Injuries and diseases of the peripheral nervous system (PNS) often result in irreversible functional deficits. Current therapeutic approaches demonstrate limited efficacy, which has driven the develop Show more
Injuries and diseases of the peripheral nervous system (PNS) often result in irreversible functional deficits. Current therapeutic approaches demonstrate limited efficacy, which has driven the development of regenerative medicine strategies. This review systematizes contemporary gene and cell therapy approaches aimed at PNS repair and regeneration. Key neurotrophic factors (NGF, BDNF, GDNF, VEGF, etc.) and the molecular mechanisms underlying their regenerative effects are discussed. Gene delivery strategies employing viral and plasmid vectors are analyzed, along with the therapeutic application of various cell populations, including Schwann cells, mesenchymal stromal cells, and derivatives of induced pluripotent stem cells. Particular attention is given to combined gene-cell-based approaches, which enable localized and sustained expression of therapeutic molecules. The integration of advances in genetic engineering, cell biology, and tissue engineering is shaping a new treatment paradigm focused on pathogenetic restoration of nerve tissue. These promising strategies pave the way toward achieving complete functional regeneration following PNS injuries. Show less
Formyl peptide receptors (FPRs) are expressed in the cells of the innate immune system and provide binding with pathogen and damage-associated molecular patterns with subsequent activation of the phag Show more
Formyl peptide receptors (FPRs) are expressed in the cells of the innate immune system and provide binding with pathogen and damage-associated molecular patterns with subsequent activation of the phagocytes for defense reactions such as chemotaxis, secretory degranulation and ROS generation. Probably, FPR2 is one of the unique receptors in the organism; it is able to recognize numerous ligands of different chemical structure, and moreover, these ligands can trigger opposite phagocyte responses promoting either pro- or anti-inflammatory reactions. Therefore, FPR2 and its signaling pathways are of intense research interest. We found only slight activation of ERK1/2 in the response to peptide ligand WKYMVM in the accelerating phase of ROS generation and more intense ERK1/2 phosphorylation in the declining phase of it in mouse bone marrow granulocytes. Lipid agonist BML-111 did not induce significant ERK phosphorylation when applied for 10-1800 s. To some extent co-localization of ERK1/2 and NADPH oxidase subunits was observed even in the intact cells and didn't change under FPR2 stimulation by WKYMVM, while direct PKC activation by PMA resulted to more efficient interaction between ERK1/2 and p47phox/p67phox and their translocation to plasma membrane. We have shown that phosphorylation and activation of ERK1/2 in bone marrow granulocytes depended on FPR2-triggered activity of PI3K and PKC, phosphatase DUSP6, and, the most but not the least, on ROS generation. Since blocking of ROS generation led to a slowdown of ERK activation indicating a significant contribution of ROS to the secondary regulation of ERK activity. Show less
Chronic kidney disease (CKD) is an important public health problem in the world. The aim of our research was to identify novel potential serum biomarkers of renal injury. ELISA assay showed that cytok Show more
Chronic kidney disease (CKD) is an important public health problem in the world. The aim of our research was to identify novel potential serum biomarkers of renal injury. ELISA assay showed that cytokines and chemokines IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, Eotaxin, FGFb, G-CSF, GM-CSF, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-1bb, RANTES, TNF-α and VEGF were significantly higher (R > 0.6, Show less