RESUMEN
Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by inflammation of the articular tissue. This study aims to evaluate the expression of microRNA (miR)-146a-5p, miR-24-3p, and miR-125a-5p in the plasma of RA patients and compare them with those of healthy controls to obtain a specific expression profile for earlier diagnosis and assistance in treating patients. This study was performed on 50 RA patients and 50 healthy controls. Five microliters of blood were taken from each patient/control. Plasma RNA was extracted using the Trisol solution. cDNAs were synthesized; using moloney murine leukemia virus (MMLV) and deoxynucleoside triphosphate (dNTP). Real-time PCR was performed using SYBR green kit. The mean expression of miR-146a-5p, miR-24-3p, and miR-125a-5p in the RA group were 8.1±1.9, 6.5±1.2, and 6.8±2.2 and in the healthy group were 4.8±1.6, 3.6±2.2, and 3.4±1.7, respectively. Significant differences were also observed in the mean expression of these three miRNAs in four subgroups of RA patients with different disease activity based on disease activity score 28 (DAS28) (p<0.05). ROC curve analysis showed that miR-146a-5p (AUC=0.8, sensitivity= 96%, specificity=86%), miR-24-3p (AUC=0.7, Sensitivity=95%, Specificity=75%) and miR-125a-5p (AUC=0.71, sensitivity=93%, specificity=84%) could be used as suitable biomarkers for RA diagnosis. Increased expressions of miR-146a-5p, miR-24-3p, and miR-125a-5p in RA patients indicate that the miRNAs are involved in disease incidence and progression, and the measurement of their expression can play an essential role in the diagnosis and treatment of the disease.
Asunto(s)
Artritis Reumatoide/diagnóstico , MicroARN Circulante/sangre , MicroARNs/sangre , Adulto , Artritis Reumatoide/sangre , Artritis Reumatoide/genética , Biomarcadores/sangre , Estudios de Casos y Controles , MicroARN Circulante/genética , Femenino , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia ArribaRESUMEN
The new coronavirus, known as "SARS-CoV-2"; is the cause of one of the most prevalent infectious viral diseases that was recently announced pandemic by the world health organization. Ongoing research in the fields of prevention, management, and therapy establishes a functional scaffold for clinics during the time of crisis. To obtain this goal, it is necessary that all pathophysiologic aspects of COVID-19 from infection to predisposing backgrounds of infection be identified, so that all the ambiguities of researchers regarding transmission mechanisms, variable clinical manifestation, and therapeutic response can be solved. Here, we firstly discuss about the homology screening between nCoV-2019 and beta-coronavirus family using phylogenetic analyses. Secondly, we analyzed the viral motifs to show that viral entry into the host cells requires a primary activation step performed by FURIN and FURIN-like-mediated enzymatic cleavage on the structural glycoprotein. The cleavage increases viral performance by 1000 folds. We then present a comprehensive view on host cells and the significance of gene variants affecting activation enzymes, supportive entry, and spread mechanisms in humans including renin-angiotensin-aldosterone system (RAAS) a pathway results in certain phenotypes or exacerbate infection-related phenotypes in different organs, hence causes variable clinical manifestations. This is followed by discussing about the importance of personalized medicine in nCoV-2019 exposure. Moreover, chemical drugs prescribed for individuals affected with COVID-19, as well as genes involved in drug transport and metabolisms are reviewed as a prelude to drug response. Finally, we suggest some therapeutic approaches developed based on new methods and technology such as anti-sense therapy and antibodies.
Asunto(s)
Enzima Convertidora de Angiotensina 2/genética , COVID-19/genética , Furina/genética , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genética , Proteína ADAM17/genética , Proteína ADAM17/metabolismo , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Enzima Convertidora de Angiotensina 2/metabolismo , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Betacoronavirus/genética , COVID-19/fisiopatología , COVID-19/transmisión , Inhibidores Enzimáticos/uso terapéutico , Furina/metabolismo , Predisposición Genética a la Enfermedad , Genoma Humano , Genoma Viral , Humanos , Hidroxicloroquina/uso terapéutico , Filogenia , Medicina de Precisión , Receptores de Coronavirus/genética , Receptores de Coronavirus/metabolismo , Sistema Renina-Angiotensina/genética , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Glicoproteína de la Espiga del Coronavirus/metabolismo , Internalización del Virus , Tratamiento Farmacológico de COVID-19RESUMEN
Gastric cancer as one of the most common cancers worldwide has various genetic and environmental risk factors including Helicobacter pylori (H.pylori) infection. Recently, loss of a tumor suppressor gene named promyelocytic leukemia (PML) has been identified in gastric cancer. However, no mutation has been found in this gene in gastric cancer samples. Cag A H.pylori protein has been shown to exert post transcriptional regulation of some tumor suppressor genes. In order to assess such a mechanism for PML degradation, we performed in silico analyses to establish any interaction between PML and Cag A proteins. In silico interaction and docking studies showed that these two proteins may have stable interactions. In addition, we showed that imatinib kinase inhibitor can restore PML function by inhibition of casein kinase 2.
Asunto(s)
Mesilato de Imatinib/farmacología , Proteínas Nucleares/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Antígenos Bacterianos/genética , Antígenos Bacterianos/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Quinasa de la Caseína II/antagonistas & inhibidores , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/virología , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/metabolismo , Helicobacter pylori/genética , Humanos , Simulación del Acoplamiento Molecular/métodos , Proteínas Nucleares/genética , Proteína de la Leucemia Promielocítica , Dominios y Motivos de Interacción de Proteínas/efectos de los fármacos , Dominios y Motivos de Interacción de Proteínas/genética , Procesamiento Postranscripcional del ARN/efectos de los fármacos , Procesamiento Postranscripcional del ARN/genética , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genéticaRESUMEN
Gastric cancer is the second most common cause of cancer death worldwide. Environmental as well as genetic factors have been shown to be involved in its genesis. Among genetic factors, loss of function of a tumor suppressive gene named promyelocytic leukemia (PML) has been demonstrated in gastric cancer. In order to cast light in the mechanism by which PML protein is under-expressed in gastric cancer cells, we analyzed all exons and intron-exon boundaries of PML gene in 50 formalin-fixed paraffin-embedded tissue blocks from gastric carcinoma tumors by means of PCR-SSCP and CSGE, with direct sequencing of abnormally shifted bands. We found a novel sequence variant of unknown significance localized in intron 5 in 3 samples (c.1398+84delA). We did not detect any deleterious mutations of the PML gene. This study shows that PML mutations may not contribute to gastric adenocarcinoma development. Post-translational modifications or protein degradation might be mechanisms by which PML is not expressed in gastric tumors.
Asunto(s)
Adenocarcinoma/genética , Mutación , Proteínas Nucleares/genética , Neoplasias Gástricas/genética , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genética , Adulto , Anciano , Anciano de 80 o más Años , Electroforesis , Exones , Femenino , Predisposición Genética a la Enfermedad , Humanos , Intrones , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Proteína de la Leucemia Promielocítica , Procesamiento Proteico-Postraduccional , Proteolisis , Análisis de Secuencia de ADNRESUMEN
The promyelocytic leukemia (PML) gene is a gene known to be a tumor suppressor, although recent data suggest that it has a dual function in tumorigenesis. It was initially discovered in acute promyelocytic leukemia (APL) in which a t(15; 17) chromosomal translocation fused it to the retinoic acid receptor alpha (RARα). It has been shown to be involved in various types of cancer. It has at least 6 nuclear isoforms and a cytoplasmic type with different characteristics. Its multiple functions in growth inhibition, apoptosis induction, replicative senescence, inhibition of oncogenic transformation, and suppression of migration and angiogenesis have made it a therapeutic target for cancer therapy. However, its dual role in the process of tumorigenesis has made this field challenging. In this review, we discuss PML structure, functions and expression in tumors.