Pharmacology Commons^™

Microrna Expression Profiling Of Normal And Malignant Human Colonic Stem Cells Identifies, Vignesh Viswanathan, Lynn Opdenaker, Shirin Modarai, Jeremy Z Fields, Gregory Gonye, Bruce M Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

MicroRNAs (miRNAs) have a critical role in regulating stem cells (SCs) during development, and because aberrant expression of miRNAs occurs in various cancers, our goal was to determine if dysregulation of miRNAs is involved in the SC origin of colorectal cancer (CRC). We previously reported that aldehyde dehydrogenase (ALDH) is a marker for normal and malignant human colonic SCs and tracks SC overpopulation during colon tumorigenesis. MicroRNA expression was studied in ALDH-positive SCs from normal and malignant human colon tissues by Nanostring miRNA profiling. Our findings show that: (1) A unique miRNA signature distinguishes ALDH-positive CRC cells from ALDH-positive normal …

Association Of Long-Term Consumption Of Repeatedly Heated Mix Vegetable Oils In Different Doses And Hepatic Toxicity Through Fat Accumulation, Gul Ambreen, Afshan Siddiq, Kashif Hussain

Department of Biological & Biomedical Sciences

Background: Hepatic diseases are one of the chief reasons for worldwide morbidity and mortality. The increased incidence in Asian countries is driving researchers to explore preventive ways from nature. It is more practical to go with healthy routine edibles like vegetable oils to avoid environmental and chemical hepatic injuries. With the use of thermally oxidized oils overproduction of reactive oxygen species (ROS) with overwhelmed cellular antioxidants defense system results in oxidative stress, the known cause of cardiovascular diseases (CVDs), cancers and neurodegenerative disorders. Little is investigated about the effect of daily used oxidized cooking oils on hepatic function changes with …

Tip60 Regulation Of Δnp63Α Is Associated With Cisplatin Resistance, Akshay Hira, Andrew Stacy, Jin Zhang, Michael P. Craig, Madhavi Kadakia

Symposium of Student Research, Scholarship, and Creative Activities Materials

About 5.4 million basal and squamous cell skin cancers are diagnosed every year in the US. ΔNp63a, a member of the p53 transcription factor family, is overexpressed in non-melanoma skin cancer and regulates cell survival, migration and invasion. TIP60 is histone acetyltransferase (HAT) which mediates cellular processes such as transcription and the DNA damage response (DDR). Previous studies in our lab have shown that overexpression of TIP60 induces ΔNp63a protein stabilization in a catalytic-dependent manner. Since ΔNp63a is known to transcriptionally regulate several DDR genes and promote cisplatin resistance, its stabilization by TIP60 may contribute to the failure of platinum-based …

Development Of Inhalable Nano-Lipid Carriers For The Treatment Of Pulmonary Aspergillosis Using Hot Melt Extrusion Technology, Gauri Shadambikar

Graduate Student Council Research Grants

Overview: I am Gauri Shadambikar, second year PhD. student in department of Pharmaceutics and Drug Delivery. Pulmonary Aspergillosis is an infection caused by a type of mold and can have serious effects on patients with a weak immune system or with underlying lung disease1. Itraconazole, a triazole is a compound with a broad antifungal spectrum. 2. An inhalation-based drug delivery system has the advantage of rapid onset of action directly at the site of infection along with controlled and prolonged delivery. 3. Hence the aim of my project was to prepare inhalable nano-lipid carriers (NLC) which would be a viable …

Assessment Of Underlying Neurocircuitry In Dysregulation Of The Hypothalamic Pituitary Adrenal Stress Axis In Hiv-1 Tat Male Mice, Salahuddin Mohammed

Graduate Student Council Research Grants

Overview: My name is Salahuddin Mohammed, a 2nd year PhD graduate student from Dr. Jason Paris’ Lab. My research dissertation focuses on investigating the neuroendocrine underpinnings of HIV-and opioid-mediated anxiety-/depression-like behavior and cognitive impairment via experiments utilizing humans and animal models. Through this work I strive to delineate the underlying mechanism for the neuroHIV symptomology and develop novel therapeutic agents which can ameliorate HIV-1 mediated Tat-neurotoxicity. Approximately 50% of the HIV infected patients suffer from HIV associated neurocognitive disorders (HAND) which can be exacerbated by drug use/abuse. Some neuroHIV symptoms include anxiety, major depressive disorder, neurocognitive impairment, and additional psychiatric …

Development Of Itraconazole Topical Formulation In Skin Cancer Treatment, Praveen Kolimi

Graduate Student Council Research Grants

Overview: I, Praveen Kolimi, pursuing a first-year graduate program at the department of pharmaceutics and drug delivery. This Graduate Student Council (GSC) grant proposal focus on topical application of Itraconazole (ICZ) in skin cancer treatment.

Intellectual Merit: 5.4 million skin cancer cases are reported each year in the United States. A study disclosed that one among five Americans are likely to develop skin cancer in their entire life. 9. Skin cancer can be distinguished into two types, malignant melanoma (MM) and non-melanoma skin cancer (NMSC) 1, 8. NMSC further classified into squamous cell carcinoma (SCC) and basal cell carcinoma (BCC)8, …

The Role Of Insulin-Like Growth Factor 1 In Specific Brain Cells Following Ischemia, Cellas Hayes

Graduate Student Council Research Grants

Overview: My name is Cellas Ari’ka Hayes, and I am a first-year graduate student in the School of Pharmacy Department of BioMolecular Sciences. I am pursuing a Ph.D. in Pharmaceutical Sciences with an emphasis in Pharmacology. My project will assess the effects of insulin-like growth factor-1(IGF-1), an anabolic polypeptide on the damage caused by ischemic stroke including glial cell death, neuronal tress, infarct size, neurological deficits, and behavioral changes.

Intellectual Merit: Ischemia is one of the largest causes of neurological deficits that in elderly individuals in the United States [1]. Since our life expectancy has increased concurrently without predispositions to …

Α-Tocopherol Succinate Nanostructured Lipid Carriers For The Ocular Delivery Of The Anti-Neoplastic Agent, Sushrut Marathe

Graduate Student Council Research Grants

Overview: Retinoblastoma (RB) is a rare form of cancer that rapidly develops from the immature cells of the retina, the light-detecting tissue of the eye. The treatment options of RB has been limited to enucleation, external beam radiotherapy, episcleral plaque radiotherapy and cryotherapy. α-Tocopherol succinate(αTS), has been proven to an effective apoptogenic agent. It can enhance the efficiency of the anticancer agent1. Paclitaxel (Ptx) is a potent chemo agent and is widely used in the treatment of various types of cancers. However, clinical use of Paclitaxelis limited by systemic toxicity, rapid clearance and resistance 2,3.The formulation of paclitaxel poses the …

The Reliability Of Histamine Pharmacodynamic Response Phenotype Classification In Children With Allergic Disease., Shaun S Kumar, Xiaoxi Liu, Catherine M Sherwin, Bridgette Jones

Manuscripts, Articles, Book Chapters and Other Papers

We have identified distinct histamine pharmacodynamic response phenotypes in children with allergic disease utilizing histamine iontophoresis with laser Doppler (HILD). These response phenotypes may be relevant in guiding therapeutic decision making for agents targeting the allergic response pathways. However, the reliability of these response phenotypes has not been assessed. Therefore, we performed HILD in children with allergic rhinitis and/or asthma on two to three separate occasions. HILD response-time data were analyzed in NONMEM using a linked effect PKPD model. Examination of observed vs. classified response phenotypes predicted response plots and the sum of residuals. The intraclass correlation coefficient (ICC) was …

Immunogenicity In Clinical Practice And Drug Development: When Is It Significant?, Valentina Shakhnovich, Bernd Meibohm, Amy Rosenberg, Andrzej M. Kierzek, Rachel Hasenkamp, Ryan S. Funk, Craig J. Thalhauser, Piet H. Van Der Graaf, Yow Ming C. Wang, Lora Hamuro

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Protection Against Acute Cerebral Ischemia/Reperfusion Injury By Qishenyiqi Via Neuroinflammatory Network Mobilization, Yule Wang, Guangxu Xiao, Xhuang He, Xinyan Liu, Lin Zhu, Xinyue Yang, Yiqian Zhang, John Orgah, Benjamin Feng, Xiaoying Wang, Boli Zhang, Yan Zhu

Peer Reviewed Articles

Cerebral ischemia/reperfusion injury (CI/RI) is a common feature of ischemic stroke, involving a period of impaired blood supply to the brain, followed by the restoration of cerebral perfusion through medical intervention. Although ischemia and reperfusion brain damage is a complex pathological process with an unclear physiological mechanism, more attention is currently focused on the neuroinflammatory response of an ischemia/reperfusion origin, and anti-inflammatory appears to be a potential therapeutic strategy following ischemic stroke. QiShenYiQi (QSYQ), a component-based Chinese medicine with Qi-tonifying and blood-activating property, has pharmacological actions of anti-inflammatory, antioxidant, mitochondrial protectant, anti-apoptosis, and antiplatelet aggregation. We have previously reported that …

Activation Of The Sonic Hedgehog Effector Smoothened Counteracts L-Dopa Induced Dyskinesia By Restoring Cholinergic Interneuron Function, Lauren Malave

Dissertations, Theses, and Capstone Projects

Many types of neurons act as multimodal signaling centers. Yet, we have only limited insight into the regulation and functional consequences of neuronal co-transmission. For example, dopamine (DA) neurons, whose degeneration causes motor deficits characteristic of Parkinson’s Diseases (PD), communicate with all their targets by DA but only a selective subset of their targets using GABA, Glutamate, and the secreted cell signaling protein Sonic Hedgehog (Shh). It is unknown whether Levo-dopamine (L-Dopa) induced dyskinesia (LIDs), a severely debilitating side effect of DA supplementation in PD, might appear because DA neuron targets are exposed to high DA- but low Shh- signaling …

Functional Significance Of Endothelial Sigma-1 Receptors In Vascular Reactivity And Barrier Function, Zeinab Y. Motawe

USF Tampa Graduate Theses and Dissertations

The sigma-1 receptor (σ1) is a single 25 kD polypeptide that acts as a chaperone protein residing primarily in the endoplasmic reticulum Its interaction with mitochondria at the mitochondria-associated ER membrane domain is well-documented. Following activation, σ1 binds to the inositol trisphosphate receptor (Hayashi & Su), and modulates intracellular calcium homeostasis. Also, the activated σ1 modulates plasma membrane receptors and ion channel functions, and may regulate cellular excitability. Further, σ1 affects trafficking of lipids and proteins essential for neurotransmission, cell growth and motility. Activation of σ1 provides neuroprotection and cardio-protection in various models. Examples of neuroprotection include but not limited …

Neurodevelopment Outcome Of Neonates Treated With Intraventricular Colistin For Ventriculitis Caused By Multiple Drug-Resistant Pathogens-A Case Series, Kashif Hussain, Muhammad Sohail Salat, Gul Ambreen, Javaid Iqbal

Department of Biological & Biomedical Sciences

Background: Multiple-drug-resistant Gram-negative bacteria (MDR-GNB)-associated neonatal ventriculitis is a life-threatening complication that needs timely diagnosis and effective treatment with broad-spectrum antimicrobials in critical-care settings. Inadequate penetration of antibiotics through the blood-brain barrier also demands an intraventricular (IVT) route of administration. This study reports mortality and neurodevelopmental sequelae of neonates till 18 months of age, who received IVT-colistin for treating MDR-GNB associated ventriculitis.
Methods: In a case series of seven neonates with ventriculitis due to MDR-GNB at NICU of Aga Khan University Hospital, Pakistan, between June 2015 and 2018, we reviewed IVT-colistin therapy in critically ill neonates. Treatment outcomes were assessed …

Xuebijing Injection Maintains Grp78 Expression To Prevent Candida Albicans–Induced Epithelial Death In The Kidney, Ting Shang, Qilin Yu, Tongtong Ren, Xin-Tong Wang, Hongyan Zhu, Jia-Ming Gao, Guixiang Pan, Xiumei Gao, Yan Zhu, Benjamin Feng, Ming-Chun Li

Peer Reviewed Articles

Sepsis and septic shock threaten the survival of millions of patients in the intensive care unit. Secondary fungal infections significantly increased the risk of mortality in sepsis patients. Chinese medicine Xuebijing injection (XBJ) has been routinely used as an add-on treatment to sepsis and septic shock in China. Our network pharmacology analysis predicted that XBJ also influences fungal infection, consisting with results of pioneer clinical studies. We conducted in vivo and in vitro experiments to verify this prediction. To our surprise, XBJ rescued mice from lethal Candida sepsis in a disseminated Candida albicans infection model and abolished the colonization of …

Exploring Tsrna Function In Aggressive Breast Cancer Cell Models, Caroline Adams

Graduate College Dissertations and Theses

Abstract

Breast cancer is highly prevalent in the United States with an estimated 260,000 women diagnosed with invasive breast cancer in 2018 alone. There is a growing need to identify the molecular drivers of metastatic breast cancer as the molecular mechanisms responsible for the transition from normal mammary epithelial cells to aggressive cancer cells remain poorly understood. Understanding this transition may reveal a therapeutic target for aggressive breast cancer. Small, noncoding RNAs (ncRNA), such as microRNAs (miRNAs), have recently been discovered to promote initiation, progression, and metastasis of breast cancer. Similar in size to miRNAs, tRNA-derived small RNAs (tsRNAs) are …

Pharmacological Inhibition Of Hif-1 Alpha And Its Effects On Dendritic Cell Metabolic Reprogramming, Warrick Sahene

Graduate College Dissertations and Theses

Dendritic cells (DCs) are antigen presenting cells (APCs), a subtype of immune cells that present cellular information to T cells in the immune system. Hypoxia inducible factor 1 alpha (HIF-1 alpha) is an important transcription factor that facilitates dendritic cell metabolism by upregulating glycolysis in activated DCs. In this project, we examined the effects of HIF-1 alpha inhibition on metabolic processes of dendritic cells. Using techniques such as flow cytometry, western blotting, and extracellular flux analyzers, we used a selective inhibitor of HIF-1 alpha to test the hypothesis that HIF-1 alpha promotes glycolytic dependent processes such as glucose production, survival, …

Reducing Reperfusion Injury In An Adult Rat Stroke Model With St-115 Treatment, Morgan Rae Lenz

Master's Theses

The restoration of blood flow to ischemic cerebral tissue can result in reperfusion injury, and blocking reperfusion injury can significantly aid in recovery of ischemic tissue. Bradykinin has been shown to exhibit protective effects, but does not reach protective levels during reperfusion due to inactivation by aminopeptidase P2 (APP2). Therefore, inhibiting APP2 during reperfusion is a potential therapeutic strategy to aid in the reduction of reperfusion injury, leading to the development of ST-115, an APP2 inhibitor. It was hypothesized that administration of ST-115 during ischemic stroke, and just prior to reperfusion, will result in reduced neurological injury and increased functional …

Tsrna Involvement In Promoting Breast Cancer Phenotypes, Stephanie Scalia

Graduate College Dissertations and Theses

The overall 5-year survival rate for woman diagnosed with breast cancer has increased significantly over the last 20 years. However, prognosis for women with stage IV, metastatic disease remains very poor. Women diagnosed with stage 0-III breast cancer have above an 85% chance of survival over a 5-year period while women diagnosed with stage IV breast cancer have a 5-year survival of less than 30%. A better understanding of the molecular mechanisms driving aggressive breast cancer is essential for the potential discovery of more targeted therapies to increase the survival rates for women diagnosed with stage IV breast cancer.

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Finding Brain Predictors Of Psychostimulant Medication Use In Adhd Using Machine Learning, Zoe Irene Hulce

Graduate College Dissertations and Theses

Psychostimulant medication is the first line of treatment for Attention deficit/hyperactivity disorder (ADHD). Despite the prevalence of ADHD, there is a lack of understanding of the underlying neurophysiological mechanisms of the disorder and its pharmacological treatments. Existing neuroimaging research shows some consistent structural differences in ADHD, but it can be difficult to discern what is relevant. Machine learning algorithms present a novel way of analyzing a large amount of data by making predictions based on pattern detection.

The present study applied an elastic-net logistic machine learning model to structural magnetic resonance imaging (sMRI) data from the Adolescent Brain Cognitive Development …