Oxidative Stress-Induced Sirtuin1 Downregulation Correlates to HIF-1α, GLUT-1, and VEGF-A Upregulation in Th1 Autoimmune Hashimoto's Thyroiditis.

In Hashimoto's thyroiditis (HT), oxidative stress (OS) is driven by Th1 cytokines' response interfering with the normal function of thyrocytes. OS results from an imbalance between an excessive production of reactive oxygen species (ROS) and a lowering of antioxidant production. Moreover, OS has been shown to inhibit Sirtuin 1 (SIRT1), which is able to prevent hypoxia-inducible factor (HIF)-1α stabilization. The aims of this study were to determine the involvement of NADPH-oxidases (NOX), SIRT1, and HIF-1α in HT pathophysiology as well as the status of antioxidant proteins such as peroxiredoxin 1 (PRDX1), catalase, and superoxide dismutase 1 (SOD1). The protein expressions of NOX2, NOX4, antioxidant enzymes, SIRT1, and HIF-1α, as well as glucose transporter-1 (GLUT-1) and vascular endothelial growth factor A (VEGF-A), were analyzed by Western blot in primary cultures of human thyrocytes that were or were not incubated with Th1 cytokines. The same proteins were also analyzed by immunohistochemistry in thyroid samples from control and HT patients. In human thyrocytes incubated with Th1 cytokines, NOX4 expression was increased whereas antioxidants, such as PRDX1, catalase, and SOD1, were reduced. Th1 cytokines also induced a significant decrease of SIRT1 protein expression associated with an upregulation of HIF-1α, GLUT-1, and VEGF-A proteins. With the exception of PRDX1 and SOD1, similar results were obtained in HT thyroids. OS due to an increase of ROS produced by NOX4 and a loss of antioxidant defenses (PRDX1, catalase, SOD1) correlates to a reduction of SIRT1 and an upregulation of HIF 1α, GLUT-1, and VEGF-A. Our study placed SIRT1 as a key regulator of OS and we, therefore, believe it could be considered as a potential therapeutic target in HT.

Effect of a commercial paratyphus vaccine on the development of pigeon circovirus infection in young pigeons (Columba livia domestica).

Infection with pigeon circovirus (PiCV) has been associated with young pigeon disease syndrome (YPDS), which is considered to be a multifactorial disease. The factors that determine whether birds succumb to clinical disease are not known. To evaluate the potential effect of vaccination with a commercial paratyphus vaccine on the progression of PiCV infection in young pigeons, forty 6-week-old pigeons naturally infected with PiCV were randomly assigned to two equal groups. The pigeons of one group were vaccinated at 6 and 9 weeks of age, and pigeons of the second group were unvaccinated controls. Cloacal swab and blood samples collected from all the birds were tested for PiCV by polymerase chain reaction (PCR) analysis. Three weeks after the second vaccination, all pigeons were euthanatized, and tissues were collected for PiCV PCR analysis and histopathologic evaluation. No significant difference in the number of PCR-positive cloacal swab and blood samples was found between the vaccinated and control pigeons. Positive PCR results in tissue samples also were not significantly different between the groups, with 18 positive samples in vaccinated birds (90%) and 16 in control birds (80%). Characteristic botryoid inclusions were detected in more vaccinated than control pigeons, but this difference was not significant. In this study, vaccination with a commercial paratyphus vaccine was not a risk factor for development of young pigeon disease syndrome.