Pharmacology, Toxicology and Environmental Health Commons^™

Metformin In Overcoming Enzalutamide Resistance In Castration-Resistant Prostate Cancer, Kendall Simpson, Derek B. Allison, Daheng He, Jinpeng Liu, Chi Wang, Xiaoqi Liu

Markey Cancer Center Faculty Publications

Androgen deprivation is the standard treatment for patients with prostate cancer. However, the disease eventually progresses as castration-resistant prostate cancer (CRPC). Enzalutamide, an androgen receptor inhibitor, is a typical drug for treating CRPC and with continuous reliance on the drug, can lead to enzalutamide resistance. This highlights the necessity for developing novel therapeutic targets to combat the gain of resistance. Metformin has been recently investigated for its potential antitumorigenic effects in many cancer types. In this study, we used enzalutamide and metformin in combination to explore the possible rescued efficacy of enzalutamide in the treatment of enzalutamide-resistant CRPC. We first …

Astrovascular Decoupling In Awake 5×Fad Mice Is Associated With Reduced Astrocytic Calcium, Ruei-Lung Lin, Sophiya L. Sims, Nicholas A. Wright, Léopoldine B. Galopin, Blaine Weiss, Susan D. Kraner, Jacquelyn E. Rhinehart, Ting-Hsuan Lu, Pradoldej Sompol, Christopher M. Norris, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

INTRODUCTION

Evidence points to dysregulated Ca²⁺ in neurons and astrocytes in models of amyloidosis. While most of these data were obtained in vitro or in vivo under anesthesia, less work has investigated these variables in awake ambulating mice.

METHODS

Astrocytic Ca²⁺ fluctuations (GCaMP8f) were imaged concomitantly with vasoreactivity in S1 on a two-photon microscope during rest and ambulation. Single-cell resolution variables were extracted using continuous wavelet transform and traditional ΔF/F measures.

RESULTS

Along with increases in amyloid beta (Aβ) accumulation, we found significant reductions in measures of astrocyte functional connectivity, pairwise correlations, and network synchronicity in older 5×FAD …

Advancing Clinical Trial Readiness In White Matter Disease And Related Dementias: Key Steps For Future Research Progress, Pradoldej Sompol, Gregory A. Jicha, Jason D. Hinman, Adam M. Brickman, Steven M. Greenberg, Konstantinos Arfanakis, Marion S. Buckwalter, Irene Lorenzo Llorente, Jeff D. Williamson, Michael S. Wolf, Eric E. Smith, Aditi Gupta, Margaret E. Flanagan, Miguel A. Vazquez, Jeffrey M. Burns, S. Thomas Carmichael, Frank C. Barone

Pharmacology and Nutritional Sciences Faculty Publications

White matter disease, a broad-spectrum term that covers various types of white matter lesions and degeneration, is strongly related to age-related neurodegenerative disorders including Alzheimer’s disease (AD), and vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer’s related dementias (ADRD). There is no specific treatment for white matter disease. Therefore, basic research and clinical studies are essential for future outcomes. Since its formation in 2020, the Albert Research Institute for White Matter and Cognition (ARIWMC) mission has been to support white matter research by providing a forum for communication where basic and clinical scientists meet to discuss and debate …

Identification Of Pharmacophore Modifications That Enhance Bmp-Receptor Agonism, An Investigation To Understand The Development Of Potential Therapeutic Interventions, Maleka T. Stewart

Theses and Dissertations

Bone morphogenetic proteins (BMPs) are the largest subfamily of the Transforming Growth Factor (TGF)-ß superfamily. BMPs are renowned for their pivotal role in cellular functions such as cell growth, apoptosis, and differentiation. Yet, BMPs have also been attributed to the maintenance of adult tissue homeostasis. BMPs elicit physiological function at the cell membrane via a heterotetrameric complex composed of two Type I and two Type II serine-threonine kinase BMP receptors. Activation of BMP transmembrane receptors results in activation of either canonical (Smad-dependent) and/or non-canonical (Smad-independent) signaling. Given the physiological importance of this intricate communication between receptor activation and induction of …

Effects Of Educational Intervention On Asthmatic Children, Zoe Coggins

Nursing | Senior Theses

Abstract

Children are more vulnerable to asthmatic symptoms due to the physiological immaturity of their respiratory systems. Therefore, irritants are deemed more hazardous for the pediatric population. Pollution is a growing health concern, and within the literature review, several approaches to the measurement of the impact of low air quality and educational interventions are discussed. The themes identified in the literature review are increased risk of pollution-induced exacerbation due to age, behavior, and residential proximity to emission-producing facilities. The review of the literature demonstrated how pollution is a growing public health concern, especially among the pediatric population. Interventions, reviewed in …

Navigating Wastewater: Minnesota Mining Wastewater Permit Challenges And Evolving Compliance Standards, Madelaine Adamich

Journal of Earth and Life Science

February of 2021 marked the beginning of Minnesota clearly establishing that groundwater qualifies as a Class 1 water in a legal battle involving United States Steel, the Minnesota Pollution Control Agency, WaterLegacy, Fond du Lac Band of Lake Superior Chippewa, the Minnesota Court of Appeals, and eventually the Minnesota Supreme Court (MNSC). Minnesota has a water classification system, as required by the federal Clean Water Act, with 7 classes of use. Class 1 waters are waters used for domestic consumption (MPCA 4, n.d.). According to Minnesota Statute § 7050.0220, the acceptable level for sulfate is 250 mg/L in Class 1 …

Aquatic Invertebrate Populations In Roadside Wetlands In Relation To Water Characteristics, Ellen P. Isakson

Journal of Earth and Life Science

The continual habitat destruction and draining of wetland systems makes the need to understand the ecology of roadside wetlands all the more necessary. Roadside wetlands provide valuable habitat to countless aquatic invertebrates, which can provide insight into the health of the wetland system due to their diversity. The objective of this study was to analyze the populations of aquatic invertebrates in roadside wetlands in relation to water characteristics such as pH, salinity, conductivity, water depth and temperature, and dissolved oxygen. This was done by collecting samples of invertebrate populations from roadside wetlands, in addition to data on water quality characteristics …

Potentiation Of Gelonin Cytotoxicity By Pulsed Electric Fields, Olga N. Pakhomova, Eleni Zivla, Giedre Silkuniene, Mantas Silkunas, Andrei G. Pakhomov

Bioelectrics Publications

Gelonin is a ribosome-inactivating protein with extreme intracellular toxicity but poor permeation into cells. Targeted disruption of cell membranes to facilitate gelonin entry is explored for cancer and tissue ablation. We demonstrate a hundreds- to thousands-fold enhancement of gelonin cytotoxicity by pulsed electric fields in the T24, U-87, and CT26 cell lines. The effective gelonin concentration to kill 50% of cells (EC₅₀) after electroporation ranged from <1 nM to about 100 nM. For intact cells, the EC₅₀ was unattainable even at the highest gelonin concentration of 1000 nM, which reduced cell survival by only 5–15%. For isoeffective electroporation treatments using 300 ns, 9 µs, and 100 µs pulses, longer pulses were more efficient at lowering gelonin EC₅₀. Increasing the electric field strength of 8, 100 µs pulses from 0.65 to 1.25 kV/cm reduced gelonin EC₅₀ from 128 nM to 0.72 nM. Conversely, the presence of 100 nM gelonin enabled a more than 20-fold reduction in the number of pulses required for equivalent cell killing. Pulsed electric field-mediated delivery of gelonin shows promise for hyperplasia ablation at concentrations sufficiently low to minimize or avoid systemic toxicity.

Verification Of Real-Time Smoke Simulations: A Case Study On Early Summer North American Wildfire Events, Daniel Bonilla

Pitzer Senior Theses

As wildfire intensity and frequency escalate in times of unprecedented climate change and severe droughts, it is important to enhance forecasting models that accurately and efficiently predict wildfire smoke movement. NOAA’s experimental Rapid-Refresh Forecasting System with Smoke and Dust (RRFS-SD) aims to improve upon the High-Resolution Rapid Refresh- Smoke (HRRR-Smoke), by extending the domain to include all of North America and incorporating new developments in physics and wildfire parameterizations. Our work explores the process of adding satellite Aerosol Optical Depth (AOD) data, through AERONET, as an additional method of verification of the RRFS-SD experimental model. Using a case study on …

Adaptation For Whom? Understanding The Impacts Of Dyke Policies On Small-Scale Farmers In Ca Mau Province Of Vietnam, Nguyen Minh Quang, Nguyen Van Minh, Nguyen Vo Chau Ngan, Martha B. Lerski

Publications and Research

Low-lying deltas worldwide are extremely vulnerable to sea-level rise. As the risks of climate-induced flooding become increasingly clear, the thirst for infrastructure-driven adaptation increases. This highlights a patent need to understand the impacts of engineering adaptation solutions, especially those targeting built structures such as dykes and sluices, on farmers from a bottom-up, farmer-centred perspective. The study addresses this call by examining cases where dyke policies, while successful in some dimensions, have undermined small-scale farmer livelihoods in Ca Mau ― Vietnam’s southernmost rural province. It identifies areas in need of attention and adds empirical data related to this group of farmers. …

Lead Bioaccessibility And Commonly Measured Soil Characteristics (Detroit, Mi, Usa) Phase Ii, Conor T. Gowan, Sabrina R. Good, Allison R. Harris, Patrick Crouch, Shawn P. Mcelmurry

Open Data at Wayne State

Urban soil contaminated with anthropogenic sources of Pb is a major contributor to child Pb exposure. To assess the Pb risk in urban areas, composite samples were collected from 142 voluntary privately owned 142 residential parcels in Detroit, Hamtramck, and Highland Park, Michigan. Samples were collected at two time periods, before and after treatment applied for those denoted as treatment sites. Samples were collected from areas covered with turf grass on the parcels from the front, middle and rear sections. Soils were collected with a bulb planter at approximately 10cm depth and were cleaned with a tap water-Liquinox detergent solution …

Racial Health Disparities Among Pregnant Women Of Color In New York City: Biological And Systemic Impacts, Kaylin Peña

Pitzer Senior Theses

Racial Health Disparities Among Pregnant Women of Color in New York City: Biological and Systemic Impacts

Abstract

This thesis aims to explore how racial health disparities, underrepresentation in gynecology, and socioeconomic barriers contribute to adverse pregnancy outcomes among women of color in New York City. Through an interdisciplinary approach that combines resources from medical anthropology and human biology, this research will examine the biological implications of chronic stress, specifically HPA axis dysregulation, and its role in maternal health outcomes. With the idea of intersectionality, as conceptualized by Kimberlé Crenshaw, the study analyzes the various effects of systemic inequities and social …

Zinc Or Swim: Investigating Zinc Pollution From Restoration Materials, Megan R. Jensik

Honors Undergraduate Theses

Zinc is an essential nutrient, but can be toxic at high concentrations, negatively affecting various biological functions. Gabions are galvanized metals coated in zinc that are used for many human purposes, including coastal restoration efforts attempting to avoid using plastic materials. However, gabions can degrade in marine environments, potentially leaching metal into the water and soil. There is a knowledge gap regarding the occurrence and impacts of zinc pollution in the areas where these gabions are deployed, including the Indian River Lagoon (IRL). To address this, sediment samples were collected from the IRL and analyzed for their physical and chemical …

Jbs’S Initial Public Offering: Threats To Environmental And Human Rights, Kayla Thompson

Indiana Journal of Law and Social Equality

This paper centers around the decision to be made regarding JBS, the world’s largest meat company, wanting to list shares on the New York Stock Exchange (NYSE), and the environmental and social impacts that could result from the Security and Exchange Commission’s (SEC) approval. JBS has been at the center of various controversies over the last several years, including sourcing cattle from ranches acquired through illegal deforestation, engaging in greenwashing practices, incorrectly reporting greenhouse gas emissions, and engaging in human rights abuses. Many environmental groups have filed complaints with the SEC concerning JBS’s bid to list on the NYSE. The …

Effect Of Paxlovid On Neurodevelopmental Disorder Diagnosis Outcomes In Offspring Of Mothers Infected With Sars-Cov-2 During Pregnancy, Simone Rogers

CMC Senior Theses

The onset of the 2020 COVID-19 pandemic brought concern over the effects that this virus would have on pregnancy and fetal outcomes, specifically neurodevelopmental outcomes. Maternal immune activation (MIA), caused by infection during pregnancy, is known to result in neurodevelopmental disorder (NDD) diagnosis in offspring, typically autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). This effect has already been observed in mothers who were infected with COVID-19 during pregnancy. However, in 2023, Paxlovid, the COVID-19 antiviral drug, became available to patients experiencing symptoms of the virus, including pregnant women. Consequently, this study seeks to determine whether the risk of …

Epilepsy: Etiology And Treatment Methods, Avital Nightingale

The Science Journal of the Lander College of Arts and Sciences

Epilepsy is a common neurological disorder that is caused by abnormal electrical activity in the brain. Due to the evolution of our understanding of epilepsy and its causes, a variety of therapeutic options have been developed to modulate seizures and limit their occurrence rate. Medication, diet and surgery have been the traditional treatments offered to individuals suffering from epilepsy but the latest advancements in neurotechnology have given patients with drug resistant epilepsy hope by providing options other than surgery. While the disorder is a complex one and its pathogenesis not yet fully understood, recent research has provided insight into the …

Strategies To Address The Growing Impact Of The Antibiotic Resistance Crisis, Rina Balter

The Science Journal of the Lander College of Arts and Sciences

As time progresses, more bacterial strains are becoming resistant to the antibiotics developed to treat them. Impeding such intractable infections should be a major clinical priority, as previously treatable diseases have begun to incur a fatality rate that will escalate catastrophically unless it is halted. This research paper explores relevant information regarding the advances in developing alternative strategies to antibiotics to combat antimicrobial resistant (AMR) bacteria, within the context of clinical application. Recognizing the profound impact antimicrobial resistance (AMR) will have on patient health enables the implementation of proactive measures to curb the expanding prevalence of multidrug-resistant (MDR) pathogens. This …

Is Placenta Stem Cell Banking Worthwhile?, Chaya Nathan

The Science Journal of the Lander College of Arts and Sciences

Regenerative medicine has gained significant traction due to its potential to repair or replace damaged tissues and organs, with stem cell therapies emerging as a promising avenue for treating various diseases. While bone marrow-derived MSCs (BM-MSCs) are commonly used in clinical settings, their limitations, such as the invasive extraction procedure and limited proliferation capacity, underscore the need for alternative stem cell sources. Placenta-derived mesenchymal stem cells (PDMSCs) represent a promising solution, offering advantages such as greater proliferative capacity, faster expansion rates, and reduced risk of immune rejection compared to adult stem cells. The placenta is a rich source of MSCs, …

Limb Regeneration In Amphibians & Mammals, Jacob Mamrout

The Science Journal of the Lander College of Arts and Sciences

This thesis will give an in-depth analysis into the mechanisms of regeneration that amphibians use and how the blastema forms. It will also discuss genes and proteins that play a role including the P53 gene, Transforming Growth Factor Beta, CD59, and others. Regenerative potential of mammals will be discussed using the information found. Findings include that mammals may have regeneration potential because of the ability we have to deactivate certain genes to allow cells to dedifferentiate.

Gut Microbiome Dysbiosis And Its Contribution To Carcinogenesis, Daphne Grabie

The Science Journal of the Lander College of Arts and Sciences

The gut microbiome, a diverse community of microorganisms within the gastrointestinal (GI) tract, plays a pivotal role in maintaining health through digestion, immune regulation, and homeostasis. Emerging evidence links gut microbiome dysbiosis—a disruption in its composition and function—to the development and progression of various cancers, particularly within the GI tract. This review explores the multifaceted relationship between the gut microbiome and carcinogenesis, highlighting key microbial mechanisms, including chronic inflammation, production of carcinogenic metabolites, and immune modulation. Specific pathogens such as Fusobacterium nucleatum, Escherichia coli, and Helicobacter pylori are implicated in colorectal, gastric, and esophageal cancers, respectively, through pathways that promote …