Diseases Commons^™

Intranasal Rapamycin Ameliorates Alzheimer-Like Cognitive Decline In A Mouse Model Of Down Syndrome, Antonella Tramutola, Chiara Lanzillotta, Eugenio Barone, Andrea Arena, Ilaria Zuliani, Luciana Mosca, Carla Blarzino, D. Allan Butterfield, Marzia Perluigi, Fabio Di Domenico

Chemistry Faculty Publications

Background: Down syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles. Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD). The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways, including insulin signaling and autophagy, involved in pathology onset and progression. Within this context, the therapeutic use of mTOR-inhibitors may prevent/attenuate the neurodegenerative phenomena. By our work we aimed to rescue mTOR signalling …

A Novel Fibroblast Growth Factor 1 Variant Reverses Nonalcoholic Fatty Liver Disease In Type 2 Diabetes., Qian Lin

Electronic Theses and Dissertations

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder and is strongly associated with type 2 diabetes (T2D). Our recently engineered FGF1 partial agonist, carrying triple mutations (FGF1^△HBS) exhibits greatly reduced proliferative potential, while preserving the full metabolic activity of wild-type FGF1. This study tests the preventive and therapeutic effects of FGF1^△HBS on NAFLD in db/db T2D and explores potential mechanisms. The results showed that administration of FGF1^△HBS to 2-month-old db/db mice for 2 months constantly lowered blood glucose levels, improved insulin sensitivity, and lowered liver weight, lipid deposition, and …

Multivariate Analysis To Identify Potential Biomarkers For Prognosis And Treatment Resistance In Head And Neck Cancer Patients, Christina Ann Wicker

Theses and Dissertations--Toxicology and Cancer Biology

It is estimated that nearly 50,000 individuals in the United States will be diagnosed with head and neck cancer in 2017 (American Cancer Society www.cancer.org). Ninety percent of oral cancers are head and neck squamous cell carcinoma (HNSCC). Major obstacles in the treatment of HNSCC are recurrence and treatment resistance, which contributes to increased mortality. Therefore, there is increased need to determine genetic alterations in HNSCC that may be ideal novel drug targets, and biomarkers to improve diagnostic and prognostic testing.

Abnormal localization and overexpression of base excision repair protein and transcriptional regulator Apurinic/Apyrimidic endonuclease (APE1) has been associated with …

Investigating Smoke Exposure And Chronic Obstructive Pulmonary Disease (Copd) With A Calibrated Agent Based Model (Abm) Of In Vitro Fibroblast Wound Healing., James A. Ratti

Theses and Dissertations

COPD is characterized by tissue inflammation and impaired remodeling that suggests fibroblast maintenance of structural homeostasis is dysregulated. Thus, we performed in vitro wound healing experiments on normal and diseased human lung fibroblasts and developed an ABM of fibroblasts closing a scratched monolayer using NetLogo to evaluate differences due to COPD or cigarette smoke condensate exposure. This ABM consists of a rule-set governing the healing response, accounting for cell migration, proliferation, death, activation and senescence rates; along with the effects of heterogeneous activation, phenotypic changes, serum deprivation and exposure to cigarette smoke condensate or bFGF. Simulations were performed to calibrate …