A5052849229- Immune Response and Inflammation
- RNA Interference and Gene Delivery
- SARS-CoV-2 and COVID-19 Research
- Extracellular vesicles in disease
- Inflammasome and immune disorders
- Immunotherapy and Immune Responses
- RNA and protein synthesis mechanisms
- COVID-19 Clinical Research Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Sphingolipid Metabolism and Signaling
- Immune Cell Function and Interaction
- vaccines and immunoinformatics approaches
- Blood Coagulation and Thrombosis Mechanisms
- Immune cells in cancer
- Glycogen Storage Diseases and Myoclonus
- Long-Term Effects of COVID-19
- Monoclonal and Polyclonal Antibodies Research
- Protein Tyrosine Phosphatases
- Lysosomal Storage Disorders Research
- Heme Oxygenase-1 and Carbon Monoxide
- interferon and immune responses
- Retinoids in leukemia and cellular processes
- Cell Adhesion Molecules Research
- NF-κB Signaling Pathways
- Adenosine and Purinergic Signaling
EN-FIST Centre of Excellence (Slovenia)
2014-2024
National Institute of Chemistry
2011-2024
Heidelberg Institute for Theoretical Studies
2020
Background: Extracellular vesicles (EVs) (isolated from blood plasma) are currently being extensively researched, both as biomarkers and for their therapeutic possibilities. One challenging aspect to this research is the efficient isolation of high-purity EVs plasma in quantities sufficient vivo experiments. In accordance with challenge, aim study was develop an method which separate majority major impurities such lipoprotein particles abundant proteins albumin fibrinogen. Methods: Samples...
The SARS-CoV-2 pandemic imposed a large burden on health and society. Therapeutics targeting different components processes of the viral infection replication cycle are being investigated, particularly to repurpose already approved drugs. Spike protein is an important target for both vaccines therapeutics. Insights into mechanisms spike-ACE2 binding cell fusion could support identification compounds with inhibitory effects. Here, we demonstrate that integrity disulfide bonds within...
Translocation of nucleic acid-sensing (NAS) Toll-like receptors (TLRs) to endosomes is essential for response microbial acids as well prevention the autoimmune response. The accessory protein UNC93B1 indispensable activation NAS TLRs because it regulates their through trafficking endosomes. We observed that poly(I:C) up-regulates transcription and promotes TLR3 plasma membrane in human epithelial cell line. Up-regulation triggered by poly(I:C). Further studies revealed expression...
The response of the adaptive immune system is augmented by multimeric presentation a specific antigen, resembling viral particles. Several vaccines have been designed based on natural or protein scaffolds, which exhibited potent to antigens; however, antibodies are also generated against scaffold, may impair subsequent vaccination. In order compare polypeptide scaffolds different size and oligomerization state with respect their efficiency, including anti-scaffold immunity, we compared...
Toll-like receptor 3 (TLR3) is a dsRNA sensing that localized in the cellular compartments but also at plasma membrane. Overexpression of UNC93B1 promoted localization TLR3, not other nucleic acid TLRs, to Here we show itself We investigated role different domains TLR3 on cell signaling by preparing chimeric receptors between and TLR9 where each transmembrane segments or cytosolic has been exchanged. While ectodomain completely governs ligand specificity TIR domain determines engagement...
Significance Oxidative stress, which accompanies sterile inflammation, induces release of extracellular vesicles (stressEVs), activate Toll-like receptor 4 (TLR4), resulting in a pattern gene expression distinct from response triggered by bacterial lipopolysaccharide. The synergy between 15-lipoxygenase and secreted phospholipase A 2 , both are induced is necessary for the formation oxidized lysophospholipids, TLR4 endogenous agonists. Moreover, was sPLA promoted K/BxN serum-induced...
Coordination among multiple signaling pathways ensures an appropriate immune response, where a pathway may impair or augment another pathway. Here, we report negative feedback regulation of through the key innate mediator MyD88 by inflammasome-activated caspase-1. NLRP3 inflammasome activation impaired agonist- infection-induced TLR and cytokine production proteolytic cleavage Site-specific mutagenesis was used to identify caspase-1 site within intermediary segment. Different location...
After three years of the SARS-CoV-2 pandemic, search and availability relatively low-cost benchtop therapeutics for people not at high risk a severe disease are still ongoing. Although vaccines new variants reduce death toll, long COVID-19 along with neurologic symptoms can develop persist even after mild initial infection. Reinfections, which further increase sequelae in multiple organ systems as well death, continue to require caution. The spike protein is an important target both...
Development of orthogonal, designable and adjustable transcriptional regulators is an important goal synthetic biology. Their activity has been typically modulated through stimulus-induced oligomerization or interaction between the DNA-binding activation/repression domain. We exploited a feature Transcription activator-like effector (TALE) domain that it winds around DNA which allows to topologically prevent from binding by intramolecular cyclization. This new approach was investigated...
Proteases regulating inflammation are versatile enzymes, usually extracellular matrix degrading enzymes that involved in wound healing, angiogenesis, coagulation, development, apoptosis and other physiological processes. Their dysregulation increased expression during can have devastating consequences, promoting etiology of vascular diseases, inflammatory arthritis, cancer, allograft rejection. In this review several proteases (ADAMTS, granzymes, plasmin, kallikreins) with different...
Various signaling pathways are essential for both the innate immune response and maintenance of cell homeostasis, requiring coordinated interactions among them. In this study, a mutation in caspase-1 recognition site within MyD88 abolished inflammasome-dependent negative regulation, causing phenotypic changes mice with some similarities to human NEMO-deficiencies. The MyD88D162E reduced protein levels colon inflammation DSS-induced colitis but did not affect cytokine expression bone...
Abstract Effective and safe vaccines against SARS-CoV-2 are highly desirable to prevent casualties societal cost caused by Covid-19 pandemic. The receptor binding domain (RBD) of the surface-exposed spike protein represents a suitable target for induction neutralizing antibodies upon vaccination. Small antigens typically induce weak immune response while particles measuring tens nanometers efficiently presented B cell follicles subsequently follicular germinal center cells in draining lymph...
Cardioprotection against ischemia/reperfusion injury is still an unmet clinical need. The transient activation of Toll-like receptors (TLRs) has been implicated in cardioprotection, which may be achieved by treatment with blood-derived extracellular vesicles (EVs). However, since the isolation EVs from blood takes considerable effort, aim our study was to establish a cellular model cardioprotective can isolated well-reproducible manner. EV release induced HEK293 cells calcium ionophore...
HIV-1 represents an elusive target for therapeutic compounds due to its high rate of mutation. Targeting structural patterns instead a constantly changing specific three-dimensional structure may represent approach that is less sensitive viral mutations. The V3 loop gp120 HIV-1, which responsible binding CCR5 or CXCR4 coreceptors, has already been identified as effective the inhibition entry. peptide derived from specifically interacts with lipid A moiety LPS, does full protein. NMR analysis...
We present an in-depth investigation of the membrane interactions peptidoglycan (PGN)-based immune adjuvants designed for lipid-based delivery systems using NMR spectroscopy. The derivatives contain a cargo (PGN) dipeptide fragment and adamantyl group, which serves as anchor to lipid bilayer. Furthermore, with mannose group that can actively target cell surface receptors on cells are also studied. showed targeting PGN both available bilayer surface, thereby enabling cognate receptors. found...
We report the enhancement of lipopolysaccharide-induced immune response by adamantane containing peptidoglycan fragments in vitro. The stimulation was detected Il-6 (interleukine 6) and RANTES (regulated on activation, normal T cell expressed secreted) chemokine expression using assays immortalized mouse bone-marrow derived macrophages. most active compound a α-D-mannosyl derivative an adamantylated tripeptide with L-chirality at adamantyl group attachment, whereby mannose moiety assumed to...