RESUMO
Posttraumatic Stress Disorder (PTSD) is an anxiety disorder which occurs after a traumatic event. The NR3C1 gene codes for the Glucocorticoid Receptor, which participate in the Hypothalamic-Pituitary-Adrenal (HPA) axis and is altered in PTSD patients. To evaluate whether the NR3C1 gene expression in peripheral blood could be useful as a diagnosis biomarker, a total of 32 PTSD patients and 59 healthy controls were analyzed with quantitative RT-PCR. Also, to assess if NR3C1 dysregulation is associated with hypocortisolism in PTSD patients, serum cortisol was quantified by ELISA in a subset of these samples. Significant NR3C1 over-expression was found in PTSD patients compared with controls, and this was higher in patients with acute PTSD. The Area Under the Curve (AUC) of NR3C1 gene expression was 0.797. The sensibility and specificity of NRC1 gene expression to diagnose PTSD was 62.5% and 89.8%, respectively. We also found that an up-regulation of NR3C1 increased the risk for being diagnosed with PTSD (OR= 12.8, 95%, CI 4-41.4). Finally, the NR3C1 gene expression was inversely related with serum cortisol in PTSD patients. The present results suggest that NR3C1 gene expression could be a promising biomarker for PTSD diagnosis and estimate the risk for disease development.
Assuntos
Marcadores Genéticos/genética , Receptores de Glucocorticoides/genética , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/genética , Adulto , Feminino , Expressão Gênica , Humanos , Hidrocortisona/genética , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino , México/epidemiologia , Sistema Hipófise-Suprarrenal/fisiologia , Receptores de Glucocorticoides/biossíntese , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Regulação para Cima/fisiologiaRESUMO
The Sonic Hegdehog/GLI (SHH/GLI) pathway has been extensively studied for its role in developmental and cancer biology. During early embryonic development the SHH pathway is involved mainly in pattern formation, while in latter stages its function in stem cell and progenitor proliferation becomes increasingly relevant. During postnatal development and in adult tissues, SHH/GLI promotes cell homeostasis by actively regulating gene transcription, recapitulating the function observed during normal tissue growth. In this review, we will briefly discuss the fundamental importance of SHH/GLI in tumor growth and cancer evolution and we will then provide insights into a possible novel mechanism of SHH action in cancer through autophagy modulation in cancer stem cells. Autophagy is a homeostatic mechanism that when disrupted can promote and accelerate tumor progression in both cancer cells and the stroma that harbors tumorigenesis. Understanding possible new targets for SHH signaling and its contribution to cancer through modulation of autophagy might provide better strategies in order to design combined treatments and perform clinical trials.
Assuntos
Autofagia/fisiologia , Proteínas Hedgehog/fisiologia , Células-Tronco Neoplásicas/patologia , Neuroblastoma/fisiopatologia , Fatores de Transcrição/fisiologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neuroblastoma/patologia , Neuroblastoma/terapia , Transdução de Sinais , Proteína GLI1 em Dedos de ZincoRESUMO
The Sonic Hegdehog/GLI (SHH/GLI) pathway has been extensively studied for its role in developmental and cancer biology. During early embryonic development the SHH pathway is involved mainly in pattern formation, while in latter stages its function in stem cell and progenitor proliferation becomes increasingly relevant. During postnatal development and in adult tissues, SHH/GLI promotes cell homeostasis by actively regulating gene transcription, recapitulating the function observed during normal tissue growth. In this review, we will briefly discuss the fundamental importance of SHH/GLI in tumor growth and cancer evolution and we will then provide insights into a possible novel mechanism of SHH action in cancer through autophagy modulation in cancer stem cells. Autophagy is a homeostatic mechanism that when disrupted can promote and accelerate tumor progression in both cancer cells and the stroma that harbors tumorigenesis. Understanding possible new targets for SHH signaling and its contribution to cancer through modulation of autophagy might provide better strategies in order to design combined treatments and perform clinical trials.
Assuntos
Humanos , Autofagia/fisiologia , Proteínas Hedgehog/fisiologia , Células-Tronco Neoplásicas/patologia , Neuroblastoma/fisiopatologia , Fatores de Transcrição/fisiologia , Linhagem Celular Tumoral , Proliferação de Células , Neuroblastoma/patologia , Neuroblastoma/terapia , Transdução de SinaisRESUMO
We sought to determine the serological test that could be used for Trypanosoma cruzi seroprevalence studies in Mexico, where lineage I predominates. In a previous study among pregnant women and their newborns in the states of Yucatan and Guanajuato, we reported a 0.8-0.9% of prevalence for T. cruzi -specific antibodies by Stat-Pak and Wiener ELISA. We have expanded this study here by performing an additional non-commercial ELISA and confirming the seropositives with Western blot, using whole antigens of a local parasite strain. We found a seroprevalence of 0.6% (3/500) in Merida and 0.4% in Guanajuato (2/488). The 5 seropositive umbilical cord samples reacted to both non-commercial ELISA and Western blot tests, and only 1 of the maternal samples was not reactive to non-commercial ELISA. A follow-up of the newborns at 10 mo was performed in Yucatan to determine the presence of T. cruzi antibodies in children as evidence of congenital infection. None of the children was seropositive. One newborn from an infected mother died at 2 wk of age of cardiac arrest, but T. cruzi infection was not confirmed. The T. cruzi seroprevalence data obtained with both commercial tests (Stat-Pak and ELISA Wiener) are similar to those from non-commercial tests using a local Mexican strain of T. cruzi.