Određivanje referentnih vrijednosti citokina i metaloproteinaza matriksa u sinovijalnoj tekućini konja različite dobi

Osteoarthritis (OA) is the most common joint disease in sport horses. Inflammatory and anti-inflammatory cytokines and metalloproteinases (MMPs) play a crucial role in the degradation of the cartilage extracellular matrix. The study of inflammatory molecular biomarkers could be useful in the diagnosis and choice of therapeutic strategies. However, little is known about the normal values of inflammatory biomarkers at different ages. Moreover, early diagnosis of OA is crucial to ensure early treatment in order to prevent chronic damage. The aim of this study was to establish a reference range for values of pro-inflammatory cytokines (IL-1β, IL-4, IL-6 and TNF-α) and MMPs (MMP-2 and MMP-9) in the synovial fluid of horses of different ages. The old horses group presented higher values of IL-4 and TNF-α than the rest of the groups studied (P<0.001 vs. all other groups). IL-1β levels were higher in foals than in all the other groups (P<0.001). No statistically significant differences were found between the groups as regards the mean IL-6 values. Synovial MMP-2 levels were statistically lower in the old horses group (P<0.001) and higher in the foals group (P<0.05). Higher MMP-9 levels were found in the foals group (55.45 ± 58.1 percentage of proteolysis) (P<0.001 vs. all other groups). This study demonstrates the existence of variations in the levels of pro-inflammatory markers in the synovial fluid of horses at different agesOsteoartritis (OA) je najčešća bolest zglobova u sportskih konja. Upalni i protuupalni citokini te metaloproteinaze (MMP) imaju ključnu ulogu u degradaciji izvanstaničnog matriksa hrskavice. Istraživanje molekularnih biomarkera upale moglo bi biti korisno u dijagnostici i izboru strategija za liječenje. No, malo se zna o normalnim vrijednostima upalnih biomarkera u različitoj dobi. Štoviše, rana dijagnoza OA ključna je za osiguranje ranog liječenja, kako bi se spriječilo kronično oštećenje. Cilj ovoga rada bio je utvrditi referentni raspon vrijednosti proupalnih citokina (IL-1β, IL-4, IL-6 i TNF-a) i MMP-a (MMP-2 i MMP-9) u sinovijalnoj tekućini konja različite dobi. Skupina starih konja pokazala je veće vrijednosti IL-4 i TNF-α od ostalih istraženih skupina (P<0,001 u odnosu na sve ostale skupine). Razina IL-1β bila je viša u ždrebadi nego u svim ostalim skupinama (P<0,001). Nije bilo statistički značajne razlike među skupinama u odnosu na prosječne vrijednosti IL-6. Razina MMP-2 u sinoviji bila je statistički niža u skupini starih konja (P<0,001) i više u skupini ždrebadi (P<0,05). Visoke razine MMP-9 pronađene su u skupini ždrebadi (55,45 ± 58,1 % proteolize) (P<0,001 u odnosu na sve ostale skupine). Ovaj rad pokazuje postojanje varijacija u razinama proupalnih markera u sinovijalnoj tekućini konja različite dobi

Prolactin and its receptor as therapeutic targets in glioblastoma multiforme

Although prolactin (PRL) and its receptor (PRLR) have been detected in glioblastoma multiforme (GBM), their role in its pathogenesis remains unclear. Our aim was to explore their contribution in GBM pathogenesis. We detected PRL and PRLR in all GBM cell lines tested. PRLR activation or overexpression using plasmid transfection increased proliferation, viability, clonogenicity, chemoresistance and matrix metalloproteinase activity in GBM cells, while PRLR antagonist ∆1–9-G129R-hPRL reduced their proliferation, viability, chemoresistance and migration. Meta-analysis of transcriptomic data indicated that PRLR was expressed in all grade II-III glioma (GII-III) and GBM samples. PRL was upregulated in GBM biopsies when compared to GII-III. While in the general population tumour PRL/PRLR expression did not correlate with patient survival, biological sex-stratified analyses revealed that male patients with PRL+/PRLRHIGH GBM performed worse than PRL+/PRLRLOW GBM. In contrast, all male PRL+/PRLRHIGH GII-III patients were alive whereas only 30% of PRL+/PRLRLOW GII-III patients survived after 100 months. Our study suggests that PRLR may be involved in GBM pathogenesis and could constitute a therapeutic target for its treatment. Our findings also support the notion that sexual dimorphism should be taken into account to improve the care of GBM patients.Fil: Asad, Antonela Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Nicola Candia, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: González, Nazareno. Laboratorio Max Planck de Biología Estructural, Química y Biofísica Molecular de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zuccato, Camila Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Abt, Araceli. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Orrillo, Santiago Jordi. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Yael, Lastra. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Fisiología Animal; ArgentinaFil: de Simone, Emilio Adrian. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Fisiología Animal; ArgentinaFil: Boutillon, Florence. Inserm; FranciaFil: Goffin, Vincent. Inserm; FranciaFil: Seilicovich, Adriana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Pisera, Daniel Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Ferraris, Maria Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Candolfi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentin

Determination of reference values for cytokines and matrix metalloproteinases in the synovial fluid of horses of different ages

Osteoarthritis (OA) is the most common joint disease in sport horses. Inflammatory and anti-inflammatory cytokines and metalloproteinases (MMPs) play a crucial role in the degradation of the cartilage extracellular matrix. The study of inflammatory molecular biomarkers could be useful in the diagnosis and choice of therapeutic strategies. However, little is known about the normal values of inflammatory biomarkers at different ages. Moreover, early diagnosis of OA is crucial to ensure early treatment in order to prevent chronic damage. The aim of this study was to establish a reference range for values of pro-inflammatory cytokines (IL-1β, IL-4, IL-6 and TNF-α) and MMPs (MMP-2 and MMP-9) in the synovial fluid of horses of different ages. The old horses group presented higher values of IL-4 and TNF-α than the rest of the groups studied (P<0.001 vs. all other groups). IL-1β levels were higher in foals than in all the other groups (P<0.001). No statistically significant differences were found between the groups as regards the mean IL-6 values. Synovial MMP-2 levels were statistically lower in the old horses group (P<0.001) and higher in the foals group (P<0.05). Higher MMP-9 levels were found in the foals group (55.45 ± 58.1 percentage of proteolysis) (P<0.001 vs. all other groups). This study demonstrates the existence of variations in the levels of pro-inflammatory markers in the synovial fluid of horses at different agesOsteoartritis (OA) je najčešća bolest zglobova u sportskih konja. Upalni i protuupalni citokini te metaloproteinaze (MMP) imaju ključnu ulogu u degradaciji izvanstaničnog matriksa hrskavice. Istraživanje molekularnih biomarkera upale moglo bi biti korisno u dijagnostici i izboru strategija za liječenje. No, malo se zna o normalnim vrijednostima upalnih biomarkera u različitoj dobi. Štoviše, rana dijagnoza OA ključna je za osiguranje ranog liječenja, kako bi se spriječilo kronično oštećenje. Cilj ovoga rada bio je utvrditi referentni raspon vrijednosti proupalnih citokina (IL-1β, IL-4, IL-6 i TNF-a) i MMP-a (MMP-2 i MMP-9) u sinovijalnoj tekućini konja različite dobi. Skupina starih konja pokazala je veće vrijednosti IL-4 i TNF-α od ostalih istraženih skupina (P<0,001 u odnosu na sve ostale skupine). Razina IL-1β bila je viša u ždrebadi nego u svim ostalim skupinama (P<0,001). Nije bilo statistički značajne razlike među skupinama u odnosu na prosječne vrijednosti IL-6. Razina MMP-2 u sinoviji bila je statistički niža u skupini starih konja (P<0,001) i više u skupini ždrebadi (P<0,05). Visoke razine MMP-9 pronađene su u skupini ždrebadi (55,45 ± 58,1 % proteolize) (P<0,001 u odnosu na sve ostale skupine). Ovaj rad pokazuje postojanje varijacija u razinama proupalnih markera u sinovijalnoj tekućini konja različite dobi