Medicine and Health Sciences Commons^™

Molecular Modulation Of Osteoblasts And Osteoclasts In Type 2 Diabetes, Selvalakshmi Rathinavelu, Crissy Guidry-Elizondo, Jameela Banu

Health & Biomedical Sciences Faculty Publications and Presentations

Diabetes is a common disease affecting majority of populations worldwide. Since 1980, there has been an increase in the number of people diagnosed as prediabetic and diabetic. Diabetes is characterized by high levels of circulating glucose and leads to most microvascular and macrovascular complications such as retinopathy, nephropathy, neuropathy, stroke, and myocardial infarction. Bone marrow vascular disruption and increased adiposity are also linked to various complications in type II diabetes mellitus. In addition to these complications, type 2 diabetic patients also have fragile bones caused by faulty mineralization mainly due to increased adiposity among diabetic patients that affects both osteoblast …

Characterization Of Nanodiamondbased Anti-Hiv Drug Delivery To The Brain, Upal Roy, Vadym Drozd, Andriy Durygin, Jesse Rodriguez, Paul Barber, Venkata Atluri, Xiaohua Liu, Thomas G. Voss, Surendra Saxena, Madhavan Nair

Health & Biomedical Sciences Faculty Publications and Presentations

Human Immunodefciency Virus Type 1 (HIV-1) remains one of the leading causes of death worldwide. Present combination antiretroviral therapy has substantially improved HIV-1 related pathology. However, delivery of therapeutic agents to the HIV reservoir organ like Central nervous system (CNS) remains a major challenge primarily due to the inefective transmigration of drugs through Blood Brain Barrier (BBB). The recent advent of nanomedicine-based drug delivery has stimulated the development of innovative systems for drug delivery. In this regard, particular focus has been given to nanodiamond due to its natural biocompatibility and non-toxic nature–making it a more efcient drug carrier than other …

Principal Component Analysis Of Early Alcohol, Drug And Tobacco Use With Major Depressive Disorder In Us Adults, Kesheng Wang, Ying Liu, Youssoufou Ouedraogo, Nianyang Wang, Xin Xie, Chun Xu, Xingguang Luo

Health & Biomedical Sciences Faculty Publications and Presentations

Early alcohol, tobacco and drug use prior to 18 years old are comorbid and correlated. This study included 6239 adults with major depressive disorder (MDD) in the past year and 72,010 controls from the combined data of 2013 and 2014 National Survey on Drug Use and Health (NSDUH). To deal with multicollinearity existing among 17 variables related to early alcohol, tobacco and drug use prior to 18 years old, we used principal component analysis (PCA) to infer PC scores and then use weighted multiple logistic regression analyses to estimate the associations of potential factors and PC scores with MDD. The …

Gfra1: A Novel Molecular Target For The Prevention Of Osteosarcoma Chemoresistance, Mihwa Kim, Dae Joon Kim

Health & Biomedical Sciences Faculty Publications and Presentations

The glycosylphosphatidylinositol-linked GDNF (glial cell derived neurotrophic factor) receptor alpha (GFRA), a coreceptor that recognizes the GDNF family of ligands, has a crucial role in the development and maintenance of the nervous system. Of the four identified GFRA isoforms, GFRA1 specifically recognizes GDNF and is involved in the regulation of proliferation, differentiation, and migration of neuronal cells. GFRA1 has also been implicated in cancer cell progression and metastasis. Recent findings show that GFRA1 can contribute to the development of chemoresistance in osteosarcoma. GFRA1 expression was induced following treatment of osteosarcoma cells with the popular anticancer drug, cisplatin and induction of …

Polymorphisms Within Ryr3 Gene Are Associated With Risk And Age At Onset Of Hypertension, Diabetes, And Alzheimer’S Disease, Shaoqing Gong, Brenda Bin Su, Hugo Tovar, Chunxiang Mao, Valeria Gonzalez, Ying Liu, Yongke Lu, Ke-Sheng Wang, Chun Xu

Health & Biomedical Sciences Faculty Publications and Presentations

Background: Hypertension affects 33% of Americans while type 2 diabetes and Alzheimer's disease (AD) affect 10% of Americans, respectively. Ryanodine receptor 3 gene (RYR3) codes for the RYR which functions to release stored endoplasmic reticulum calcium ions (Ca2+) to increase intracellular Ca2+ concentration. Increasing studies demonstrate that altered levels of intracellular Ca2+ affect cardiac contraction, insulin secretion, and neurodegeneration. In this study, we investigated associations of the RYR3 genetic variants with hypertension, AD, and diabetes.

Methods: Family data sets were used to explore association of RYR3 polymorphisms with risk and age at onset (AAO) of hypertension, diabetes, and AD.

Results: …

Cyp2a6 Is Associated With Obesity: Studies In Human Samples And A High Fat Diet Mouse Model, Kesheng Wang, Xue Chen, Stephen C. Ward, Ying Liu, Youssoufou Ouedraogo, Chun Xu, Arthur I. Cederbaum, Yongke Lu

Health & Biomedical Sciences Faculty Publications and Presentations

Background/objectives

CYP2A6 (CYP2A5 in mice) is mainly expressed in the liver. Hepatic CYP2A6 expression is increased in patients with non-alcoholic fatty liver disease (NAFLD). In mice, hepatic CYP2A5 is induced by high fat diet (HFD) feeding. Hepatic CYP2A5 is also increased in monosodium glutamate-induced obese mice. NAFLD is associated with obesity. In this study, we examined whether obesity is related to CYP2A6.

Subjects/methods

Obesity genetic association study: The SAGE is a comprehensive genome-wide association study (GWAS) with case subjects having a lifetime history of alcohol dependence and control subjects never addicted to alcohol. We used 1030 control individuals with self-reported …

Association Of Interleukin-6 Polymorphisms With Obesity Or Metabolic Traits In Young Mexican-Americans, K. Boeta-Lopez, J. Duran, D. Elizondo, E. Gonzales, Anne R. Rentfro, Andrea E. Schwarzbach, Saraswathy Nair

Health & Biomedical Sciences Faculty Publications and Presentations

Objective The objective of the study is to investigate the association of interleukin-6 (IL6) promoter single-nucleotide polymorphisms rs1800797 (-597 G/A) and rs1800796 (-572 G/C) with obesity or metabolic syndrome in Mexican-Americans.

Methods The rs1800797 and rs1800796 single-nucleotide polymorphisms were genotyped in Mexican-Americans (n = 437) from South Texas, and results were correlated with measures of obesity and metabolic syndrome including body mass index, waist circumference, blood pressure, cholesterol, triglycerides, glucose, liver enzymes, plasma IL6 and high-sensitive C-reactive protein (hs-CRP).

Results Significant associations were found for the rs1800796 variant with increased waist circumference, insulin resistance, lower IL6 levels and higher hs-CRP …

Genetic Differences In The Aryl Hydrocarbon Receptor And Cyp1a2 Affect Sensitivity To Developmental Polychlorinated Biphenyl Exposure In Mice: Relevance To Studies Of Human Neurological Disorders, Kelsey Klinefelter, Molly Kromme Hooven, Chloe Bates, Breann T. Colter, Alexandra Dailey, Smitha Krishnan Infante, Izabela Kania-Korwel, Hans-Joachim Lehmler, Alejandro Lopez-Juarez, Clare Pickering Ludwig, Christine Perdan Curran

Health & Biomedical Sciences Faculty Publications and Presentations

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that remain a human health concern with newly discovered sources of contamination and ongoing bioaccumulation and biomagnification. Children exposed during early brain development are at highest risk of neurological deficits, but highly exposed adults reportedly have an increased risk of Parkinson's disease. Our previous studies found allelic differences in the aryl hydrocarbon receptor and cytochrome P450 1A2 (CYP1A2) affect sensitivity to developmental PCB exposure, resulting in cognitive deficits and motor dysfunction. High-affinity Ahr b Cyp1a2(-/-) mice were most sensitive compared with poor-affinity Ahr d Cyp1a2(-/-) and wild-type Ahr b Cyp1a2(+/+) mice. Our follow-up …

Ghrelin Upregulates The Phosphorylation Of The Glun2b Subunit Of The Nmda Receptor By Activating Ghsr1a And Fyn In The Rat Hippocampus, Liza Berrout, Masako Isokawa

Health & Biomedical Sciences Faculty Publications and Presentations

Ghrelin and its receptor GHSR1a have been shown to exert numerous physiological functions in the brain, in addition to the well-established orexigenic role in the hypothalamus. Earlier work indicated that ghrelin stimulated the phosphorylation of the GluN1 subunit of the NMDA receptor (NMDAR) and enhanced synaptic transmission in the hippocampus. In the present study, we report that the exogenous application of ghrelin increased GluN2B phosphorylation. This increase was independent of GluN2B subunit activity or NMDAR channel activity. However, it depended on the activation of GHSR1a and Fyn as it was blocked by D-Lys3-GHRP-6 and PP2, respectively. Inhibitors for G-protein-regulated second …

Molecular Modulation Of Osteoblasts And Osteoclasts In Type 2 Diabetes, Selvalakshmi Rathinavelu, Crissy Guidry-Elizondo, Jameela Banu

Health & Biomedical Sciences Faculty Publications and Presentations

Diabetes is a common disease affecting majority of populations worldwide. Since 1980, there has been an increase in the number of people diagnosed as prediabetic and diabetic. Diabetes is characterized by high levels of circulating glucose and leads to most microvascular and macrovascular complications such as retinopathy, nephropathy, neuropathy, stroke, and myocardial infarction. Bone marrow vascular disruption and increased adiposity are also linked to various complications in type II diabetes mellitus. In addition to these complications, type 2 diabetic patients also have fragile bones caused by faulty mineralization mainly due to increased adiposity among diabetic patients that affects both osteoblast …

Analysis Of Ptprk Polymorphisms In Association With Risk And Age At Onset Of Alzheimer’S Disease, Cancer Risk, And Cholesterol, Yang Chen, Chun Xu, Sam Harirforoosh, Xingguang Luo, Ke-Sheng Wang

Health & Biomedical Sciences Faculty Publications and Presentations

The human receptor-type protein-tyrosine phosphatase kappa (PTPRK) gene is highly expressed in human brain and is previously associated with neuropsychiatric disorders and cancer. This study investigated the association of 52 single nucleotide polymorphisms (SNPs) in the PTPRK with the risk and age at onset (AAO) of Alzheimer’s disease (AD) in 791 AD patients and 782 controls. Five SNPs (top SNP rs4895829 with p=0.0125) were associated with the risk of AD based on a multiple logistic regression (p<0.05); while 6 SNPs (top SNP rs1891150 with p=8.02×10−6) were associated with AAO by using a multiple linear regression analysis. Interestingly, rs2326681 was associated with both the risk and AAO of AD (p=4.65×10−2 and 5.18×10−3, respectively). In a replication study, the results from family-based association test - generalized estimating equation (GEE) statistics and Wilcoxon test showed that seven SNPs were associated with the risk of AD (top SNP rs11756545 with p=1.02×10−2) and 12 SNPs were associated with the AAO (top SNP rs11966128 with p=1.39×10−4), respectively. One additional sample showed that four SNPs were associated with risk of cancer (top SNP rs1339197 with p=4.1×10−3), 12 SNPs associated with LDL-cholesterol (top SNP rs4544930 with p=3.47×10−3), and 8 SNPs associated with total cholesterol (top SNP rs1012049 with p=6.09×10−3). In addition, the AD associated rs4895829 was associated with the gene expression level in the cerebellum (p=7.3×10−5). The present study is the first study providing evidence of several genetic variants within the PTPRK gene associated with the risk and AAO of AD, risk of cancer, LDL and total cholesterol levels.