exists. Emerging evidence indicates that TBI activates cellular aging programs, including telomere erosion and persistent inflammation, that contribute to progressive neurodegeneration. Telomerase reverse transcriptase (TERT) preserves telomere homeostasis and provides cytoprotective effects in the central nervous system, but has not been therapeutically targeted after TBI. Here, we developed an mRNA nanotherapy consisting of mouse TERT mRNA encapsulated in lipid nanoparticles (mTERT-LNPs) and evaluated it in a controlled cortical impact model of moderate TBI. We first established that TBI transiently disrupts TERT biology, with reduced cortical TERT mRNA and shortened telomeres at 3 days post-injury (dpi), followed by partial recovery by 14 dpi. mTERT-LNPs were well tolerated in vitro and in vivo. Following intravenous delivery in the acute post-injury window, LNPs localized to the injured brain and displayed expected peripheral biodistribution. A single systemic dose increased cortical TERT mRNA and protein and partially restored telomere length at 3 dpi. TERT mRNA delivery significantly reduced Iba1+ microglial activation and suppressed pro-inflammatory cytokines, with modest increases in anti-inflammatory markers. Systemically, mTERT-LNPs lowered serum C-reactive protein and malondialdehyde, indicating reduced peripheral inflammation and oxidative stress, without adverse effects on body weight or peripheral organ histology. Several outcomes showed sex-dependent patterns. Collectively, these data provide the first in vivo evidence that telomerase therapy can modulate telomere biology and neuroinflammation after TBI, supporting mRNA-LNP-mediated TERT restoration as a scalable, mechanistically grounded strategy for disease modification in TBI and related disorders. Significant statementTraumatic brain injury (TBI) can initiate progressive brain changes that worsen long after the initial impact, and no therapy directly slows or prevents this decline. A key contributor may be "accelerated aging" in injured tissue, including telomere damage (protective chromosome ends) and persistent neuroinflammation driven by activated immune cells. This study is significant because it tests a targeted way to disrupt these processes by restoring telomerase reverse transcriptase (TERT), which helps maintain telomeres and cellular resilience. Using a clinically validated mRNA-lipid nanoparticle platform, a single intravenous dose increased brain TERT, partially restored telomere length, and reduced neuroinflammation and systemic oxidative stress without obvious toxicity. These findings connect telomere dysfunction to a scalable disease-modifying strategy for TBI and related neurodegenerative conditions.

neuroscience↗

bioRxiv2025

Telomerase mRNA Reduces Radiation-induced DNA Damage of human skin

Over four million people undergo radiation therapy annually in the United States. Among these, more than 90% experience varying degrees of radiation-induced skin injury. Despite the enormity of the problem, there is currently no FDA-approved agent to prevent or treat skin damage caused by ionizing radiation. In the current study, ionizing radiation induced dose-dependent genomic and mitochondrial DNA damage, leading to apoptosis in primary cutaneous cells. Prior treatment with mRNA encoding telomerase reverse transcriptase (TERT) substantially reduced radiation-induced DNA damage in human primary skin cells and tissues. Mechanistically, TERT mRNA pretreatment enhances DNA repair, reduces mitochondrial ROS, and decreases apoptosis without extending telomere length during the experimental period, suggesting a non-canonical function of TERT to accelerate the cellular recovery from radiation. These findings highlight a potential therapeutic approach for preventing radiation-induced skin injury. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=197 HEIGHT=200 SRC="FIGDIR/small/636031v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@5bcee4org.highwire.dtl.DTLVardef@16c0c28org.highwire.dtl.DTLVardef@922c5dorg.highwire.dtl.DTLVardef@9eafd0_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2023

Sex-dependent improvement in traumatic brain injury outcomes after liposomal delivery of dexamethasone in mice.

Traumatic Brain Injury (TBI) can have long-lasting physical, emotional, and cognitive consequences due to the neurodegeneration caused by its robust inflammatory response. Despite advances in rehabilitation care, effective neuroprotective treatments for TBI patients are lacking. Furthermore, current drug delivery methods for TBI treatment are inefficient in targeting inflamed brain areas. To address this issue, we have developed a liposomal nanocarrier (Lipo) encapsulating dexamethasone (Dex), an agonist for the glucocorticoid receptor utilized to alleviate inflammation and swelling in various conditions. In vitro studies show that Lipo-Dex were well tolerated in human and murine neural cells. Lipo-Dex showed significant suppression of inflammatory cytokines, IL-6 and TNF-, release after induction of neural inflammation with lipopolysaccharide. Further, the Lipo-Dex were administered to young adult male and female C57BL/6 mice immediately after a controlled cortical impact injury. Our findings demonstrate that Lipo-Dex can selectively target the injured brain, thereby reducing lesion volume, cell death, astrogliosis, the release of proinflammatory cytokines, and microglial activation compared to Lipo-treated mice in a sex-dependent manner, showing a major impact only in male mice. This highlights the importance of considering sex as a crucial variable in developing and evaluating new nano-therapies for brain injury. These results suggest that Lipo-Dex administration may effectively treat acute TBI.

neuroscience↗

bioRxiv2023

Image-guided deployment and monitoring of a novel tungsten nanoparticle-infused radiopaque absorbable inferior vena cava filter in pig

The use of absorbable inferior vena cava filters (IVCFs) constructed with poly-p-dioxanone (PPDO) eliminates risks and complications associated with the use of retrievable metallic filters. Radiopacity of radiolucent PPDO IVCFs can be improved with the incorporation of nanoparticles (NPs) made of high-atomic number materials such as gold and bismuth. In this study, we focused on incorporating tungsten NPs (WNPs), along with polyhydroxybutyrate (PHB), polycaprolactone (PCL), and polyvinylpyrrolidone (PVP) polymers to increase the surface adsorption of the WNPs. We compared the imaging properties of WNPs with single-polymer PHB (W-P) and WNPs with polymer blends consisting of PHB, PCL, and PVP (W-PB). Our in vitro analyses using PPDO sutures showed enhanced radiopacity with either W-P or W-PB coating, without compromising the inherent physico-mechanical properties of the PPDO sutures. We observed a more sustained release of WNPs from W-PB-coated sutures than W-P-coated sutures. We successfully deployed W-P- and W-PB-coated IVCFs into the inferior vena cava of pig models, with monitoring by fluoroscopy. At the time of deployment, W-PB-coated IVCFs showed a 2-fold increase in radiopacity compared to W-P-coated IVCFs. Longitudinal monitoring of in vivo IVCFs over a 12-week period showed a drastic decrease in radiopacity at week 3 for both filters. Results of this study highlight the utility of NPs and polymers for enhancing radiopacity of medical devices; however, different methods of incorporating NPs and polymers can still be explored to improve the efficacy, safety, and quality of absorbable IVCFs.

bioengineering↗

bioRxiv2023

Rosuvastatin-Eluting Gold Nanoparticle-Loaded Perivascular Implantable Wrap for Enhanced Arteriovenous Fistula Maturation in a Murine Model

BackgroundArteriovenous fistulas (AVFs) are a vital intervention for patients requiring hemodialysis, but they also contribute to overall mortality due to access malfunction. The most common cause of both AVF non-maturation and secondary failure is neointimal hyperplasia (NIH). Absorbable polycaprolactone (PCL) perivascular wraps can address these complications by incorporating drugs to attenuate NIH, such as rosuvastatin (ROSU), and metallic nanoparticles for visualization and device monitoring. ObjectivesThis study aimed to assess the impacts of gold nanoparticle (AuNP) and ROSU-loaded perivascular wraps on vasculature NIH and AVF maturation and patency in a chronic kidney disease rat model. MethodsElectrospun wraps containing combinations of PCL, AuNP, and ROSU were monitored for in vitro drug elution, nanoparticle release, tensile strength, and cell viability. Perivascular wraps were implanted in chronic kidney disease rats for in vivo ultrasound (US) and micro-computed tomography (mCT) imaging. AVF specimens were collected for histological analyses. ResultsNo difference in cell line viability was observed in ROSU-containing grafts. In vitro release studies of ROSU and AuNPs correlated with decreasing radiopacity over time on in vivo mCT analysis. The mCT study also demonstrated increased radiopacity in AuNP-loaded wraps compared with PCL and control. The addition of ROSU demonstrated decreased US and histologic measurements of NIH. ConclusionsThe reduced NIH seen with ROSU-loading of perivascular wraps suggests a synergistic effect between mechanical support and anti-hyperplasia medication. Furthermore, the addition of AuNPs increased wrap radiopacity. Together, our results show that radiopaque, AuNP-, and ROSU-loaded PCL grafts induce AVF maturation and suppress NIH while facilitating optimal implanted device visualization.

bioengineering↗

bioRxiv2018

Novel cytonuclear combinations modify Arabidopsis seed physiology and vigor

The influence of intraspecific variation in cytoplasmic genomes and cytonuclear interactions on key seed traits that can impact adaptation and agriculture has not been thoroughly explored, so far. Here, dormancy, germination performance and longevity of seeds have been assessed in Arabidopsis plants with novel cytonuclear combinations that disrupt coadaptation between natural variants of nuclear and cytoplasmic genomes. Although all three traits were affected by cytonuclear reshuffling, the sensitivity of seed traits to cytoplasmic change was dependent on the nuclear background. Both deleterious and, more surprisingly, favorable effects of novel cytonuclear combinations (in comparison with the nuclear parent) were observed, suggesting suboptimal genetic combinations exist in natural populations for these traits. Significant changes on dormancy and germination performance due to specific cytonuclear interacting combinations mainly occurred in opposite directions, in accordance with the previously proposed dormancy continuum. Consistently, reduced sensitivity to exogenous ABA and faster endogenous ABA decay during germination were observed in a novel cytonuclear combination that also exhibited enhanced longevity and better germination performance, compared to its natural nuclear parent. Cytoplasmic genomes, therefore, represent an additional resource of natural variation for breeding seed vigor traits.\n\nIssue sectionGrowth and development\n\nHighlightNatural variation in Arabidopsis organelles and cytonuclear interactions influence seed dormancy, longevity and germination performance. Enhanced seed vigor was obtained through the creation of novel cytonuclear combinations.

plant biology↗