To vectorize drug delivery from electrospun-produced scaffolds, we introduce a thin outer drug retention layer produced by electrospinning from activated carbon nanoparticles (ACNs)-enriched polycaprolacton (PCL) suspension. Homogeneous or coaxial fibers filled with ACNs were produced by electrospinning from different PCL-based suspensions. Stable ACN suspensions were selected by sorting through solvents, stabilizers and auxiliary components. The ACN-enriched scaffolds produced were characterized for fiber diameter, porosity, pore size and mechanical properties. The scaffold structure was analyzed by scanning electron microscopy and X-ray photoelectron spectroscopy. It was found that ACNs were mainly coated with a polymer layer for both homogeneous and coaxial fibers. Drug binding and release from the scaffolds were tested using tritium-labeled sirolimus. We showed that the kinetics of sirolimus binding/release by ACN-enriched scaffolds was determined by the fiber composition and differed from that obtained with a free ACN. ACN-enriched scaffolds with coaxial and homogeneous fibers had a biocompatibility close to scaffold-free AC, as was shown by the cultivation of human gingival fibroblasts and umbilical vein cells on scaffolds. The data obtained demonstrated that ACN-enriched scaffolds had good physico-chemical properties and biocompatibility and, thus, could be used as a retaining layer for vectored drug delivery.

Orthoflavivirus encephalitidis (tick-borne encephalitis virus, TBEV) is of high concern due to its ability to cause severe neurological manifestations. Despite the fact that the role of NS1 proteins from various mosquito-borne flaviviruses in pathogenesis and their ability to affect human endothelial permeability have been investigated, TBEV NS1 has thus far been insufficiently studied. In this study, human endothelial permeability was assessed using TEER and transwell permeability assays. Signaling pathways were determined by RNAseq. The ability of the NS1 protein of TBEV to affect human endothelial permeability was investigated for the first time. It was shown that recombinant TBEV NS1 produced in eucaryotic cells directly affected human lung microvascular endothelial cells (HLMVECs) in vitro but not human umbilical vein endothelial cells (HUVECs). It was indicated that TBEV NS1 induced endothelial hyperpermeability of HLMVECs through activating TNF-α and other inflammatory signaling pathways.

Orthoflavivirus omskense (Omsk hemorrhagic fever virus, OHFV) is a tick-borne flavivirus that causes Omsk hemorrhagic fever (OHF), a severe zoonotic disease endemic to Western Siberia. Despite the fact that the role of NS1 proteins of various mosquito-borne flaviviruses in pathogenesis was investigated and their ability to affect human endothelial permeability was shown, the role of the NS1 protein of OHFV in pathogenesis is unstudied. In this work, the ability of OHFV NS1 to induce human endothelial permeability was investigated for the first time. It was shown that recombinant OHFV NS1 produced in eucaryotic cells directly affects both human lung microvascular endothelial cells (HLMVEC) and human umbilical vein endothelial cells (HUVEC) in vitro. RNAseq of endothelial cells treated with OHFV NS1 indicated that OHFV NS1 enhances the expression of genes associated with cellular stress responses, vascular signaling, and cell–cell junction regulation, resulting in a nonspecific increase in the endothelial permeability of various vessels. These results suggest that the NS1 protein may contribute to OHFV pathogenesis by disrupting endothelial barrier function and promoting vascular leakage, potentially playing a role in the hemorrhagic manifestations of Omsk hemorrhagic fever.

Background/Objectives: Orthoflavivirus encephalitidis (tick-borne encephalitis virus, TBEV) is of high concern due to its ability to cause severe neurological manifestations. Despite the fact that the role of NS1 proteins of various mosquito-borne flaviviruses in pathogenesis and their ability to affect human endothelial permeability was investi-gated, TBEV NS1 is insufficiently studied. Methods: Human endothelial permeability was assessed using PEER and transwell permeability assays. Signaling pathways were determined by RNAseq. Results: The ability of NS1 protein of TBEV to affect human endothelial permeability was investigated for the first time. It was shown that recombinant TBEV NS1 produced in eucaryotic cell directly affected on human lung microvascular endothelial cells (HLMVEC) in vitro but not on human umbilical vein endothelial cells (HUVEC). Conclusions: it was indicated that TBEV NS1 induced endothelial hyperpermeability of HLMVEC through activation TNF-α and other inflammatory signaling pathways.

Orthoflavivirus omskense (Omsk hemorrhagic fever virus, OHFV) is a tick-borne flavivirus that causes Omsk hemorrhagic fever (OHF), a severe zoonotic disease endemic to Western Siberia. Despite the fact that the role of NS1 proteins of various mosquito-borne flaviviruses in pathogenesis was investigated and their ability to affect human endothelial permeability was shown, the role of NS1 protein of OHFV in pathogenesis is unstudied. In this work, the ability of OHFV NS1 to induce human endothelial permeability was investigated for the first time. It was shown that recombinant OHFV NS1 produced in eucaryotic cells directly affects both human lung microvascular endothelial cells (HLMVEC) and human umbilical vein endothelial cells (HUVEC) in vitro. RNAseq of endothelial cells treated with OHFV NS1 indicated that OHFV NS1 enhances the expression of genes associated with cellular stress responses, vascular signaling, and cell–cell junction regulation, resulting in a nonspecific increase in the endothelial permeability of various vessels.