Search the repository

A+ | A- | | SLO | ENG

Abstract: Profound and transient thrombocytopenia of functional platelets without bleeding was observed in patients envenomed by Vipera a. ammodytes (Vaa). This condition was rapidly reversed by administration of F(ab)2 fragments of immunoglobulin G targeting the whole venom, leaving platelets fully functional. To investigate the potential role of snake venom C-type lectin-like proteins (snaclecs) in this process, Vaa-snaclecs were isolated from the crude venom using different liquid chromatographies. The purity of the isolated proteins was confirmed by Edman sequencing and mass spectrometry. The antithrombotic effect was investigated by platelet agglutination and aggregation assays and blood coagulation tests. Using flow cytometry, the platelet activation and binding of Vaa-snaclecs to various platelet receptors was analyzed. Antithrombotic efficacy was tested in vivo using a mouse model of vascular injury. Two Vaa-snaclecs were purified from the venom. One of them, Vaa-snaclec-3/2, inhibited ristocetin-induced platelet agglutination. It is a covalent heterodimer of Vaa-snaclec-3 (α-subunit) and Vaa-snaclec-2 (β-subunit). Our results suggest that Vaa-snaclec-3/2 induces platelet agglutination and consequently thrombocytopenia by binding to the platelet receptor glycoprotein Ib. Essentially, no platelet activation was observed in this process. In vivo, Vaa-snaclec-3/2 was able to protect the mouse from ferric chloride-induced carotid artery thrombosis, revealing its applicative potential in interventional angiology and cardiology.
Keywords: reversible thrombocytopenia, snaclec, arterial occlusion
Published in DiRROS: 26.03.2026; Views: 144; Downloads: 63
Full text (4,39 MB)
This document has many files! More...

Keywords: eksperimentalna onkologija, imunoterapija, elektrokemoterapija
Published in DiRROS: 18.03.2026; Views: 236; Downloads: 98
Full text (106,92 KB)
This document has many files! More...

Keywords: eksperimentalna onkologija, miši, celice ubijalke
Published in DiRROS: 11.03.2026; Views: 182; Downloads: 79
Full text (106,48 KB)

Keywords: rak debelega črevesa in danke, eksperimentalna onkologija, onkologija
Published in DiRROS: 25.02.2026; Views: 243; Downloads: 63
Full text (86,54 KB)

Abstract: This study investigated the antitumor efficacy of chemokine CCL5 gene therapy using gene electrotransfer (GET) in combination with radiotherapy (RT) in solid murine tumors CT26 and 4T1. In vitro, CT26 and 4T1 tumor cells transfected with plasmid DNA (pDNA) encoding CCL5 induced migration of RAW264.7 macrophages. In vivo, CCL5 overexpression achieved via GET of pDNA encoding CCL5 led to increased splenocyte infiltration in dorsal window chamber models. When combined with RT, GET of pDNA encoding CCL5 shifted the tumor cytokine profile toward a proinflammatory state, with elevated Ifn-γ, Cxcl9, Cxcl10, and Il-12α. Although CD8 + and CD4 + T cells were reduced post-treatment, due to radiation-induced cell death, the combination of GET of pDNA encoding CCL5 and RT significantly delayed tumor growth in both models. In 4T1 tumors, this delay was also significant compared to the equivalent treatment with GET of control pDNA. These findings support GET of pDNA encoding CCL5 combined with RT as a strategy to enhance immune-mediated tumor control.
Keywords: chemokines, gene electrotransfer, gene therapy, mouse, radiotherapy
Published in DiRROS: 13.02.2026; Views: 426; Downloads: 100
Full text (12,90 MB)