Pharmacology, Toxicology and Environmental Health Commons^™

Structural Characterization And In Vitro Antiproliferative Activity Of Non-Specific Lipid Transfer Protein 1 (Nsltp1) From Fennel (Foeniculum Vulgare) Seeds, Mekdes Megeressa

Pharmaceutical Sciences (PhD) Dissertations

Non-specific lipid transfer proteins (nsLTPs) are cationic proteins involved in intracellular lipid shuttling, in growth and reproduction, as well as in defense against pathogenic microbes. Even though the primary and spatial structures of some nsLTPs from different plants indicate their similar features, they exhibit distinct lipid-binding specificities signifying their various biological roles that dictate further structural study. The present study determined the complete amino acid sequence, in silico 3D structure modeling, and in vitro antiproliferative activity of nsLTP1 from fennel (Foeniculum vulgare) seeds.

Fennel is a member of the family Umbelliferae (Apiaceae) native to southern Europe and the …

Upadacitinib, Inderbir S. Padda, Rajat Bhatt, Mayur S. Parmar

HPD Articles

No abstract provided.

Tofacitinib, Inderbir S. Padda, Rajat Bhatt, Mayur S. Parmar

HPD Articles

No abstract provided.

What Common Factors May Influence The Success Of Dental Implant?, Yehuda Taavar

The Science Journal of the Lander College of Arts and Sciences

The aim of this study is to investigate the common factors that may influence the success of dental implants. Addressing these factors may potentially aid experts in the field in delivering dental implants without approaching or decreasing the number of failures. Smoking, diabetes, implant maintenance, age, and implant size have significantly influenced implant success. It is suggested that patients are advised to quit smoking at least one week before surgery to minimize risk factors. Inadequate glycemic control also contributes to periodontal destruction and is associated with the severity of peri-implant complications. However, if patients maintain good glycemic control, dental implants …

Early Insulin Deficiency-Related Hyperphagia Antecedes Hyperinsulinemia And Obesity, Rana Abdelgawad

Browse all Theses and Dissertations

Insulin secretion plays a crucial role in energy homeostasis. Accordingly, disrupted insulin secretion has been associated with metabolic disorders such as insulin resistance syndrome and diabetes mellitus. Insulin secretion from pancreatic β-cells is tightly regulated by complex ionic mechanisms usually included in a consensus mechanism involving ATP-sensitive K+ channels as the only key player. However, K+ channels solely do not reflect the whole mechanism. Anionic channels also contribute to the machinery of insulin secretion by initiating electrogenic Cl– fluxes in β-cells. The Na+K+2Cl– cotransporter 1 (Nkcc1) and other Cl– transporters participate in the non-equilibrium distribution of Cl– in β-cells. Recent …

Propranolol Sensitizes Vascular Sarcoma Cells To Doxorubicin By Altering Lysosomal Drug Sequestration And Drug Efflux, Jhuma Saha, Jong Hyuk Kim, Clarissa N. Amaya, Caleb M. Witcher, Ali Khammanivong, Derek M. Korpela, David R. Brown, Josephine Taylor, Brad A. Bryan, Erin B. Dickerson

Faculty Publications

Angiosarcoma is a rare cancer of blood vessel–forming cells with a high patient mortality and few treatment options. Although chemotherapy often produces initial clinical responses, outcomes remain poor, largely due to the development of drug resistance. We previously identified a subset of doxorubicin-resistant cells in human angiosarcoma and canine hemangiosarcoma cell lines that exhibit high lysosomal accumulation of doxorubicin. Hydrophobic, weak base chemotherapeutics, like doxorubicin, are known to sequester within lysosomes, promoting resistance by limiting drug accessibility to cellular targets. Drug synergy between the beta adrenergic receptor (β-AR) antagonist, propranolol, and multiple chemotherapeutics has been documented in vitro, and …

Anticancer Effect Of Indanone-Based Thiazolyl Hydrazone Derivative On P53 Mutant Colon Cancer Cell Lines: In Vitro And In Vivo Study, Silpa Narayanan

Theses and Dissertations

Colorectal cancer is the third leading cause of cancer related deaths in the United States. Currently, irinotecan, a topoisomerase I inhibitor, is an important anticancer drug approved for patients with advanced or recurrent colorectal cancer. Considering the low response rate and the events of high toxicity caused by irinotecan, we evaluated a series of thirteen thiazolyl hydrazone derivatives of 1-indanone for their potential antineoplastic activity and four compounds showed promising anticancer activity against most of the tested colon cancer cell lines with IC50 values ranging from 0.41 ± 0.19 to 6.85 ± 1.44 μM. It is noteworthy that the compound, …

Effect Of Inhibition Of Glycogen Catabolism In Hepatocellular Carcinoma Cells, Shrikant Barot

Theses and Dissertations

Metabolic reprogramming is one of the important features of cancers, and there has been growing interest in targeting metabolic proteins to treat cancer. Glycogen is a polymer of glucose and serves as its storage unit in cells. Glycogen can provide energy to cells during the situations of high energy demand. A number of tumors are known to contain high levels of glycogen than their normal tissue counterparts. The liver plays an essential role in maintaining glucose homeostasis in the body via storing it into glycogen. The significance of glycogen metabolism in patients suffering from hepatocellular carcinoma (HCC) has not been …

Boost The Dsicovery Of Mrp7/Abcc10 Substrates And Inhibitors: Establishment Of New In Vitro And In Silico Models, Jingquan Wang

Theses and Dissertations

ATP-binding cassette (ABC) transporters are responsible for the efflux of structurally distinct endo- and xenobiotics energized by ATP hydrolysis. MRP7/ABCC10 belongs to the 10th member of subfamily C and responsible for mediating MDR against a series of chemotherapeutic drugs such as taxanes, epothilones, Vinca alkaloids, anthracyclines and epipodophyllotoxins. Establishment of new in silico and in vitro models for MRP7 substrates/inhibitors prediction Considering the limited knowledge of MRP7, we established a homology model based on bovine MRP1 cryo-EM models. The final model was used for protein global motion analysis and docking analysis. Before docking, potential drug binding pockets were identified and …

Design, Synthesis And Pharmacological Evaluation Of Quinazolinamine Derivatives As Bcrp And P-Gp Inhibitors With Improved Metabolic Stability, Chao-Yun Cai

Theses and Dissertations

A series of twenty-two quinazolinamine derivatives showing potent inhibitory activities on BCRP and P-gp was synthesized. The reversal study showed that when combined with the potent dual BCRP and P-gp inhibitors 7-8, 29-31, and 34, the IC50 value of mitoxantrone was decreased from 6.50 µM to the range of 0.24 - 0.35 µM for BCRP, and IC50 value of colchicine was decreased from 7.34 μM to the range of 0.12 - 0.29 µM for P-gp. Cyclopropyl quinazolinamine 29 (VKCY-1), which was a dual BCRP and P-gp inhibitor, and azide quinazolinamine 40 (VKCY-2), which was a BCRP inhibitor, were selected for …

Understanding Pathophysiology Of Nonsyndromic Autism By Examining And Extrapolating From Syndromic Variants, Alexander Labkowsky

The Science Journal of the Lander College of Arts and Sciences

Autism spectrum disorder (ASD) is a broad, heterogeneous neurodevelopmental disorder encompassing a range of presentation and severity. The common characteristics include communication deficits, impaired social skills, dependency on routine, sensitivity to environmental change, and stereotyped behavior (DSM-5, 2013). When ASD is accompanied by a host of other symptoms it is often referred to as syndromic autism. Syndromic autism is usually severe and can usually be traced to deletions or duplications on a specific gene. These monogenic disorders are by definition easier to diagnose and are good candidates for study since specific biological markers can be assessed and tracked. There have …

The Role Of Immunotherapy In Treating High-Risk Neuroblastoma, Mollie Raczkowski

The Science Journal of the Lander College of Arts and Sciences

Neuroblastoma originates from the cells in the neural crest. High-risk neuroblastoma, patients have poor outcomes even with the multi-step treatment plans, including immunotherapy maintenance treatment. Researchers in developmental biology search for unique antigens in neuroblastoma cells to utilize monoclonal antibodies (mAbs). Currently, GD2 is the most effective antigen that scientists have isolated in the tumor; these anti-GD2 mAbs are administered in the forms of Dinutuximab or Dinutuximab beta to attack the tumor. Monoclonal antibodies are currently administered in neuroblastoma instead of CAR T (that has seen success in curing different types of leukemias) due to the heterogeneity of this tumor. …

Etiology And Associations Of Oral And Oropharyngeal Cancer, Aron Yaghar

The Science Journal of the Lander College of Arts and Sciences

This research paper discusses oral cavity cancer, which is one of the 11th most common cancers in the world. According to newer research, some important possible causes include smokeless tobacco, marijuana, and citrus fruits. Some research attributes it to one’s genetic makeup and include exposure to Human Papillomavirus (HPV) and diagnosis of Diabetes mellitus, all in conjunction with one’s age. In this research paper, each of these factors are discussed in depth, and their association with this illness is considered and debated. Review of the literature reveals that the high concentrations of nicotine found in smokeless tobacco products is deleterious …

Open Neuroscience Initiative, Austin Lim

College of Science and Health Full Text Publications

The Open Neuroscience Initiative is a free-to-use textbook

This project began as a means to overcoming the financial burden that face undergraduate neuroscience students when buying textbooks. By compiling and writing a completely free-to-access textbook that covers the foundations of a typical college introduction to neuroscience course, students would have one less obstacle to overcome in their educational career, allowing them to focus their valuable time and attention on learning rather than finances. To make this project a reality, I began with a humble tweet in May 2019 that managed to gain a tiny bit of traction among the neuroscience …

Pharmaceuticals In The Environment: Health Implications And Environmental Toxicity, Jessica Phillips

Wayne State University Dissertations

Approximately 2.9 billion prescriptions are written annually in the United States, with a multitude of biochemical actions, with 63151 tons used by food producing animals worldwide and an additional 55-77 million prescriptions written for companion animals. With increasing prescription and unknown toxicologic effects of many of these chemicals, zebrafish (danio rerio), an NIH approved human model, were used to model potentially health effects. Significant abnormalities were seen with extended duration metformin exposure from 4 hours post fertilization up to 5 days post fertilization, although short term metformin exposure for 24 hours at 4-5 days post fertilization did not lead to …

Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Tools And Antimicrobial Agents, David Salehi

Pharmaceutical Sciences (MS) Theses

Cell-penetrating peptides containing arginine as positively charged residues and tryptophan or diphenylalanine as hydrophobic residues were synthesized. The synthesis was accomplished through the Fmoc solid-phase peptide synthesis in the presence of HBTU and DIPEA. The side-chain protected linear peptides were cleaved from the resin and cyclized in the presence of DIC and HOAt in the solution phase overnight. MALDI-TOF mass spectrometry was used to characterize the peptides.

The cytotoxicity of the synthesized peptides was determined in CCRF-CEM (human, lymphoblast peripheral blood), and HEK-293 (human, embryonic epithelial kidney healthy) cells using the MTS assay. A concentration of 10 µM was found …

The Effect Of Nutrition Education On Nutrition Knowledge In Low-Income Minority Adults, Samantha Lindsay, Isabella Dillon

Williams Honors College, Honors Research Projects

The availability of health and nutrition knowledge is disproportionately lower in minority populations compared to their majority counterparts despite minority populations at higher risk for health problems related to poor dietary habits from cultural and social influences. The purpose of this project was to determine if a weekly, culturally competent, group-delivered, nutrition education intervention affected nutrition knowledge in minority adults. The project was a smaller arm of the FABU study, which provided the education intervention. This study was guided by Bandura’s Social Cognitive Theory and used a quantitative non-experimental design with a convenience sample of adults living in lower-income, minority …

Valorization Of Xylan In Agroforestry Waste Streams, Harrison Appiah

Graduate Theses, Dissertations, and Problem Reports (ETD)

Valorization of Xylan in Agroforestry Waste Streams.

Harrison Appiah

Microwave-assisted deep eutectic solvent and gamma-valerolactone metallic chloride catalyzed conversion of xylan to furfural were investigated using a 2x3 factorial experimental design at two levels of percent microwave power, reaction time, and catalyst concentration. The levels of each factor studied were (20%, 60% microwave power, 2, 4 minutes, and 10, 20mg) respectively. The effect of three metallic chloride catalysts (LiCl, FeCl3.6H20, CuCl2) on the conversion of xylan to furfural was also investigated. The gamma-valerolactone-ferric chloride sent system exhibited the highest mean yield of furfural (56.50%). The next highest furfural yield of …

Investigating Lifespan And Legacy Health Effects Of Developmental Exposure To Environmental Toxicants, Danielle Meyer

Wayne State University Dissertations

The environmental presence of toxicants such as persistent organic pollutants, heavy metals, and contaminants of emerging concern is estimated to contribute to over 2 million deaths worldwide and health care costs ranging from ~3-9% of total global expenditures yearly. Many of the above toxicants are classified as endocrine-disrupting chemicals capable of interfering with endogenous hormonal function at environmentally relevant levels. Exposures during sensitive developmental windows can lead to reproductive, neurodevelopmental, and metabolic dysfunction that can last across the lifespan and/or be passed down to future generations. Such long-term effects remain to be well-understood; therefore, we modeled the effects of various …

Maternal Proximity To Mountaintop Removal Mining And Birth Defects In Appalachian Kentucky, 1997-2003, Daniel B. Cooper

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Background: Extraction of coal through mountaintop removal mining (MTR) alters many dimensions of the landscape, and explosive blasts, exposed rock, and coal washing have the potential to pollute air and water with substances known to increase risk of developmental and birth anomalies. Previous research suggests that infants born to mothers living in MTR coal mining counties have higher prevalence of most types of birth defects.

Objectives: This study seeks to examine further the relationship between MTR activity and birth defects by employing individual level exposure estimation through precise satellite data of MTR activity in the Appalachian region and maternal residence …