RESUMO
Rheumatoid arthritis (RA) is a chronic inflammatory disease. Despite new methods of diagnostics and treatment as well as extensive biological and immunosuppressive treatment, the etiology of RA is not fully understood. Moreover, the problem of diagnosis and treatment of RA patients is still current and affects a large group of patients. It is suggested that endoplasmic reticulum (ER)-related features may impair adaptation to chronic stress, inferring the risk of rheumatoid arthritis. The main goal in this study was evaluation of changes in mRNA translation to determine chronic ER stress conditions in rheumatoid arthritis patients. The study group consist of 86 individuals including a total of 56 rheumatoid arthritis patients and 30 healthy controls. The expression level of mRNA form blood samples of RA patients as well as controls of the unfolded protein response (UPR)-associated genes (p-eIF2, BCL-2, PERK, ATF4, and BAX) were investigated using real-time qPCR. GAPDH expression was used as a standard control. Considering the median, the expression levels of PERK, BCL-2, p-eIF2, ATF4, and BAX were found to be significantly increased in the blood of RA patients compared with the control group. The p-value for the PERK gene was 0.0000000036, the p-value for the BCL-2 gene was 0.000000014, the p-value for the p-eIF2 gene was 0.006948, the p-value for the ATF4 gene was 0.0000056, and the p-value for the BAX gene was 0.00019, respectively. Thus, it can be concluded that the targeting of the components of the PERK-dependent UPR signaling pathway via small-molecule PERK inhibitors may contribute to the development of novel, innovative treatment strategies against rheumatoid arthritis.
Assuntos
Artrite Reumatoide , Estresse do Retículo Endoplasmático , Perfilação da Expressão Gênica , Resposta a Proteínas não Dobradas , eIF-2 Quinase , Humanos , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Artrite Reumatoide/sangue , Resposta a Proteínas não Dobradas/genética , Feminino , Masculino , Pessoa de Meia-Idade , Estresse do Retículo Endoplasmático/genética , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismo , Adulto , Idoso , Fator 4 Ativador da Transcrição/metabolismo , Fator 4 Ativador da Transcrição/genética , Estudos de Casos e Controles , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Iniciação 2 em Eucariotos/metabolismo , Fator de Iniciação 2 em Eucariotos/genéticaRESUMO
Background: The role of miRNA in depression is widely described by many researchers. miRNA is a final product of many genes involved in its formation (maturation). One of the final steps in the formation of miRNAs is the formation of the RISC complex, called the RNA-induced silencing complex, which includes, among others, GEMIN proteins. Single-nucleotide polymorphisms (SNPs) may lead to disturbance of miRNA biogenesis and function. The objective of our research was to assess the relationship between the appearance of depression and single nucleotide polymorphisms in the GEMIN3 (rs197388) and GEMIN4 (rs7813; rs3744741) genes. Our research provides new knowledge on the genetic factors that influence the risk of depression. They can be used as an element of diagnostics helpful in identifying people at increased risk, as well as indicating people not at risk of depression. Methods: A total of 218 participants were examined, including individuals with depressive disorders (n = 102; study group) and healthy people (n = 116, control group). All the patients in the study group and the people in the control group were non-related native Caucasian Poles from central Poland. Blood was collected from study and control groups in order to assess the SNPs of GEMIN genes. Results: An analysis of the results obtained showed that in patient population, the risk of depression is almost doubled by polymorphic variants of the genes: rs197388/GEMIN3 genotype A/A in the recessive model and rs3744741/GEMIN4 genotype T/T, codominant and recessive model. The dual role of rs7813/GEMIN4 is noteworthy, where the G/A genotype in the codominant and over dominant model protects against depression.
Assuntos
Depressão , MicroRNAs , Humanos , Polônia/epidemiologia , Depressão/epidemiologia , MicroRNAs/genética , Genótipo , Proteínas do Complexo SMN/genéticaRESUMO
The article presents a case of deep intestinal endometriosis in a 27-year-old woman who complained of dysmenorrhea and infertility. The diagnostic process included ultrasonography as well as colonoscopy, barium enema and CT imaging. Because of the presence of two distant changes which involved nearly the full thickness of the rectal wall and the major part of its circumference, the decision to perform an anterior rectal resection with a simultaneous retroperitoneal colorectostomy was made. The Knight technique was implemented. The surgery involved the anterior rectal resection, the transverse rectal stump closure by use of a stapling device (TA50), and the creation of colorectal circular anastomosis with the CEEA 31 stapler.
