Chronic hypoxia (CH) activates the Ca(2+)-dependent transcription factor nuclear factor of activated T cells isoform c3 (NFATc3) in mouse pulmonary arteries. However, the mechanism of this response has not been explored. Since we have demonstrated that NFATc3 is required for CH-induced pulmonary arterial remodeling, establishing how CH activates NFATc3 is physiologically significant. The goal of this study was to test the hypothesis that endothelin-1 (ET-1) contributes to CH-induced NFATc3 activation. We propose that this mechanism requires increased pulmonary arterial smooth muscle cell (PASMC) intracellular Ca(2+) concentration ([Ca(2+)](i)) and stimulation of RhoA/Rho kinase (ROK), leading to calcineurin activation and actin cytoskeleton polymerization, respectively. We found that: 1) CH increases pulmonary arterial pre-pro-ET-1 mRNA expression and lung RhoA activity; 2) inhibition of ET receptors, calcineurin, L-type Ca(2+) channels, and ROK blunts CH-induced NFATc3 activation in isolated intrapulmonary arteries from NFAT-luciferase reporter mice; and 3) both ET-1-induced NFATc3 activation in isolated mouse pulmonary arteries ex vivo and ET-1-induced NFATc3-green fluorescence protein nuclear import in human PASMC depend on ROK and actin polymerization. This study suggests that CH increases ET-1 expression, thereby elevating PASMC [Ca(2+)](i) and RhoA/ROK activity. As previously demonstrated, elevated [Ca(2+)](i) is required to activate calcineurin, which dephosphorylates NFATc3, allowing its nuclear import. Here, we demonstrate that ROK increases actin polymerization, thus providing structural support for NFATc3 nuclear transport.
The Mescalero Apache Family Listening Program (MAFLP) is a culturally centered family prevention program with third, fourth, and fifth graders; a parent/caregiver; and a family elder. The program follows a positive youth development model to develop stronger communication and shared cultural practices between elders, parents, and youth in the tribe to reduce substance initiation of use among the youth. The MAFLP was created using a community-based participatory research (CBPR) approach in partnership with the University of New Mexico. The research focus of MAFLP is centered on the adaptation of a family curriculum from a Navajo and Pueblo version of the Family Listening Program to an Apache version, the establishment of a (Apache) Tribal Research Team, and the piloting of the curriculum with Apache families. MAFLP was piloted twice, and evaluation measures were collected focused on formative and impact evaluation. This article provides a background on Mescalero Apache then introduces the Navajo and Pueblo version of a Family Listening and Family Circle Program, respectively, next, the CBPR research partnership between Mescalero Apache and the University of New Mexico and the creation of a Mescalero Apache Tribal Research Team followed by the development and adaptation of a Mescalero Apache Family Listening Program including implementation and evaluation, and concluding with preliminary findings.
Presence of follicular epithelial cells, large MNGCs and dirty background of cellular debris, mixed inflammatory cells with predominance of lymphocytes and macrophages were the most striking and consistent features for diagnosis of DQT in cytological smears. The above findings in consideration with the clinical history will help us to reach a definitive diagnosis. FNA also proves to be a useful tool in excluding other thyroid lesions with similar clinical presentations.
Background:The pbreakdown of phospholipids lead to accumulation of malondialdehyde (MDA) that is preferred as a surrogate marker of oxidative stress in diabetics.Objective:To compare serum MDA levels along with other biochemical parameters between type 2 diabetic patients with and without complications.Materials and Methods:This cross-sectional study was carried out in the Department of Biochemistry of a tertiary care teaching hospital in Sikkim on 60 type 2 diabetics and compared with 100 non-diabetic participants. The un-hemolyzed blood samples were used for estimation of biochemical parameters; MDA was estimated in serum by using trichloroacetic acid (TCA) and 1% thiobarbituric acid (TBA). Whole blood was used for estimation of glycated hemoglobin. The comparison of different parameters between cases and control was calculated by using Student's t test.Results:In the study and control groups, no significant difference was noted with regard to independent variables. The fasting and postprandial serum glucose along with glycated hemoglobin from whole blood and the lipid profile differed significantly between the study and control groups. Overall, tmean serum MDA level in the study group was significantly higher thanin the controls. Male sex, addiction to tobacco (smoking and smokeless inclusive), longer duration of diabetes (≥5 years), and presence of complications (both microvascular and macrovascular) significantly increased the MDA level.Conclusion:To sum up, the serum MDA level was observed to be significantly high in diabetics with and without complication along with other parameters.
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