Project description:Background: Low-density neutrophils (LDN) are increased in several inflammatory diseases, and may also play a role in low-grade chronic inflammation in obesity. Yet their role in obesity or the effect of bariatric surgery-induced weight loss is unknown. Methods: We compared circulating LDN, their function, and gene expression between morbidly obese patients (MOP; BMI > 40 Kg/m2) and normal-weight controls (NWC; BMI < 25 Kg/m2) in a case-control study. Additionally, in a prospective longitudinal study, we measure changes in the frequency of LDN before and after bariatric surgery, and tested possible associations with metabolic and inflammatory parameters. Findings: LDN and inflammatory markers were significantly increased in MOP (n=27) compared to NWC (n=20). Transcriptome analysis of LDN from MOP showed an increased neutrophil-related gene expression signature associated with inflammation, neutrophil activation, and immunosuppressive function. However, LDN did not suppress T cells proliferation and produced low levels of ROS. Circulating LDN in MOP significantly decreased after surgery in parallel with BMI, metabolic syndrome and inflammatory markers. Interpretation: Obesity increases LDN with inflammatory gene signature. Bariatric surgery has anti-inflammatory effect including reduction of LDN. Gene expression and phenotype suggest that LDN represent a neutrophil subset that may be associated with obesity-associated chronic inflammation that promotes co-morbidities.
Project description:<p>Mucopolysaccharidosis (MPS) types I, II, IV, VI and VII, are inherited diseases that result from the bodies inability to break down large sugar molecules that are by-products of metabolism. MPS affects most organs of the body and causes abnormalities in the liver, spleen, bones, and brain. We are studying the central nervous system (primarily the brain) so we can better understand the nature of the problems individuals with MPS I, II, IV, VI and VII have so we can find ways of better treating these problems. We would like to find out about the changes in the brain of individuals with MPS I, II, IV, VI and VII using data from MRI and neuropsychological tests. This is a longitudinal study so patients who enroll will need to be seen 3 times over 5 years. The longitudinal nature of the study allows us to make conclusions about how changes in some structures of the brain and changes in cognitive ability are related.</p> <p>The research objectives are: <ol> <li>To identify abnormalities of brain (and central nervous system) structure and function in patients with MPS I, II, IV, VI and VII, regardless of how they are being treated or have been treated in the past; and to track disease progression over time.</li> <li>To examine the degree to which independent variables (e.g., age at first treatment, severity of disease, types of medical abnormalities, mutation, medical events, and sensory abnormalities) have an impact on both functional and structural outcomes as well as on quality-of-life.</li> <li>To identify, through longitudinal study, those measures that most accurately reflect the current disease state.</li> </ol> </p> <p>This is a longitudinal study of 75-100 individuals with either MPS I, II, IV, VI and VII. Those participating in the study will be evaluated 3 times over 5 years. The primary site for this study is the University of Minnesota but there are an additional 6 centers in the United States and Canada that are also participating and will provide data for analysis. You will need to be able to travel to Minnesota or one of the participating centers in order to be a part of this study.</p>
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
