RESUMO
Vimentin, an intermediate filament protein primarily recognized for its intracellular role in maintaining cellular structure, has recently garnered increased attention and emerged as a pivotal extracellular player in immune regulation and host-pathogen interactions. While the functions of extracellular vimentin were initially overshadowed by its cytoskeletal role, accumulating evidence now highlights its significance in diverse physiological and pathological events. This review explores the multifaceted role of extracellular vimentin in modulating immune responses and orchestrating interactions between host cells and pathogens. It delves into the mechanisms underlying vimentin's release into the extracellular milieu, elucidating its unconventional secretion pathways and identifying critical molecular triggers. In addition, the future perspectives of using extracellular vimentin in diagnostics and as a target protein in the treatment of diseases are discussed.
Assuntos
Doenças Transmissíveis , Filamentos Intermediários , Humanos , Vimentina , Citoesqueleto , Interações Hospedeiro-PatógenoRESUMO
Alterations in miRNA levels have been observed in various types of cancer, impacting numerous cellular processes and increasing their potential usefulness in combination therapies also in brain tumors. Recent advances in understanding the genetics and epigenetics of brain tumours point to new aberrations and associations, making it essential to continually update knowledge and classification. Here we conducted molecular analysis of 123 samples of childhood brain tumors (pilocytic astrocytoma, medulloblastoma, ependymoma), focusing on identification of genes that could potentially be regulated by crucial representatives of OncomiR-1: miR-17-5p and miR-20a-5p. On the basis of microarray gene expression analysis and qRTPCR profiling, we selected six (WEE1, CCND1, VEGFA, PTPRO, TP53INP1, BCL2L11) the most promising target genes for further experiments. The WEE1, CCND1, PTPRO, TP53INP1 genes showed increased expression levels in all tested entities with the lowest increase in the pilocytic astrocytoma compared to the ependymoma and medulloblastoma. The obtained results indicate a correlation between gene expression and the WHO grade and subtype. Furthermore, our analysis showed that the integration between genomic and epigenetic pathways should now point the way to further molecular research.
Assuntos
Neoplasias Encefálicas , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs , Humanos , MicroRNAs/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Criança , Masculino , Feminino , Adolescente , Pré-Escolar , Meduloblastoma/genética , Meduloblastoma/patologia , Astrocitoma/genética , Astrocitoma/patologia , Ependimoma/genética , LactenteRESUMO
BACKGROUND: Microbial biofilms, as a hallmark of cystic fibrosis (CF) lung disease and other chronic infections, remain a desirable target for antimicrobial therapy. These biopolymer-based viscoelastic structures protect pathogenic organisms from immune responses and antibiotics. Consequently, treatments directed at disrupting biofilms represent a promising strategy for combating biofilm-associated infections. In CF patients, the viscoelasticity of biofilms is determined mainly by their polymicrobial nature and species-specific traits, such as Pseudomonas aeruginosa filamentous (Pf) bacteriophages. Therefore, we examined the impact of microbicidal ceragenins (CSAs) supported by mucolytic agents-DNase I and poly-aspartic acid (pASP), on the viability and viscoelasticity of mono- and bispecies biofilms formed by Pf-positive and Pf-negative P. aeruginosa strains co-cultured with Staphylococcus aureus or Candida albicans. METHODS: The in vitro antimicrobial activity of ceragenins against P. aeruginosa in mono- and dual-species cultures was assessed by determining minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC). Inhibition of P. aeruginosa mono- and dual-species biofilms formation by ceragenins alone and in combination with DNase I or poly-aspartic acid (pASP) was estimated by the crystal violet assay. Additionally, the viability of the biofilms was measured by colony-forming unit (CFU) counting. Finally, the biofilms' viscoelastic properties characterized by shear storage (G') and loss moduli (G"), were analyzed with a rotational rheometer. RESULTS: Our results demonstrated that ceragenin CSA-13 inhibits biofilm formation and increases its fluidity regardless of the Pf-profile and species composition; however, the Pf-positive biofilms are characterized by elevated viscosity and elasticity parameters. CONCLUSION: Due to its microbicidal and viscoelasticity-modifying properties, CSA-13 displays therapeutic potential in biofilm-associated infections, especially when combined with mucolytic agents.