Project description:In this study, to delineate the radiation-induced changes in miRNAs and protein cargo, we established the microRNA and proteome profiles of plasma EVs collected from mice that had been sham- (SI), whole body (WBI), or partial body irradiated (PBI) with 2 Gy X-rays 24 hours before. The radiation-induced changes in the miRNA and protein composition of EVs can influence the stress response of distant cells by propagating damaging or protective signals. Testing EVs in functional assays may be a read out of the multiple radiation-induced signaling networks, crucial for gaining an understanding of the EVs properties. Therefore, to functionally elucidate the pathophysiological changes in the contents of EVs induced by irradiation, we here investigated the EV-induced cellular responses in vivo, by injecting WBI, PBI and SI plasma-derived EVs in the cerebellum of neonatal mice, highly susceptible to radiation injury, and evaluating the level of apoptosis.
Project description:The study aimed to investigate the biological significance and role of the SNAT8 gene in retinal physiology and biological processes.
Project description:Major depression is a multidimensional disorder highly prevalent in modern society. Although several classes of antidepressants (ADs) are currently available to treat depression, the effectiveness of treatment is still limited, as many patients do not show full remission; thus, there is a need to find better patients’ directed therapeutic strategies. Neuroplastic changes in several brain regions, namely in the hippocampal dentate gyrus (DG), are amongst the best correlates of depression and of ADs actions. In this study the targets and molecular mediators of chronic stress and of four ADs from different pharmacological classes (fluoxetine, imipramine, tianeptine and agomelatine) were investigated in the DG. Using the unpredictable chronic mild stress (uCMS) animal model of depression, the molecular commonalities and specificities of the ADs were determined. All ADs, except agomelatine, could reverse the behavioral deficits produced by uCMS, and the neuroplastic changes in the DG; agomelatine reversed only the anhedonic profile in the sucrose consumption test. Chronic stress induced mild but relevant molecular changes that were mostly reversed by fluoxetine, imipramine and tianeptine. Fluoxetine reduced pro-inflammatory response and increased cell metabolism pathways. Its actions were mostly dependent on molecular changes occurring in neurons. Similarities were found between imipramine and tianeptine molecular actions and targets, as both activated pathways related to cellular protection. Moreover, no particular neural cell type enrichment was found with both treatments. Agomelatine presented a very dissimilar molecular pattern impacting greatly on Rho-GTPases-related pathways in oligodendrocytes and neurons. The recognition of these molecular alterations contributes to the understanding of the processes implicated in the onset and treatment of depression and may pave the way for more effective therapeutic interventions. We compared gene expresssion in the dentate gyros of rats which were either untreated, exposed to unpredictable chronic mild stress, or exposed to the same stress and treated with either fluoxetine, imipramine, tianeptine, or agomelatine
Project description:A Proliferation Inducing Ligand (APRIL) is a member of the tumour necrosis factor (TNF) superfamily and has recently been shown to modulate pro-inflammatory astrocyte responses, as well as to ameliorate disease outcome in the experimental autoimmune encephalomyelitis mouse model for multiple sclerosis (MS). In this new study, an unbiased proteomic analysis first confirmed that adeno-associated virus (AAV)-mediated delivery of APRIL was able to rescue immune-stimulated murine iPSC-derived neurospheroids from detrimental cell death and neurodegenerative processes. Next, we investigated whether AAV-mediated secretion of APRIL by cortical neurons could influence cuprizone-induced neuro-inflammation and/or demyelination in the splenium of the corpus callosum. Applying both T2 and diffusion-weighted magnetic resonance imaging (MRI), with subsequent histological confirmation, our results indicated that cortical secretion of APRIL is able to reduce neuro-inflammatory and demyelinating events in the splenium. To further document the beneficial effect of APRIL, a transcriptome-proteome integration study for the splenium revealed the activation of cellular pathways associated with alternative immune cell polarisation, cell survival and neuroregeneration. Lastly, even though our MRI and transcriptome-proteome integration study for the cortical AAV injection site noted a local activation of cellular pathways associated with inflammation, these events were not associated with major abnormalities in histological appearance. Concluding, our findings highlight that APRIL has strong anti-inflammatory and neuroprotective effects in the CNS which may have the potential to improve MS-like disease outcome.
Project description:The canine transmissible veneral tumour (CTVT) is one of the few known clonally transmissible cancers in nature. CTVT regresses spontaneously or after a single treatment with vincristine, however we know little of the mechanisms. To understand CTVT regression, we performed transcriptional analyses on serial biopsies of regressing and non-regressing CTVT, aiming to identify the likely drivers of CTVT regression.
Project description:The canine transmissible veneral tumour (CTVT) is one of the few known clonally transmissible cancers in nature. CTVT regresses spontaneously or after a single treatment with vincristine, however we know little of the mechanisms. To understand CTVT regression, we performed methylome analyses on serial biopsies of regressing and non-regressing CTVT, aiming to identify the likely drivers of CTVT regression.
Project description:In this study, we compared gene expression profiles of sensorimotor striatum tissue derived from LID and non-LID 6-hydroxydopamine-lesioned rats treated with L-DOPA. Total RNA were amplified, transcribed and hybridized to Agilent Whole Rat Genome Oligo Microarray chips.
Project description:The urgent need to understand the molecular modulation associated with chronic cardiotoxicity of doxorubicin (DOX) has prompted us to investigate the ubiquitome profile of aged cardiac muscle. Using old CD-1 male mice administered with a DOX dosage established to induce cardiotoxicity, we performed a comprehensive analysis of the proteomic profile of the enriched pool of poly-ubiquitinated proteins obtained from cardiac muscle using tandem ubiquitin-binding entities (TUBEs). GeLC-MS/MS and subsequent bioinformatic analysis revealed several proteins with the poly-ubiquitination modification involved in DOX-induced cardiotoxicity. Increased poly-ubiquitination levels were found for sarcomeric proteins including alpha-actinin-2 and desmin as well as mitochondrial proteins such as ATP synthase subunit beta and cytochrome b-c1 complex subunit 1. Thus, impaired protein ubiquitination emerges as an enduring consequence of DOX-induced cardiotoxicity. The present exploratory analysis could be considered an important starting point for further studies targeting molecular pathways under the side effects of the widely used anticancer drug DOX.
Project description:Background: Racehorses undergo profound physiological changes in response to training and competition, yet current tools to assess training adaptation and overload remain limited. Traditional biomarkers often fail to reflect the complex molecular dynamics induced by physical effort. This study aimed to identify new plasma biomarkers of exercise adaptation in racehorses using high-throughput proteomics. Objectives: We hypothesized that systematic training and racing efforts induce distinct proteomic signatures in plasma, enabling the identification of novel candidate biomarkers reflecting training status, oxidative stress, inflammation, and metabolic remodeling. Study Design: This was an in vivo longitudinal study using repeated blood sampling in the same horses across different phases of training and racing. Methods: Forty-nine Arabian and Thoroughbred racehorses underwent standardized high-intensity training. Plasma samples were collected at rest, immediately post-exercise, and after recovery, during three phases: early training (T1), mid-season conditioning (T2), and racing (R). A total of 314 samples were analyzed using TMT-based quantitative proteomics and high-resolution mass spectrometry. Protein expression changes were evaluated with statistical correction for multiple comparisons (FDR < 0.05), and functional pathway enrichment was conducted via STRING and ShinyGO. Results: The proteomic response evolved across phases: T1 revealed a broad activation of inflammatory (S100A8/A9), antioxidant (SOD1, catalase), and metabolic proteins (G6PD, PGK1), while T2 showed refined expression of remodeling and redox regulators (decorin, thymosin β4, glutathione S-transferase). The racing phase induced the strongest response, with >100 upregulated proteins involved in energy metabolism, oxidative stress defense, and cytoskeletal adaptation. Several proteins (e.g., S100A8, thymosin β4, prothymosin α, cofilin-1, lipocalins) consistently changed across all phases, indicating their biomarker potential. Conclusions: This study identified a panel of promising plasma biomarkers reflecting exercise adaptation and overload in racehorses. These novel candidates may enhance monitoring of performance, training status, and early signs of overtraining in equine athletes.
Project description:Transcriptomic analysis was performed to gain further insights into the molecular and cellular mechanisms underlying cardiac pathology.