A5030144019- Cancer Cells and Metastasis
- Adipose Tissue and Metabolism
- Cancer, Hypoxia, and Metabolism
- Caveolin-1 and cellular processes
- Angiogenesis and VEGF in Cancer
- Regulation of Appetite and Obesity
- Lipid metabolism and disorders
- Immune cells in cancer
- Tissue Engineering and Regenerative Medicine
- Mitochondrial Function and Pathology
- Pancreatic function and diabetes
- Diet and metabolism studies
- Adipokines, Inflammation, and Metabolic Diseases
- Ubiquitin and proteasome pathways
- Radiomics and Machine Learning in Medical Imaging
- Lymphatic System and Diseases
- Mesenchymal stem cell research
- Sarcoma Diagnosis and Treatment
- Clusterin in disease pathology
- Cardiac Fibrosis and Remodeling
- Virus-based gene therapy research
- Hippo pathway signaling and YAP/TAZ
- Muscle metabolism and nutrition
- Axon Guidance and Neuronal Signaling
- Sirtuins and Resveratrol in Medicine
International Centre for Genetic Engineering and Biotechnology
2009-2024
University of Trieste
2012-2017
Azienda Sanitaria Universitaria Integrata di Trieste
2017
Mounting evidence indicates that the function of members vascular endothelial growth factor (VEGF) family extends beyond blood vessel formation. Here, we show prolonged intramyocardial expression VEGF-A165 and VEGF-B167 on adeno-associated virus-mediated gene delivery determined a marked improvement in cardiac after myocardial infarction rats, by promoting contractility, preserving viable tissue, preventing remodeling left ventricle (LV) over time. Consistent with this functional outcome,...
Over the last several years, mesenchymal stromal cells (MSCs) have been isolated from different tissues following a variety of procedures. Here, we comparatively assess ex vivo and in properties MSCs either adipose tissue or bone marrow by purification protocols. After MSC transplantation into mouse model hindlimb ischemia, clinical histological analysis revealed that purified on adhesive substrates exerted best therapeutic activity, preserving viability promoting formation new arterioles...
Functional screening of expression libraries in vivo would offer the possibility identifying novel biotherapeutics without a priori knowledge their biochemical function. Here we describe procedure for functional selection tissue-protective factors based on delivery arrayed cDNA from mouse secretome using adeno-associated virus (AAV) vectors. Application this technique, which call FunSel, context acute ischaemia, revealed that peptide ghrelin protects skeletal muscle and heart ischaemic...
Excess reactive oxygen species (ROS) generation and inflammation may contribute to obesity-associated skeletal muscle insulin resistance. Ghrelin is a gastric hormone whose unacylated form (UnAG) associated with whole-body sensitivity in humans reduce oxidative stress nonmuscle cells vitro. We hypothesized that UnAG 1) lowers ROS production enhances tissue action lean rats 2) prevents metabolic alterations normalizes resistance hyperglycemia high-fat diet (HFD)-induced obesity. In...
Therapies for patients with myocardial infarction and heart failure are urgently needed, in light of the breadth these conditions lack curative treatments. To systematically identify previously unidentified cardioactive biologicals an unbiased manner vivo, we developed cardiac FunSel, a method systematic, functional selection effective factors using library 1198 barcoded adeno-associated virus (AAV) vectors encoding mouse secretome. By pooled vector injection into heart, this was screened to...
Improving tumor perfusion, thus tempering tumor-associated hypoxia, is known to impair cancer progression. Previous work from our laboratory has shown that VEGF-A165 and semaphorin 3A (Sema3A) promote vessel maturation through the recruitment of a population circulating monocytes expressing neuropilin-1 (Nrp1) receptor (Nrp1-expressing monocytes; NEM). Here, we define characteristics bone marrow NEMs assess whether these cells might represent an exploitable tool induce maturation. Gene...
Abstract Background Chronic heart failure (CHF) is associated with skeletal muscle abnormalities contributing to exercise intolerance, loss, and negative impact on patient prognosis. A primary role has been proposed for mitochondrial dysfunction, which may be induced by systemic tissue inflammation further contribute low insulin signalling. The acylated form of the gastric hormone ghrelin (AG) improve oxidative capacity signalling in both healthy diseased rodent models. Methods We...
Unacylated ghrelin (UnAG) may lower skeletal muscle oxidative stress, inflammation, and insulin resistance in lean obese rodents. UnAG-induced autophagy activation contribute to these effects, likely involving removal of dysfunctional mitochondria (mitophagy) redox state maintenance. In chronic kidney disease (CKD) inflammation negatively influence patient outcome by worsening nutritional through mass loss. Here we show a 5/6 nephrectomy (Nx) CKD rat model that 4 d s.c. UnAG administration...
Transplantation of cells into the infarcted heart has significant potential to improve myocardial recovery; however, low efficacy cell engraftment still limits therapeutic benefit. Here, we describe a method for unbiased, in vivo selection cytokines that mesenchymal stromal both normal conditions and after infarction.An arrayed library 80 secreted factors, including most currently known interleukins chemokines, were individually cloned adeno-associated viral vectors. Pools from this then...
Abstract Background New drugs to tackle the next pathway or mutation fueling cancer are constantly proposed, but 97% of them doomed fail in clinical trials, largely because they identified by cellular silico screens that cannot predict their vivo effect. Methods We screened an Adeno-Associated Vector secretome library (> 1000 clones) directly a mouse model and validated therapeutic effect first hit, EMID2, both orthotopic genetic models lung pancreatic cancer. Results EMID2 overexpression...
Abstract Muscle regeneration depends on satellite cells (SCs), quiescent precursors that, in consequence of injury or pathological states such as muscular dystrophies, activate, proliferate, and differentiate to repair the damaged tissue. A subset SCs undergoes self-renewal, thus preserving SC pool its regenerative potential. Unacylated ghrelin (UnAG) is a circulating hormone that protects muscle from atrophy, promotes myoblast differentiation, enhances ischemia-induced regeneration. Here we...
Abstract Viral myocarditis (VM) is an important cause of heart failure (HF) in children and adults. However, the molecular determinants involved cardiac inflammation cardiomyocyte necrosis remain poorly characterized, cardioprotective molecules are currently missing. Here, we applied vivo method based on functional selection (FunSel) factors using AAV vectors for unbiased identification novel immunomodulatory a Coxsackievirus B3 (CVB3)-induced mouse model. Two consecutive rounds FunSel...
<p>PDF file - 3482K, Proliferative activity of 4T1 tumors in vivo. A. Immunofluorescence staining frozen tumor sections from mice injected with PBS, Gr1+ cells or NEMs using an antibody against PCNA (red); nuclei are counterstained blue DAPI. Analysis was performed after the animal sacrifice at day 18 inoculation. Scale bar: 100 �m. B. Quantitative analysis showing percentage PCNA+ sections. Data mean�s.e.m.; n=5 per group.</p>
<p>PDF file - 3704K, The vessel normalization effect of NEMs is independent tumor size. B16.F10 tumors were inoculated in mice, which then injected at days 11 and 13 after inoculation with PBS, Gr1+ cells NEMs. Mice sacrificed when reached 1700 mm3 , irrespective the day. A. Immunofluorescence analysis vasculature representative images. Frozen sections stained antibodies against CD31 (green) α-SMA (red).Nuclei are counterstained DAPI. Scale bar: 100 μm. B. Quantitative evaluation...
<p>PDF file - 1214K, Levels of expression HIF-1 target genes in tumors inoculated with bone marrow Gr1+ cells or NEMs. Quantification the mRNA levels indicated factors (VEGF-A, Angiopoietin-2 and Interleukin-6) was obtained by real-time PCR. The results are shown after normalization for GAPDH gene. Data mean �s.e.m. **=P<0.01; *=P<0.05.</p>
<p>PDF file - 1560K, Quantification of the flow cytometry profiles for characterization four bone marrow cell populations sorted according to expression Nrp1 and Gr1. The results (shown as bar charts in upper part figure a table bottom part) refer independent experiments; shown are mean � s.d. markers analyzed same representative experiment Figure 1D.</p>
<p>PDF file - 3108K, Flow cytometry analysis of NEMs purified from the bone marrow. marrow CD11b+/Gr1-/Nrp1+ cells (NEMs) using indicated antibodies conjugated with phycoerythrin (PE). Percentages positive cells, referred to total number NEMs, are reported. The plots reported in first row also shown Figure 1D, fourth column.</p>
<p>PDF file - 1471K, Levels of expression plexins in CD11b+ Gr1+ Nrp1+ cells and NEMs. Real-time PCR quantifications were normalized to the levels GAPDH mRNA. Data are mean �s.e.m. **=P<0.01; *=P<0.05.</p>
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