Digital Commons Network^™

Pluronic Polymer-Based Ormeloxifene Nanoformulations Induce Superior Anticancer Effects In Pancreatic Cancer Cells, Neeraj Chauhan, Amber Kruse, Hilary Newby, Meena Jaggi, Murali M. Yallapu, Subhash C. Chauhan

School of Medicine Publications and Presentations

Utilization of safe cytotoxic agents with precise anticancer activity is considered as the prime focus of cancer therapeutics research. A greater incentive for such agents arises from the molecules/drugs that are already being used for other indications. Ormeloxifene (ORM) is a nonsteroidal, nonhormonal selective estrogen receptor modulator (SERM), which has been in human use for contraception purposes. Although in the recent past, many reports have suggested its emerging role as an anticancer agent, no significant attention was paid toward generating simple and safe nanoformulation( s) for improved therapeutic activity and tumor cell-specific delivery. Our aim is to develop nanoformulation(s) of …

Highly Efficient Induced Pluripotent Stem Cell Reprogramming Of Cryopreserved Lymphoblastoid Cell Lines, Satish Kumar, Joanne E. Curran, Erika C. Espinoza, David C. Glahn, John Blangero

School of Medicine Publications and Presentations

Tissue culture based in-vitro experimental modeling of human inherited disorders provides insight into the cellular and molecular mechanisms involved and the underlying genetic component influencing the disease phenotype. The breakthrough development of induced pluripotent stem cell (iPSC) technology represents a quantum leap in experimental modeling of human diseases, providing investigators with a self-renewing and thus unlimited source of pluripotent cells for targeted differentiation into functionally relevant disease specific tissue/cell types. The existing rich bio-resource of Epstein-Barr virus (EBV) immortalized lymphoblastoid cell line (LCL) repositories generated from a wide array of patients in genetic and epidemiological studies worldwide, many of them …

Biophysical Changes Caused By Altered Muc13 Expression In Pancreatic Cancer Cells, Andrew E. Massey, Kyle Doxtater, Murali M. Yallapu, Subhash C. Chauhan

School of Medicine Publications and Presentations

Background

Pancreatic cancer is one of the most lethal cancers in the United States. This is partly due to the difficulty in early detection of this disease as well as poor therapeutic responses to currently available regimens. Our previous reports suggest that mucin 13 (MUC13, a transmembrane mucin common to gastrointestinal cells) is aberrantly expressed in this disease state, and has been implicated with a worsened prognosis and an enhanced metastatic potential in PanCa. However, there is virtually no information currently to describe the biophysical ramifications of this protein.

Methods

To demonstrate the biophysical effect of MUC13 in PanCa, we …

Detecting Invasive Fungal Disease In Surgical Patients: Utility Of The (1 3)- B-D-Glucan Assay, Jeffrey Skubic, Sharven Taghavi, Manuel Castillo-Angeles, Ramsis Ramsis, Ali Salim, Reza Askari

School of Medicine Publications and Presentations

Background: The specificity and sensitivity of the (1 3)-b-d-glucan (BDG) assay in surgical patients needs further investigation. We hypothesized that the BDG assay would have lower sensitivity/specificity compared with that of medical patients.

Methods: We reviewed patients who had undergone laparotomy, gastrectomy, hepatectomy, or colectomy and had a BDG assay post-operatively.

Results: A total of 71 patients met study criteria. There were 29 (40.8%) who had proven/probable invasive fungal infection. Sensitivity for BDG level ‡80 diagnosed within one week of the assay draw was 77.3% (95% confidence interval [CI], 54.6–92.2%), and specificity was 44.9% (95% CI, 30.7–59.8). The positive predictive …

Recent Advances On Visual Cycle Protein Research And Progress On Clinical Translation, Xin Yee Ooi, Rujman Khan, Anjalee Choudhury, Francisco Xavier Elisarraras, Jeff Grigsby, Brandi Obregon, Andrew T C Tsin

School of Medicine Publications and Presentations

Since the publication of our previous paper, Visual cycle proteins: Structure, function, and roles in human retinal disease (Tsin, et.al, JBC 293:13016, 2018) there has been significant progress on multiple topics discussed in this paper. In the present communication, we further explore research advances on two visual cycle proteins: DES1 and IRBP. In addition, we emphasize the progress of clinical translation of other visual cycle protein research, including the breakthrough of FDA-approved gene therapy for Leber’s congenital amaurosis, and additional gene therapies at different stages of clinical trials for various retinal diseases such as retinitis pigmentosa, diabetic retinopathy, and Stargardt’s …

Tannic Acid Inhibits Lipid Metabolism And Induce Ros In Prostate Cancer Cells, Prashanth K.B. Nagesh, Elham Hatami, Pallabita Chowdhury, Shashi Jaun, Nirnoy Dan, Vivek Kumar Kashyap, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu

School of Medicine Publications and Presentations

Prostate cancer (PCa) cells exploit the aberrant lipid signaling and metabolism as their survival advantage. Also, intracellular storage lipids act as fuel for the PCa proliferation. However, few studies were available that addressed the topic of targeting lipid metabolism in PCa. Here, we assessed the tannic acid (TA) lipid-targeting ability and its capability to induce endoplasmic reticulum (ER) stress by reactive oxygen species (ROS) in PCa cells. TA exhibited dual effects by inhibiting lipogenic signaling and suppression of lipid metabolic pathways. The expression of proteins responsible for lipogenesis was down regulated. The membrane permeability and functionality of PCa were severely …

Hypothetical Human Immune Genome Complex Gradient May Help To Explain The Congenital Zika Symdrome Catastrophe In Brazil: A New Theory, F. R. S. Oliveira, C. C. Bresani-Salvi, C. N. L. Morais, A. W. Bigham, U. Braga-Neto, Gladys E. Maestre, John L. Vandeberg, E. T. A. Marques, B. Acioli-Santos

School of Medicine Publications and Presentations

There are few data considering human genetics as an important risk factor for birth abnormalities related to ZIKV infection during pregnancy, even though sub-Saharan African populations are apparently more resistant to CZS as compared to populations in the Americas. We hypothesized that single nucleotide variants (SNVs), especially in innate immune genes, could make some populations more susceptible to Zika congenital complications than others. Differences in the SNV frequencies among continental populations provide great potential for Machine Learning techniques. We explored a key immune genomic gradient between individuals from Africa, Asia and Latin America, working with complex signatures, using 297 SNVs. …

Cardiometabolical Risk Factors Associated With Renal Function In Apparently Healthy Young Students: A Cross-Sectional Study, Lucia M. Perez-Navarro, Rafael Valdez-Ortiz, Araceli Alegria-Diaz, Miguel Murgia-Romero, Rafael Jimenez-Flores, Rafael Villalobos-Molina, Srinivas Mummidi, Ravindranath Duggirala, Juan C. Lopez-Alvarenga

School of Medicine Publications and Presentations

Background: Cardiometabolic risk factors (CMRFs) appear decades before developing chronic kidney disease (CKD) in adulthood.

Objective: The objective of the study was to identify the prevalence and association between CMRFs and kidney function in apparently healthy young adults (18-25 years old).

Methods: We included 5531 freshman year students. Data collected on CMRFs included central obesity, high body mass index (hBMI >25), blood pressure, glycemia, lipids, uric acid (UA >6.8 mg/dL), and insulin. Glomerular filtration rate (GFR) was estimated by CKD-Epidemiology Collaboration formula. We used logistic regression and a log linear for odds ratio (OR) (95% confidence level) and probabilities.

Results: …

Uncovering The Complex Genetics Of Human Personality: Response From Authors On The Pgmra Model, Igor Zwir, Pashupati Mishra, Coral Del-Val, C. Charles Gu, Gabriel A. De Erausquin, Terho Lehtimäki, C. Robert Cloninger

School of Medicine Publications and Presentations

Following publication of our two articles [1, 2], a critique of the methodology of Phenotype-Genotype Many-to-Many Relations Analysis (PGMRA) [1, 3, 4] questioned the validity of our results from the perspective of polygenic risk scores (PRS) [5]. We appreciate the importance of these questions, and here provide a concise discussion of the assumptions and mathematical constraints of both approaches. We thank this commentator and others who have discussed our articles with us for their thoughtful questions and critiques

Intrauterine Exposure To Chronic Hypoxia In The Rat Leads To Progressive Diastolic Function And Increased Aortic Stiffness From Early Postnatal Developmental Stages, Praveen Kumar, Jude S. Morton, Amin Shah, Victor Do, Consolato Sergi, Jesus Serrano-Lomelin, Sandra T. Davidge, Donna Beker, Jody Levasseur, Lisa K. Hornberger

School of Medicine Publications and Presentations

Aim

We sought to explore whether fetal hypoxia exposure, an insult of placental insufficiency, is associated with left ventricular dysfunction and increased aortic stiffness at early postnatal ages.

Methods

Pregnant Sprague Dawley rats were exposed to hypoxic conditions (11.5% FiO2) from embryonic day E15‐21 or normoxic conditions (controls). After delivery, left ventricular function and aortic pulse wave velocity (measure of aortic stiffness) were assessed longitudinally by echocardiography from day 1 through week 8. A mixed ANOVA with repeated measures was performed to compare findings between groups across time. Myocardial hematoxylin and eosin and picro‐sirius staining were performed to evaluate myocyte …

Tgif1-Twist1 Axis In Pancreatic Ductal Adenocarcinoma, Mohammad S. Razzaque, Azeddine Atfi

School of Medicine Publications and Presentations

TG-interacting factor 1 (TGIF1) exerts inhibitory effects on transforming growth factor-beta (TGF-β) signaling by suppressing Smad signaling pathway at multiple levels. TGIF1 activity is important for normal embryogenesis and organogenesis, yet its dysregulation can culminate in tumorigenesis. For instance, increased expression of TGIF1 correlates with poor prognosis in triple-negative breast cancer patients, and enforced expression of TGIF1 facilitates Wnt-driven mammary tumorigenesis, suggesting that TGIF1 might function as an oncoprotein. Quite surprisingly, TGIF1 has recently been shown to function as a tumor suppressor in pancreatic ductal adenocarcinoma (PDAC), possibly owing to its ability to antagonize the pro-malignant transcription factor …

Cardiometabolic Risk Factors Associated With Renal Function In Apparently Healthy Young Students: A Cross-Sectional Study, Lucia M. Perez-Navarro, Rafael Valdez-Ortiz, Araceli Alegria-Diaz, Miguel Murgia-Romero, Rafael Jimenez-Flores, Rafael Villalobos-Molina, Srinivas Mummidi, Ravindranath Duggirala, Juan Carlos Lopez Alvarenga

School of Medicine Publications and Presentations

Background: Cardiometabolic risk factors (CMRFs) appear decades before developing chronic kidney disease (CKD) in adulthood.

Objective: The objective of the study was to identify the prevalence and association between CMRFs and kidney function in apparently healthy young adults (18-25 years old).

Methods: We included 5531 freshman year students. Data collected on CMRFs included central obesity, high body mass index (hBMI >25), blood pressure, glycemia, lipids, uric acid (UA >6.8 mg/dL), and insulin. Glomerular filtration rate (GFR) was estimated by CKD-Epidemiology Collaboration formula. We used logistic regression and a log linear for odds ratio (OR) (95% confidence level) and probabilities.

Results: …

One-Year Changes In Brain Microstructure Differentiate Preclinical Huntington's Disease Stages, Chris Patrick Pflanz, Marina Charquero-Ballester, D S. Majid, Anderson M. Winkler, Emmanuel Vallée, Adam R. Aron, Mark Jenkinson, Gwenaëlle Douaud

School of Medicine Publications and Presentations

OBJECTIVE: To determine whether brain imaging markers of tissue microstructure can detect the effect of disease progression across the preclinical stages of Huntington's disease.

METHODS: Longitudinal microstructural changes in diffusion imaging metrics (mean diffusivity and fractional anisotropy) were investigated in participants with presymptomatic Huntington's disease (N = 35) stratified into three preclinical subgroups according to their estimated time until onset of symptoms, compared with age- and gender-matched healthy controls (N = 19) over a 1y period.

RESULTS: Significant differences were found over the four groups in change of mean diffusivity in the posterior basal ganglia and the splenium of the …