RESUMEN
Multiple sclerosis (MS) is a chronic neurodegenerative disease characterized by immune-mediated inflammation and neurodegeneration in the central nervous system (CNS). In this study; we aimed to investigate the gene expression and plasma protein levels of three neuroprotective genes-heat shock proteins (HSP90 and HSP60) and glial cell line-derived neurotrophic factor (GDNF)-in MS patients compared to healthy controls. Forty patients with relapsing-remitting MS and 40 healthy volunteers participated in this study. Gene expression was measured using reverse transcription quantitative real-time PCR, and protein levels were assessed via ELISA. The results showed a significant increase in HSP90 (1.7-fold) and HSP60 (2-fold) gene expression in MS patients compared to controls, along with corresponding increases in protein levels (1.5-fold for both HSP90 and HSP60). In contrast, GDNF gene expression and protein levels were significantly reduced in MS patients, with a 7-fold decrease in gene expression and a 1.6-fold reduction in protein levels. Notably, a non-linear relationship between GDNF gene expression and protein concentration was observed in MS patients, suggesting complex regulatory mechanisms influencing GDNF in the disease. The upregulation of HSP90 and HSP60 in MS highlights their roles in immune regulation and stress responses, while the reduction in GDNF indicates impaired neuroprotection. These findings suggest that HSP90, HSP60, and GDNF could serve as biomarkers for disease progression and as potential therapeutic targets in MS, offering promising avenues for future research and treatment development.
Asunto(s)
Neoplasias , Triaje , Humanos , Niño , Ucrania/epidemiología , Salud Pública , Neoplasias/diagnóstico , Neoplasias/epidemiología , Neoplasias/terapiaRESUMEN
Multiple sclerosis (MS) is a chronic, autoimmune neurodegenerative disease affecting the central nervous system. It is a major cause of non-traumatic neurological disability among young adults in North America and Europe. This study focuses on neuroprotective genes (BDNF, NT4/5, SIRT1, HSP70, and HSP27). Gene expression and protein levels of these markers were compared between MS patients and healthy controls. Blood samples were collected from 42 patients with multiple sclerosis (MS) and 48 control subjects without MS. Quantitative real-time PCR was performed to measure the expression of specific genes. The samples were analyzed in duplicate, and the abundance of mRNA was quantified using the 2-ΔCt method. ELISA assay was used to measure the concentration of specific proteins in the plasma samples. The results show that a 3.5-fold decrease in the gene expression of BDNF corresponds to a 1.5-fold downregulation in the associated plasma protein concentration (p < 0.001). Similar trends were observed with NT-4 (five-fold decrease, slight elevation in protein), SIRT1 (two-fold decrease, two-fold protein decrease), HSP70 (four-fold increase, nearly two-fold protein increase), and HSP27 (four-fold increase, two-fold protein increase) (p < 0.001). This study reveals strong correlations between gene expression and protein concentration in MS patients, emphasizing the relevance of these neuroprotective markers in the disease.
Asunto(s)
Esclerosis Múltiple , Enfermedades Neurodegenerativas , Adulto Joven , Humanos , Esclerosis Múltiple/genética , Esclerosis Múltiple/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteínas de Choque Térmico HSP27 , Sirtuina 1/genética , ARN Mensajero/genética , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas SanguíneasRESUMEN
<br><b>Aim:</b> Gem-associated protein 4 (GEMIN4), a member of the GEMIN gene family, is a key compound of the regulating factors responsible for miRNA biogenesis. Genetic variability within this gene can alter the risk for development of colorectal cancer (CRC) as was shown for other genes involved in miRNA biogenesis. Therefore, presented study was intended to identify genetic variants of three single nucleotide polymorphisms (SNPs) in the GEMIN4 gene (rs1062923, rs2740348 and rs910925) and their relationship with CRC.</br> <br><b>Methods:</b> The study comprised 203 patients and 179 age and sex matched controls. Genotyping of GEMIN4 gene variants was done using Taqman® assay. The association of GEMIN4 variants with CRC was done by odds ratio analysis. Haplotype analysis was done to see the combined effect of studied variants on CRC.</br> <br><b>Results:</b> Patients carrying all variant genotypes for GEMIN4 rs1062923 (odds ratio [OR]= 0.205; 95% confidence interval [CI] = 0.1034-0.4065 for CC variant and [OR] = 0.1436; [CI] = 0.0869-0.2373 for CT variant, respectively) and GEMIN4 rs2740348 (odds ratio [OR] = 0.4498; 95% confidence interval [CI] = 0.2342-0.8637 for CC variant and [OR] = 0.3986; [CI] = 0.2043-0.7776 for CG variant, respectively) showed significant association in lower occurrence of cancer, whereas in case of GEMIN4 G/C rs910925 variant genotype, no significance correlation was found.</br> <br><b>Conclusion:</b> Our study gives a substantive support for the association between the GEMIN4 gene variants/miRNA biogenesis and CRC risk.</br>.